Derivatives of 3,4-dihydroisoquinoline and pharmaceutical agent comprising its as active component

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention proposes derivative of 3,4-dihydroisoquinoline of the formula (I) or its nontoxic salt and a pharmaceutical agent comprising its as an active component (wherein all symbols have the same values as given in description). Compound of the formula (I) possesses agonistic effect on CB2-receptors and, therefore, it can be used for prophylaxis and/or treatment of different diseases, for example, asthma, nasal allergy, atopic dermatitis, autoimmune diseases, rheumatic arthritis, immune dysfunction, postoperative pain and carcinomatous pain.

EFFECT: valuable medicinal properties of derivatives.

14 cl, 33 tbl, 561 ex

 

The technical field

The present invention relates to a derivative of 3,4-dihydroisoquinoline.

More specifically, the present invention relates to

(1) to the compound of formula (I)

(where all the symbols have the same meanings as described below) and its non-toxic salt,

(2) a method for obtaining and

(3) a pharmaceutical agent comprising it as active ingredient.

Background of invention

Cannabinoid is the generic name Δ9-tetrahydrocannabinol (abbreviated hereinafter as Δ9-THC), which is the main ingredient of marijuana, and which is produced out of hemp and its analogues (Deway, Pharmacol. Rev., 38, 15-178 (1996)), known as the substance that causes euphoria, drowsiness, hallucination, relieves mental stress, etc. (Hollister, Pharmacol. Rev., 38, 1-20 (1986)).

In addition to the previous actions on the Central nervous system reported that systematic consumers marijuana decreases the reactivity of lymphocytes (Naha et al., Science, 183, 419-420 (1974))that marijuana or Δ9-THC reduces the ability of cells to migrate and function of macrophages in vitro (Schwartzfarb et al., J. Clin. Pharmacol., 14, 35-41 (1974); Lopez-Capero et al., J. Leuk. Biol., 39, 679-686 (1986)) and it lowers the resistance to viral infection (Morahan etc., Infect. Immun., 23, 670-674 (1979)), etc., These facts indicate that cannabinoids act not only on the Central nervous system, but also on the peripheral system (especially the immune system).

First described by receptor cannabinoid is SW-receptor, cloned from a cDNA library of the cerebral cortex in 1990 (Matsuda et al., Nature, 346, 561-564 (1990)). Subsequently SW-receptor cloned from a cDNA library HL-60 cell line promilhanes human leukemia (Murano et al., Nature, 365, 61-65 (1993)). Discovered that SW-receptors mainly expressed in the brain and SW receptors expressed in those cells, which are responsible for immunity, for example in the cells of the spleen.

For a long time conceived to adapt cannabinoids for medical uses (Mechiulan, CRC Press, Boca Exploration., 1-20 (1986); Razdan et al., Med. Res. Rev., 3, 119-146 (1983)) and some of them have already been used as a medicine in medicine, for example cesamet (Ward and Holmes, Drugs, 30, 127-144 (1985)). It is assumed that they have an effect through SW-receptor.

On the other hand, the physiological role SV-receptor, which is a peripheral receptor, is still quite unknown, but it is assumed that the connection that acts specifically on SW-receptor (agonist, antagonist), modulates inflammation and/or immune system. In addition, it is assumed that it is effective for relieving pain, inflammation (Calignano et al., Nature, 394, 277-281 (1998)).

p> This serves as proof that those compounds which act specifically on SW-receptor useful for the prophylaxis and/or treatment of various diseases, such as asthma, nasal Allergy, atopic dermatitis, autoimmune disease, rheumatoid arthritis, immune dysfunction, postoperative pain, cancerous pain, etc.

Known derivatives of isoquinoline. For example, in JP63-280069(A) described that the compound of formula (A)

(where aAndrepresents benzo or thieno and R2Aand R3Aare independently hydrogen or (C1-5)alkyl or, taken together with the carbon atom to which they are attached, form a 5 - or 6-membered carbocycle, and R11Arepresents (C1-4)alkyl, halogen, hydroxy and mA is 0, 1, 2 or 3, And whenAndis benzo, DAis IbAetc.;

R1Arepresents hydrogen, (C1-10)alkyl, etc., R5'Arepresents hydrogen or (C1-4)alkyl, R4Arepresents (C1-4)alkoxy or-NR9AR10A(where R9Aand R10Aare independently hydrogen, C1-12 branched or unbranched alkyl, alkenyl or quinil etc. or R9Aand R10Ataken together with the carbon atom to which they are attached, form pyrrolidinyl, piperidinyl, morpholinyl or p is pyrazinyl etc.)) has cardiotoxins activity (groups selected as examples of the description).

In Khim. Geterotsikl. Soedin., 946-949, 7 (1994) described the compound 2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-phenylmethane-1-he (the register. No. 163769-77-5).

Description of the invention

The authors of the present invention conducted intensive study to detect such compounds, which are specifically associated with SW receptor, at the same time found that a derivative of 3,4-dihydroisoquinoline of the formula (I) allows to achieve this goal and created the present invention.

The present invention relates to

(1) a derivative of 3,4-dihydroisoquinoline of the formula (I)

(where R1and R2represent, each independently,

1) hydrogen or

2) C1-8-alkyl or

R1and R2taken together with the carbon atom to which they are attached, form a Cyc1, provided that R1and R2do not represent hydrogen at the same time.

Z represents

1) -CR3R4or

2) -O-,

R3and R4represent, each independently,

1) hydrogen,

2) C1-8-alkyl,

3) C1-8-alkoxy or

4) hydroxy or

R3and R4taken together with the carbon atom to which they are attached, form a Cyc1 or-C(O)-,

R5and R6represent, each independently,

1) hydrogen or

2) C1-8-alkyl, or

R5and R6taken together with the carbon atom to which they recognize the ENES, form Cyc1,

Cyc1, presents R1and R2, R3and R4and R5and R6represent, each independently,

1) C3-10-cycloalkyl or

2) 3-10-membered monocyclic heterocycle comprising 1-2 of heteroatom selected from oxygen, nitrogen or sulphur,

Cyc1 may be substituted for R10.

R10is 1) C1-8-alkyl, 2) C1-8-alkoxy, 3) hydroxy, 4) -COOR11, 5) keto, 6) -SO2R12or 7) -COR13,

R11represents hydrogen or C1-8-alkyl,

R12and R13are 1) C1-8-alkyl or 2) phenyl which may be substituted by C1-8-alkyl,

R7and R8represent, each independently,

1) hydrogen,

2) C1-8-alkyl,

3) C1-8-alkoxy,

4) hydroxy,

5) cyano,

6) halogen,

7) -COOR14,

8) -CONR15R16,

9) Cyc2,

10) C2-8-alkenyl,

11) C2-8-quinil,

12) -NR51R52,

13) nitro,

14) formyl,

15) C2-8 acyl,

16) C1-8-alkyl, substituted hydroxy, C1-8-alkoxy, SUS, -NR51R52or-NR53-Cyc2,

17) -NR54COR55,

18) -NR56SO2R57,

19) -SO2NR58R59,

20) C2-8-alkenyl, replaced by a-COOR14,

21) -CH=N-OH,

22) -(C1-8-alkylene)-NR60-(C1-8-alkylene)-R61or

23) C1-8 alkylthio.

R14represents hydrogen or C1-8-alkyl,

R15and R16represent, each independently, vodor the d or C1-8-alkyl,

R51and R52, R58and R59represent, each independently, hydrogen or C1-8-alkyl,

R53, R54, R56and R60represent, each independently, hydrogen or C1-8-alkyl,

R55represents hydrogen, C1-8-alkyl or C1-8-alkoxy,

R57represents C1-8-alkyl,

R61is-NR62R63or hydroxy,

R62and R63represents, each independently, hydrogen or C1-8-alkyl.

hereinafter referred to as the "ring"

is Cyc2, but the atom attached to the carbonyl is carbon.

Cyc2, presents R7, R8and "ring"means, each independently,

1) C3-15 mono-, bi - or tricyclic (condensed or Spiro) Carballo or

2) 3-15 membered mono-, bi - or tricyclic (condensed or Spiro) heterokonta comprising 1-4 heteroatoms selected from oxygen, nitrogen or sulphur,

Cyc2 may be substituted by 1-5 R17.

R17is

1) C1-8-alkyl, 2) C2-8-alkenyl, 3) C2-8-quinil, 4) C1-8-alkoxy, 5) C1-8 alkylthio, 6) hydroxy, (7) halogen, (8) nitro, 9) keto, 10) carboxy, 11) formyl, 12) cyano, 13) -NR18R19, 14) phenyl, phenoxy or phenylthio, which may be substituted by 1-5 R20, 15) C1-C8-alkyl, C2-8-alkenyl, C1-8-alkoxy or C1-8-alkylthio, which may be substituted by 1-5 R21, 16) -OCOR22 , 17) -CON23R24, 18) -SO2N25R26, 19) -COOR27, 20) -COCOOR28, 21) -COR29, 22) -COCOR30, 23) -NR31COR32, 24) -SO2R33, 25) -NR34SO2R35or 26) -SOR64,

R18and R19, R31and R34represent, each independently, hydrogen or C1-8-alkyl,

R20and R21represent C1-8-alkyl, C1-8-alkoxy, hydroxy, halogen, nitro or-COOR36,

R22and R64represent, each independently, C1-8-alkyl,

R23and R24, R25and R26represent, each independently, hydrogen, C1-8-alkyl or phenyl,

R27, R28, R29, R30, R32, R33and R35are 1) C1-8-alkyl, 2) C2-8-alkenyl, 3) C1-8-alkyl, substituted 1-5 R37, 4) diphenylmethyl, 5) triphenylmethyl, 6) Cyc3, 7) C1-8-alkyl or C2-8-alkenyl, substituted Cyc3, 8) C1-8-alkyl, substituted-O-Cyc3, -S-Cyc3 or-SO2-Cyc3,

R36represents hydrogen or C1-8-alkyl,

R37represents C1-8-alkoxy, C1-8-alkylthio, benzyloxy, halogen, nitro or-COOR38,

R38represents hydrogen, C1-8-alkyl or C2-8-alkenyl,

Cyc3 is

1) C3-15 mono-, bi - or tricyclic (condensed or Spiro) Carballo or

2) 3-15 membered mono-, bi - or tricyclic (condensed or Spiro) heterokonta comprising 1-4 heteroatoms selected from oxygen, azo is a or sulfur, Cyc3 may be substituted by 1-5 R39.

R39is

1) C1-8-alkyl,

2) C2-8-alkenyl,

3) C2-8-quinil,

4) C1-8-alkoxy,

5) C1-8 alkylthio,

6) hydroxy,

7) halogen,

8) nitro,

9) keto,

10) cyano,

11) benzyl,

12) benzyloxy,

13) C1-C8-alkyl, C1-8-alkoxy or C1-8-alkylthio, substituted 1-5 R40,

14) phenyl, phenoxy, phenylthio, phenylsulfonyl or benzoyl which may be substituted by 1-5 R41,

15) -OCOR42,

16) -SO2R43,

17) -NR44COR45,

18) -SO2NR46R47,

19) -COOR48or

20) -NR49R50,

R40represents halogen,

R41represents C1-C8-alkyl, C1-8-alkoxy, halogen or nitro,

R42, R43and R45represent C1-8-alkyl,

R44and R48represent hydrogen or C1-C8-alkyl,

R46and R47, R49and R50represent, each independently, hydrogen or C1-C8-alkyl.

Cyc4 is

1) C5-7-monocyclic Carballo or

2) C5-7-membered monocyclic heterokonta comprising 1-2 of heteroatom selected from the group consisting of oxygen, nitrogen or sulphur,

(called below the dashed line (a)

and

(called below the dashed line (b)

present

1) the bond or 2) a double bond.

R9

1) when the dashed line a represents a bond, the dotted line b represents a double bond and R9no,

2) when the dotted line represents a double bond, the dotted line b represents a bond, R9is hydrogen and R6no, and

3) excluded 2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he),

or its non-toxic salt,

(2) a method for obtaining and

(3) a pharmaceutical agent comprising it as active ingredient.

In the formula (I) C1-8-alkyl is methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl and their isomers.

In the formula (I) C2-8-alkenyl is ethynyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl and their isomers.

In the formula (I) C2-8-quinil is ethinyl, PROPYNYL, butynyl, pentenyl, hexenyl, heptenyl, octenyl and their isomers.

In the formula (I) C1-8-alkoxy is methoxy, ethoxy, propoxy, butoxy, pentox, hexose, heptose, actoxy and their isomers.

In the formula (I) C1-8 alkylthio represents methylthio, ethylthio, propylthio, butylthio, pentylthio, hexylthio, Reptilia, octylthio and their isomers.

In the formula (I) halogen means chlorine atom, bromine, fluorine, iodine.

In the formula (I) C3-10-cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cycloocta is l, cycloneii, cyclodecyl.

In the formula (I) C2-8 acyl is acetyl, propanol, butanol, pentanol, hexanol, heptanol, octanol and their isomers.

In the formula (I) C1-8-alkylene represents methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptameron, octamethylene and their isomers.

In the formula (I) C5-7-monocyclic Carballo is, for example, cyclopentane, cyclohexane, Cycloheptane, cyclopentene, cyclohexene, cycloheptene, cyclopentadiene, cyclohexadiene, cycloheptadiene, benzene, etc.

In the formula (I) a 5-7 membered monocyclic heterokonta comprising 1-2 of heteroatom selected from oxygen, nitrogen or sulfur, a is a 5-7-membered monocyclic heteroaryl comprising 1-2 of heteroatom selected from oxygen, nitrogen or sulfur, or a partially or fully saturated analogues.

5-7-Membered monocyclic heteroaryl comprising 1-2 of heteroatom selected from oxygen, nitrogen or sulphur, represents, for example, pyrrole, imidazole, pyrazole, pyridine, pyrazin, pyrimidine, pyridazine, azepine, diazepine, furan, Piran, oxepin, thiophene, Tian (thiopyran), tiepin, oxazol, isoxazol, thiazole, isothiazol, oxazin, oxazepine, teasin, diazepin etc.

Partially or fully saturated 5 to 7-membered monocyclic heteroaryl comprising 1-2 of heteroatom selected from oxygen, nitrogen or sulfur, pre is is, for example, the ring of pyrroline, pyrrolidine, imidazoline, imidazolidine, pyrazoline, pyrazolidine, dihydropyridines, tetrahydropyridine, piperidine, dihydropyrazine, tetrahydropyridine, piperazine, dihydropyrimidine, tetrahydropyrimidine, perhydrofluorene, dihydropyridine, tetrahydropyridine, perhydrophenanthrene, dihydroetorphine, tetrahydroazepine, perhydroanthracene, dihydrovitamin, tetrahydroazepine, targetrotation, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dehydration (dihydrothiophene), tetrahydrothieno (tetrahydrothiopyran), dihydrooxazolo, tetrahydrooxazolo, dihydroisoxazole, tetrahydrooxazolo, dihydrothiazolo, tetrahydrocarbazole, dihydrothiazolo, tetrahydrocortisol, tetrahydroazepine, perhydroanthracene, tetrahydroazepine, targetrotation, morphine, Timofey, dioxolane, dioxane, dithiolane, dithiane etc.

In the formula (I) 3-10-membered monocyclic heterokonta comprising 1-2 of heteroatom selected from oxygen, nitrogen or sulphur, represents 3-10-membered monocyclic heteroaryl comprising 1-2 of heteroatom selected from 1-2 atoms of oxygen, nitrogen or sulfur, and it is fully saturated analogue.

Fully saturated 3-10 membered monocyclic heteroaryl, including 1-2 heteroatoms, select the data from 1-2 oxygen atoms, nitrogen or sulphur, represents, for example, the ring pyrrolidine, imidazolidine, pyrazolidine, piperidine, piperazine, perhydrofluorene, perhydrophenanthrene, perhydroanthracene, targetrotation, tetrahydrofuran, tetrahydropyran, tetrahydrothiophene, tetrahydrothieno (tetrahydrothiopyran), tetrahydrooxazolo, tetrahydrooxazolo, tetrahydrocarbazole, tetrahydrocortisol, perhydroanthracene, targetrotation, research, thiomorpholine, dioxolane, dioxane, dithiolane, dithiane etc.

In the formula (I) C3-15 mono-, bi - or tricyclic (condensed or Spiro) Carballo is, for example, cyclopropane, CYCLOBUTANE, cyclopentane, cyclohexane, Cycloheptane, cyclooctane, cyclonona, cyclodecane, cyclodecane, cyclododecane, cycletrader, cyclopentene, cyclohexene, cycloheptene, cyclooctene, cyclopentadiene, cyclohexadiene, cycloheptadiene, cyclooctadiene, benzene, inden, naphthalene, indan, tetrahydronaphthalen, bicyclo[3,3,0]octane, bicyclo[4,3,0]nonan, bicyclo[4,4,0]decane, Spiro[4,4]nonan, Spiro[4,5]decane, Spiro[5,5]undecane, fluorene, anthracene, 9,10-dihydroanthracene, bicyclo[3,1,1]heptane, bicyclo[3,3,1]-2-hepten, adamantane, noradsanta, bicyclo[2,2,2]octane, etc.

In the formula (I) C3-15-membered mono-, bi - or tricyclic (condensed or Spiro) heterokonta comprising 1-4 heteroatoms selected from oxygen, nitrogen or sulfur, PR is dstanley C3-15-membered mono-, -bi - or tricyclic (condensed or Spiro) heteroaryl comprising 1-4 heteroatoms selected from oxygen, nitrogen or sulfur, or a partially or fully saturated analogues.

C3-15-membered mono-, bi - or tricyclic (condensed or Spiro) heteroaryl comprising 1-4 heteroatoms selected from oxygen, nitrogen or sulphur, represents, for example, pyrrole, imidazole, triazole, tetrazole, pyrazole, pyridine, pyrazin, pyrimidine, pyridazine, azepine, diazepine, furan, Piran, oxepin, thiophene, Tian (thiopyran), tiepin, oxazol, isoxazol, thiazole, isothiazol, furazan, oxadiazole, oxazin, oxadiazon, oxazepine, oxadiazon, thiadiazole, teasin, thiadiazin, diazepin, thiadiazin, indole, isoindole, benzofuran, isobenzofuran, benzothiophene, isobenzofuran, indazole, quinoline, isoquinoline, phthalazine, naphthiridine, cinoxacin, hinzelin, cinnolin, benzoxazole, benzothiazole, benzoimidazole, pyrazolo[5,4-b]pyridine, benzocain, benzoxazepin, benzodiazepine, benzodiazepine, benzofurazan, benzothiadiazole, benzotriazole, carbazole, acridine, dibenzofuran, dibenzothiophen, phenothiazines, etc.

Partially or fully saturated C3-to 15-membered mono-, bi - or tricyclic (condensed or Spiro) heteroaryl comprising 1-4 heteroatoms selected from oxygen, nitrogen or sulphur, represents, for example, a ring of pyrroline, pyrrolidine, they are azalina, imidazolidine, pyrazoline, pyrazolidine, triazoline, thiazolidine, tetryzoline, tetryzoline, dihydropyridines, tetrahydropyridine, piperidine, dihydropyrazine, tetrahydropyridine, piperazine, dihydropyrimidine, tetrahydropyrimidine, perhydrofluorene, dihydropyridine, tetrahydropyridine, perhydrophenanthrene, dihydroetorphine, tetrahydroazepine, perhydroanthracene, dihydrovitamin, tetrahydroazepine, targetrotation, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dehydration (dihydrothiophene), tetrahydrothieno (tetrahydrothiopyran), dihydrooxazolo, tetrahydrooxazolo (oxazolidine), dihydroisoxazole, tetrahydrooxazolo (isoxazolidine), dihydrothiazolo, tetrahydrocarbazole (thiazolidine), dihydrothiazolo, tetrahydrocortisol (isothiazolinone), dihydrooxazolo, tetrahydrooxazolo (oxadiazolidine), dihydrothiazolo, tetrahydroindazole (thiadiazolidine), dihydrotriazine, tetrahydrothiophene, Dihydrocodeine, tetrahydroazepine, dihydrothiazine, tetrahydroazepine, targetrotation, dihydrothiazine, tetrahydroazepine, targetrotation, morphine, Timofey, indoline, isoindoline, dihydrobenzofuran, perhydroanthracene, dihydroisobenzofuran, perhydroanthracene, dihydrobenzo the dryer, perhydroanthracene, dihydroisobenzofuran, perhydroanthracene, dihydroindole, peritoneal, dihydroquinoline, tetrahydroquinoline, perhydrosqualene, dihydroisoquinoline, tetrahydroisoquinoline, perhydrosqualene, dihydrophenazine, tetrahydropalmatine, perhydrofluorene, dihydronaphthalene, tetrahydronaphthalene, perhydroanthracene, dihydroquinoxaline, tetrahydroquinoxaline, perhydrophenanthrene, dihydroquinazolin, tetrahydroquinazoline, perhydrophenanthrene, dihydroindolone, tetrahydroquinoline, perhydrosqualene, dihydroisoxazole, perhydroanthracene, dihydrobenzofuran, perhydroanthracene, dehydrobenzperidol, perhydroanthracene, dihydrocarvone, tetrahydrocarbazole, peritoneal, dihydrouridine, tetrahydrouridine, perhydrosqualene, dihydrobenzofuran, dihydrobenzofuran, tetrahydroxybenzophenone, tetrahydrolipstatin, perhydrophenanthrene, perhydrophenanthrene, dioxolane, dioxane, dithiolane, dithiane, benzodioxane, chromane, benzodithiophene, benzocaine, 2,4,6-dioxaspiro[bicyclo[3,3,0]oxan-3,1'-cyclohexane]-1,3-dioxolane[4,5-g]chromene, 2-oxabicyclo[2,2,1]heptane, etc.

If not expressly agreed, all isomers are included in the present invention. For example, alkyl, alkoxy and alkylene groups include closely with evennou chain as well as branched chain. In addition, in the present invention includes all isomers of the double(s) connection(s), rings(EC), condensed(s) ring(EC) (E-, Z-, CIS-, TRANS-isomers), isomers formed in an asymmetric carbon(s), etc., (R-, S-, α-, β-isomer, enantiomer, diastereoisomer), optically active isomers having optical rotation (D-, L-, d-l-isomer), polar compounds, which are separated by chromatography (more polar compound, less polar compound), equilibrium compounds, mixtures thereof with arbitrary relations and racemic mixture.

In the present invention, as can be easily understood by a person skilled in the art, the symbol

specifies that substituent attached thereto is behind the sheet (α-position), if not stated otherwise,

specifies that substituent attached thereto is in front of the page (β-position), if not stated otherwise,

specifies that the Deputy attached to it, is β-position or α-position or mixtures thereof, and

specifies that the Deputy attached to it, is a mixture of the substituent in βposition α-position.

In the compounds of formula (I) compound, which PU is Ktima line a is a double bond, the dashed line b is a single bond, R9is hydrogen and R6missing, i.e. the compound of formula (Ia)and the compound, which the dotted line a is single bond, dashed line b is a double bond, R9is hydrogen and R6missing, i.e. the compound of formula (Ib)are tautomers.

(where all the symbols have the same meanings as described above).

The compound of formula (Ia) also includes a compound of formula (Ia') and the compound of formula (Ia"), and mixtures thereof.

(where all the symbols have the same meanings as described above).

The compound of formula (I) can be transformed into a non-toxic salt conventional methods.

Non-toxic salts include salts of alkali metals, salts of alkaline earth metals, ammonium salts, salts of amines, acid additive salt, etc.

Preferred are non-toxic and water-soluble salts. Suitable salts include salts of alkali metals (potassium, sodium etc), salts of alkaline earth metals (calcium, magnesium etc), ammonium salt, pharmaceutically acceptable salts of organic amines (Tetramethylammonium, triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, Tris(gidron imethyl)aminomethane, lysine, arginine, N-methyl-D-glucamine etc).

Preferred are non-toxic and water-soluble acid additive salt. Suitable acid additive salts include salts of inorganic acids such as hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, nitrate, or salts of organic acids, such as acetate, lactate, tartrate, benzoate, citrate, methanesulfonate, aconsultant, bansilalpet, toluensulfonate, isetionate, glucuronate, gluconate, etc.

The compound of formula (I) and its salt can be converted into its MES.

Preferred are non-toxic and water-soluble solvate. Suitable are the solvate water and an alcoholic solvent (e.g. ethanol, etc).

In the formula (I) R1and R2are preferably C1-8-alkyl, more preferably methyl.

In the formula (I), Z represents-CR3R4- or-O-.

In the formula (I) R3and R4are preferably hydrogen or C1-8-alkyl, more preferably hydrogen or methyl.

In the formula (I) R5and R6are preferably hydrogen.

In the formula (I) Cyc4 is preferably C5-7-monocyclic Carballo and more preferably a benzene ring.

In the formula (I) "the ring" is preferably C3-15-monocyclic or bicyclic carbocyclic ring or 3-15-anatilicheskaya or bicyclic heterokonta, more preferably benzene, cyclohexane, Cycloheptane, adamantane, naphthalene, quinoline, isoquinoline, piperidine or pyridine.

Among the compounds of formula (I), preferred are the following compounds: compound of formula (Ia'-1)

(where all the symbols have the same meanings as described above),

the compound of formula (Ia'-2)

(where all the symbols have the same meanings as described above),

the compound of formula (Ia'-3)

(where all the symbols have the same meanings as described above),

the compound of formula (Ia'-4)

(where all the symbols have the same meanings as described above).

Specific preferred compounds are the compounds described in tables 1-8, the compounds of the examples and their non-toxic salts, an acid additive salt and solvate.

In the following tables, Me represents methyl, Et represents ethyl, BOC represents tert-butoxycarbonyl and other symbols have the same meanings as described above.

Table 1

No.R17No.R17
12-Me2 2-COOH
23-IU293-COOH
34-IU304-COOH
42-OMe312-acetyl
53-OMe323-acetyl
64-OMe334-acetyl
72-SMe342 mesyl
83-SMe353 mesyl
94-SMe364 mesyl
102-HE372-NH2
113-HE383-NH2
124-HE394-NH2
132-F402-NO2
143-F413-NO2
154-F424-NO2
162-Cl432-CH2OH
173-Cl443-CH2OH
184-Cl454-CH2OH
192-CF3462-CH2NH2
203-CF3473-CH2NH2
214-CF3484-CH2NH2
222-OCF3492-OEt
233-OCF3503-OEt
244-OCF3514-OEt
252-CN522-CHO
263-CN533-CHO
274-CN544-CHO

Table 2

No.R17No.R17
12-Me282-COOH
23-IU293-COOH
34-IU304-COOH
42-OMe312-acetyl
53-OMe323-acetyl
6 4-OMe334-acetyl
72-SMe342 mesyl
83-SMe353 mesyl
94-SMe364 mesyl
102-HE372-NH2
113-HE383-NH2
124-HE394-NH2
132-F402-NO2
143-F413-NO2
154-F424-NO2
162-Cl432-CH2OH
173-Cl443-CH2OH
184-Cl454-CH2OH
192-CF3462-CH2NH2
203-CF3473-CH2NH2
214-CF3484-CH2NH2
222-OCF349 2-OEt
233-OCF3503-OEt
244-OCF3514-OEt
252-CN522-CHO
263-CN533-CHO
274-CN544-CHO

Table 3

No.R17No.R17
12-Me192-COOH
23-IU203-COOH
32-OMe212-acetyl
43-OMe223-acetyl
52-SMe232 mesyl
63-SMe243 mesyl
72-OH252-NH2
83-OH263-NH2
92-F272-NO2
103-F28 3-NO2
112-Cl292-CH2OH
123-Cl303-CH2OH
132-CF3312-CH2NH2
143-CF3323-CH2NH2
152-OCF3332-OEt
163-OCF3343-OEt
172-CN352-CHO
183-CN363-CHO

Table 4

No.R17No.R17
1IU12
2Vos13
314
4acetyl15
516
6benzoyl17mesyl
718
819
920
1021
1122

Table 5

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-OH267-NH2
96-F276-NO2
107-F287-NO2
116-Cl296-CH2HE
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

6-Me
Table 6

No.R7No.R7
1196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-OH267-NH2
96-F276-NO2
107-F287-NO2
116-Cl296-CH2OH
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
18 8-CN367-CHO

Table 7

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-OH267-NH2
96-F276-NO2
107-F287-NO2
116-Cl296-CH2OH
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF332 7-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

Table 8

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-ome216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-HE267-NH2
96-F276-NO2
107-F287-NO2
116Cl 296-CH2OH
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

2 mesyl
Table 9

No.R17No.R17
12-Me282-COOH
23-IU293-COOH
34-IU304-COOH
42-OMe312-acetyl
53-OMe323-acetyl
64-OMe334-acetyl
72-SMe34
83-SMe353 mesyl
94-SMe364 mesyl
102-HE372-NH2
113-HE383-NH2
124-HE394-NH2
132-F402-NO2
143-F413-NO2
154-F424-NO2
162-Cl432-CH2OH
173-Cl443-CH2OH
184-Cl454-CH2OH
192-CF3462-CH2NH2
203-CF3473-CH2NH2
214-CF3484-CH2NH2
222-OCF3492-OEt
233-OCF3503-OEt
24 4-OCF3514-OEt
252-CN522-CHO
263-CN533-CHO
274-CN544-CHO

Table 10

No.R17No.R17
12-Me282-COOH
23-IU293-COOH
34-IU304-COOH
42-OMe312-acetyl
53-OMe323-acetyl
64-OMe334-acetyl
72-SMe342 mesyl
83-SMe353 mesyl
94-SMe364 mesyl
102-HE372-NH2
113-HE383-NH2
124-HE394-NH2
132-F402-NO2
143-F413-NO2
154-F424-NO2
162-Cl432-CH2OH
173-Cl443-CH2OH
184-Cl454-CH2OH
192-CF3462-CH2NH2
203-CF3473-CH2NH2
214-CF3484-CH2NH2
222-OCF3492-OEt
233-OCF3503-OEt
244-OCF3514-OEt
252-CN522-CHO
263-CN533-CHO
274-CN544-CHO

Table 11

No.R17No.R17
12-Me192-COOH
23-IU203-COOH
32-OMe212-acetyl
43-OMe223-acetyl
52-SMe232 mesyl
63-SMe243 mesyl
72-OH252-NH2
83-OH263-NH2
92-F272-NO2
103-F283-NO2
112-Cl292-CH2OH
123-Cl303-CH2OH
132-CF3312-CH2NH2
143-CF3323-CH2NH2
152-OCF3332-OEt
163-OCF3343-OEt
172-CN352-CHO
183-CN363-CHO

Table 12

No.R17No.R17
1IU12
2Vos13
314
4acetyl15
516
6benzoyl17mesyl
718
819
9 20
1021
1122

Table 13

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-HE267-NH2
96-F276-NO2
107-F287-NO2/sub>
116-Cl296-CH2OH
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

Table 14

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-OH267-NH2
96-F276-NO2
107-F287-NO2
116-Cl296-CH2HE
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

Table 15

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
3 6-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-HE267-NH2
96-F276-NO2
107-F287-NO2
116-Cl296-CH2OH
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

Table 16

img src="https://img.russianpatents.com/827/8271060-s.jpg" height="61" width="76" >
No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-OH267-NH2
96-F276-NO2
107-F287-NO2
116-Cl296-CH2OH
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3 347-OEt
176-CN356-CHO
188-CN367-CHO

40
Table 17

No.R17No.R17
12-Me282-COOH
23-IU293-COOH
34-IU304-COOH
42-OMe312-acetyl
53-OMe323-acetyl
64-OMe334-acetyl
72-SMe342 mesyl
83-SMe353 mesyl
94-SMe364 mesyl
102-HE372-NH2
113-HE383-NH2
124-HE394-NH2
132-F2-NO2
143-F413-NO2
154-F424-NO2
162-Cl432-CH2OH
173-Cl443-CH2OH
184-Cl454-CH2OH
192-CF3462-CH2NH2
203-CF3473-CH2NH2
214-CF3484-CH2NH2
222-OCF3492-OEt
233-OCF3503-OEt
244-OCF3514-OEt
252-CN522-CHO
263-CN533-CHO
274-CN544-CHO

Table 18

No.R17 No.R17
12-Me282-COOH
23-IU293-COOH
34-IU304-COOH
42-OMe312-acetyl
53-OMe323-acetyl
64-OMe334-acetyl
72-SMe342 mesyl
83-SMe353 mesyl
94-SMe364 mesyl
102-OH372-NH2
113-OH383-NH2
124-OH394-NH2
132-F402-NO2
143-F413-NO2
154-F424-NO2
162-Cl432-CH2OH
173-Cl443-CH2OH
184-Cl454-CH2OH
192-CF3462-CH2NH2
203-CF3473-CH2NH2
214-CF3484-CH2NH2
222-OCF3492-OEt
233-OCF3503-OEt
244-OCF3514-OEt
252-CN522-CHO
263-CN533-CHO
274-CN544-CHO

Table 19

No.R17No.R17
12-Me192-COOH
23-IU203-COOH
32-OMe212-acetyl
43-OMe223-acetyl
52-SMe232 mesyl
63-SMe243 mesyl
72-OH252-NH2
83-OH263-NH2
92-F272-NO2
103-F283-NO2
112-Cl292-CH2OH
123-Cl303-CH2OH
132-CF3312-CH2NH2
143-CF3323-CH2NH2
152-OCF3332-OEt
163-OCF3343-OEt
172-CN352-CHO
183-CN363-CHO

Table 20

No.R17No.R17
1IU12
2Vos13
314
4acetyl15
516
6benzoyl17mesyl
718
819
920
1021
1122

Table 21

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-OH267-NH2
96-F276-NO2
107-F287-NO2
116-Cl296-CH2HE
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

Table 22

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-OH267-NH2
96-F276-NO2
107-F287-NO2
116-Cl296-CH2OH
127-Cl307-CH2H
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

Table 23

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-OH267-NH2
9 6-F276-NO2
107-F287-NO2
116-Cl296-CH2OH
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

Table 24

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe 6 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-OH267-NH2
96-F276-NO2
107-F287-NO2
116-Cl296-CH2HE
127-Cl307-CH2HE
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

2-COOH
Table 25

No.R17No.R17
12-Me28
23-IU293-COOH
34-IU304-COOH
42-OMe312-acetyl
53-OMe323-acetyl
64-OMe334-acetyl
72-SMe342 mesyl
83-SMe353 mesyl
94-SMe364 mesyl
102-HE372-NH2
113-HE383-NH2
124-HE394-NH2
132-F402-NO2
143-F413-NO2
154-F424-NO2
162-Cl432-CH2OH
173-Cl443-CH2OH
184-Cl454-CH2OH
192-CF3462-CH2NH2
203-CF3473-CH2NH2
214-CF3484-CH2NH2
222-OCF3492-OEt
233-OCF3503-OEt
244-OCF3514-OEt
252-CN522-CHO
263-CN533-CHO
274-CN544-CHO

Table 26

No.R17No.R17
12-Me282-COOH
23-IU293-COOH
34-IU304-COOH
42-OMe312-acetyl
53-OMe323-acetyl
6 4-OMe334-acetyl
72-SMe342 mesyl
83-SMe353 mesyl
94-SMe364 mesyl
102-HE372-NH2
113-HE383-NH2
124-HE394-NH2
132-F402-NO2
143-F413-NO2
154-F424-NO2
162-Cl432-CH2OH
173-Cl443-CH2OH
184-Cl454-CH2OH
192-CF3462-CH2NH2
203-CF3473-CH2NH2
214-CF3484-CH2NH2
222-OCF349 2-OEt
233-OCF3503-OEt
244-OCF3514-OEt
252-CN522-CHO
263-CN533-CHO
274-CN544-CHO

Table 27

No.R17No.R17
12-Me192-COOH
23-IU203-COOH
32-OMe212-acetyl
43-OMe223-acetyl
52-SMe232 mesyl
63-SMe243 mesyl
72-OH252-NH2
83-OH263-NH2
92-F272-NO2
103-F28 3-NO2
112-Cl292-CH2OH
123-Cl303-CH2OH
132-CF3312-CH2NH2
143-CF3323-CH2NH2
152-OCF3332-OEt
163-OCF3343-OEt
172-CN352-CHO
183-CN363-CHO

Table 28

No.R17No.R17
1IU12
2Vos13
314
4acetyl15
516
6benzoyl17mesyl
718
819
920
1021
1122

tr>
Table 29

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-OH267-NH2
96-F276-NO2
107-F287-NO2
116-Cl296-CH2HE
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

Table 30

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-OH267-NH2
96-F276-NO2
107-F287-NO2
116-Cl296-CH2HE
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

Table 31

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-HE267-NH2
96-F276-NO2
107-F287-NO2
116-Cl296-CH2OH
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3 327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

Table 32

No.R7No.R7
16-Me196-COOH
27-IU207-COOH
36-OMe216-acetyl
47-OMe227-acetyl
56-SMe236 mesyl
67-SMe247 mesyl
76-OH256-NH2
87-OH267-NH2
96-F276-NO2
107-F287-NO2
11/td> 6-Cl296-CH2OH
127-Cl307-CH2OH
136-CF3316-CH2NH2
147-CF3327-CH2NH2
156-OCF3336-OEt
167-OCF3347-OEt
176-CN356-CHO
188-CN367-CHO

The method of obtaining the compounds of the present invention

The compound of formula (I) of the present invention can be obtained in the following ways and methods described in the examples.

[1] Among the compounds of formula (I) of the present invention compound, where R6represents hydrogen, i.e. the compound of formula (IA)

(where all the symbols have the same meanings as described above), can be obtained by the method [a], [b] or [c].

[a] the Compound of formula (IA) can be obtained by the coupling of compounds of formula (II)

(where Z' represents-CR3-1R4-1- or-O-, R1-1, R2-1, R3-1, R4-1, R7-1and R8-1have the same value as R1, R2, R3, R4, R7and R8accordingly, hydroxy, amino and carboxy, included in the group R1-1, R2-1, R3-1, R4-1, R7-1or R8-1if necessary, protect) and the compounds of formula (III)

(wherehereinafter designated as the ring'has the same meaning as the ring, but hydroxy, amino or carboxy, included in the ring', if necessary, protect), obtaining the compound of formula (IA')

(where all the symbols have the same meanings as described above) is optional, with subsequent reaction of removing the protective groups.

The reaction of the compound of formula (II) and compounds of formula (III) are known, it is conducted, for example, the interaction of the compounds of formula (II) and compounds of formula (III) at a temperature between -20 and ˜100°in concentrated sulphuric acid.

The reaction of removing the protection can be performed in the following ways :

The reaction of removing the protective groups for carboxy, hydroxy and amino known, for example:

(1) reaction unprotect carried out in alkaline medium,

(2) the reaction unprotect carried out in acidic environments

(3) the reaction of removing protection, ongoing recovery,

(4) the reaction of removal of the silyl protective groups, etc.

Description of the case the ways

(1) the Reaction of removing the protection under alkaline conditions is carried out, for example, in an organic solvent (methanol, tetrahydrofuran, dioxane and so on) using a hydroxide of alkaline metal (sodium hydroxide, potassium hydroxide, lithium hydroxide, etc.), hydroxide of alkaline earth metal (barium hydroxide, calcium hydroxide, etc.) or carbonates (sodium carbonate, potassium carbonate, etc. or their solution or their mixture at a temperature between 0 and 40°C.

(2) the Reaction of removing protection in acidic conditions is carried out, for example, in an organic solvent or without an organic solvent (methylene chloride, chloroform, dioxane, ethyl acetate, anisole etc) using organic acids (acetic acid, triperoxonane acid, methanesulfonic acid, etc. or an inorganic acid (hydrochloric acid, sulfuric acid, etc. or a mixture thereof (Hydrobromic acid/acetic acid, etc. at temperatures between 0 and 100°C.

(3) the Reaction of removing the protection, restoration carried out, for example, in a solvent (ethers include tetrahydrofuran, dioxane, dimethoxyethane, diethyl ether, etc.), alcohols (methanol, ethanol etc), benzenes (benzene, toluene etc), ketones (acetone, methyl ethyl ketone, etc.), NITRILES (acetonitrile etc), amido (dimethylformamide etc), water, ethyl acetate, acetic acid or a mixture of more than the boom of the above solvents, etc. in the presence of a catalyst (palladium-carbon, palladium black, palladium hydroxide, platinum oxide, Raney Nickel, etc. in an atmosphere of hydrogen under normal or elevated pressure or in the presence of ammonium formate at a temperature between 0 and 200°C.

As should be clear to the person skilled in the art, the compounds of the present invention can easily get these reactions.

(4) the Reaction of removal of the silyl protective groups are, for example, in an organic solvent which is miscible with water (tetrahydrofuran, acetonitrile, etc.) using tetrabutylammonium fluoride at a temperature between 0 and 40°C.

Protective groups for carboxy is, for example, methyl, ethyl, tert-butyl and benzyl.

Protective groups for hydroxy are, for example, methoxymethyl, 2-tetrahydropyranyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, acetyl, benzyl.

Protective groups for amino include, for example, benzyloxycarbonyl, tert-butoxycarbonyl, TRIFLUOROACETYL, 9-fluorenylmethoxycarbonyl.

Protective groups for carboxy, hydroxy or amino are not limited to the above, but instead you can also use other groups, if they are easily and selectively removed. For example, you can use groups described in T.W. Greene, Protective Groups in Organic Synthesis, 3rdedition, Wiley, New York, 1999.

As should be clear to the expert in this on the authority the target compounds of the present invention can easily get these reactions.

[b] a Compound of formula (IA) can be obtained by the coupling of compounds of formula (IV)

(where all the symbols have the same meanings as described above) and compounds of formula (V)

(where X represents a halogen atom and other symbols have the same meanings as above), and thus obtain the compound of formula (IA'), as defined above, optionally followed by removal of protective groups.

The reaction of the compound of formula (IV) and compounds of formula (V) is known, for example, is performed by the interaction in an organic solvent (xylene, toluene, benzene, acetonitrile, tetrahydrofuran, methylene chloride, chloroform, etc.) in the presence of a phosphine reagent (triphenylphosphine, tributylphosphine etc) or Fofanova reagent (trimethylphosphite, triethylphosphite, Tripropylamine, tributylphosphite etc) and a base (triethylamine, Diisopropylamine, dimethylaminopyridine and so on) at a temperature between 30°and temperature of reflux distilled.

The reaction of removing the protective group can be performed as described above.

[c] Among the compounds of formula (IA) compound, where R5represents hydrogen, i.e. the compound of formula (IA-1)

(where all the symbols have the same meanings as described above), can be obtained by the coupling of compounds of formula (VI) and compounds of formula (VII) with the formation of the compounds of formula (IA'-1)

(where all the symbols have the same meanings as described above) and optionally followed by reaction of removing the protective groups.

The reaction of the compound of formula (VI) and compounds of formula (VII) is known, it is conducted, for example, in an inert organic solvent is tetrahydrofuran (THF), diethyl ether, benzene etc. in the presence of base - isopropylamino lithium (LDA), hexamethyldisilazide lithium (LHMDS), n-utility, tert-utility and so on) at a temperature between -78°C and room temperature.

The reaction of removing the protective group can be performed as described herein above.

[2] Among the compounds of formula (I) of the present invention compound, where R5and R6represent C1-8-alkyl, or R5and R6taken together with the carbon atom to which they are attached, form a Cyc1, i.e. the compound of formula (IB)

(where R5-1and R6-1are independently C1-8-alkyl, or R5-1and R6-1taken together with the carbon atom to which they are attached, form a Cyc1 and other symbols have the same meanings as described above), you will receive the following method.

The compound of formula (IB) can be obtained by reaction of compound (IA'-1)above, and the compounds of formula (VIII)

(where R65represents C1-8-alkyl and X has the same meanings as above) or the compounds of formula (IX)

(where Y represents -(CH2)m- (where m is an integer 2-9) and the carbon atom in -(CH2)m- may be substituted with 1-2 heteroatoms, selected from oxygen, nitrogen and sulfur, and, when he was replaced by nitrogen, if necessary, defend it, Y can be replaced by R10-1(R10-1has the same meanings as R10provided that the hydroxy included in R10-1if necessary, protected) and X has the same meanings as described above), with the formation of the compounds of formula (IB')

(where all the symbols have the same meanings as described above) and an optional subsequent reaction of removing the protective groups.

The reaction of compounds of formula (IA'-1) and the compounds of formula (VIII) or the compound of formula (IX) is known, it is conducted, for example, in an inert organic solvent (e.g. tetrahydrofuran, diethyl ether, dimethylformamide, benzene, dioxane, etc. in the presence of a base (sodium hydroxide, LDA, n ' utility, tert-utility etc.) optionally in the presence of iodi the sodium, at temperatures between -20°and temperature of reflux distilled.

The reaction of removing the protective group can be performed as described herein above.

[3] Among the compounds of formula (I) compound, where R7is Cyc2, i.e. the compound of formula (IC)

(where all the symbols have the same meanings as described above), can be obtained in the following ways :

The compound of formula (IC) can be obtained by the coupling of compounds of formula (X)

(where R5-2and R6-2have the same meanings as R5and R6respectively , hydroxy, amino, included in R5-2and R6-2if necessary, protected, and other symbols have the same meanings as described above) and compounds of formula (XI)

(where R66represents-B(OH)2and- (C1-8-alkyl)2and Cyc2' has the same meanings as Cyc2, provided that the hydroxy, amino or carboxy, included in Cyc2', if necessary, protected) with the formation of the compounds of formula (IC')

(where all the symbols have the same meanings as described above) with optional subsequent reaction of removing the protective groups.

The reaction of the compound of formula (X) and the compounds of formula (XI) is known, it is conducted, for example, in an organic solvent (which insole, acetonitrile, dimethoxyethane, acetone, etc. in the presence of a base (atrata sodium, sodium hydroxide, potassium hydroxide, triethylamine, sodium carbonate, sodium bicarbonate, potassium carbonate, cesium carbonate, carbonate, thallium, potassium phosphate, fluoride, cesium, barium hydroxide, tetrabutylammonium fluoride, etc.) and catalyst (tetrakis(triphenylphosphine)palladium (PdCl2(PPh3)2), palladium acetate (Pd(OAc)2), palladium mobiles, 1,1'-bis(diphenylphosphinomethyl)dichloropalladium (PdCl2(dppf)2), dichlorodimethylsilane (PdCl2(allyl)2), phenylbis(triphenylphosphine)plagiaadiga (PhPdI(PPh3)2and so on) at a temperature between room temperature and 120°C.

The reaction of removing the protective group can be performed as described herein above.

[4] Among the compounds of formula (I) of the present invention compound, where at least one ring is Amida or group, which includes amide, i.e. the compound of formula (ID)

(where the ring' has the same meanings as ring, provided that at least one ring' is Amida or group, which contains amide, and other symbols have the same meanings as described above)can be obtained as follows.

The compound of formula (ID) can be obtained by the coupling of compounds of formula (XII)

(where calico' has the same meanings as ring, provided that at least one calico' is amino or a group that contains amine and the other is amino, hydroxy or carboxy, if necessary, protected, and other symbols have the same meanings as described above) and the carboxylic acid or the corresponding connection, which is galogenangidridy acid, with an optional reaction of removing the protective groups of the amides.

How the amidation reaction is known, they include, for example:

(1) the method using gelegenheid acid,

(2) the method using mixed anhydride,

(3) the method using a condensing agent, etc.

Particular description of the above methods

(1) the Method using gelegenheid acid is carried out, for example, by the interaction of the carboxylic acid in an organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran etc.) or without solvent and acid halogenation agent (oxalicacid, thionyl chloride, etc. at temperatures between -20°and temperature of reflux distilled and then by the interaction of the thus obtained gelegenheid acid in the presence of tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine and so on) at a temperature between 0 and 40°S. This with the persons are also interaction with galogenangidridy acid using aqueous alkaline solution (sodium bicarbonate or sodium hydroxide, etc. in an organic solvent (dioxane, tetrahydrofuran, etc. at temperatures between 0 and 40°C.

(2) the Method using mixed anhydride is carried out, for example, the interaction in an organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc. or without a solvent in the presence of tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine etc.) carboxylic acids with galogenangidridy acid (revalorisation, mozillateam, methylchloride etc) or acid derivative (characiformes, horizontalposition etc.) at temperatures between -20 and 40°and then by the interaction of the thus obtained mixed anhydride with the amine at a temperature between 0 and 40°C.

(3) the Method using a condensing agent is carried out, for example, in an inert organic solvent (chloroform, methylene chloride, dimethylformamide, diethyl ether, tetrahydrofuran, etc. or without a solvent in the presence or in the absence of tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, N-methylmorpholine etc) using a condensing reagent (1,3-dichlorophenylisocyanate (DCC), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC), 1,1'-carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium etc), in the presence or in the absence of 1-hydroxybenzotriazole, in what aimogasta carboxylic acid and amine at a temperature between 0 and 40° C.

Reaction (1), (2) and (3) is preferably carried out in an atmosphere of inert gas (argon, nitrogen etc) in anhydrous conditions.

The reaction of removing the protective group can be conducted in much the same way as described above.

[5] In the compounds of formula (I) of the present invention compound, which at least one group represented by the ring, is a sulfonamide or a group that contains it, i.e., the compound of formula (IE)

(where ring2'has the same meanings as ring, provided that at least one group represented by ring2that is a sulfonamide or a group that contains it, and the other symbols have the same meanings as described above), can be obtained in the following ways :

The compound of formula (IE) can be obtained by reaction of sulfonmethane the compounds of formula (XIII)

(where ring2'has the same meanings as ring, provided that at least one of the groups represented by ring2'is amino or a group comprising amino, and the other is amino, hydroxy or carboxy, if necessary, protected, and other symbols have the same meanings as described above) sulfonic acid or the corresponding compound with sulfonylmethane, with optional subsequent reactie the removal of the protective groups.

Sulfenamidovy is known, it is done, for example, in an inert organic solvent (chloroform, dichloromethane, dichloroethane, diethyl ether, tetrahydrofuran etc.) or without solvent interaction sulfonic acid with galogenangidridy acid (oxalylamino, thionyl chloride, pentachloride phosphorus, trichloride phosphorus and so on) at a temperature between -20°and temperature of reflux distilled with getting sulphonylchloride with subsequent interaction with the amine in the presence of tertiary amine (isopropylethylene, pyridine, triethylamine, dimethylaniline, dimethylaminopyridine and so on) at a temperature between 0 and 40°C.

The reaction of removing the protective group can be conducted in much the same way as described here above.

Compounds of formula (II), (III), (IV), (V), (VI), (VII), (VIII), (IX) and (XI) can be obtained by known methods or are commercially available.

For example, the compound of formula (IV) can be obtained according to the following reaction scheme 1.

In the reaction scheme 1 LDA represents diisopropylamide lithium, DPPA is diphenylphosphinite, Et3N represents the triethylamine, the PPA is polyphosphoric acid and other symbols have the same meanings as described above.

The scheme of reactions 1

In the diagram reacts the th 1 compounds of formula (XIV), (XV), (XIX) and (XX), which are used as starting substances are known or can easily be obtained by known methods.

In each reaction of the present description, the obtained products can be cleaned by using common methods. For example, purification can be carried out by distillation at atmospheric or reduced pressure or high performance liquid chromatography, thin-layer chromatography or column chromatography using silica gel or magnesium silicate, washing or recrystallization. Cleaning can be performed after each reaction or after a series of reactions.

[Pharmacological action]

The following experiment was confirmed that the compound of formula (I) of the present invention has the activity of the agonist SW-receptor in the analysis of signal transmission in vitro.

The experimental technique

For analyses used SW receptors person, expressed by cells of the SNO. Cells were seeded in dispersion in 96-well tablets with density 5×104cells/well and were subjected to the experiment the next day. After removal of culture medium was added to 1 mm solution isobutylmethylxanthine (IBMX) and cells were incubated for 10 minutes at room temperature. Then was added a mixture of 10 μm of Forskolin and compounds of the present invention. After an additional in the of ubytovanie for 15 minutes at room temperature, the supernatant of the culture was unloaded and was added 200 μl lisanova reagent (associated with camp EIA). The number of camp lysate was determined by a set of cyclic amp EIA (Amersham) in terms of induced Forskolin production of camp. The compound of the present invention was dissolved in DMSO and the solution was diluted to establish the final concentration of DMSO of 0.1%. The value of the IC50was calculated from the ratio of inhibition of the compound of the present invention to the number of induced Forskolin production of camp. The same experiment using cells SNO confirmed that this inhibitory activity against the production of cyclic amp compound is mediated through receptors SW person.

The results are shown in table 33.

Table 33
# exampleIC50(nm)
12,4
1(11)0,4
1(33)0,8

[Toxicity]

The toxicity of the compounds of the present invention of formula (I) is low enough for its use as a medical drug.

[Application for treatment in medicine]

It is believed that the compounds of the present invention, because they act specifically on SW receptors, are useful for prevention and/or treatment of various diseases, such as asthma, nasal the Oh allergies, atopic dermatitis, autoimmune diseases, rheumatoid arthritis, immune dysfunction, postoperative pain, cancerous pain, etc.

For the above purpose the compounds of formula (I) of the present invention, a non-toxic salt or solvate is usually administered systemically or locally, usually oral or parenteral administration.

Input dose determined, for example, the age, body weight, symptom, the desired therapeutic effect, the route of administration and duration of treatment. In the treatment of adult dose for the individual typically range from 1 to 1000 mg, by oral administration, up to several times per day and 1 to 100 mg, for parenteral administration (preferably intravenous administration) up to several times per day or continuous treatment by the introduction within 1 to 24 hours per day intravenously.

As indicated above, the doses depend on various conditions. Therefore, there are cases when you can use a dose lower than or higher than the above ranges.

The compounds of formula (I) of the present invention can be introduced in the form of solid compositions, liquid compositions or other compositions for oral administration, injections, liniments or suppositories for parenteral administration.

Solid compositions for oral is doing include compressed tablets, pills, capsules, dispersible powders and granules.

Capsules include hard capsules and soft capsules.

In such solid compositions one or more active compounds can be mixed, at least one inert diluent (e.g., lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone or metasilicate-magnesium aluminate). The composition may also include, as in normal practice, additional substances other than inert diluents: e.g. lubricating agents (e.g. magnesium stearate), dezintegriruetsja agents (e.g., calcium salt glycolate, cellulose), stabilizing agents (e.g., lactose) and agents that help dissolve (for example, glutamic acid or aspartic acid). Tablets or pills may, if necessary, to cover with a film soluble in the stomach or Intercollege material (for example, sugar, gelatin, hydroxypropylcellulose or phthalate of hydroxypropylmethylcellulose) or two or more films. In addition, the coating capsules may include a protective shell made of absorbable materials such as gelatin.

Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, syrups and elixirs. In such composition is x one or more active compounds may be contained in inert diluent(s), usually used(s) in this area (for example, purified water or ethanol). Besides inert diluents such compositions may also include additives (for example, wetting agents or suspendresume agents), sweetening agents, corrigentov, fragrances and preservatives.

Other compositions for oral administration include spray compositions which can be obtained by known methods and which comprise one or more active compounds. Spray compositions may include additional substances other than inert diluents: e.g. stabilizing agents (e.g. sodium bisulfite), isotonic buffers (e.g. sodium chloride, sodium citrate or citric acid). To obtain such sprayable compositions can be used, for example, the method described in the patent of the United States No. 2868691 or No. 3095355.

Injections for parenteral administration include sterile aqueous or nonaqueous solutions, suspensions and emulsions. Aqueous solutions and suspensions include distilled water for injection and physiological salt solution. Non-aqueous solutions or suspensions can include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, alcohol such as ethanol, or Polysorbate 80 (registered trademark). Sterile water and h is water solutions, suspensions and emulsions can be used in the form of a mixture. Injections may include additional ingredients, such as preservatives, wetting agents, emulsifying agents, dispersing agents, stabilizing agents, auxiliary agents, such as agents that help dissolve (for example, glutamic acid or aspartic acid). They can be sterilized, for example, by filtration through a retaining bacteria filter, by incorporation of sterilizing agents in the composition or exposure. They can also be manufactured in the form of sterile solid compositions which can be dissolved in sterile water or some other sterile diluent for injection immediately prior to use.

Other compositions for parenteral administration include liquids for external use and ointments, percutaneous liniments, suppositories for rectal administration and pessaries for vaginal administration, which include one or more active compounds and which can be obtained by methods known as such.

The best way of carrying out the invention

The following reference examples and examples illustrate the present invention without limiting them present invention.

The solvents in the parentheses are the eluting or manifesting solvents and relations used solvent is th is given by the volume in chromatographic separation or TLC.

The solvents in parentheses in the mean NMR solvents used in the measurement.

Reference example 1

3-Cyclohexyl-3-oxopropanenitrile

To a solution of sodium amide (1,87 g) in tetrahydrofuran (1,87 g) added dropwise acetonitrile (2,72 ml) at a temperature of from -50 to approximately -40°With, then add methyl ether cyclohexanecarbonyl acid (2,86 ml) and the mixture is stirred for 1 hour at -20°C. the Reaction mixture was poured into cold dilute hydrochloric acid and extracted with ethyl acetate. The extract is washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=4:1), obtaining specified in the header connection (0,91 g)having the following physical data.

TLC: Rf of 0.33 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 3,50 (s, 2H), by 2.55 (m, 1H), 2.00 in to 1.60 (m, 5H), 1,50-1,10 (m, 5H).

Example 1

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

To concentrated sulfuric acid is added the compound obtained in reference example 1 (890 mg), to this mixture a solution of 2-methyl-1-phenylpropane-2-ol (1061 mg) in benzene (1 ml) at 0°and the mixture is stirred is for 30 minutes at 60° C. the Reaction mixture was neutralized with an aqueous solution of sodium hydroxide under ice cooling and the mixture is extracted with ethyl acetate. The extract is washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=9:1)to give the compound of the present invention (1170 mg)having the following physical data.

TLC: Rf of 0.36 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,32 (W, 1H), 7,71 (DD, J=8,0, 1.5 Hz, 1H), 7,39 (DDD, J=8,0, to 8.0, 1.5 Hz, 1H), 7,28 (DDD, J=8,0, to 8.0, 1.5 Hz, 1H), 7,16 (DD, J=8,0, 1.5 Hz, 1H), 5,64 (s, 1H), 2,84 (s, 2H), 2,39 (m, 1H), 2.00 in of 1.20 (m, 10H), of 1.29 (s, 6H).

Examples 1(1)-1(81)

By the same procedure as described in example 1 using the compound obtained in reference example 1, or the corresponding derived nitrile and 2-methyl-1-phenylpropane-2-ol or the corresponding derivative of the alcohol produced the following compounds of the present invention.

Example 1(1)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-ethoxycarbonylphenyl)ethane-1-he

TLC: Rf of 0.18 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,95 (W, 1H), 8,10 (d, J=8.0 Hz, 2H), to 7.99 (d, J=8.0 Hz, 2H), 7,83 (d, J=7.5 Hz, 1H), 7,45 (DD, J=7,5, 7.5 Hz, 1H), 7,35 (DD, J=7,5, 7.5 Hz, 1H), 7,22 (d, J=7.5 Hz, 1H), 6,33 (s, 1H ), 3,94 (s, 3H), 2.91 in (s, 2H), of 1.37(s, 6H).

Example 1(2)

(Z)-2-(3,3-Di is ethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclopentolate-1-he

TLC: Rf of 0.38 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,27 (W, 1H), of 7.70 (m, 1H), 7,45-7,10 (m, 3H), to 5.66 (s, 1H), 2,84 (s, 2H), and 2.83 (m, 1H), 2.00 in a 1.50 (m, 8H), of 1.29 (s, 6H).

Example 1(3)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-were)ethane-1-he

TLC: Rf of 0.33 (ethyl acetate:hexane=1:4).

NMR (CDCl3): δ 11,58 (W, 1H), of 7.70 (d, J=8.0 Hz, 1H), 7,50-to 7.15 (m, 7H), 5,90 (s, 1H), 2.91 in (s, 2H), of 2.51 (s, 3H), of 1.37 (s, 6H).

Example 1(4)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-were)ethane-1-he

TLC: Rf of 0.33 (ethyl acetate:hexane=1:4).

NMR (CDCl3): δ 11,84 (W, 1H), of 7.90-of 7.70 (m, 3H), 7,50-to 7.15 (m, 5H), 6,32 (s, 1H), 2,90 (s, 2H), 2,42 (s, 3H), of 1.36 (s, 6H).

Example 1(5)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-were)ethane-1-he

TLC: Rf of 0.33 (ethyl acetate:hexane=1:4).

NMR (CDCl3): δ 11,80 (W, 1H), 7,86 (d, J=8.0 Hz, 2H), 7,83 (m, 1H), 7,50-7,20 (m, 3H), from 7.24 (d, J=8.0 Hz, 2H), 6,33 (s, 1H), 2,90 (s, 2H), 2.40 a (s, 3H), of 1.36 (s, 6H).

Example 1(6)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(furan-2-yl)Ethan-1-he

TLC: Rf of 0.37 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,59 (W, 1H), to 7.84 (m, 1H), 7,49 (DD, J=2.0 a, 1.0 Hz, 1H), 7,50-to 7.15 (m, 3H),? 7.04 baby mortality (DD, J=3,5, 1.0 Hz, 1H), of 6.49 (DD, J=3,5, 2.0 Hz, 1H), 6.30-in (s, 1H), 2,90 (s, 2H), of 1.34 (s, 6H).

Example 1(7)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-chlorine is phenyl)ethane-1-he

TLC: Rf 0.25 in (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ 11,55 (W, 1H), 7,72 (d, J=7.5 Hz, 1H), EUR 7.57-7,52 (m, 1H), 7,45-7,38 (m, 2H), 7,33-7,26 (m, 3H), 7,21 (DD, J=7,5, 1.0 Hz, 1H), 5,97 (s, 1H), 2,92 (s, 2H), 1,38 (s, 6H).

Example 1(8)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(thiophene-2-yl)Ethan-1-he

TLC: Rf of 0.54 (ethyl acetate:hexane=1:2).

NMR (CDCl3): δ 11,51 (W, 1H), 7,81 (d, J=7,0 Hz, 1H), to 7.64 (d, J=3.0 Hz, 1H), 7,50-7,30 (m, 3H), 7,21 (d, J=7,0 Hz, 1H), 7,10 (DD, J=3,0, 3.0 Hz, 1H), 6,21 (s, 1H), 2,89 (s, 2H), of 1.34 (s, 6H).

Example 1(9)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-chlorophenyl)ethane-1-he

TLC: Rf and 0.46 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,85 (W, 1H), 7,92-to $ 7.91 (m, 1H), 7,84-7,80 (m, 2H), 7,47-7,34 (m, 4H), 7,22 (d, J=7,0 Hz, 1H), of 6.26 (s, 1H), 2.91 in (s, 2H), of 1.37 (s, 6H).

Example 1(10)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclobutylmethyl-1-he

TLC: Rf of 0.43 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,34 (W, 1H), 7,69 (d, J=7,0 Hz, 1H), 7,45-7,20 (m, 2H), 7,16 (d, J=7,0 Hz, 1H), 5.56mm (s, 1H), 3,26 (m, 1H), 2,84 (s, 2H), 2,45 is 1.70 (m, 6H), of 1.30 (s, 6H).

Example 1(11)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.50 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,23 (W, 1H), 6,70 (d, J=8.0 Hz, 1H), 7,45-7,20 (m, 2H), 7,16 (d, J=8.0 Hz, 1H), ceiling of 5.60 (s, 1H), 2,84 (s, 2H), 2,45 (m, 1H), 2.00 in of 1.30 (m, 12H), of 1.29 (s, 6H).

Example 1(12)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-chlorophenyl)ethane-1-he

TLC: Rf of 0.48 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,82 (W, 1H), to $ 7.91-7,87 (m, 2H), 7,81 (d, J=8.0 Hz, 1H), 7,47-to 7.32 (m, 4H), 7,22 (DD, J=7,5, 1.0 Hz, 1H), 6,27 (s, 1H), 2.91 in (s, 2H), of 1.37 (s, 6H).

Example 1(13)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.34 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,48 (W, 1H), 7,72 (d, J=8.0 Hz, 1H), 7,45-7,25 (m, 2H), 7,16 (d, J=8.0 Hz, 1H), 5,79 (s, 1H), 2,84 (s, 2H), 2.05 is (m, 3H), 1.91 a (m, 6H), of 1.75 (m,6H), of 1.29 (s,6H).

Example 1(14)

(Z)-2-(3,3,5-Trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf is 0.24 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,92 (W, 1H), 7,95 (m, 2H), 7,71 (d, J=7.5 Hz, 1H), 7,50-7,40 (m, 3H), 7,32 (d, J=7.5 Hz, 1H), 7.23 percent (DD, J=7,5, 7.5 Hz, 1H), 6,32 (s, 1H), and 2.83 (s, 2H), 2,32 (s, 3H), of 1.37 (s, 6H).

Example 1(15)

(Z)-2-(3,3,6-Trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.27 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,83 (W, 1H), 7,95 (m, 2H), 7,71 (d, J=8.0 Hz, 1H), 7,50-7,40 (m, 3H), 7,13 (d, J=8.0 Hz, 1H), 7,01 (s, 1H), 6.30-in (s, 1H), 2,85 (s, 2H), 2,39 (s, 3H), of 1.35 (s, 6H).

Example 1(16)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-2-yl)Ethan-1-he

TLC: Rf 0.26 (ethyl acetate:hexane=1:5).

NMR (CDCl3): 4 11,95 (W, 1H), 8,46 (s, 1H), 8,07 (DD, J=8,5, 1.0 Hz, 1H), 8,00-7,80 (m, 4H), 7,60-7,20 (m, 5H), of 6.49 (s, 1H), 2,93 (s, 2H), 1.39 in (s, 6H).

Example 1(17)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methoxyphenyl)Ethan-1-he

TLC: Rf 0.28 in (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,74 (W, 1H), 7,98-to $ 7.91 (m, 2H), 7,83 (d, J=7,0 Hz, 1H), 7,45-7,29 (m, 2H), 7,21 (d, J=7.5 Hz, 1H), 6,97-6,91 (m, 2H), of 6.31 (s, 1H), 3,86 (s, 3H), 2,89 (s, 2H), of 1.35 (s, 6H).

Example 1(18)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.48 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,83 (W, 1H), 7,83 (d, J=8.0 Hz, 1H), 7,55-7,29 (m, 5H), 7,22 (d, J=7.5 Hz, 1H), 7.03 is-6,97 (m, 1H), 6,32 (s, 1H), 3,88 (s, 3H), 2.91 in (s, 2H), of 1.37 (s, 6H).

Example 1(19)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-forfinal)ethane-1-he

TLC: Rf value of 0.52 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,78 (W, 1H), 7,98-to $ 7.91 (m, 2H), 7,81 (d, J=7.5 Hz, 1H), 7,47-7,30 (m, 2H), 7,21 (d, J=7,0 Hz, 1H), 7,14-7,05 (m, 2H), 6,27 (s, 1H), 2,90 (s, 2H), 1,36 (s, 6H).

Example 1(20)

(Z)-2-(3,3,7-Trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.38 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,84 (W, 1H), of 7.96 (m, 2H), 7.62mm (s, 1H), 7,50-7,40 (m, 3H), from 7.24 (d, J=7.5 Hz, 1H), 7,10 (d, J=7.5 Hz, 1H), 6,32 (s, 1H), 2,85 (s, 2H), 2,42 (s, 3H), of 1.35 (s, 6H).

Example 1(21)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-1-yl)Ethan-1-he

p>

TLC: Rf of 0.27 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,78 (W, 1H), and 8.50 (m, 1H), of 7.90-7,80 (m, 2H), 7,75-the 7.65 (m, 2H), 7,55-to 7.15 (m, 6H), 6,09 (s, 1H), 2,94 (s, 2H), 1,41 (s, 6H).

Example 1(22)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.38 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ of 11.69 (W, 1H), 7,74 (d, J=8.0 Hz, 1H), to 7.67 (DD, J=8,0, 2.0 Hz, 1H), 7,43-7,29 (m, 3H), 7,19 (DD, J=7,0, 0.5 Hz, 1H), 7.03 is-to 6.95 (m, 2H), 6,27 (s, 1H), 3,91 (s, 3H), 2,89 (s, 2H), 1,36 (s, 6H ).

Example 1(23)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-forfinal)ethane-1-he

TLC: Rf 0,59 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ to 11.79 (W, 1H), 7,86 (DDD, J=8,0, to 8.0, 2.0 Hz, 1H), 7,79 (d, J=7,0 Hz, 1H), 7,45-7,30 (m, 3H), 7.24 to to 7.18 (m, 2H), 7,10 (DDD, J=11,5, to 8.0, 1.0 Hz, 1H), 6.30-in (s, 1H), 2.91 in (s, 2H), of 1.37 (s, 6H).

Example 1(24)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-forfinal)ethane-1-he

TLC: Rf to 0.63 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,84 (W, 1H), 7,82 (d, J=8.0 Hz, 1H), 7,72 (d, J=8.0 Hz, 1H), 7,63 (d, J=10.0 Hz, 1H), 7,47-7,33 (m, 3H), 7,22 (d, J=7.5 Hz, 1H), 7,17-7,10 (m, 1H), 6,27 (s, 1H), 2.91 in (s, 2H), of 1.37 (s, 6H).

Example 1(25)

A mixture of (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-2-methyl-1-Penilaian-1-it 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-phenylpropane-1-it

A and b take the form of a mixture (A:B=5:4).

TLC: R of 0.29 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ of 13.05 (W, 1H of A), 7,92 (m, 2H, A), 7,81 (m, 1H of A), 7,60-7,10 (m, 6H from A and from 9H (B)4,80 (q, J=7,0 Hz, 1H of B), 2,84 (s, 2H, A), 2,58 (s, 2H, B), of 2.56 (d, J=7,0 Hz, 3H of B), of 2.10 (s, 3H of A)of 1.27 (s, 6H from A)a 1.08 (s, 3H of B)to 0.97 (s, 3H of B).

Example 1(26)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-cyclohexane]-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.58 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 12,21 (W, 1H), 7,99-7,94 (m, 2H), 7,82 (d, J=7,0 Hz, 1H), 7,47-7,28 (m, 5H), 7,21 (d, J=7,0 Hz, 1H), 6.35mm (s, 1H), 2.91 in (s, 2H), 1,80-of 1.30 (m, 10H).

Example 1(27)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-cyclopentane]-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.54 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ a 12.03 (W, 1H), 7,98-to 7.93 (m, 2H), 7,82 (d, J=7.5 Hz, 1H), 7,47-7,29 (m, 5H), of 7.23 (d, J=7.5 Hz, 1H), 6,34 (s, 1H), 2,98 (s, 2H), 1,95-of 1.62 (m, 8H).

Example 1(28)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-Cycloheptane]-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0,41 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ 12,16 (W, 1H), 7,99-7,94 (m, 2H), 7,82 (d, J=7.5 Hz, 1H), 7,47-7,29 (m, 5H), 7,20 (d, J=7,0 Hz, 1H), 6,33 (s, 1H), 2,92 (s, 2H), 1.91 a-a 1.45 (m, 12H).

Example 1(29)

(Z)-2-(3,3-Diethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.35 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ 11,98 (W, 1H), 7,99-7,94 (m, 2H), 7,82 (d, J=7.5 Hz, 1H), 7,45-7,29 (m, 5H), 7,21 (d, J=7,0 Hz, 1H), 6,36 (s, 1H), 2,90 (s, 2H), 1.70 to was 1.58 (m, 4H), of 0.95 (t, J=7.5 Hz, 6H).

the example 1(30)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-ethoxycarbonylphenyl)ethane-1-he

TLC: Rf to 0.19 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,91 (W, 1H), at 8.60 (DD, J=1.5 and 1.5 Hz, 1H), 8,20-8,10 (m, 2H), 7,86 (DD, J=8,5, 1.5 Hz, 1H), 7,60-7,20 (m, 4H), 6,36 (s, 1H), 3,95 (s, 3H), of 2.92 (s, 2H), 1,38 (s, 6H).

Example 1(31)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-CYCLOBUTANE]-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.35 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ 11,99 (W, 1H), 7,97-7,94 (m, 2H), 7,80 (d, J=7.5 Hz, 1H), 7,47-7,41 (m, 4H), 7,37-7,26 (m, 2H), 6,34 (s, 1H), 3,09 (s, 2H), 2,33-of 2.23 (m, 2H), 2,18-of 2.09 (m, 2H), 1,96-to 1.79 (m, 2H).

Example 1(32)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(quinoline-6-yl)ethane-1-he

TLC: Rf is 0.22 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 11,99 (W, 1H), 8,95 (DD, J=4,0, 1.5 Hz, 1H), 8,44 (d, J=1.5 Hz, 1H), 8.30 to (DD, J=9,0, 1.5 Hz, 1H), 8,27 (m, 1H), 8,15 (d, J=9.0 Hz, 1H), of 7.90 (m, 1H), 7,50-7,20 (m, 4H), 6,47 (s, 1H), 2,94 (s, 2H,), of 1.40 (s, 6H).

Example 1(33)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,4'-3,4,5,6-tetrahydropyran]-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0,49 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 12,41 (W, 1H), 7,99-7,94 (m, 2H), 7,83 (d, J=7,0 Hz, 1H), of 7.48-7.23 percent (m, 6H), to 6.39 (s, 1H), 3,90-a-3.84 (m, 4H), 2,96 (s, 2H), 1,80-of 1.73 (m, 4H).

Example 1(34)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,4'-1'-methylpiperidin]-1-ilidene)-1-Penilaian-1-he

NMR (CDCl3): δ 12,22 (W, 1H), 7,98-to 7.95 (m, 2H), 7,82 (d, J=7.5 Hz, 1H), 7,46-7,41 (m, 4H), 7,34 (t, J=7.5 Hz, 1H), 7,24 (d, J=7.5 Hz, 1H), 6,36 (s, 1H), 2,92 (s, 2H), 2,73-2,69 (m, 2H), 2,53 at 2.45 (m, 2H), 2,38 (s, 3H), 1,81-to 1.77 (m, 4H).

Example 1(35)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-triptoreline)ethane-1-he

TLC: Rf to 0.19 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,42 (W, 1H), 7,75-to 7.15 (m, 8H), of 5.82 (s, 1H), 2,92 (s, 2H), 1,38 (s, 6H).

Example 1(36)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-triptoreline)ethane-1-he

TLC: Rf of 0.47 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,92 (W, 1H), 8,21 (s, 1H), 8,12 (d, J=8.0 Hz, 1H), a 7.85 (d, J=7.5 Hz, 1H), of 7.70 (d, J=8.0 Hz, 1H), EUR 7.57 (d, J=7.5 Hz, 1H), 7,55-7,20 (m, 3H), of 6.31 (s, 1H), 2,93 (s, 2H), 1.39 in (s, 6H).

Example 1(37)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-triptoreline)ethane-1-he

TLC: Rf of 0.27 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,93 (W, 1H), 8,03 (d, J=8.0 Hz, 2H), 7,83 (m, 1H), 7,69 (d, J=8.0 Hz, 2H), 7,50-7,20 (m, 3H), 6.30-in (s, 1H), 2,92 (s, 2H), 1,38 (s, 6H).

Example 1(38)

(Z)-2-(3,3,6,8-Tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf and 0.46 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 12,06 (W, 1H), 7,88 (m, 2H), 7,50-7,35 (m, 3H), 7,03 (s, 1H), 6,86 (s, 1H), 6,11 (s, 1H), and 2.79 (s, 2H), 2,65 (s, 3H), of 2.34 (s, 3H), of 1.30 (s, 6H).

Example 1(39)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ylides is n)-1-(pyridine-3-yl)ethane-1-he

TLC: Rf of 0.36 (ethyl acetate:hexane=2:1).

NMR (CDCl3): δ 11,89 (W, 1H), 9,16 (DD, J=2.0 a, 0.5 Hz, 1H), 8,66 (DD, J=5.0 and 2.0 Hz, 1H), they were 8.22 (DDD, J=8.0 a, 2,0, 2,0 Hz, 1H), 7,83 (m, 1H), 7,50-7,20 (m, 4H), of 6.29 (s, 1H), 2,92 (s, 2H), 1,38 (s, 6H).

Example 1(40)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(pyridine-4-yl)Ethan-1-he

TLC: Rf of 0.34 (ethyl acetate:hexane=2:1).

NMR (CDCl3): δ 11,98 (W, 1H), 8,72 (d, J=6.0 Hz, 2H), 7,82 (m, 1H), of 7.75 (d, J=6.0 Hz, 2H), 7,50-7,20 (m, 3H), of 6.29 (s, 1H), 2,92 (s, 2H), 1,38 (s, 6H).

Example 1(41)

(Z)-2-(8-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.36 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ to 12.28 (W, 1H), to 7.93 (m, 2H), 7,50-7,35 (m, 3H), 7,35 (DD, J=7,0, 7,0 Hz, 1H), of 6.96 (s, 1H), 6,92 (d, J=7,0 Hz, 1H), for 6.81 (d, J=7,0 Hz, 1H), of 3.97 (s, 3H), 2,85 (s, 2H), of 1.34 (s, 6H).

Example 1(42)

(Z)-2-(6-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0.28 in (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,84 (W, 1H), to 7.93 (m, 2H), to 7.77 (d, J=9.0 Hz, 1H), 7,50-7,35 (m, 3H), 6,85 (DD, J=9,0, 2.5 Hz, 1H), 6,72 (d, J=2.5 Hz, 1H), and 6.25 (s, 1H), a 3.87 (s, 3H), of 2.86 (s, 2H), 1,36 (s, 6H).

Example 1(43)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,4'-piperidine]-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0.14 (water:methanol:chloroform=1:10:50).

NMR (CDCl3): δ 12,40 (s, 1H), of 7.96 (m, 2H), 7,82 (d, J=7.5 Hz, 1H), 7,50-7,20 (m, 6H), to 6.39(s, 1H), 3,12 (m, 4H), 2,96 (s, 2H)and 1.83 (m, 4H).

Example 1(44)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2,6-dimetilfenil)ethane-1-he

TLC: Rf is 0.24 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ to 11.52 (W, 1H), to 7.64 (d, J=7.5 Hz, 1H), 7,45-to 6.95 (m, 6H), 5,71 (s, 1H), 2,92 (s, 2H), 2,33 (s, 6H), to 1.38 (s, 6H).

Example 1(45)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-4'-ethoxycarbonylmethoxy]-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.50 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 12,04 (W, 1H), 7,98-to 7.93 (m, 2H), 7,82 (d, J=8.0 Hz, 1H), 7,46-7,20 (m, 6H), 6.35mm (s, 1H), 4,15 (q, J=7,0 Hz, 2H), 2,98 (s, 2H), 2,55-to 2.42 (m, 1H), 2,03 of 1.50 (m, 8H), of 1.27 (t, J=7.0 Hz, 3H).

(This connection has two stereoisomer due to the presence of carbon*, attached ethoxycarbonyl group. This connection corresponds to the less polar compound thin layer of silica gel. And the more polar compound corresponding to the compound described in example 1(46).

Example 1(46)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-4'-ethoxycarbonylmethoxy]-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0.36 and (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ of 12.26 (W, 1H), 7,98-of 7.90 (m, 2H), 7,82 (d, J=7,0 Hz, 1H), EUR 7.57-7,27 (m, 5H), 7,21 (d, J=6,5 Hz, 1H), 6,34 (s, 1H), 4,15 (q, J=7,0 Hz, 2H), 2,89 (s, 2H), 2,34 was 2.25 (m, 1H), 1,98-of 1.40 (m, 8H), 1.27mm (t, J=7.0 Hz, 3H).

(This connection has two stereoisomer thanks deliciousity*, attached ethoxycarbonyl group. This connection corresponds to a more polar compound thin layer of silica gel. And the less polar compound corresponding to the compound described in example 1(45)).

Example 1(47)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclododecyl-1-he

TLC: Rf of 0.35 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,32 (W, 1H), 7,72 (m, 1H), 7,45-7,10 (m, 3H), 5,61 (s, 1H), 2,84 (m, 2H), by 2.55 (m, 1H), 1.70 to of 1.20 (m, 22H), of 1.29 (s, 6H).

Example 1(48)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-tert-butylphenyl)ethane-1-he

TLC: Rf 0.26 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,78 (W, 1H), 7,89 (d, J=8.5 Hz, 2H), 7,82 (m, 1H), 7,45 (d, J=8.5 Hz, 2H), 7,45-to 7.15 (m, 3H), 6,33 (s, 1H), 2,90 (m, 2H), 1,36 (s, 6H), of 1.35 (s, 9H).

Example 1(49)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-4'-oxocyclohexyl]-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.38 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 12,63 (W, 1H), of 7.96 (m, 2H), 7,87 (m, 1H), 7,50-7,20 (m, 6H), of 6.45 (s, 1H), 3.04 from (s, 2H), 2,77 (m, 2H), 2,39 (m, 2H), 2,17 (m, 2H), 1.93 and (m, 2H).

Example 1(50)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(piperidine-4-yl)Ethan-1-he

TLC: Rf 0,18 (water:methanol:chloroform=1:10:50).

NMR (CDCl3): δ 11,31 (W, 1H), of 7.70 (m, 1H), 7,45-to 7.15 (m, 3H), 5,64 (s, 1H), 3,17 (dt, J=12,0,, 3.5 Hz, 2H), 2,85 (s, 2H) to 2.67 (dt, J=3,5, 12.0 Hz, 2H), 2,42 (TT, J=12,0, 4.0 Hz, 1H), to 1.86 (m, 2H), by 1.68 (m, 2H), of 1.30 (s, 6H).

Example 1(51)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-isopropylphenyl)ethane-1-he

TLC: Rf of 0.38 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,78 (s, 1H), 7,88 (d, J=8.0 Hz, 2H), 7,86-7,80 (m, 1H), 7,44-to 7.18 (m, 3H), 7,28 (d, J=8.0 Hz, 2H), 6,32 (s, 1H), 3,02-of 2.81 (m, 1H), 2,89 (s, 2H), 1,36 (s, 6H), of 1.28 (d, J=8.0 Hz, 6H).

Example 1(52)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclooctylmethyl-1-he

TLC: Rf is 0.42 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,21 (W, 1H), 7,71 (d, J=7.5 Hz, 1H), 7,45-7,20 (m, 2H), 7,16 (d, J=7.5 Hz, 1H), ceiling of 5.60 (s, 1H), 2,84 (s, 2H), of 2.51 (m, 1H), 2.00 in of 1.40 (m, 14H), of 1.29 (s, 6H).

Example 1(53)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(1-methylcyclohexyl)ethane-1-he

TLC: Rf of 0.44 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,36 (W, 1H), of 7.70 (m, 1H), 7,45-7,10 (m, 3H), of 5.83 (s, 1H), 2,84 (s, 2H), 2,10-of 1.95 (m, 2H), 1,65-of 1.20 (m, 8H), of 1.30 (s, 6H)and 1.15 (s, 3H).

Example 1(54)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-ethylphenyl)ethane-1-he

TLC: Rf of 0.35 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,80 (SHS, 1H), of 7.90-7,80 (m, 3H), 7,46-to 7.18 (m, 5H), 6,33 (s, 1H), 2,89 (s, 2H), 2,70 (kV, J=7.8 Hz, 2H), 1,36 (s, 6H), of 1.27 (t, J=7.8 Hz, 3H).

Example 1(55)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-butylphenyl)ethane-1-he

TLC: Rf of 0.20 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ to 11.79 (SHS, 1H), 7,89-7,81 (m, 3H), 7,46-7,19 (m, 5H), 6,33 (s, 1H), 2,90 (s, 2H), 2,66 (t, J=7.4 Hz, 2H), and 1.63 (m, 2H), 1.39 in (m, 2H), 1,36 (s, 6H), of 0.93 (t, J=7.4 Hz, 3H).

Example 1(56)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(1-phenylcyclohexyl)ethane-1-he

TLC: Rf of 0.37 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,12 (W, 1H), 7,50-7,10 (m, 9H), of 5.55 (s, 1H), 2,78 (s, 2H), 2,45-of 2.30 (m, 2H), 2,15-2,00 (m, 2H), 1,80-of 1.30 (m, 6H), 1.26 in (s, 6H).

Example 1(57)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-propylphenyl)ethane-1-he

TLC: Rf of 0.33 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ to 11.79 (SHS, 1H), 7,87 (d, J=8.0 Hz, 2H), 7,82 (m, 1H), 7,46-7,19 (m, 3H), from 7.24 (d, J=8.0 Hz, 2H), 6,33 (s, 1H), 2,90 (s, 2H), 2,64 (t, J=7.4 Hz, 2H), 1.69 in (m, 2H), 1,36 (s, 6H), of 0.95 (t, J=7,4 Hz, 3H).

Example 1(58)

2-(3,3-Dimethyl-3,4-dihydroisoquinoline-1-yl)-1-phenylbutane-1-he

TLC: Rf is 0.42 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 7,95-to $ 7.91 (m, 2H), to 7.59-7,10 (m, 7H), 4,60 (m, 1H), 2.57 m (s, 2H), of 2.21 (m, 1H), up to 1.98 (m, 1H), 1,09 (s, 3H), of 1.02 (t, J=8.0 Hz, 3H), and 1.00 (s, 3H).

Example 1(59)

2-(3,3-Dimethyl-3,4-dihydroisoquinoline-1-yl)-1-phenylpentane-1-he

TLC: Rf of 0.44 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 8,06-to $ 7.91 (m, 3H), to 7.59-of 7.24 (m, 5H), 7,11 (m, 1H), 4,69 (DD, J=7,5, 6.0 Hz, 1H), 2,61 (s, 2H), measuring 2.20 (m, 1H), of 1.85 (m, 1H), 1,40 (m, 2H), of 1.05 (s, 3H), and 1.00 (s, 3H), and 0.98 (t, J=8.0 Hz, 3H).

Example 1(60)

(Z)-CIS-2-(3,3-Di is ethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methylcyclohexyl)ethane-1-he

TLC: Rf of 0.37 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,25 (W, 1H), of 7.70 (m, 1H), 7,45-7,10 (m, 3H), 5,65 (s, 1H), and 2.83 (s, 2H), 2,50 (dt, J=to 11.0, 4.5 Hz, 1H), 2,28 (m, 1H), 1,90-1,10 (m, 8H), of 1.29 (s, 3H), 1.28 (in s, 3H), of 0.90 (d, J=7,0 Hz, 3H).

Example 1(61)

(Z)-TRANS-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methylcyclohexyl)ethane-1-he

TLC: Rf of 0.35 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,38 (W, 1H), 7,71 (m, 1H), 7,45-7,10 (m, 3H), ceiling of 5.60 (s, 1H), 2,84 (s, 2H), 2.00 in 0,90 (m, 10H), of 1.30 (s, 6H), to 0.88 (d, J=7.5 Hz, 3H).

Example 1(62)

(Z)-TRANS-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-methylcyclohexyl)ethane-1-he

TLC: Rf to 0.39 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,27 (W, 1H), 7,71 (m, 1H), 7,45-7,10 (m, 3H), of 5.68 (s, 1H), 2,84 (s, 2H), 2,59 (m, 1H), 2,10-of 1.10 (m, 9H), of 1.29 (s, 6H), and 0.98 (d, J=7,0 Hz, 3H).

Example 1(63)

(Z)-CIS-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-methylcyclohexyl)ethane-1-he

TLC: Rf of 0.34 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,34 (W, 1H), 7,71 (m, 1H), 7,45-7,10 (m, 3H), 5,64 (s, 1H), 2,84 (s, 2H), 2,39 (m, 1H), 1,95-to 0.80 (m, 9H), of 1.29 (s, 6H), to 0.92 (d, J=6.5 Hz, 3H).

Example 1(64)

(Z)-CIS-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methylcyclohexyl)ethane-1-he

TLC: Rf of 0.43 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,30 (W, 1H), of 7.70 (m, 1H), 7,45-7,10 (m, 3H), of 5.68 (s, 1H), 2,84 (s, 2H), of 2.38 (m, 1H), 2.00 in of 1.30(m, 9H), of 1.29 (s, 6H), of 0.97 (d, J=7,0 Hz, 3H).

Example 1(65)

(Z)-TRANS-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methylcyclohexyl)ethane-1-he

TLC: Rf of 0.37 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,33 (W, 1H), of 7.70 (m, 1H), 7,45-7,10 (m, 3H), 5,64 (s, 1H), 2,84 (s, 2H), 2,24 (TT, J=12,0,, 3.5 Hz, 1H), 2.00 in of 0.90 (m, 9H), of 1.29 (s, 6H), of 0.90 (d, J=6.5 Hz, 3H).

Example 1(66)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3,5-dimethylisoxazol-4-yl)Ethan-1-he

TLC: Rf of 0.25 (ethyl acetate:hexane=4:1).

NMR (CDCl3): δ 11,55 (SHS, 1H), 7,68 (d, J=7.8 Hz, 1H), 7,49-7,20 (m, 3H), 5,80 (s, 1H), 2,90 (s, 2H), 2,66 (s, 3H), of 2.50 (s, 3H), of 1.36 (s, 6H).

Example 1(67)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-trifloromethyl)ethane-1-he

TLC: Rf of 0.54 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,83 (W, 1H), 8,00-to 7.95 (m, 2H), 7,82 (d, J=7.5 Hz, 1H), 7,45 (t, J=7.5 Hz, 1H), 7,35 (t, J=7.5 Hz, 1H), 7,27-7,21 (m, 3H), 6,27 (s, 1H), 2.91 in (s, 2H), of 1.37 (s, 6H).

Example 1(68)

(Z)-2-(6-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.50 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,82 (W, 1H), 7.95 is-a 7.92 (m, 2H), of 7.75 (d, J=8.0 Hz, 1H), 7,47-7,40 (m, 3H), 7,32 (DD, J=8,0, 2.0 Hz, 1H), 7,22 (d, J=2.0 Hz, 1H), 6,23 (W, 1H), 2,88 (s, 2H), of 1.37 (s, 6H).

Example 1(69)

(Z)-2-(5-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

The SH: Rf and 0.61 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,83 (W, 1H), of 7.96-a 7.92 (m, 2H), to 7.77 (d, J=8.0 Hz, 1H), 7,52 (d, J=8.0 Hz, 1H), of 7.48-7,42 (m, 3H), 7,32-7,26 (m, 1H), of 6.31 (W, 1H), 3,03 (s, 2H), 1.39 in (s, 6H).

Example 1(70)

(Z)-2-(7-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.48 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,81 (W, 1H), 7,97-to 7.93 (m, 2H), 7,78 (d, J=2.0 Hz, 1H), of 7.48-the 7.43 (m, 3H), 7,41 (DD, J=8,0, 2.0 Hz, 1H), 7,17 (d, J=8.0 Hz, 1H), 6,23 (W, 1H), 2,88 (s, 2H), of 1.37 (s, 6H).

Example 1(71)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(5-methyl-2-phenyloxazol-4-yl)Ethan-1-he

TLC: Rf of 0.37 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,65 loops, 1H), 8,11-8,08 (m, 2H), of 7.96 (d, J=7,6 Hz, 1H), 7,49 and 7.36 (m, 5H), 7,20 (d, J=7,6 Hz, 1H), 6,72 (SHS, 1H), 2.91 in (s, 2H), and 2.79 (s, 3H), of 1.38 (s, 6H).

Example 1(72)

(Z)-2-(7-Fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.45 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,80 (W, 1H), of 7.96-to 7.93 (m, 2H), 7,51 (DD, J=9.5mm, 2.5 Hz, 1H), of 7.48-7,41 (m, 3H), 7,22-7,11 (m, 2H), 6,24 (W, 1H), 2,87 (s, 2H), of 1.37 (s, 6H).

Example 1(73)

(Z)-2-(6-Fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.45 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,83 (W, 1H), of 7.96-a 7.92 (m, 2H), 7,82 (DD, J=8,5, and 5.5 Hz, 1H), of 7.48-7,40 (m, 3H),? 7.04 baby mortality (DDD, J=8.5 a, 8.5 a, 3.0 Hz, 1H), 6,94 (DD, J=8,5, 3.0 Hz, 1H), 6,23 (W, 1H), 2,90 (s, 2H), 1,38 (s, 6H).

Example 1(74)

(Z)-2-(5-fluoro-3,3-dimethy the -3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.54 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,80 (W, 1H), of 7.96-to 7.93 (m, 2H), 7,65 (d, J=8.0 Hz, 1H), 7,47-7,40 (m, 3H), 7,35-7,30 (m, 1H), 7,19 (DD, J=8,0, 8.0 Hz, 1H), of 6.31 (W, 1H), 2,93 (s, 2H), 1.39 in (s, 6H).

Example 1(75)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methyl-2-phenylthiazol-5-yl)Ethan-1-he

TLC: Rf of 0.37 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ to 11.56 (SHS, 1H), 8,00-of 7.97 (m, 2H), to 7.77 (d, J=7.8 Hz, 1H), 7,46-7,42 (m, 4H), of 7.36 (m, 1H), 7,22 (d, J=7.5 Hz, 1H), between 6.08 (s, 1H), 2.91 in (s, 2H), 2,85 (s, 3H), of 1.37 (s, 6H).

Example 1(76)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-pativilca[2,2 .2]octane-1-yl)Ethan-1-he

TLC: Rf of 0.54 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ is 11.39 (SHS, 1H), of 7.70 (d, J=7.5 Hz, 1H), was 7.36 (m, 1H), 7,28 (m, 1H), 7,16 (d, J=7.5 Hz, 1H), 5,73 (s, 1H), and 2.83 (s, 2H), 1,81 to 1.76 (m, 6H), and 1.56 (s, 2H), 1,44-to 1.38 (m, 6H), of 1.28 (s, 6H), 1,23-1,16 (m, 4H), 1,11-of 1.07 (m, 2H), from 0.88 (t, J=7.0 Hz, 3H).

Example 1(77)

(Z)-TRANS-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-tert-butylcyclohexyl)ethane-1-he

TLC: Rf value of 0.52 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,32 (SHS, 1H), 7,71 (d, J=7.8 Hz, 1H), 7,39 (m, 1H), 7,33 (m, 1H), 7,17 (d, J=7.2 Hz, 1H), 5,64 (s, 1H), 2,84 (s, 2H), 2.05 is (m, 1H), 1,92 (m, 2H), to 1.86 (m, 2H), 1,45 (m, 2H), 1.28 (in, 6H), 1,18-a 1.01 (m, 3H), 0,86 (s, 9H).

Example 1(78)

(Z)-2-(3,3,4,4-Tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

<> TLC: Rf of 0.35 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,80 (W, 1H), of 7.96 (m, 2H), 7,81 (m, 1H), 7,55-7,40 (m, 5H), 7,32 (m, 1H), 6.30-in (W, 1H), 1,50 to 1.00 (m, 12H).

Example 1(79)

(Z)-2-(Spiro[3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-4,1'-cyclohexane]-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.45 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 12,22 (W, 1H), 7,99 (m, 2H), 7,81 (m, 1H), 7,50-7,40 (m, 5H), 7,32 (m, 1H), 6,32 (W, 1H), 2,20-1,00 (m, 16H).

Example 1(80)

(Z)-2-(6,7-Dimethoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0,59 (hexane:ethyl acetate=1:1).

NMR (DMSO-d6) δ: 11,91 (W, 1H), 8,00-of 7.97 (m, 2H), of 7.48-7,41 (m, 4H), 6,91 (s, 1H), 6,36 (s, 1H), 3,88 (s, 3H), 3,83 (s, 3H), 2,84 (s, 2H), 1.28 (in, 6H).

Example 1(81)

(Z)-2-(Spiro[3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-4,1'-cyclopentane]-1-ilidene)-1-Penilaian-1-he

TLC: Rf is 0.49 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,92 (W, 1H), 7,97 (m, 2H), to 7.84 (d, J=8.0 Hz, 1H), 7,55-7,30 (m, 6H), 6,33 (W, 1H), 2,00-1,10 (m, 14H).

Example 2

Hydrochloride of 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-cyclopentolate-1-it

To a solution of the compound obtained in example 1(2) (1132 mg)in dioxane (5 ml) is added dropwise a solution of 4 M hydrochloric acid in dioxane (2 ml). The residue is washed with hexane, obtaining the compound of the present invention (1212 mg)having the following physical the data.

TLC: Rf of 0.38 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 14, 48mm (W, 1H), 7,68 (DD, J=7,5, 7.5 Hz, 1H), 7.62mm (d, J=7.5 Hz, 1H), 7,46 (DD, J=7,5, 7.5 Hz, 1H), 7,34 (d, J=7.5 Hz, 1H), 4,35 (W, 2H), 3,26 (m, 1H), 3,06 (s, 2H), 2,20-of 1.55 (m, 8H), to 1.59 (s, 6H).

Examples 2(1)-2(5)

By the same procedure as described in example 2 using the compound obtained in example 1(11), example 1(25), example 1(50), example 1(58) and example 1(59)instead of the compound obtained in example 1(2)obtain compounds of the present invention.

Example 2(1)

Hydrochloride of 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-cyclohepten-1-it

TLC: Rf of 0.40 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ to 7.67 (DD, J=7,5, 7.5 Hz, 1H), to 7.61 (d, J=7.5 Hz, 1H), 7,45 (DD, J=7,5, 7.5 Hz, 1H), 7,34 (d, J=7.5 Hz, 1H), 4.75 in (W, 2H), 3,05 (s, 2H), 2,93 (m, 1H), to 2.06 (m, 2H), 1.85 to 1,50 (m, 10H), was 1.58 (s, 6H).

Example 2(2)

Hydrochloride of 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-phenylpropane-1-it

TLC: Rf of 0.29 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 8,13 (m, 2H), 7,78 (d, J=8.0 Hz, 1H), 7,60 (DDD, J=8,0, to 8.0, 1.0 Hz, 1H), 7,55-7,35 (m, 4H), from 7.24 (d, J=8.0 Hz, 1H), of 6.31 (q, J=7,0 Hz, 1H), 3,03 (d, J=16.5 Hz, 1H), 2,85 (d, J=16.5 Hz, 1H), 1,81 (d, J=7,0 Hz, 3H), 1,71 (s, 3H), of 1.46 (s, 3H).

Example 2(3)

The dihydrochloride of (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(piperidine-4-yl)Ethan-1-it

TLC: Rf 0,18 (water:methanol:chloroform=1:10:50).

NMR (DMSO-d6): δ 11,19 (W, 1H), 9,02 (W, 1H), 8,75 (W, 1H) 7,80 (d, J=7.5 Hz, 1H), 7,47 (DD, J=7,5, 7.5 Hz, 1H), 7,34 (DD, J=7,5, 7.5 Hz, 1H), 7,29 (d, J=7.5 Hz, 1H), 5,73 (s, 1H), 3,25 (m, 2H), 2.95 and is 2.80 (m, 4H), of 2.56 (m, 1H), 1,95-of 1.65 (m, 4H), 1,22 (s, 6H).

Example 2(4)

Hydrochloride of 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-phenylbutane-1-it

TLC: Rf 0,77 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 8,21-8,16 (m, 2H), 7,87 (d, J=8.0 Hz, 1H), 7,65-7,34 (m, 5H), 7,25 (d, J=8.6 Hz, 1H), 6,20 (DD, J=6,2, 5.8 Hz, 1H), 3,00 (d, J=16.6 Hz, 1H), 2,86 (d, J=16.6 Hz, 1H), has 2.56 (m, 1H), 2,13 (m, 1H), to 1.70 (s, 3H), of 1.48 (s, 3H)and 1.15 (t, J=7.4 Hz, 3H).

Example 2(5)

Hydrochloride of 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-phenylpentane-1-it

TLC: Rf 0.36 and (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ to 8.20 (m, 2H), 7,88 (d, J=7,6 Hz, 1H), of 7.64-to 7.35 (m, 5H), from 7.24 (d, J=7,0 Hz, 1H), 6,24 (DD, J=6,0, 6.2 Hz, 1H), 3,01 (d, J=16,8 Hz, 1H), and 2.83 (d, J=16,8 Hz, 1H), 2,48 (m, 1H), 1,99 (m, 1H), 1,80 (m, 1H), 1,71 (s, 3H), 1,45 (s, 3H), of 1.35 (m, 1H), 0,99 (t, J=7.4 Hz, 3H).

Reference example 2

1,3 .3m-Trimethyl-3,4-dihydroisoquinoline

To concentrated sulfuric acid (10 ml) is added dropwise a solution of 2-methyl-1-phenylpropane-2-ol (7.0 g) and acetonitrile (of 1.62 ml) in benzene (7.0 ml) and the mixture is stirred for 24 hours at room temperature. The mixture is neutralized by adding to the mixture of ice and added dropwise to saturated aqueous sodium bicarbonate solution and extracted twice with ethyl acetate. The extract is dried over anhydrous magnesium sulfate and concentrate in on igenom pressure. The residue is dissolved in ether and extracted with 1 N. hydrochloric acid and 2 N. hydrochloric acid. The extract is washed with ether to the mixture add 5 N. aqueous sodium hydroxide solution and extracted twice with ether. The extract is washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, obtaining specified in the header connection (2,53 g)having the following physical data.

TLC: Rf is 0.22 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ of 7.48 (DD, J=7,5, 1.5 Hz, 1H), 7,35 (dt, J=1.5 and 7.5 Hz, 1H), 7,30-7,25 (m, 1H), 7,14 (d, J=7.5 Hz, 1H), 2,69 (s, 2H), of 2.38 (s, 3H), of 1.20 (s, 6H).

Example 3

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-cyanophenyl)ethane-1-he

To a solution of Diisopropylamine (of 0.43 ml) in tetrahydrofuran (5 ml) is added dropwise n-utility (1.6 M solution in hexane, to 2.15 ml) and the mixture is stirred for 30 minutes at 0°C. To the reaction mixture are added dropwise the compound obtained in reference example 2 (478 mg)in tetrahydrofuran (2 ml) for 90 minutes at -78°C. To the reaction mixture add a solution of 3-cyanobenzaldehyde (571 mg) in tetrahydrofuran (2 ml) and the mixture is stirred with by heating to -10°C for a period of 90 minutes. To the reaction mixture are added water and extracted twice with ether. Extract.premium consistently 1 N. hydrochloric acid, water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=30:1→10:1)to give the compound of the present invention (61 mg)having the following physical data.

TLC: Rf 0,49 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,89 (W, 1H), they were 8.22 (DD, J=1.5 and 1.5 Hz, 1H), 8,17 (DDD, J=7,5 a, 1.5 a, 1.5 Hz, 1H), 7,83 (d, J=7,0 Hz, 1H), 7,71 (DDD, J=7,5 a, 1.5 a, 1.5 Hz, 1H), 7,55 (DD, J=7,5, 7.5 Hz, 1H), 7,47 (t, J=7,0 Hz, 1H), 7,38 (t, J=7,0 Hz, 1H), 7,24 (d, J=7,0 Hz, 1H), and 6.25 (s, 1H), 2,93 (s, 2H), 1,38 (s, 6H).

Examples 3(1)-3(4)

By the same procedure as described in example 3, using 4-cyanobenzoyl, 2-cryptomaterial, 2-cyanobenzoate or 3-cryptomathematical instead of 3 cyanobenzaldehyde get the following compounds of the present invention.

Example 3(1)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.47 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,96 (W, 1H), 8,02 (d, J=8.5 Hz, 2H), 7,81 (d, J=7.5 Hz, 1H), 7,72 (d, J=8.5 Hz, 2H), 7,47 (t, J=7.5 Hz, 1H), was 7.36 (t, J=7.5 Hz, 1H), 7,24 (d, J=7.5 Hz, 1H), 6,28 (s, 1H), 2,92 (s, 2H), 1,38 (s, 6H).

Example 3(2)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-trifloromethyl)ethane-1-he

TLC: Rf is 0.69 (hexane:this is laatat=2:1).

NMR (CDCl3): δ 11,65 (W, 1H), 7,79-7,72 (m, 2H), 7,45-7,25 (m, 5H), 7,21 (d, J=7.5 Hz, 1H), 6,12 (s, 1H), 2,92 (s, 2H), 1,38 (s, 6H).

Example 3(3)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-cyanophenyl)ethane-1-he

TLC: Rf of 0.44 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,76 (W, 1H), 7,87 (DD, J=7,5, 1.5 Hz, 1H), 7,81 (d, J=7,0 Hz, 1H), 7,76 (DD, J=7,5, 1.5 Hz, 1H), 7.62mm (dt, J=1.5 and 7.5 Hz, 1H), 7,52-7,42 (m, 2H), 7,34 (t, J=7,0 Hz, 1H), 7,22 (d, J=7,0 Hz, 1H), 6,21 (s, 1H), 2,92 (s, 2H), 1.39 in (s, 6H).

Example 3(4)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-trifloromethyl)ethane-1-he

TLC: Rf of 0.53 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11.87 per (W, 1H), 7,88-7,80 (m, 3H), of 7.48-the 7.43 (m, 2H), was 7.36 (t, J=7.5 Hz, 1H), 7,31-7,27 (m, 1H), 7.23 percent (d, J=7.5 Hz, 1H), 6,27 (s, 1H), 2,92 (s, 2H), 1,38 (s, 6H).

Example 4

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-carboxyphenyl)ethane-1-he

To a mixture of methanol (5 ml) and tetrahydrofuran (5 ml) is added the compound obtained in example 1(1) (662 mg), add 2 N. aqueous sodium hydroxide solution (5 ml) at room temperature and the mixture is stirred for 3 hours at room temperature. The reaction mixture is neutralized with hydrochloric acid and the mixture is stirred over night. Aggregated mass, which appears is filtered and dried. Washed with a mixture (hexane:ethyl acetate=1:1)to give compounds is the development of the present invention (575 mg), having the following physical data.

TLC: Rf of 0.29 (methanol:chloroform=1:10).

NMR (DMSO-d6): δ 13,12 (W, 1H), 11,94 (s, 1H), 8,09 (d, 7.0 Hz, 1H), of 8.09 (d, J=8.5 Hz, 2H), to 7.99 (d, J=8.5 Hz, 2H), 7,52 (DD, J=7,0, 7,0 Hz, 1H), 7,39 (DD, J=7,0, 7,0 Hz, 1H), 7,33 (d, J=7,0 Hz, 1H), 6,50 (s, 1H), to 2.94 (s, 2H), 1,29 (s, 6H).

Examples 4(1)-4(3)

By the same procedure as described in example 4 using the compound obtained in example 1(30), example 1(45) or example 1(46), instead of the compound obtained in example 1(1), obtain the following compounds of the present invention.

Example 4(1)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-carboxyphenyl)ethane-1-he

TLC: Rf of 0.37 (methanol:chloroform=1:10).

NMR (DMSO-d6): δ 13,10 (W, 1H), 11,90 (s, 1H), of 8.47 (DD, J=1.5 and 1.5 Hz, 1H), 8,25 (d, J=8.0 Hz, 1H), 8,10-of 8.00 (m, 2H), 7,65-7,30 (m, 4H), 6,47 (s, 1H), 2,94 (s, 2H), 1,29 (s, 6H).

Example 4(2)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-4'-carboxylicacid]-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.35 (chloroform:methanol:water=10:1:0,1).

NMR (CDCl3): δ 12,08 (W, 1H), 7,97-7,94 (m, 2H), 7,83 (d, J=7.5 Hz, 1H), 7,47-7,41 (m, 4H), 7,35 (t, J=7.5 Hz, 1H), 7,22 (d, J=7.5 Hz, 1H), 6,36 (s, 1H), 2,99 (s, 2H), 2,63-of 2.56 (m, 1H), 2.06 to 1,95 (m, 2H), 1,95 is 1.75 (m, 4H), 1,75-to 1.60 (m, 2H).

(This connection has two stereoisomer due to the presence of carbon*, attached to carboxypropyl. This connection corresponds to the less polar compound thin layer is of silicagel. And the more polar compound corresponding to the compound described in example 4(3)).

Example 4(3)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-4'-carboxylicacid]-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.32 (chloroform:methanol:water=10:1:0,1).

NMR (CDCl3): δ 12,32 (W, 1H), 7.95 is-a 7.92 (m, 2H), 7,82 (d, J=7.5 Hz, 1H), 7,44-7,42 (m, 4H), 7,34 (t, J=7.5 Hz, 1H), 7,22 (d, J=7.5 Hz, 1H), 6,33 (s, 1H), 2,90 (s, 2H), 2.40 a-to 2.29 (m, 1H), 2,02 is 1.91 (m, 6H), 1,52 was 1.43 (m, 2H).

(This connection has two stereoisomer due to the presence of carbon*, attached to carboxypropyl. This connection corresponds to a more polar compound thin layer of silica gel. And the less polar compound corresponding to the compound described in example 4(2)).

Example 5

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-hydroxyphenyl)ethane-1-he

To the compound obtained in example 1(18) (200 mg), added 47% Hydrobromic acid (3 ml) and the mixture is stirred for 1 hour at 115°C. the Reaction mixture is allowed to cool, neutralized by adding saturated aqueous sodium bicarbonate solution and then extracted twice with ethyl acetate. The extract is washed with water, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue is purified column chromatography on silica gel (who exan:ethyl acetate=3:1→ 1:1)to give the compound of the present invention (147 mg)having the following physical data.

TLC: Rf of 0.48 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,78 (W, 1H), 7,81 (d, J=8.0 Hz, 1H), 7,53-7,25 (m, 5H), 7,21 (d, J=7.5 Hz, 1H), 6,95 (DD, J=8.0 a, 3.0 Hz, 1H), 6.30-in (s, 1H), 6,13 (W, 1H), 2,90 (s, 2H), 1,36 (s, 6H).

Examples 5(1)-5(3)

By the same procedure as described in example 5 using the compound obtained in example 1(17), example 1(22) or example 1(42)instead of the compound obtained in example 1(18), obtain the following compounds of the present invention.

Example 5(1)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-4-hydroxyphenyl)ethane-1-he

TLC: Rf to 0.19 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,72 (W, 1H), to $ 7.91-7,87 (m, 2H), 7,82 (d, J=7,0 Hz, 1H), 7,42 (t, J=7,0 Hz, 1H), 7,33 (t, J=7,0 Hz, 1H), 7,21 (d, J=7,0 Hz, 1H), 6.90 to-6,85 (m, 2H), 6,29 (s, 1H), 2,89 (s, 2H), of 1.35 (s, 6H).

Example 5(2)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-hydroxyphenyl)ethane-1-he

TLC: Rf 0,70 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,34 (W, 1H), 7,83 (d, J=7,0 Hz, 1H), 7,76 (DD, J=8,0, 1.5 Hz, 1H), 7,46 (dt, J=1.5 and 8.0 Hz, 1H), 7,40-7,31 (m, 2H), 7.23 percent (d, J=7.5 Hz, 1H), 6,94 (DD, J=8.0 a, 1.0 Hz, 1H), 6,83 (dt, J=1,0, 8.0 Hz, 1H), 6,34 (s, 1H), 2.91 in (s, 2H), 1,38 (s, 6H).

Example 5(3)

(Z)-2-(6-Hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.18 (ethyl acetate:hexane=1:2).

NMR (DM what About the-d 6): δ 11,84 (s, 1H), 10,15 (s, 1H), 8,00-a 7.85 (m, 3H), 7,50-7,35 (m, 3H), of 6.73 (DD, J=8,5, 2.5 Hz, 1H), to 6.67 (d, J=2.5 Hz, 1H), 6.30-in (s, 1H), 2,82 (s, 2H), 1.27mm (s, 6H).

Example 6

2-(3,3-Dimethyl-3,4-dihydroisoquinoline-1-yl)-2-methyl-1-phenylpropane-1-he

To a solution of (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-she (277 mg; see Khim Geterotsiki. Soedin., 7, 946-949 (1994)) in tetrahydrofuran (5 ml) are added sequentially 62,7% sodium hydride (77 mg) and methyliodide (0,14 ml) at 0°C, the mixture is heated to room temperature and stirred for two hours. To the reaction mixture are added successively water and a saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The extract is dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=10:1)to give the compound of the present invention (110 mg)having the following physical data.

TLC: Rf 0,62 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 8,03 (m, 2H), 7,37 (TT, J=7,5, 2.0 Hz, 1H), 7,26 (m, 2H), 7,20-7,00 (m, 4H), 2,65 (s, 2H), 1,64 (s, 6H), of 1.23 (s, 6H).

Examples 6(1)-6(3)

By the same procedure as described in example 6, using 1,4-dibromobutane, 1,5-dibromethane or 2-bromo-1-(2-bromoethoxy)ethane instead of under the conditions get the following compounds of the present invention.

Example 6(1)

1-(3,3-Dimethyl-3,4-dihydroisoquinoline-1-yl)cycle is intervention

TLC: Rf 0,66 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ of 7.97 (m, 2H), 7,40-of 6.90 (m, 7H), to 2.57 (s, 2H), 2,70-of 2.30 (m, 4H), at 1.73 (m, 4H), 1,19 (s, 6H).

Example 6(2)

1-(3,3-Dimethyl-3,4-dihydroisoquinoline-1-yl)cyclohexylaniline

TLC: Rf 0,70 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ of 8.09 (m, 2H), 7,40-7,00 (m, 7H), to 2.66 (s, 2H), 2.40 a-2,05 (m, 4H), 1,80-of 1.30 (m, 6H), 1,24 (s, 6H).

Example 6(3)

4-(3,3-Dimethyl-3,4-dihydroisoquinoline-1-yl)-3,4,5,6-tetrahydropyran-4-infinicon

TLC: Rf 0,41 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 8,11 (m, 2H), 7,45-7,00 (m, 7H), 3,80 (m, 4H), 2,68 (s, 2H), 2.40 a (m, 4H), 1.26 in (s, 6H).

Example 7

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-4'-hydroxycyclohexyl]-1-ilidene)-1-Penilaian-1-he

To a solution of the compound obtained in example 1(49) (52 mg), in methanol (3 ml) add borohydride sodium (6 mg) at room temperature and the mixture is stirred at room temperature for 10 minutes. The reaction mixture was added to water and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by thin-layer chromatography on silica gel (hexane:ethyl acetate=5:1)to give the compound of the present invention (11 mg less on the popular isomer, 33 mg of the more polar isomer).

This connection has two stereoisomer due to the presence of carbon*is attached to the hydroxy-group. The less polar compound means a compound of the less polar position on thin-layer silica gel and the more polar compound means a compound more polar of its provisions.

The less polar compound

TLC: Rf of 0.33 (ethyl acetate:hexane=2:1).

NMR (CDCl3): δ 12,19 (W, 1H), 7,95 (m, 2H), 7,82 (m, 1H), 7,50-7,20 (m, 6H), 6,36 (s, 1H), was 4.02 (m, 1H), 2,97 (s, 2H), 2,10-of 1.55 (m, 8H).

The more polar compound

TLC: Rf 0.28 in (ethyl acetate:hexane=2:1).

NMR (CDCl3): δ 12,34 (W, 1H), of 7.96 (m, 2H), 7,83 (m, 1H), 7,50-7,20 (m, 6H), 6,37 (s, 1H), 3,66 (m, 1H), 2,89 (s, 2H), 2.00 in of 1.40 (m, 8H).

Example 8

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(1-acetylpiperidine-4-yl)Ethan-1-he

To a solution of the compound obtained in example 2(3) (77 mg), and triethylamine (0.15 ml) in dichloromethane (5 ml) add acetylchloride (0,02 ml) at room temperature and the mixture is stirred at room temperature for 30 minutes. The reaction mixture was added to water and extracted with ethyl acetate. The extract is washed successively with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, receiving from the Association of the present invention (65 mg), having the following physical data.

TLC: Rf 0,72 (water:methanol:chloroform=1:10:50).

NMR (CDCl3): δ 11,33 (W, 1H), 7,69 (m, 1H), 7,45-to 7.15 (m, 3H), 5,62 (s, 1H)and 4.65 (m, 1H), 3,88 (m, 1H), 3,11 (m, 1H), 2,85 (s, 2H), 2,75-to 2.40 (m, 2H), 2,11 (s, 3H), 2.00 in to 1.60 (m, 4H), to 1.31 (s, 6H).

Examples 8(1)-8(3)

By the same procedure as described in example 8 using the compound obtained in example 2(3), or corresponding derivative amine and halide derivative, it is suitable to acetylchloride receive the following compounds of the present invention.

Example 8(1)

(Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,4'-1'-acetylpiperidine]-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.53 (water:methanol:chloroform=1:10:100).

NMR (CDCl3): δ 12,47 (s, 1H), of 7.96 (m, 2H), to 7.84 (d, J=7.5 Hz, 1H), 7,50-7,20 (m, 6H), 6.42 per (s, 1H), 4,35 (m, 1H), 3,80 is-3.45 (m, 2H), 3,24 (m, 1H), 2,94 (s, 2H), 2,11 (s, 3H), 1,90 of 1.50 (m, 4H).

Example 8(2)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(1-tert-butoxycarbonylamino-4-yl)Ethan-1-he

TLC: Rf of 0.34 (ethyl acetate:hexane=1:2).

NMR (CDCl3): δ 11,32 (W, 1H), 7,69 (m, 1H), 7,45-to 7.15 (m, 3H), 5,62 (s, 1H), 4,17 (m, 2H), 2,85 (s, 2H), 2,77 (m, 2H), 2,42 (TT, J=11,5, 3.5 Hz, 1H), of 1.84 (m, 2H), of 1.66 (m, 2H), 1,47 (s, 9H), of 1.30 (s, 6H).

Example 8(3)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(1-methylpiperidin-4-yl)Ethan-1-he

TLC: Rf of 0.34 (ethyl acetate:hexane=2:1).

NMR (CDCl3): ; 11,35 (W, 1H), 7,68 (m, 1H), 7,45-to 7.15 (m, 3H), 5,61 (s, 1H), 3,85 (m, 2H), 2,90-2,70 (m, 2H), 2,86 (s, 2H), of 2.81 (s, 3H), 2,42 (m, 1H), 2.05 is and 1.80 (m, 4H), 1,32 (s, 6H).

Example 9

(Z)-2-(6-Phenyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

In an argon atmosphere a solution of the compound obtained in example 1(68) (312 mg), dimethoxyethane (10 ml) Tegaserod and to the mixture is added tetrakis(triphenylphosphine)palladium (58 mg), saturated aqueous sodium bicarbonate solution (2.5 ml) and bendovervideo acid and the mixture is refluxed for 3 days. The reaction mixture is allowed to cool, add water and extracted twice with ethyl acetate. The extract is washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by thin-layer chromatography on silica gel (hexane:ethyl acetate=5:1)to give the compound of the present invention (121 mg)having the following physical data.

TLC: Rf to 0.39 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,82 (W, 1H), 7,99-of 7.96 (m, 2H), 7,89 (d, J=8.0 Hz, 1H), 7,66-7,63 (m, 2H), 7,58 (DD, J=8,0, 2.0 Hz, 1H), 7,51-7,38 (m, 7H), 6,36 (W, 1H), 2,98 (s, 2H), 1,41 (s, 6H).

Example 9(1)

(Z)-2-(6-(Pyridin-3-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

By the same procedure as described in example 9, using diethyl(3-pyridyl)borane in the seat benthivorous acid, get the connection of the present invention having the following physical data.

TLC: Rf 0.31 in (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,81 (W, 1H), 8,91 (d, J=1.5 Hz, 1H), 8,65 (DD, J=5.0 and 1.5 Hz, 1H), 7,98-to 7.93 (m, 4H), EUR 7.57 (DD, J=8,0, 2.0 Hz, 1H), of 7.48-7,41 (m, 5H), 6,38 (s, 1H), 2,99 (s, 2H), 1,41 (s, 6H).

Example 10

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-hydroxymethylene)ethane-1-he

To a suspension of sociallyengaged (95 mg) in anhydrous tetrahydrofuran (9 ml) is added the compound obtained in example 1(1) (317 mg)in anhydrous tetrahydrofuran (6 ml) and the mixture is stirred for 1 hour at room temperature. To the reaction mixture is added saturated aqueous solution of sodium sulfate (1.0 ml) and the mixture is stirred. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=3:1→1:1)to give the compound of the present invention (251 ml)having the following physical data.

TLC: Rf of 0.33 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,84 (W, 1H), 7,95 (d, J=8.0 Hz, 2H), 7,83 (d, J=7,0 Hz, 1H), 7,46-7,41 (m, 3H), 7,35 (t, J=7,0 Hz, 1H), 7,22 (d, J=7,0 Hz, 1H), 6,33 (s, 1H), amounts to 4.76 (s, 2H), 2.91 in (s, 2H), 1,75 (W, 1H), 1,37 (s, 6H).

Example 10(1)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-hydroxymethylene)ethane-1-he

By the same procedure as described in example 10, using the compound obtained in example 1(30), westseite, obtained in example 1(1), obtain the following compound of the present invention.

TLC: Rf of 0.33 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ up 11,86 (W, 1H), 7,94 (s, 1H), of 7.90-7,83 (m, 2H), 7,49-7,41 (m, 3H), 7,35 (t, J=7,0 Hz, 1H), 7,22 (d, J=7,0 Hz, 1H), 6,34 (s, 1H), of 4.77 (s, 2H), 2.91 in (s, 2H), 1.77 in (W, 1H), of 1.37 (s, 6H).

Reference example 3

3-(4-Isopropylphenyl)-2,2-dimethylpropanoate acid

Tetrahydrofuran (40 ml) dissolved in Diisopropylamine (is 3.08 ml), to this mixture n-utility (13,8 ml; 1.6 M solution in hexane) at -78°then added dropwise isobutylamino acid (0,93 ml) and the mixture is stirred for 1 hour at 30°C. To the reaction mixture add a solution of 4-isopropylbenzylamine (2,19 g) in tetrahydrofuran (10 ml) at -78°and the mixture is stirred at room temperature for 2 hours. The reaction mixture was poured into cold dilute hydrochloric acid and extracted with ethyl acetate. The extract was concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=5:1), obtaining mentioned in the title compound (1.73 g)having the following physical data.

TLC: Rf of 0.32 (ethyl acetate:hexane=1:4).

NMR (CDCl3): δ 7,15-7,05 (m, 4H), 2,88 (m, 1H), 2,86 (s, 2H), 1,23 (d, J=7,0 Hz, 6H), of 1.20 (s, 6H).

Reference example 4

2-Methyl-1-(4-isopropylphenyl)propane-2-isocyanate

Connection, receiving the Noah in reference example 3 (1,71 g), diphenylphosphinite (2.15 g) and triethylamine (1.2 ml) are added to a dioxane (20 ml) and the mixture refluxed for 1 hour. The reaction mixture is allowed to cool, poured into a mixture of ice-water and extracted with ether. The extract was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated, obtaining the crude product indicated in the title compound (1.70 g). It is used in the next reaction without purification.

Reference example 5

3,3-Dimethyl-7-isopropyl-3,4-dihydro-(2H)-isoquinoline-1-he

To the compound obtained in reference example 4 (1.70 g), added polyphosphoric acid (100 g) and the mixture is stirred for 2 hours at room temperature. To the reaction mixture is added a mixture of ice-water and extracted with ethyl acetate. The extract is washed with water, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=3:2), getting mentioned in the title compound (60 mg)having the following physical data.

TLC: Rf of 0.36 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 7,94 (d, J=2.0 Hz, 1H), 7,31 (DD, J=8,0, 2.0 Hz, 1H), 7,10 (d, J=8.0 Hz, 1H), 5,73 (W, 1H), 2.95 and (m, 1H), 2,89 (s, 2H), 1,31 (s, 6H), 1.27mm (d, J=7,0 Hz, 6H).

Ref CNY example 6

3,3-Dimethyl-7-isopropyl-3,4-dihydro-(2H)-isoquinoline-1-tion

The compound obtained in reference example 5 (52 mg), and the reagent Lawesson (48 mg) are added to a toluene (5 ml) and the mixture refluxed for 1 hour. The reaction mixture is allowed to cool and purified column chromatography on silica gel (hexane:ethyl acetate=9:1), obtaining mentioned in the title compound (48 mg)having the following physical data.

TLC: Rf of 0.35 (chloroform:hexane=1:4).

NMR (CDCl3): δ 8,39 (d, J=2.0 Hz, 1H), 7,97 (W, 1H), 7,33 (DD, J=7,5, 2.0 Hz, 1H), 7,05 (d, J=7.5 Hz, 1H), 2,98 (m, 1H), 2,90 (s, 2H), of 1.34 (s, 6H), of 1.28 (d, J=7,0 Hz, 6H).

Reference example 7

3,3-Dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-he

To the chloroform (30 ml) is added 2-hydroxybenzamide (2,74 g) and acetonylacetone (2,6 ml), add concentrated sulfuric acid at room temperature and the mixture is refluxed for 8 hours. The reaction mixture is allowed to cool and filtered. The filtrate is concentrated. To the residue is added ether, the mixture is washed sequentially 2 N. aqueous sodium hydroxide solution, water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated, obtaining specified in the header connection (1,62 g)having the following physical data.

TLC: Rf 0.45 in (e is ylacetic:hexane=1:1).

NMR (CDCl3): δ a 7.92 (DD, J=7,5, 1.5 Hz, 1H), 7,45 (DDD, J=8,0, to 7.5, 1.5 Hz, 1H), 7,15 (W, 1H), 7,07 (DDD, J=7,5, to 7.5, 1.0 Hz, 1H), 6,92 (DD, J=8.0 a, 1.0 Hz, 1H), of 1.66 (s, 6H).

Reference example 8

3,3-Dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-tion

To toluene (70 ml) is added the compound obtained in reference example 7 (1.20 g), and the reagent Lawesson (1,37 g) and the mixture refluxed for 2 hours. The reaction mixture was purified column chromatography on silica gel (hexane: ethyl acetate=5:1), obtaining specified in the header connection (1,34 g)having the following physical data.

TLC: Rf of 0.45 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 8,45 (W, 1H), 8,31 (DD, J=8,0, 1.5 Hz, 1H), 7,46 (DDD, J=8,0, to 7.5, 1.5 Hz, 1H), 7,07 (DDD, J=8,0, to 7.5, 1.0 Hz, 1H), 6.89 in (DD, J=8.0 a, 1.0 Hz, 1H), of 1.66 (s, 6H).

Example 11

(Z)-2-(7-Isopropyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

The compound obtained in reference example 6 (45 mg), dissolved in xylene (5 ml), add benzoylmethylene (46 mg) and the mixture is stirred for 1.5 hours. To the reaction mixture is added triethylamine (0.04 ml) and the mixture is stirred for 15 minutes. To the reaction mixture are added triphenylphosphine (61 mg), the mixture is stirred for 15 minutes, add triethylamine (0.04 ml) and the mixture refluxed for 1 hour. The reaction mixture is allowed about ladisa and purified column chromatography on silica gel (hexane:ethyl acetate=20:1), receiving a connection of the present invention (58 mg)having the following physical data.

TLC: Rf to 0.19 (ethyl acetate:hexane=1:10).

NMR (CDCl3): δ 11,88 (W, 1H), of 7.96 (m, 2H), to 7.64 (d, J=1.5 Hz, 1H), 7,50-7,40 (m, 3H), 7,30 (DD, J=8,0, 1.5 Hz, 1H), 7,14 (d, J=8.0 Hz, 1H), 6,32 (s, 1H), 2,98 (m, 1H), 2,86 (s, 2H), 1,36 (s, 6H), of 1.30 (d, J=7,0 Hz, 6H).

Examples 11(1)-11(203)

By the same procedure as described in example 11 using the compound obtained in reference example 6, or a corresponding derivative and benzoylmethylene or corresponding derivative are provided the following compounds of the present invention.

Example 11(1)

(Z)-2-(3,3-Dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf is 0.22 (chloroform:hexane=1:1).

NMR (CDCl3): δ 11,65 (W, 1H), 7,94 (m, 2H), 7,74 (d, J=7,5, 1.5 Hz, 1H), 7,50-7,40 (m, 4H), 7,07 (DDD, J=7,5, to 7.5, 1.0 Hz, 1H), of 6.96 (DD, J=7,5, 1.0 Hz, 1H), 6,34 (s, 1H), rate of 1.67 (s, 6H).

Example 11(2)

(Z)-2-(7-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.20 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,82 (W, 1H), 7,94 (m, 2H), 7,50-7,40 (m, 3H), 7,34 (d, J=2.5 Hz, 1H), 7,13 (d, J=8.0 Hz, 1H), 6,98 (DD, J=8,0, 2.5 Hz, 1H), 6,28 (s, 1H), a 3.87 (s, 3H), and 2.83 (s, 2H), of 1.35 (s, 6H).

Example 11(3)

(Z)-2-(7-Ethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0.31 in (ethyl acetate:hexane=1:5).

NMR (CDCl3): ; up 11,86 (W, 1H), of 7.96 (m, 2H), 7,63 (s, 1H), 7,50-7,40 (m, 3H), 7,27 (m, 1H), 7,12 (d, J=8.0 Hz, 1H), 6,32 (s, 1H), 2,86 (s, 2H), 2,71 (kV, J=7.5 Hz, 2H), 1,36 (s, 6H), of 1.29 (t, J=7.5 Hz, 3H).

Example 11(4)

(Z)-2-(7-tert-Butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.37 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,90 (W, 1H), 7,95 (m, 2H), 7,81 (d, J=2.0 Hz, 1H), 7,50-7,40 (m, 4H), 7,14 (d, J=8.0 Hz, 1H), 6,32 (s, 1H), 2,86 (s, 2H), to 1.38 (s, 9H), of 1.36 (s, 6H).

Example 11(5)

(Z)-2-(7-Propyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.34 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ up 11,86 (W, 1H), of 7.96 (m, 2H), to 7.61 (d, J=1.5 Hz, 1H), 7,50-7,40 (m, 3H), 7,24 (DD, J=8,0, 1.5 Hz, 1H), 7,11 (d, J=8.0 Hz, 1H), 6,32 (s, 1H), 2,86 (s, 2H), 2,65 (t, J=7.5 Hz, 2H), 1.69 in (m, 2H), of 1.36 (s, 6H), and 0.98 (t, J=7.5 Hz, 3H).

Example 11(6)

(Z)-2-(7-Butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.27 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ up 11,86 (W, 1H), of 7.96 (m, 2H), to 7.61 (d, J=2.0 Hz, 1H), 7,50-7,40 (m, 3H), 7,25 (DD, J=8,0, 2.0 Hz, 1H), 7,11 (d, J=8.0 Hz, 1H), of 6.31 (s, 1H), 2,86 (s, 2H), to 2.67 (t, J=7.5 Hz, 2H), 1,65 (m, 2H), of 1.39 (m, 2H), 1,36 (s, 6H), is 0.96 (t, J=7.5 Hz, 3H).

Example 11(7)

(Z)-2-(7-Bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.27 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,75 (W, 1H), 8,00-of 7.90 (m, 3H), 7,54 (DD, J=8,0, 2.0 Hz, 1H), 7,50-7,40 (m, 3H), 7,10 (d, J=8.0 Hz, 1H), of 6.26 (s, 1H) 2,85 (s, 2H), 1,36 (s, 6H).

Example 11(8)

(Z)-2-(7-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf and 0.46 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 10,98 (W, 1H), 7,56 (d, J=2.5 Hz, 1H), 7,31 (DD, J=8,5, 2.5 Hz, 1H), 6,86 (d, J=2.5 Hz, 1H), of 5.55 (s, 1H), 2.49 USD (m, 1H), 1,95-of 1.40 (m, 12H), was 1.58 (s, 6H).

Example 11(9)

(Z)-2-(7-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf is 0.42 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,07 (W, 1H), EUR 7.57 (d, J=2.5 Hz, 1H), 7,32 (DD, J=8,5, 2.5 Hz, 1H), 6,86 (d, J=8.5 Hz, 1H), 5,59 (s, 1H), 2,32 (m, 1H), 1,95-of 1.15 (m, 10H)to 1.59 (s, 6H).

Example 11(10)

(Z)-2-(7-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.20 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,40 (W, 1H), 7,65 (DD, J=7,5, 2.0 Hz, 1H), 7,60 (d, J=2.5 Hz, 1H), 7,39 (m, 1H), 7,33 (DD, J=8,5, 2.5 Hz, 1H), 7,05-to 6.95 (m, 2H), 6.89 in (d, J=8.5 Hz, 1H), and 6.25 (s, 1H), 3,93 (s, 3H), of 1.65 (s, 6H).

Example 11(11)

(Z)-2-(7-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf to 0.19 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,67 (W, 1H), 8,01 (d, J=9.0 Hz, 2H), of 7.75 (d, J=9.0 Hz, 2H), to 7.67 (d, J=2.5 Hz, 1H), 7,40 (DD, J=8,5, 2.5 Hz, 1H), 6,93 (d, J=8.5 Hz, 1H), 6,21 (s, 1H), 1,68 (s, 6H).

Example 11(12)

(Z)-2-(3,3,7-Trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-on the Sabbath.

TLC: Rf to 0.39 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ of 11.15 (W, 1H), 7,40 (d, J=1.5 Hz, 1H), 7,18 (DD, J=8,5, 1.5 Hz, 1H), for 6.81 (d, J=8.5 Hz, 1H), 5,62 (s, 1H), 2,33 (s, 3H), 2,31 (m, 1H), 1,95-of 1.15 (m, 10H), was 1.58 (s, 6H).

Example 11(13)

(Z)-2-(7-Methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf 0.31 in (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,14 (W, 1H), was 7.08 (d, J=3.0 Hz, 1H), of 6.96 (DD, J=9,0, 3.0 Hz, 1H), 6,85 (d, J=9.0 Hz, 1H), to 5.57 (s, 1H), 3,83 (s, 3H), 2,32 (m, 1H), 1,95-of 1.15 (m, 10H), was 1.58 (s, 6H).

Example 11(14)

(Z)-2-(7-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf 0,41 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,07 (W, 1H), 7,29 (DD, J=9,0, 3.0 Hz, 1H), was 7.08 (DDD, J=9,0, of 8.0, 3.0 Hz, 1H), to 6.88 (DD, J=9,0, 5.0 Hz, 1H), 5.56mm (s, 1H), 2,32 (m, 1H), 1,95-of 1.15 (m, 10H)to 1.59 (s, 6H).

Example 11(15)

(Z)-2-(3,3,7-Trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.38 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,48 (W, 1H), to 7.64 (DD, J=7,5, 1.5 Hz, 1H), 7,42 (d, J=2.0 Hz, 1H), 7,37 (DDD, J=8,0, to 7.5, 1.5 Hz, 1H), 7,19 (DD, J=8,0, 2.0 Hz, 1H), 7,01 (DDD, J=7,5, 7,5,1,0 Hz, 1H), 6,97 (DD, J=8.0 a, 1.0 Hz, 1H), 6,83 (d, J=8.0 Hz, 1H), 6,23 (s, 1H), 3,92 (s, 3H), 2,32 (s, 3H), of 1.65 (s, 6H).

Example 11(16)

(Z)-2-(7-Methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf 0.31 in (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,46 (W, 1H), 7,66 (DD, J=7,5, 2.0 Hz, 1H), 7,38 (DDD, J=8,0, to 7.5, 2.0 Hz, 1H), 7,12 (d, J=3.0 Hz, 1H), 7,05-to 6.95 (m, 3H), 6.87 in (d, J=8.0 Hz, 1H), 6,23 (s, 1H), 3,91 (s, 3H), 3,81 (s, 3H ), 1,64 (, 6H).

Example 11(17)

(Z)-2-(7-fluoro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.40 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,40 (W, 1H), to 7.67 (DD, J=7,5, 2.0 Hz, 1H), 7,39 (DDD, J=8,0, to 7.5, 2.0 Hz, 1H), 7,32 (DD, J=9,0, 3.0 Hz, 1H), 7,10 (DDD, J=9,0, of 8.0, 3.0 Hz, 1H), 7,02 (DDD, J=7,5, to 7.5, 1.5 Hz, 1H), 6,98 (DD, J=8,0, 1.5 Hz, 1H), 6.90 to (DD, J=9,0, 4.5 Hz, 1H), and 6.25 (s, 1H), 3,93 (s, 3H), of 1.65 (s, 6H).

Example 11(18)

(Z)-2-(3,3,7-Trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf is 0.49 (ethyl acetate:hexane=1:4).

NMR (CDCl3): δ 11,07 (W, 1H), 7,39 (d, J=1.5 Hz, 1H), 7,17 (DD, J=8,0, 1.5 Hz, 1H), for 6.81 (d, J=8.0 Hz, 1H), 5,58 (s, 1H), 2,48 (m, 1H), 2,33 (s, 3H), 2.00 in of 1.40 (m, 12H), to 1.59 (s, 6H).

Example 11(19)

(Z)-2-(7-Methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.43 (ethyl acetate:hexane=1:4).

NMR (CDCl3): δ 11,06 (W, 1H), 7,07 (d, J=3.0 Hz, 1H), of 6.96 (DD, J=9,0, 3.0 Hz, 1H), 6,85 (d, J=9.0 Hz, 1H), 5,54 (s, 1H), 3,83 (s, 3H), 2.49 USD (m, 1H), 2.00 in of 1.40 (m, 12H), was 1.58 (s, 6H).

Example 11(20)

(Z)-2-(7-Fluoro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0.53 per share (tracecut:hexane=1:4).

NMR (CDCl3): δ 10,98 (W, 1H), 7,29 (DD, J=9,0, 3.0 Hz, 1H), was 7.08 (DDD, J=9,0, of 8.0, 3.0 Hz, 1H), 6.87 in (DD, J=9,0, 5.0 Hz, 1H), of 5.53 (s, 1H), 2,48 (m, 1H), 2.00 in of 1.40 (m, 12H), to 1.59 (s, 6H).

Example 11(21)

(Z)-2-(3,3,7-Trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf 0.26 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,74 (W, 1H), 8,02 (d, J=8.0 Hz, 2H), 7,74 (d, J=8.0 Hz, 2H), 7,49 (d, J=1.5 Hz, 1H), 7,26 (DD, J=8,0, 1.5 Hz, 1H), 6.87 in (d, J=8.0 Hz, 1H), 6,24 (s, 1H), of 2.38 (s, 3H), rate of 1.67 (s, 6H).

Example 11(22)

(Z)-2-(7-Methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.16 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,72 (W, 1H), 8,00 (d, J=8.0 Hz, 2H), 7,74 (d, J=8.0 Hz, 2H), 7,17 (d, J=3.0 Hz, 1H),? 7.04 baby mortality (DD, J=9,0, 3.0 Hz, 1H), 6,92 (d, J=9.0 Hz, 1H), to 6.19 (s, 1H), 3,86 (s, 3H), rate of 1.67 (s, 6H).

Example 11(23)

(Z)-2-(7-fluoro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf is 0.24 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,66 (W, 1H), 8,01 (d, J=8.5 Hz, 2H), of 7.75 (d, J=8.5 Hz, 2H), 7,40 (DD, J=9,0, 3.0 Hz, 1H), 7,17 (DDD, J=9,0, of 8.0, 3.0 Hz, 1H), 6,95 (DD, J=9,0, 4.5 Hz, 1H), 6,18 (s, 1H), 1,68 (s, 6H).

Example 11(24)

(Z)-2-(3,3-Dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.29 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,49 (W, 1H), 7.68 per-7,63 (m, 2H), 7,42-7,35 (m, 2H), 7,05-6,93 (m, 4H), 6.30-in (s, 1H), 3,92 (who, 3H), of 1.66 (s, 6H).

Example 11(25)

(Z)-2-(3,3-Dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf 0.36 and (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,75 (W, 1H), 8,03-to 7.99 (m, 2H), 7,75-7,71 (m, 3H), 7,46 (dt, J=1.5 and 8.0 Hz, 1H), to 7.09 (t, J=8.0 Hz, 1H), 6,98 (d, J=8.0 Hz, 1H), 6,27 (s, 1H), 1.69 in (s, 6H).

Example 11(26)

(Z)-2-(3,3-Dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0,59 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,08 (W, 1H), to 7.61 (DD, J=8,0, 1.5 Hz, 1H), 7,37 (DDD, J=8,0, to 7.5, 1.5 Hz, 1H), 7,01 (DDD, J=8,0, to 7.5, 1.0 Hz, 1H), 6,91 (DD, J=8.0 a, 1.0 Hz, 1H), 5,61 (s, 1H), 2,53 is 2.43 (m, 1H), 1,94-of 1.85 (m, 2H), 1,82-of 1.45 (m, 16H).

Example 11(27)

(Z)-2-(3,3-Dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.56 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,16 (W, 1H), to 7.61 (DD, J=8,0, 1.5 Hz, 1H), 7,37 (DDD, J=8,0, to 7.5, 1.5 Hz, 1H), 7,01 (DDD, J=8,0, to 7.5, 1.0 Hz, 1H), 6,91 (DD, J=8.0 a, 1.0 Hz, 1H), 5,64 (s, 1H), 2,31 (TT, J=11,5, 3.5 Hz, 1H), 1,89-to 1.79 (m, 4H), 1,71-to 1.67 (m, 1H), 1,61 (s, 6H), 1,49-1,19 (m, 5H).

Example 11(28)

(Z)-2-(3,3,7-Trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.35 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,65 (W, 1H), 7,95 (m, 2H), 7,51 (d, J=1.5 Hz, 1H), 7,50-7,40 (m, 3H), of 7.23 (m, 1H), 6,86 (d, J=9.0 Hz, 1H), of 6.31 (s, 1H), is 2.37 (s, 3H), of 1.66 (s, 6H).

Example 11(29)

(Z)-2-(7-Methoxy-3,3-dimethyl-4-oxa-3,4-dihyd what about-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0.31 in (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ are 11.62 (W, 1H), 7,94 (m, 2H), 7,50-7,40 (m, 3H), 7,20 (d, J=3.0 Hz, 1H), 7,01 (DD, J=9,0, 3.0 Hz, 1H), make 6.90 (d, J=9.0 Hz, 1H), of 6.26 (s, 1H), 3,86 (s, 3H), of 1.65 (s, 6H).

Example 11(30)

(Z)-2-(7-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0.31 in (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ to 11.56 (W, 1H), 7,95 (m, 2H), of 7.70 (d, J=2.5 Hz, 1H), 7,50-7,40 (m, 3H), of 7.36 (DD, J=8,5, 2.5 Hz, 1H), 6,91 (d, J=8.5 Hz, 1H), 6,28 (s, 1H), of 1.66 (s, 6H).

Example 11(31)

(Z)-2-(7-Fluoro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0.31 in (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,55 (W, 1H), to 7.93 (m, 2H), 7,50-7,40 (m, 3H), 7,41 (DD, J=9,0, 3.0 Hz, 1H), 7,13 (DDD, J=9,0, of 8.0, 3.0 Hz, 1H), 6,92 (DD, J=9,0, 4.5 Hz, 1H), and 6.25 (s, 1H), of 1.66 (s, 6H).

Example 11(32)

(Z)-2-(7-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf 0.28 in (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,31 (W, 1H), 7,22 (d, J=2.5 Hz, 1H), was 7.08 (d, J=8.5 Hz, 1H), 6,94 (DD, J=8,5, 2.5 Hz, 1H), 5,58 (s, 1H), 3,86 (s, 3H), 2,77 (s, 2H), 2,30 (m, 1H), 1,95-of 1.20 (m, 10H), of 1.28 (s, 6H).

Example 11(33)

(Z)-2-(7-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.29 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,23 (W, 1H), 7,21 (d, J=2.5 Hz, 1H), was 7.08 (d, J=8,5 is C, 1H), 6,94 (DD, J=8,5, 2.5 Hz, 1H), of 5.55 (s, 1H), 3,86 (s, 3H), 2,77 (s, 2H), 2,46 (m, 1H), 2.00 in of 1.40 (m, 12H), of 1.28 (s, 6H).

Example 11(34)

(Z)-2-(7-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoindoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.23 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,67 (W, 1H), to 7.67 (DD, J=7,5, 2.0 Hz, 1H), was 7.36 (DDD, J=8,0, to 7.5, 2.0 Hz, 1H), 7,26 (d, J=2.5 Hz, 1H), 7,11 (d, J=8.0 Hz, 1H), 7,05-of 6.90 (m, 3H), from 6.22 (s, 1H), 3,91 (s, 3H), of 3.84 (s, 3H), 2,82 (, 2H), of 1.35 (s, 6H).

Example 11(35)

(Z)-2-(7-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.29 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,95 (W, 1H), 8,00 (d, J=8.5 Hz, 2H), 7,72 (d, J=8.5 Hz, 2H), 7,31 (d, J=2.5 Hz, 1H), 7,16 (d, J=8.5 Hz, 1H), 7,02 (DD, J=8,5, 2.5 Hz, 1H), 6,21 (s, 1H), 3,88 (s, 3H), 2,85 (s, 2H), 1,37 (s, 6H).

Example 11(36)

(Z)-2-(7-tert-Butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.34 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,41 (W, 1H), 7,69 (d, J=2.0 Hz, 1H), 7,42 (DD, J=8,0, 2.0 Hz, 1H), 7,10 (d, J=8.0 Hz, 1H), 5,61 (s, 1H), and 2.79 (s, 2H), 2,33 (m, 1H), 1,95-of 1.20 (m, 10H), of 1.36 (s, 9H), of 1.29 (s, 6H).

Example 11(37)

(Z)-2-(7-tert-Butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.34 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,33 (W, 1H), 7,69 (d, J=2.0 Hz, 1H), 7,42 (DD, J=8,0, 2.0 Hz, 1H), to 7.09 (d, J=8.0 Hz, 1H), 5,58 (s, 1H), and 2.79 (s, 2H), 2.49 USD (m, 1H), 2.00 in of 1.40(m, 12H), of 1.36 (s, 9H), of 1.28 (s, 6H).

Example 11(38)

(Z)-2-(7-tert-Butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.33 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,71 (W, 1H), to 7.77 (d, J=2.0 Hz, 1H), 7,72 (DD, J=7,5, 2.0 Hz, 1H), 7,44 (DD, J=8,0, 2.0 Hz, 1H), 7,37 (DDD, J=8,0, to 7.5, 2.0 Hz, 1H), 7,12 (d, J=8.0 Hz, 1H), 7,02 (DDD, J=7,5, to 7.5, 1.0 Hz, 1H), 6,98 (DD, J=8,0, 1.0 Hz, 1H), 6,34 (s, 1H), 3,93 (s, 3H), 2,85 (s, 2H), of 1.35 (s, 6H), of 1.34 (s, 9H).

Example 11(39)

(Z)-2-(7-tert-Butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.40 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ a 12.03 (W, 1H), 8,01 (d, J=8.5 Hz, 2H), 7,78 (d, J=2.0 Hz, 1H), 7,74 (d, J=8.5 Hz, 2H), 7,50 (d, J=8.0 a, 2.0 Hz, 1H), 7,17 (d, J=8.0 Hz, 1H), and 6.25 (s, 1H), 2,88 (s, 2H), 1,38, (s, 9H), 1,38 (, 6H).

Example 11(40)

(Z)-2-(7-Fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.33 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,89 (W, 1H), 8,03-to 7.99 (m, 2H), 7,76-7,72 (m, 2H), 7,50 (DD, J=9.5mm, 2.5 Hz, 1H), 7,22-7,14 (m, 2H), to 6.19 (s, 1H), 2,89 (s, 2H), 1,38 (s, 6H).

Example 11(41)

(Z)-2-(7-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.33 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,89 (W, 1H), 8,04 shed 8.01 (m, 2H), to 7.77-7,73 (m, 3H), 7,43 (DD, J=8,0, 2.0 Hz, 1H), 7,19 (d, J=8.0 Hz, 1H), 6,21 (s, 1H), 2,89 (s, 2H), 1,38 (s, 6H).

Example 11(42)

(Z)-2-(7-Fluoro-3,3-imethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.40 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ to 11.61 (W, 1H), 7,68 (DD, J=8,0, 2.0 Hz, 1H), 7,45-7,34 (m, 2H), 7,19-7,07 (m, 2H),? 7.04 baby mortality-of 6.96 (m, 2H), from 6.22 (s, 1H), 3,92 (s, 3H), 2,85 (s, 2H), of 1.35 (s, 6H).

Example 11(43)

(Z)-2-(7-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.40 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,59 (W, 1H), of 7.70 (d, J=2.0 Hz, 1H), 7,66 (DD, J=8,0, 2.0 Hz, 1H), 7,40-7,34 (m, 2H), 7,14 (d, J=8.0 Hz, 1H),? 7.04 baby mortality-of 6.96 (m, 2H), from 6.22 (s, 1H), 3,92 (s, 3H), 2,85 (s, 2H), of 1.35 (s, 6H).

Example 11(44)

(Z)-2-(7-Fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf value of 0.52 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,24 (W, 1H), 7,39 (DD, J=10,0, 2.5 Hz, 1H), 7,16-7,05 (m, 2H), 5.56mm (s, 1H), 2,80 (s, 2H), 2,36 was 2.25 (m, 1H), 1,90-to 1.79 (m, 4H), 1,71 by 1.68 (m, 1H), 1,50-of 1.20 (m, 11H).

Example 11(45)

(Z)-2-(7-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.55 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,16 (W, 1H), 7,39 (DD, J=9.5mm, 2.5 Hz, 1H), 7,16-7,05 (m, 2H), 5,52 (s, 1H), 2,80 (s, 2H), 2,50-to 2.42 (m, 1H), 1,95-of 1.88 (m, 2H), 1,82-of 1.45 (m, 10H), of 1.29 (s, 6H).

Example 11(46)

(Z)-2-(7-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf value of 0.52 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,23 (W, 1H), to 7.67 (d, J=2.0 Hz, 1H), 7,35 (DD, J=8,0, 2.0 Hz, 1H), 7,2 (d, J=8.0 Hz, 1H), 5,58 (s, 1H), 2,80 (s, 2H), 2,31 (TT, J=11,5, 3.0 Hz, 1H), 1,90 and 1.80 (m, 4H), 1,71 by 1.68 (m, 1H), 1,51 is 1.20 (m, 11H).

Example 11(47)

(Z)-2-(7-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.55 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ of 11.15 (W, 1H), to 7.67 (d, J=2.0 Hz, 1H), 7,35 (DD, J=8,0, 2.0 Hz, 1H), 7,11 (d, J=8.0 Hz, 1H), 5,54 (s, 1H), 2,80 (s, 2H), 2,48 (TT, J=9,5, 4.0 Hz, 1H), 1,95-of 1.88 (m, 2H), 1,82 to 1.47 (m, 10H), 1.28 (in with, 6H).

Example 11(48)

(Z)-2-(3,3,7-Trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.30 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,32 (W, 1H), 7,51 (s, 1H), 7,19 (m, 1H), 7,05 (d, J=8.0 Hz, 1H), 5,62 (s, 1H), and 2.79 (s, 2H), of 2.38 (s, 3H), 2,30 (m, 1H), 1,95-of 1.20 (m, 10H), of 1.28 (s, 6H).

Example 11(49)

(Z)-2-(3,3,7-Trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.34 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,23 (W, 1H), 7,50 (s, 1H), 7,18 (m, 1H), 7,05 (d, J=7.5 Hz, 1H), 5,59 (s, 1H), 2,78 (s, 2H), 2,46 (m, 1H), of 2.38 (s, 3H), 2.00 in of 1.40 (m, 12H), of 1.28 (s, 6H).

Example 11(50)

(Z)-2-(3,3,7-Trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.34 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,67 (W, 1H), 7,65 (DD, J=7,5, 2.0 Hz, 1H), 7,54 (s, 1H), 7,35 (DDD, J=8,0, to 7.5, 2.0 Hz, 1H), 7,20 (m, 1H), 7,07 (d, J=7.5 Hz, 1H), 7,00 (DDD, J=8,0, to 8.0, 1.0 Hz, 1H), of 6.96 (DD, J=8.0 a, 1.0 Hz, 1H), 6.22 per (s, 1H), 3,91 (s, 3H), 2,84 (s, 2H), is 2.37 (s, 3H), of 1.34 (s, 6H).

Example 11(51)

(Z)-2-(3,3,7-Trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.40 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,96 (W, 1H), 8,03 (d, J=8.5 Hz, 2H), 7,73 (d, J=8.5 Hz, 2H), 7,60 (s, 1H), 7,27 (m, 1H), 7,12 (d, J=7.5 Hz, 1H), of 6.26 (s, 1H), 2,87 (s, 2H), 2,43 (s, 3H), of 1.37 (s, 6H).

Example 11(52)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-nitrophenyl)Ethan-1-he

TLC: Rf 0,41 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,40 (W, 1H), a 7.85 (d, J=7.5 Hz, 1H), 7,69 (d, J=7.5 Hz, 1H), of 7.64-EUR 7.57 (m, 2H), 7,52-7,41 (m, 2H), 7,33-7,27 (m, 1H), 7,21 (d, J=7.5 Hz, 1H), 5,86 (s, 1H), 2,92 (s, 2H), of 1.37 (s, 6H).

Example 11(53)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-nitrophenyl)Ethan-1-he

TLC: Rf of 0.53 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,94 (W, 1H), 8,77 (DD, J=2,0, 2,0 Hz, 1H), 8,32-of 8.27 (m, 2H), 7,86 (DD, J=7,5, 1.0 Hz, 1H), 7.62mm (DD, J=8,0, 8.0 Hz, 1H), of 7.48 (DDD, J=7,5, to 7.5, 1.0 Hz, 1H), 7,39 (DDD, J=7,5, to 7.5, 1.0 Hz, 1H), 7,27-of 7.23 (m, 1H), 6,32 (s, 1H), 2,94 (s, 2H), 1.39 in (s, 6H).

Example 11(54)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-nitrophenyl)Ethan-1-he

TLC: Rf of 0.56 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 12,00 (W, 1H), 8.30 to be compared to 8.26 (m, 2H), 8,09-with 8.05 (m, 2H), 7,83 (DD, J=7,5, 1.0 Hz, 1H), of 7.48 (DDD, J=7,5, to 7.5, 1.0 Hz, 1H), 7,37 (DDD, J=7,5, to 7.5, 1.0 Hz, 1H), 7,27-of 7.23 (m, 1H), 6.30-in (s, 1H), 2,93 (s, 2H), of 1.39 (s, 6H).

Example 11(55)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ylides is n)-1-(2,5-acid)ethane-1-he

TLC: Rf 0.36 and (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ of 11.69 (W, 1H), of 7.75 (d, J=7.5 Hz, 1H), 7,41 (t, J=7.5 Hz, 1H), 7,33-7,25 (m, 2H), 7,20 (d, J=7.5 Hz, 1H), 6,92-6,91 (m, 2H), 6,37 (s, 1H), 3,88 (s, 3H), 3,81 (s, 3H), 2,90 (s, 2H), 1,36 (s, 6H).

Example 11(56)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2,4-acid)ethane-1-he

TLC: Rf 0.31 in (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,67 (W, 1H), 7,78 to 7.75 (m, 2H), 7,39 (t, J=7.5 Hz, 1H), 7,33-7,25 (m, 1H), 7,19 (d, J=7.5 Hz, 1H), 6,55 (DD, J=8,5, 2.5 Hz, 1H), 6,50 (d, J=2.5 Hz, 1H), 6,40 (s, 1H), 3,91 (s, 3H), 3,85 (s, 3H), is 2.88 (s, 2H), of 1.34 (s, 6H).

Example 11(57)

(Z)-2-(7-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-1-yl)Ethan-1-he

TLC: Rf is 0.22 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,78 (W, 1H), 8,48 (m, 1H), of 7.90-7,80 (m, 2H), 7,69 (DD, J=7,0, 1.0 Hz, 1H), 7,55 was 7.45 (m, 3H), 7,22 (d, J=2.5 Hz, 1H), 7,14 (d, J=8.5 Hz, 1H), 6,98 (DD, J=8,0, 2.5 Hz, 1H), 6,04 (s, 1H), 3,80 (, 3H), 2,88 (s, 2H), 1,40 (s, 6H).

Example 11(58)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(thiazol-2-yl)Ethan-1-he

TLC: Rf of 0.40 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,63 (W, 1H), 7,97-a 7.92 (m, 2H), 7,52 (d, J=3.0 Hz, 1H), 7,45 (dt, J=1,0, 7.5 Hz, 1H), 7,35 (t, J=7.5 Hz, 1H), 7,21 (d, J=7.5 Hz, 1H), 6,80 (s, 1H), 2,92 (s, 2H), 1,38 (s, 6H).

Example 11(59)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(pyrrol-2-yl)Ethan-1-he

TLC: Rf 0,19 (Gex is n:ethyl acetate=3:1).

NMR (CDCl3): δ 11,14 (W, 1H), 9,42 (W, 1H), 7,80 (DD, J=7,5, 1.0 Hz, 1H), 7,41 (dt, J=1,0, 7.5 Hz, 1H), 7,33 (dt, J=1,0, 7.5 Hz, 1H), 7,20 (DD, J=7,5, 1.0 Hz, 1H), 6,94 (m, 1H), 6,80 (m, 1H), 6,27 (m, 1H), 6,14 (, 1H), 2,88 (s, 2H), of 1.34 (s, 6H).

Example 11(60)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(anthracene-9-yl)ethane-1-he

TLC: Rf 0.28 in (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,93 (W, 1H), 8,44 (s, 1H), compared to 8.26 is 8.22 (m, 2H), 8,03-7,98 (m, 2H), to 7.59 (d, J=7.5 Hz, 1H), of 7.48-7,37 (m, 5H), 7,26-7,17 (m, 2H), 6,03 (s, 1H), 3,01 (s, 2H), 1,49 (s, 6H).

Example 11(61)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(pyrazin-2-yl)Ethan-1-he

TLC: Rf of 0.13 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,96 (W, 1H), 9,35 (d, J=1.5 Hz, 1H), 8,63 (d, J=2.5 Hz, 1H), 8,59 (DD, J=2.5 and 1.5 Hz, 1H), of 7.96 (d, J=7.5 Hz, 1H), 7,46 (t, J=7.5 Hz, 1H), was 7.36 (t, J=7.5 Hz, 1H), 7,22 (d, J=7.5 Hz, 1H), 7,02 (s, 1H), 2,93 (s, 2H), 1,40 (s, 6H).

Example 11(62)

(Z)-2-(3,3-Dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(substituted-1)Ethan-1-he

TLC: Rf of 0.60 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,34 (W, 1H), to 7.64 (DD, J=8,0, 1.5 Hz, 1H), 7,37 (DDD, J=8,0, to 7.5, 1.5 Hz, 1H), 7,02 (DDD, J=8,0, to 7.5, 1.0 Hz, 1H), 6,91 (DD, J=8.0 a, 1.0 Hz, 1H), 5,80 (s, 1H), 2.06 to (W, 3H), 1,90-1,89 (m, 6H), 1,74 (W, 6H), to 1.60 (s, 6H).

Example 11(63)

(Z)-2-(3,3,7-Trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf and 0.61 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,51 (W, 1H), 7,51 (who, 1H), 7,20 (d, J=7.5 Hz, 1H), 7,05 (d, J=7.5 Hz, 1H), USD 5.76 (s, 1H), and 2.79 (s, 2H), 2.40 a (s, 3H), 2.06 to (W, 3H), 1.93 and (W, 6H), 1.75 of (W, 6H), of 1.28 (s, 6H).

Example 11(64)

(Z)-2-(7-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.50 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,47 (W, 1H), 7,25 (d, J=2.5 Hz, 1H), to 7.09 (d, J=8.0 Hz, 1H), 6,94 (DD, J=8,0, 2.5 Hz, 1H), 5,73 (s, 1H), a 3.87 (s, 3H), 2,77 (s, 2H), 2.05 is (W, 3H), 1.91 a (W, 6H), 1,74 (W, 6H), of 1.28 (s, 6H).

Example 11(65)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(thiophene-3-yl)ethane-1-he

TLC: Rf of 0.47 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,67 (W, 1H), to 7.93 (DD, J=3,0, 1.0 Hz, 1H), 7,80 (d, J=7.5 Hz, 1H), 7,56 (DD, J=5.0 and 1.0 Hz, 1H), 7,43 (t, J=7.5 Hz, 1H), 7,37-7,29 (m, 2H), 7,21 (d, J=7,5 Hz, 1H), 6,18 (s, 1H), 2,89 (s, 2H)that is 1.35 (s, 6H).

Example 11(66)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(5-methylfuran-2-yl)Ethan-1-he

TLC: Rf to 0.39 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,54 (W, 1H), to 7.84 (DD, J=7,5, 1.0 Hz, 1H), 7,42 (dt, J=1,0, 7.5 Hz, 1H), 7,34 (dt, J=1,0, 7.5 Hz, 1H), 7,20 (DD, J=7,5, 1.0 Hz, 1H), 6,95 (d, J=3.5 Hz, 1H), 6,23 (s, 1H), 6,10 (d, J=3.5 Hz, 1H), is 2.88 (s, 2H), 2,39 (s, 3H), of 1.34 (s, 6H).

Example 11(67)

(Z)-2-(7-Fluoro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf and 0.61 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,24 (W, 1H), 7,32 (DD, J=9,5, 3.0 Hz, 1H), to 7.09 (DDD, J=9,5, at 9.0, 3.0 Hz, 1H), to 6.88 (DD, J=9,0,4,5 Hz, 1H), 5,72 (s, 1H), 2,07 (W, 3H), 1,89 (W, 6H), 1.75 of (W, 6H), to 1.59 (s, 6H).

Example 11(68)

(Z)-2-(7-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf and 0.61 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,25 (W, 1H), 7,58 (d, J=2.5 Hz, 1H), 7,32 (DD, J=9,0, 2.5 Hz, 1H), 6.87 in (d,J=9.0 Hz, 1H), 5,74 (s, 1H), 2,07 (W, 3H), 1,89 (W, 6H), 1.75 of (W, 6H), to 1.59 (s, 6H).

Example 11(69)

(Z)-2-(7-Methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.56 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,32 (W, 1H), 7,11 (d, J=3.0 Hz, 1H), 6,97 (DD, J=9,0, 3.0 Hz, 1H), 6,85 (d, J=9.0 Hz, 1H), 5,73 (s, 1H), 3,84 (s, 3H), 2.06 to (W, 3H), 1,89 (W, 6H), 1,74 (W, 6H), was 1.58 (s, 6H).

Example 11(70)

(Z)-2-(7-Bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-1-yl)Ethan-1-he

TLC: Rf of 0.20 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,70 (W, 1H), 8,46 (m, 1H), of 7.90-a 7.85 (m, 2H), 7,83 (d, J=2.0 Hz, 1H), of 7.70 (DD, J=7,0, 1.5 Hz, 1H), 7,55 was 7.45 (m, 4H), 7,11 (d, J=8.0 Hz, 1H), 6,03 (s, 1H), 2,89 (s, 2H), 1,41 (s, 6H).

Example 11(71)

(Z)-2-(3,3,7-Trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf and 0.61 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,35 (W, 1H), 7,40 (d, J=2.0 Hz, 1H), 7,18 (DD, J=8,5, 2.0 Hz, 1H), for 6.81 (d, J=8.5 Hz, 1H), 5,77 (s, 1H), 2,35 (s, 3H), 2,07 (W, 3H), 1,90 (W, 6H), 1.75 of (W, 6H), was 1.58 (s, 6H).

Example 11(72)

(Z)-2-(6-Chloro-3,3-dimethyl-3,4-dihydro-2H-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf 0,49 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,90 (W, 1H), 8,00 (d, J=8.5 Hz, 2H), 7,76-7,71 (m, 3H), 7,34 (DD, J=8,5, 2.5 Hz, 1H), 7,24 (d, J=2.5 Hz, 1H), from 6.22 (s, 1H), 2,90 (s, 2H), 1,38 (s, 6H).

Example 11(73)

(Z)-2-(8-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.34 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 12,18 (W, 1H), to 7.99 (d, J=8.5 Hz, 2H), 7,72 (d, J=8.5 Hz, 2H), 7,45 (d, J=7.5 Hz, 1H), 7,33 (t, J=7.5 Hz, 1H), 7,15 (d, J=7.5 Hz, 1H), for 6.81 (s, 1H), 2,87 (s, 2H), of 1.34 (s, 6H).

Example 11(74)

(Z)-2-(8-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf 0,49 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,49 (W, 1H), 7,37 (DD, J=8.0 a, 1.0 Hz, 1H), 7,24 (t, J=8.0 Hz, 1H), was 7.08 (DD, J=8.0 a, 1.0 Hz, 1H), 6,11 (s, 1H), and 2.79 (s, 2H), and 2.27 (TT, J=11,5, 3.5 Hz, 1H), 1,91-to 1.87 (m, 2H), 1,82-of 1.78 (m, 2H), 1,67 (m, 1H), 1,53-1,25 (m, 11H).

Example 11(75)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(5-methylthiophene-2-yl)Ethan-1-he

TLC: Rf 0,41 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,40 (W, 1H), 7,79 (DD, J=7,5, 1.5 Hz, 1H), 7,46-7,39 (m, 2H), 7,33 (dt, J=1.5 and 7.5 Hz, 1H), 7,20 (DD, J=7,5, 1.5 Hz, 1H), 6,76 (DQC, J=4,0, 1.0 Hz, 1H), x 6.15 (s, 1H), 2,88 (s, 2H), 2,53 (d, J=1.0 Hz, 3H), of 1.33 (s, 6H).

Example 11(76)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2,5-dimethylfuran-3-yl)ethane-1-he

TLC: Rf of 0.45 (hexane:ethyl acetate=31).

NMR (CDCl3): δ 11,50 (W, 1H), 7,74 (DD, J=7,5, 1.5 Hz, 1H), 7,40 (dt, J=1.5 and 7.5 Hz, 1H), 7,31 (dt, J=1.5 and 7.5 Hz, 1H), 7,19 (DD, J=7,5, 1.5 Hz, 1H), 6,23 (d, J=1.0 Hz, 1H), of 5.92 (s, 1H), 2,87 (s, 2H), 2,61 (s, 3H), and 2.26 (d, J=1.0 Hz, 3H), of 1.33 (s, 6H).

Example 11(77)

(Z)-2-(6-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf 0.21 in (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ of 11.69 (W, 1H), to 7.99 (d, J=9.0 Hz, 2H), 7,74 (d, J=9.0 Hz, 2H), 7,65 (d, J=8.5 Hz, 1H), 7,07 (DD, J=8,5, 2.0 Hz, 1H), 7,01 (d, J=2.0 Hz, 1H), from 6.22 (s, 1H), 1,68 (s, 6H).

Example 11(78)

(Z)-2-(7-Fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.53 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,41 (W, 1H), 7,41 (DD, J=10,0, 2.5 Hz, 1H), 7,17-7,05 (m, 2H), 5,71 (s, 1H), 2,80 (s, 2H), 2.06 to (W, 3H), 1.91 a (W, 6H), 1.75 of (W, 6H), of 1.29 (s, 6H).

Example 11(79)

(Z)-2-(7-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.53 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,42 (W, 1H), to 7.67 (d, J=2.0 Hz, 1H), 7,35 (DD, J=8,0, 2.0 Hz, 1H), 7,12 (d, J=8.0 Hz, 1H), 5,72 (s, 1H), 2,80 (s, 2H), 2,07 (W, 3H), 1.91 a (W, 6H), 1.75 of (W, 6H), of 1.29 (s, 6H).

Example 11(80)

(Z)-2-(6-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.57 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,43 (W, 1H), 7,65 (d, J=8.0 Hz, 1H), 7,27 (DD, J=8,0, 2.0 Hz, 1H), 7,17 (d, J=2.0 Hz, 1H), 5,74 (who, 1H), 2,81 (s, 2H), 2.05 is (W, 3H), 1,90 (W, 6H), 1,74 (W, 6H), of 1.29 (s, 6H).

Example 11(81)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-bromophenyl)ethane-1-he

TLC: Rf of 0.45 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,84 (W, 1H), 7,84-7,80 (m, 3H), 7,56 (d, J=8.5 Hz, 2H), 7,44 (t, J=7.5 Hz, 1H), 7,35 (t, J=7.5 Hz, 1H), 7,22 (d, J=7.5 Hz, 1H), 6,27 (s, 1H), 2.91 in (s, 2H), of 1.37 (s, 6H).

Example 11(82)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(5-cyanothiophene-2-yl)Ethan-1-he

TLC: Rf of 0.29 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,63 (W, 1H), 7,78 (d, J=7.5 Hz, 1H), 7,58 (d, J=4.0 Hz, 1H), 7,53 (d, J=4.0 Hz, 1H), of 7.48 (t, J=7.5 Hz, 1H), 7,37 (t, J=7.5 Hz, 1H), 7,24 (d, J=7.5 Hz, 1H), x 6.15 (s, 1H), 2,92 (s, 2H), 1,36 (s, 6H).

Example 11(83)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methylthiophenyl)ethane-1-he

TLC: Rf 0.31 in (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,81 (W, 1H), 7,89 (d, J=8.5 Hz, 2H), 7,83 (d, J=7.5 Hz, 1H), 7,43 (t, J=7.5 Hz, 1H), 7,34 (t, J=7.5 Hz, 1H), 7,28 (d, J=8.5 Hz, 2H), 7,21 (d, J=7.5 Hz, 1H), of 6.31 (s, 1H), 2,90 (s, 2 H), of 2.53 (s, 3H), of 1.36 (s, 6H).

Example 11(84)

(Z)-2-(6-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.36 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,59 (W, 1H), to 7.93 (m, 2H), 7,66 (d, J=8.5 Hz, 1H), 7,50-7,40 (m, 3H),? 7.04 baby mortality (DD, J=8,5, 2.0 Hz, 1H), 6,98 (d, J=2.0 Hz, 1H), 6,29 (s, 1H), of 1.66 (s, 6H).

Example 11(85)

(Z)-2-(6-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.44 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ to 11.11 (W, 1H), 7,53 (d, J=8.5 Hz, 1H), 6,98 (DD, J=8,5, 2.0 Hz, 1H), 6,94 (d, J=2.0 Hz, 1H), ceiling of 5.60 (s, 1H), 2,30 (m, 1H), 1,90-of 1.20 (m, 10H), of 1.66 (s, 6H).

Example 11(86)

(Z)-2-(6-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.60 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,02 (W, 1H), 7,53 (d, J=8.5 Hz, 1H), 6,98 (DD, J=8,5, 2.0 Hz, 1H), 6,93 (d, J=2.0 Hz, 1H), 5.56mm (s, 1H), 2,47 (m, 1H), 1,95-of 1.40 (m, 12H), to 1.59 (s, 6H).

Example 11(87)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-dimethylaminophenyl)ethane-1-he

TLC: Rf to 0.19 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,65 (W, 1H), to $ 7.91 (d, J=9.0 Hz, 2H), 7,83 (d, J=7.5 Hz, 1H), 7,40 (t, J=7.5 Hz, 1H), 7,33 (t, J=7.5 Hz, 1H), 7,19 (d, J=7.5 Hz, 1H), of 6.71 (d, J=9.0 Hz, 2H), 6,32 (s, 1H), 3.04 from (s, 6H), 2,88 (s, 2H), of 1.34 (s, 6H).

Example 11(88)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methylphenyl)ethane-1-he

TLC: Rf of 0.32 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ of $ 11.97 (W, 1H), 8,10 (d, J=9.0 Hz, 2H), 8,00 (d, J=9.0 Hz, 2H), 7,83 (d, J=7.5 Hz, 1H), 7,47 (t, J=7.5 Hz, 1H), 7,37 (t, J=7.5 Hz, 1H), 7,24 (d, J=7.5 Hz, 1H), 6.30-in (s, 1H), to 3.09 (s, 3H), 2,93 (s, 2H), 1.39 in (s, 6H).

Example 11(89)

(Z)-2-(8-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf to 0.39 (hexane:ethyl acetate=3:1).

NMR (CDCl3): 4 a 12.03 (W, 1H), 7.95 is-to $ 7.91 (m, 2H), 7,44-7,41 (m, 4H), 7,29 (m, 1H), 7,13 (DD, J=7,5, 1.5 Hz, 1H), 6,85 (s, 1H), 2,86 (s, 2H), 1,33 (s, 6H).

Example 11(90)

(Z)-2-(6-Chloro-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0.28 in (ethyl acetate:hexane=1:10).

NMR (CDCl3): δ 11,28 (W, 1H), 7,56 (d, J=8.5 Hz, 1H), 6,99 (DD, J=8,5, 2.0 Hz, 1H), 6,93 (d, J=2.0 Hz, 1H), USD 5.76 (s, 1H), 2.06 to (m, 3H), of 1.88 (m, 6H), of 1.74 (m, 6H), to 1.59 (s, 6H).

Example 11(91)

(Z)-2-(6-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(tetrahydropyran-4-yl)Ethan-1-he

TLC: Rf of 0.38 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 11,27 (W, 1H), 7,63 (d, J=8.5 Hz, 1H), 7,27 (DD, J=8,5, 2.0 Hz, 1H), 7,19 (d, J=2.0 Hz, 1H), 5,59 (s, 1H), of 4.05 (m, 2H), of 3.45 (dt, J=3.0 a, and 11.5 Hz, 2H), 2,82 (s, 2H), of 2.51 (m, 1H), 1,90 is 1.70 (m, 4H), of 1.30 (s, 6H).

Example 11(92)

(Z)-2-(7-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(tetrahydropyran-4-yl)Ethan-1-he

TLC: Rf to 0.39 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 11,24 (W, 1H), 7,66 (d, J=2.0 Hz, 1H), 7,37 (DD, J=8,0, 2.0 Hz, 1H), 7,13 (d, J=8.0 Hz, 1H), 5,58 (s, 1H), of 4.05 (m, 2H), 3.46 in (dt, J=3.0 a, and 11.5 Hz, 2H), 2,81 (s, 2H), 2,54 (m, 1H), 1,90 is 1.70 (m, 4H), of 1.30 (s, 6H).

Example 11(93)

(Z)-2-(7-Fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(tetrahydropyran-4-yl)Ethan-1-he

TLC: Rf of 0.38 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 11,25 (W, 1H), 7,38 (DD, J=9.5mm, 2.5 Hz, 1H), 7,20-7,05 (m, 2H), 5.56mm (s, 1H), of 4.05 (m, 2H), 3.46 in (dt, J=3,0, 11.5g is, 2H), 2,82 (s, 2H), 2,53 (m, 1H), 1,90 is 1.70 (m, 4H), of 1.30 (s, 6H).

Example 11(94)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2,4-dichlorophenyl)Ethan-1-he

TLC: Rf of 0.29 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ to 11.56 (W, 1H), 7,71 (d, J=7.5 Hz, 1H), 7,50 (d, J=8.0 Hz, 1H), 7,46-7,41 (m, 2H), 7,34-7,26 (m, 2H), 7,21 (d, J=7.5 Hz, 1H), 5,94 (s, 1H), 2,92 (s, 2H), 1,38 (s, 6H).

Example 11(95)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2,5-dichlorothiophene-3-yl)ethane-1-he

TLC: Rf 0.36 and (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ to 11.61 (W, 1H), 7,76 (d, J=7.5 Hz, 1H), 7,44 (t, J=7.5 Hz, 1H), 7,34 (t, J=7.5 Hz, 1H), 7,21 (d, J=7.5 Hz, 1H), 7,16 (s, 1H), 6,17 (s, 1H), 2,90 (s, 2H), 1,36 (s, 6H).

Example 11(96)

(Z)-2-(6-Fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.35 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,48 (W, 1H), 7,72 (DD, J=8,5, and 5.5 Hz, 1H), 6,99 (DDD, J=8,5, an 8.5 and 2.5 Hz, 1H), to 6.88 (DD, J=8,5, 2.5 Hz, 1H), 5,72 (s, 1H), 2,82 (s, 2H), 2.05 is (m, 3H), 1.91 a (m, 6H), of 1.74 (m, 6H), of 1.30 (s, 6H).

Example 11(97)

(Z)-2-(6-Fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.13 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,94 (W, 1H), 8,00 (d, J=8.5 Hz, 2H), 7,82 (DD, J=8,5, and 5.5 Hz, 1H), 7,72 (d, J=8.5 Hz, 2H), 7,05 (DDD, J=8,5, an 8.5 and 2.5 Hz, 1H), 6,95 (DD, J=8,5, 2.5 Hz, 1H), 6,21 (s, 1H), 2.91 in (s, 2H), 1,38 (s, 6H).

Example 11(98)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-Liden)-1-(4-methylnaphthalene-1-yl)Ethan-1-he

TLC: Rf of 0.45 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,76 (W, 1H), 8,54 (m, 1H), 8,03 (m, 1H), 7,71 (d, J=7.5 Hz, 1H), to 7.61 (d, J=7,0 Hz, 1H), 7,56 is 7.50 (m, 2H), 7,41 (t, J=7.5 Hz, 1H), 7,35-7,25 (m, 2H), 7,22 (d, J=7.5 Hz, 1H), between 6.08 (s, 1H), to 2.94 (s, 2H), by 2.73 (s, 3H), of 1.41 (s, 6H).

Example 11(99)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-fornatale-1-yl)Ethan-1-he

TLC: Rf and 0.46 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,76 (W, 1H), 8,55 (m, 1H), 8,14 (m, 1H), 7,72 (d, J=7.5 Hz, 1H), to 7.67 (DD, J=8.0 a, and 5.5 Hz, 1H), 7,60-7,53 (m, 2H), 7,43 (t, J=7.5 Hz, 1H), 7,29 (t, J=7.5 Hz, 1H), 7.23 percent (d, J=7.5 Hz, 1H), 7,14 (DD, J=10,5, 8.0 Hz, 1H), the 6.06 (s, 1H), 2.95 and (s, 2H), 1,41 (s, 6H).

Example 11(100)

(Z)-2-(7-Nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.53 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,78 (SHS, 1H), 8,69 (d, J=2.4 Hz, 1H), 8,29 (DD, J=8,4, 2.4 Hz, 1H), 8,00-to 7.95 (m, 2H), 7,52-7,44 (m, 3H), 7,42 (d, J=8,4 Hz, 1H), 6,40 (s, 1H), 3,01 (s, 2H), 1.39 in (s, 6H).

Example 11(101)

(Z)-2-(Spiro[6-chloro-3,4-dihydro-(2H)-isoquinoline-3,4'-3,4,5,6-tetrahydropyran]-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.43 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 12,35 (W, 1H), 7,94 (m, 2H), 8,76 (d, J=8.5 Hz, 1H), 7,50-7,40 (m, 3H), 7,32 (DD, J=8,5, 2.0 Hz, 1H), 7,25 (d, J=2.0 Hz, 1H), 6,34 (s, 1H), 3,86 (m, 4H), of 2.93 (s, 2H), 1,74 (m, 4H).

Example 11(102)

(Z)-2-(Spiro[6-chloro-3,4-dihydro-(2H)-isoquinoline-3,4'-3,4,5,6-tetrahydropyran]-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

p>

TLC: Rf of 0.35 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 12,48 (W, 1H), 8,02 (d, J=8.5 Hz, 2H), 7,74 (d, J=8.5 Hz, 2H), 7,74 (d, J=8.5 Hz, 1H), 7,34 (DD, J=8,5, 2.0 Hz, 1H), 7,28 (d, J=2.0 Hz, 1H), 6,28 (s, 1H), 3,86 (m, 4H), 2.95 and (s, 2H), 1,76 (m, 4H).

Example 11(103)

(Z)-2-(Spiro[6-chloro-3,4-dihydro-(2H)-isoquinoline-3,4'-3,4,5,6-tetrahydropyran]-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.56 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 11,92 (W, 1H), to 7.64 (d, J=8.5 Hz, 1H), 7,28 (DD, J=8,5, 2.0 Hz, 1H), 7,20 (d, J=2.0 Hz, 1H), 5,79 (s, 1H), 3,80 (m, 4H), of 2.86 (s, 2H), 2.06 to (m, 3H), 1.91 a (m, 6H), 1,80-to 1.60 (m, 10H).

Example 11(104)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(noradsanta-1-yl)Ethan-1-he

TLC: Rf of 0.47 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,35 (W, 1H), of 7.70 (DD, J=7,5, 1.0 Hz, 1H), 7,38 (dt, J=1,0, 7.5 Hz, 1H), 7,29 (dt, J=1,0, 7.5 Hz, 1H), 7,17 (DD, J=7,5, 1.0 Hz, 1H), 5,74 (s, 1H), 2,85 (s, 2H), 2,72 (t, J=6,5 Hz, 1H), 2,32 (W, 2H), 2,12-2,07 (m, 2H), 1,89-of 1.81 (m, 4H), 1,67-to 1.63 (m, 4H), of 1.30 (s, 6H).

Example 11(105)

(Z)-2-(6-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(noradsanta-1-yl)Ethan-1-he

TLC: Rf of 0.50 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,30 (W, 1H), 7,63 (d, J=8.5 Hz, 1H), 7,26 (DD, J=8,5, 2.0 Hz, 1H), 7,18 (d, J=2.0 Hz, 1H), 5,69 (s, 1H), 2,82 (s, 2H), 2,71 (t, J=6,5 Hz, 1H), 2,32 (W, 2H), 2,10-2,05 (m, 2H), 1,88 and 1.80 (m, 4H), 1,69-to 1.63 (m, 4H), of 1.30 (s, 6N).

Example 11(106)

(Z)-2-(6-Methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-yl) - Rev. den)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf 0.26 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,75 (W, 1H), to 7.99 (d, J=8.5 Hz, 2H), 7,73 (d, J=8.5 Hz, 2H), 7,63 (d, J=9.0 Hz, 1H), only 6.64 (DD, J=9,0, 2.5 Hz, 1H), 6.48 in (d, J=2.5 Hz, 1H), 6,17 (s, 1H), 3,85 (s, 3H), 1.69 in (C, 6N).

Example 11(107)

(Z)-2-(6-Methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.34 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,66 (W, 1H), 7.95 is-a 7.92 (m, 2H), 7,65 (d, J=8.5 Hz, 1H), 7,49-7,40 (m, 3H), 6,63 (DD, J=8,5, 2.5 Hz, 1H), 6,46 (d, J=2.5 Hz, 1H), 6,24 (s, 1H), 3,84 (s, 3H), 1,67 (C, 6N).

Example 11(108)

(Z)-2-(6-Methoxy-3,3-dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0,49 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,37 (W, 1H), 7,55 (d, J=9.0 Hz, 1H), return of 6.58 (DD, J=9,0, 2.5 Hz, 1H), 6.42 per (d, J=2.5 Hz, 1H), 5,70 (s, 1H), 3,82 (s, 3H), 2.05 is (W, 3H), 1,89 (W, 6N), 1,74 (W, 6N), 1,60 (C, 6N).

Example 11(109)

(Z)-2-(3,3,6-Trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.51 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,63 (W, 1H), 7,94 (m, 2H), 7.62mm (d, J=8.0 Hz, 1H), 7,50-7,40 (m, 3H), 6.87 in (m, 1H), 6,77 (s, 1H), 6.30-in (s, 1H), is 2.37 (s, 3H), of 1.66 (s, 6N).

Example 11(110)

(Z)-2-(3,3,6-Trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(cyanophenyl)ethane-1-he

TLC: Rf to 0.39 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,73 (W, 1H),8,00 (d, J=8.0 Hz, 2H), 7,73 (d, J=8.0 Hz, 2H), to 7.59 (d, J=8.0 Hz, 1H), 6.89 in (m, 1H), 6,79 (s, 1H), 6,23 (s, 1H), of 2.38 (s, 3H), 1,67 (C, 6N).

Example 11(111)

(Z)-2-(3,3,6-Trimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0,70 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,34 (W, 1H), 7,51 (d, J=8.0 Hz, 1H), PC 6.82 (m, 1H), 6.73 x (s, 1H), USD 5.76 (s, 1H), 2,35 (s, 3H), of 2.05 (m, 3H), 1,90 (m, 6N), 1,74 (m, 6N), 1,59 (C, 6N).

Example 11(112)

(Z)-2-(3,3-Dimethyl-4-oxa-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(tetrahydropyran-4-yl)Ethan-1-he

TLC: Rf to 0.17 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,17 (W, 1H), 7,60 (DD, J=8,0, 1.5 Hz, 1H), 7,39 (DDD, J=8,0, to 8.0, 1.5 Hz, 1H), 7,02 (DDD, J=8,0, to 8.0, 1.0 Hz, 1H), 6,92 (DD, J=8.0 a, 1.0 Hz, 1H), 5,64 (s, 1H), of 4.05 (m, 2H), 3.46 in (m, 2H), 2,54 (m, 1H), 1,90 is 1.70 (m, 4H), 1.61 of (C, 6N).

Example 11(113)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-chloro-4-methylphenyl)ethane-1-he

TLC: Rf 0,09 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,58 (W, 1H), 8,00 (d, J=1.5 Hz, 1H), 7,86 (DD, J=8,0, 1.5 Hz, 1H), 7,72-of 7.70 (m, 2H), 7,46 (t, J=7.5 Hz, 1H), 7,32 (t, J=7.5 Hz, 1H), 7.23 percent (d, J=7.5 Hz, 1H), of 5.89 (s, 1H), to 3.09 (s, 3H), 2,94 (s, 2H), 1,40 (C, 6N).

Example 11(114)

(Z)-2-(6,6-Dimethyl-4,5,6,7-tetrahydrothieno[3,2-C]pyridine-4-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.44 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,08 (W, 1H), 7,94-to $ 7.91 (m, 2H), 7,46-7,40 (m, 3H), 7,32 (d, J=5.0 Hz, 1H), 7,17 (d, J=5.0 Hz, 1H), 6,14 (s, 1H), 3.00 and(C, 2H), USD 1.43 (s, 6N).

Example 11(115)

(Z)-2-(6,6-Dimethyl-4,5,6,7-tetrahydrothieno[3,2-C]pyridine-4-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.58 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ a 10.74 (W, 1H), 7.23 percent (d, J=5.5 Hz, 1H), 7,12 (d, J=5.5 Hz, 1H), 5,59 (s, 1H), 2,93 (s, 2H), 2.05 is (W, 3H), 1,89 (W, 6N), 1,73 (W, 6N), 1,36 (C, 6N).

Example 11(116)

(Z)-2-(6,6-Dimethyl-4,5,6,7-tetrahydrothieno[3,2-C]pyridine-4-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf 0.26 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,21 (W, 1H), to 7.99 (d, J=8.0 Hz, 2H), 7,72 (d, J=8.0 Hz, 2H), 7,31 (d, J=5.0 Hz, 1H), 7,20 (d, J=5.0 Hz, 1H), 6,07 (s, 1H), to 3.02 (s, 2H), 1,45 (s, 6N).

Example 11(117)

(Z)-2-(6-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.40 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,51 (W, 1H), to 7.67 (d, J=8.5 Hz, 1H), for 6.81 (DD, J=8,5, 2.5 Hz, 1H), of 6.68 (d, J=2.5 Hz, 1H), 5,70 (s, 1H), 3,85 (s, 3H), 2,80 (s, 2H), 2.05 is (W, 3H), 1.91 a (W, 6N), 1,74 (W, 6N), 1,29 (C, 6N).

Example 11(118)

(Z)-2-(6-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.18 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,96 (W, 1H), 8,01 (d, J=8.5 Hz, 2H), to 7.77-of 7.70 (m, 3H), 6.87 in (DD, J=8,5, 2.5 Hz, 1H), 6,74 (d, J=2.5 Hz, 1H), of 6.20 (s, 1H), 3,88 (s, 3H), 2,88 (s, 2H), 1,38 (C, 6N).

Example 11(119)

(Z)-2-(7-Bromo-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-yl)ethane-1-he

TLC: Rf of 0.36 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ is 11.39 (W, 1H), to $ 7.91 (s, 1H), 7,28 (s, 1H), 5,69 (s, 1H), was 2.76 (s, 2H), 2,07 (m, 3H), 1.91 a (m, 6N), a 1.75 (m, 6N), 1,29 (C, 6N).

Example 11(120)

(Z)-2-(2-Chloro-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-C]pyridine-4-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.44 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 10,96 (W, 1H), 7,92-7,89 (m, 2H), 7,46-7,40 (m, 3H), 7,14 (s, 1H), 6,02 (s, 1H), 2,90 (s, 2H), USD 1.43 (s, 6N).

Example 11(121)

(Z)-2-(2-Chloro-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-C]pyridine-4-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.56 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ to 10.62 (W, 1H), 7,05 (s, 1H), vs. 5.47 (s, 1H), 2,82 (s, 2H), 2.05 is (W, 3H), 1,87 (W, 6N), 1,73 (W, 6N), 1,36 (C, 6N).

Example 11(122)

(Z)-2-(2-Chloro-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-C]pyridine-4-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.29 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,09 (W, 1H), of 7.97 (d, J=8.5 Hz, 2H), 7,72 (d, J=8.5 Hz, 2H), 7,13 (s, 1H), 5,95 (s, 1H), 2,92 (s, 2H), 1,45 (s, 6N).

Example 11(123)

(Z)-2-(5-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0,49 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,84 (SHS, 1H), 7,97-to $ 7.91 (m, 2H), of 7.48-7,40 (m, 4H), 7,30 (t, J=8,1 Hz, 1H), 7,00 (d, J=8,1 Hz, 1H), 6,33 (s, 1H), a 3.87 (s, 3H), 2,90 (s, 2H), 1,37 (C, 6N).

Example 11(124)

(Z)-2-(3,3,6-T is imethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0,41 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,48 (SHS, 1H), to 7.61 (d, J=8,1 Hz, 1H), 7,09 (sm, J=8,1 Hz, 1H), 6,97 (SHS, 1H), of 5.75 (s, 1H), and 2.79 (s, 2H), is 2.37 (s, 3H), 2.05 is (CL, 3H), at 1.91 (d, J=3.0 Hz, 6N), 1,74 (d, J=3.0 Hz, 6N), of 1.29 (s, 6N).

Example 11(125)

(Z)-2-(3,3,6-Trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.13 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,94 (SHS, 1H), 8,01 (d, J=8,4 Hz, 2H), 7,72 (d, J=8,4 Hz, 2H), of 7.70 (d, J=8,4 Hz, 1H), 7,16 (sm, J=8,4 Hz, 1H),? 7.04 baby mortality (SHS, 1H), and 6.25 (s, 1H), 2,87 (s, 2H), 2,41 (s, 3H), of 1.37 (s, 6N).

Example 11(126)

(Z)-2-(7-Nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf 0.14 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 11,91 (W, 1H), 8,67 (d, J=2.0 Hz, 1H), 8,32 (DD, J=8,0, 2.0 Hz, 1H), with 8.05 (d, J=8.5 Hz, 2H), to 7.77 (d, J=8.5 Hz, 2H), 7,45 (d, J=8.0 Hz, 1H), 6,34 (s, 1H), 6,04 (s, 2H), 1,41 (C, 6N).

Example 11(127)

(Z)-2-(6-Chloro-7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.29 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ of 11.15 (W, 1H), 8,23 (s, 1H), 7,38 (s, 1H), 5,61 (s, 1H), 2,88 (s, 2H), 2,33 (m, 1H), 1,90-of 1.65 (m, 5H), 1.55V is 1.20 (m, 5H), 1,31 (C, 6N).

Example 11(128)

(Z)-2-(6-Chloro-7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.30 (ethyl acetate=hexane=1:3).

NMR (CDCl3/sub> ): δ 11,08 (W, 1H), 8,23 (s, 1H), 7,39 (s, 1H), 5,58 (s, 1H), 2,88 (s, 2H), of 2.51 (m, 1H), 1,95-1,20 (m, N), 1,31 (C, 6N).

Example 11(129)

(Z)-2-(6-Chloro-7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.13 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,83 (W, 1H), 8.34 per (s, 1H), 8,01 (d, J=8.5 Hz, 2H), 7,76 (d, J=8.5 Hz, 2H), 7,46 (s, 1H), 6,24 (s, 1H), 2,97 (s, 2H), 1,41 (C, 6N).

Example 11(130)

(Z)-2-(6-Chloro-7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.35 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,36 (W, 1H), they were 8.22 (s, 1H), 7,39 (s, 1H), of 5.75 (s, 1H), 2,88 (s, 2H), 2,07 (m, 3H), 1,90 (m, 6N), a 1.75 (m, 6N), 1,32 (C, 6N).

Example 11(131)

(Z)-2-(7-Dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf 0,41 (water:methanol:chloroform=1:10:100).

NMR (CDCl3): δ 12,01 (W, 1H), 8,03 (d, J=8.0 Hz, 2H), 7,74 (s, 1H), 7,73 (d, J=8.0 Hz, 2H), 7,41 (d, J=7.5 Hz, 1H), 7,19 (d, J=7.5 Hz, 1H), 6,29 (s, 1H), 3,48 (s, 2H), 2,90 (s, 2H), 2,28 (C, 6N), to 1.37 (s, 6N).

Example 11(132)

(Z)-2-(7-Dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0.39 to (water:methanol:chloroform=1:10:100).

NMR (CDCl3): δ 11,55 (W, 1H), 7,66 (s, 1H), 7,40 (d, J=7.5 Hz, 1H), 7,15 (d, J=7.5 Hz, 1H), 5,80 (s, 1H), 3,55 (W, 2H), 2,82 (s, 2H), 2,33 (C, 6N), e 2.06 (m, 3H), of 1.92 (m, 6N), a 1.75 (m, 6N), of 1.29(s, 6N).

Example 11(133)

(Z)-2-(7-Amino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.35 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,91 (W, 1H), 8,00 (d, J=8.5 Hz, 2H), 7,71 (d, J=8.5 Hz, 2H), 7,13 (s, 1H), 6,59 (s, 1H), 6,12 (s, 1H), 3,92 (s, 3H), 3,88 (W, 2H), 2,80 (s, 2H), 1,37 (C, 6N).

Example 11(134)

(Z)-2-(7-Amino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.56 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,46 (W, 1H), 7,07 (s, 1H), is 6.54 (s, 1H), 5,62 (s, 1H), with 3.89 (s, 3H), 3,82 (W, 2N), of 2.72 (s, 2H), 2.05 is (W, 3H), 1.91 a (W, 6N), 1,74 (W, 6N), 1.28 (in C, 6N).

Example 11(135)

(Z)-2-(6-Chloro-7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.32 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,33 (W, 1H), was 7.36 (s, 1H), 7,17 (s, 1H), 5,54 (s, 1H), 2,86 (C, 6N), is 2.74 (s, 2H), 2,32 (m, 1H), 1,95-of 1.20 (m, 10H), 1.28 (in C, 6N).

Example 11(136)

(Z)-2-(6-Chloro-7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.34 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,25 (W, 1H), 7,35 (s, 1H), 7,17 (s, 1H), 5,51 (s, 1H), 2,86 (C, 6N), is 2.74 (s, 2H), 2,48 (m, 1H), 1,95-of 1.40 (m, N), 1.28 (in C, 6N).

Example 11(137)

(Z)-2-(6-Chloro-7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf is 0.24 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,95 (W, 1H), 8,00 (d, J=8.5 Hz, 2H), 7,73 (d, J=8.5 Hz, 2H), 7,43 (s, 1H), 7,24 (s, 1H), 6,17 (s, 1H), 2,89 (C, 6N), 2,82 (s, 2H), 1,37 (C, 6N).

Example 11(138)

(Z)-2-(6-Chloro-7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.36 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,51 (W, 1H), was 7.36 (s, 1H), 7,16 (s, 1H), 5,69 (s, 1H), 2,86 (C, 6N), 2,73 (s, 2H), 2.06 to (m, 3H), 1.91 a (m, 6N), 1,74 (m, 6N), 1.28 (in C, 6N).

Example 11(139)

(Z)-2-(7-Dimethylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.16 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,98 (SHS, 1H), 8,01 (d, J=8,4 Hz, 2H), 7,73 (d, J=8,4 Hz, 2H), 7,40 (s, 1H), 7,01 (s, 1H), to 6.19 (s, 1H), 2,81 (s, 2H), was 2.76 (s, 6N), is 2.37 (s, 3H), of 1.37 (s, 6N).

Example 11(140)

(Z)-2-(7-Dimethylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0.36 and (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,55 (SHS, 1H), 7,33 (s, 1H), 6,95 (s, 1H), 5,71 (s, 1H), 2,74 (C, 6N), 2,73 (s, 2H), 2,34 (s, 3H), 2,09-2,03 (m, 3H), 1,94-1,90 (m, 6N), 1,77-of 1.73 (m, 6N), 1.28 (in C, 6N).

Example 11(141)

(Z)-2-(7-Dimethylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf to 0.39 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,36 (SHS, 1H), 7,32 (s, 1H), 6,95 (s, 1H), 5.56mm (s, 1H),2,74 (s, 8H), was 2.34 (s, 3H), 2,31 (m, 1H), 1,92 is 1.20 (m, 10H), 1.28 (in C, 6N).

Example 11(142)

(Z)-2-(7-Dimethylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0,41 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,29 (SHS, 1H), 7,32 (s, 1H), 6,94 (s, 1H), 5,52 (s, 1H), 2,74 (C, 6N), 2,73 (s, 2H), 2,47 (m, 1H), 2,34 (s, 3H), 1,97 was 1.43 (m, N), 1.27mm (C, 6N).

Example 11(143)

(Z)-2-(7-Dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.44 (water:methanol:chloroform=1:10:100).

NMR (CDCl3): δ 11,34 (W, 1H), 7,63 (d, J=1.5 Hz, 1H), 7,34 (DD, J=8,0, 1.5 Hz, 1H), 7,12 (d, J=8.0 Hz, 1H), to 5.66 (s, 1H), 3.46 in (s, 2H), 2,82 (s, 2H), 2,32 (m, 1H), 2,28 (C, 6N), 1,90-of 1.20 (m, 10H), 1.28 (in C, 6N).

Example 11(144)

(Z)-2-(7-Dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0,46 (water:methanol:chloroform=1:10:100).

NMR (CDCl3): δ 11,27 (W, 1H), 7,63 (s, 1H), 7,33 (d, J=7.5 Hz, 1H), 7,12 (d, J=7.5 Hz, 1H), 5,62 (s, 1H), 3.45 points (s, 2H), 2,82 (s, 2H), 2,48 (m, 1H), and 2.27 (s, 6N), 1,95-of 1.40 (m, N), 1.28 (in C, 6N).

Example 11(145)

(Z)-2-(6-Methoxy-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.13 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ of $ 11.97 (W, 1H), 8,00 (d, J=8.5 Hz, 2H), 7,72 (d, J=8.5 Hz, 2H), 6.89 in (s, 1H), 6,56 (s, 1H), 6,17 (s, 1H), 4,33 (W, 1H), 3,92 (s, 3H), 2.95 and (s, 3H), of 2.81 (s, 2H) to 1.37 (s, 6N).

Example 11(146)

(Z)-2-(6-Methoxy-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.34 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,57 (W, 1H), 6,55 (s, 1H), 6,50 (s, 1H), of 5.68 (s, 1H), 4,23 (W, 1H), 3,88 (s, 3H), equal to 2.94 (s, 3H), of 2.72 (s, 2H), 2.05 is (W, 3H), 1,92 (W, 6N), 1,74 (W, 6N), 1,29 (C, 6N).

Example 11(147)

(Z)-2-(7-Dimethylamino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.20 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,37 (W, 1H), 7.23 percent (s, 1H), 6,60 (s, 1H), 5,51 (s, 1H), 3,93 (s, 3H), 2,82 (C, 6N), was 2.76 (s, 2H), 2,30 (TT, J=11,5, 3.5 Hz, 1H), 1,89-to 1.79 (m, 4H), 1.69 in (m, 1H), 1.56 to 1,20 (m, 11N).

Example 11(148)

(Z)-2-(7-Dimethylamino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.20 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,30 (W, 1H), 7.23 percent (s, 1H), 6,60 (s, 1H), 5,48 (s, 1H), 3,93 (s, 3H), 2,82 (C, 6N), was 2.76 (s, 2H), 2,46 (m, 1H), 1,95-of 1.88 (m, 2H), 1,83-of 1.45 (m, 10H), 1,29 (C, 6N).

Example 11(149)

(Z)-2-(7-Dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf 0.14 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 12,02 (SHS, 1H), 8,00 (d, J=8.7 Hz, 2H), 7,72 (d, J=8.7 Hz, 2H), to 7.09 (d, J=8.7 Hz, 1H), was 7.08 (d, J=2.4 Hz, 1H), 6,86 (DD, J=8,7, 2.4 Hz, 1H), 6,21 (s, 1H), 3,02 (C, 6N), of 2.81 (s, 2H), 1,36 (s, 6N).

Example 11(150)

(Z)-2-(7-Dimetil the Ino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.35 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,57 (SHS, 1H), 7,05 (d, J=2.4 Hz, 1H), 7,03 (d, J=8,4 Hz, 1H), 6,80 (DD, J=8,4, 2.4 Hz, 1H), 5,73 (s, 1H), 2,99 (C, 6N), 2,73 (s, 2H), 2,08-2,02 (m, 3H), 1,94-1,90 (m, 6N), 1,76-1,72 (m, 6N), 1,28 (C, 6N).

Example 11(151)

(Z)-2-(7-Amino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf 0.26 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,28 (W, 1H), 7,05 (s, 1H), is 6.54 (s, 1H), 5,48 (s, 1H), with 3.89 (s, 3H), 3,80 (W, 2N), of 2.72 (s, 2H), 2.26 and (TT, J=11,5, 3.5 Hz, 1H), 1,89-to 1.79 (m, 4H), by 1.68 (m, 1H), 1.56 to 1,22 (m, 11N).

Example 11(152)

(Z)-2-(7-Amino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0.31 in (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,19 (W, 1H), 7,05 (s, 1H), 6,53 (s, 1H), 5,44 (s, 1H), with 3.89 (s, 3H), 3,80 (W, 2N), of 2.72 (s, 2H), 2,42 (m, 1H), 1,95-to 1.87 (m, 2H), 1,82 of 1.46 (m, 10H), 1.28 (in C, 6N).

Example 11(153)

(Z)-2-(7-Bromo-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.25 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,19 (W, 1H), to $ 7.91 (s, 1H), 7,28 (s, 1H), 5,54 (s, 1H), was 2.76 (s, 2H), 2,31 (m, 1H), 1,90-of 1.20 (m, 10H), 1,29 (C, 6N).

Example 11(154)

(Z)-2-(7-Bromo-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf is 0.24 (ethyl acetate:hexane=1:5).

NMR (CDCl3): 4 to 11.11 (W, 1H), to $ 7.91 (s, 1H), 7,28 (s, 1H), 5,51 (s, 1H), was 2.76 (s, 2H), 2,48 (m, 1H), 1,95-of 1.40 (m, N), 1.28 (in C, 6N).

Example 11(155)

(Z)-2-(7-Nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.67 (ethyl acetate:hexane=2:3).

NMR (CDCl3): δ 11,23 (W, 1H), 8,56 (d, J=2.5 Hz, 1H), 8,24 (DD, J=8,0, 2.5 Hz, 1H), 7,37 (d, J=8.0 Hz, 1H), 5,71 (s, 1H), 2.95 and (s, 2H), is 2.37 (m, 1H), 1,95-of 1.20 (m, 10H), 1,31 (C, 6N).

Example 11(156)

(Z)-2-(7-Bromo-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0.28 in (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ of 11.45 (W, 1H), 7,86 (s, 1H), to 6.67 (s, 1H), 5,65 (s, 1H), 3,94 (s, 3H), 2,78 (s, 2H), 2.06 to (W, 3H), 1.91 a (W, 6N), 1,75 (W, 6N), 1,29 (C, 6N).

Example 11(157)

(Z)-2-(7-Nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf to 0.63 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ of 11.45 (SHS, 1H), 8,56 (d, J=2.1 Hz, 1H), 8,24 (DD, J=8,1, 2.1 Hz, 1H), 7,37 (d, J=8,1 Hz, 1H), to 5.85 (s, 1H), 2,94 (s, 2H), 2,12-to 2.06 (m, 3H), 1,94-1,90 (m, 6N), 1,78-of 1.74 (m, 6N), 1,31 (C, 6N).

Example 11(158)

(Z)-2-(7-Dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf is 0.24 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,40 (SHS, 1H), 7,03 (d, J=8,4 Hz, 1H), 7,03 (d, J=2.4 Hz, 1H), 6,80 (DD, J=8,4, 2.4 Hz, 1H), to 5.57 (s, 1H), 2,99 (C, 6N), 2,73 (s, 2H), 2,31 (m, 1H), 1.93 and-1,10 (m, 10H), 1.28 (in C, 6N).

Example 11(159)

(Z)-2-(7-Dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0.26 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,32 (SHS, 1H), 7,03 (d, J=8,4 Hz, 1H), 7,02 (d, J=2.4 Hz, 1H), 6,80 (DD, J=8,4, 2.4 Hz, 1H), 5,54 (s, 1H), 2,99 (C, 6N), 2,73 (s, 2H), 2,47 (m, 1H), 1,97-of 1.40 (m, N), 1.28 (in C, 6N).

Example 11(160)

(Z)-2-(7-Methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.55 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,34 (SHS, 1H), 6,98 (d, J=8,1 Hz, 1H), 6,91 (d, J=2.4 Hz, 1H), 6,66 (DD, J=8,1, 2.4 Hz, 1H), 5.56mm (s, 1H), 3,76 (SHS, 1H), 2,89 (s, 3H), of 2.72 (s, 2H), to 2.29 (m, 1H), 1.93 and-1,10 (m, 10H), 1.27mm (s, 6N).

Example 11(161)

(Z)-2-(7-Methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0,59 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ of 11.26 (SHS, 1H), 6,98 (d, J=8,4 Hz, 1H), 6,91 (d, J=2.4 Hz, 1H), 6,66 (DD, J=8,4, 2.4 Hz, 1H), of 5.53 (s, 1H), of 3.77 (SHS, 1H), 2,89 (s, 3H), 2,71 (s, 2H), 2,45 (m, 1H), 1,97-of 1.42 (m, N), 1.27mm (s, 6N).

Example 11(162)

(Z)-2-(7-Methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf to 0.19 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ of $ 11.97 (W, 1H), 8,00 (d, J=8.7 Hz, 2H), 7,72 (d, J=8.7 Hz, 2H), 7,05 (d, J=8,1 Hz, 1H), 6,99 (d, J=2.4 Hz, 1H), 6.73 x (DD, J=8,1, 2.4 Hz, 1H), to 6.19 (s, 1H), 3,90 (W, 1H), 2.91 in (s, 3H), 2,80 (s, 2H), 1,36 (C, 6N).

Example 11(163)

(Z)-2-(7-Cyano--methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.23 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,88 (W, 1H), 8,03-of 8.00 (m, 3H), of 7.75 (d, J=8.5 Hz, 2H), PC 6.82 (s, 1H), 6,16 (s, 1H), was 4.02 (s, 3H), 2.95 and (s, 2H), 1.39 in (C, 6N).

Example 11(164)

(Z)-2-(7-Dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.55 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,51 (W, 1H), 6,99 (d, J=8,1 Hz, 1H), 6,94 (d, J=2.4 Hz, 1H), 6,66 (DD, J=8,1, 2.4 Hz, 1H), 5,70 (s, 1H), 3,78 (W, 1H), 2,89 (s, 3H), of 2.72 (s, 2H), 2.05 is (s, 3H), 1.91 a (W, 6N), 1,74 (W, 6N), 1.27mm (C, 6N).

Example 11(165)

(Z)-2-(7-Cyano-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.23 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,41 (W, 1H), to 7.93 (s, 1H), 6,76 (s, 1H), 5,67 (s, 1H), 3,99 (s, 3H), of 2.86 (s, 2H), 2,07 (W, 3H), 1,90 (W, 6N), 1,75 (W, 6N), of 1.30 (s, 6N).

Example 11(166)

(Z)-2-(7-Cyano-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf is 0.22 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,25 (W, 1H), to $ 7.91 (s, 1H), 6,76 (s, 1H), of 5.53 (s, 1H), 3,98 (s, 3H), 2,87 (s, 2H), 2,30 (m, 1H), 1,89 and 1.80 (m, 4H), to 1.70 (m, 1H), 1,57 is 1.16 (m, 11N).

Example 11(167)

(Z)-2-(7-Cyano-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0.26 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,16 (W, 1H), to $ 7.91 (s, 1H), 6,5 (s, 1H), 5,49 (s, 1H), 3,98 (s, 3H), of 2.86 (s, 2H), 2,46 (m, 1H), 1,95-to 1.87 (m, 2H), 1,82 to 1.47 (m, 10H), of 1.30 (s, 6N).

Example 11(168)

(Z)-2-(7-Bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0.36 and (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,42 (SHS, 1H), 7,82 (d, J=1.8 Hz, 1H), 7,50 (DD, J=7,8, 1.8 Hz, 1H), 7,06 (d, J=7.8 Hz, 1H), 5,71 (s, 1H), 2,78 (s, 2H), 2,10-2,04 (m, 3H), 1.93 and-1,89 (m, 6N), 1,78-of 1.73 (m, 6N), 1,31 (C, 6N).

Example 11(169)

(Z)-2-(7-Dimethylaminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf is 0.42 (chloroform:methanol=10:1).

NMR (CDCl3): δ 11,28 (W, 1H), to 7.59 (s, 1H), 6,62 (s, 1H), of 5.55 (s, 1H), a 3.87 (s, 3H), of 3.45 (s, 2H), 2,80 (s, 2H), 2,46 (m, 1H), 2,29 (C, 6N), 1,95-to 1.87 (m, 2H), 1,82 to 1.47 (m, 10H), 1,29 (C, 6N).

Example 11(170)

(Z)-2-(7-Bromo-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.27 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,24 (W, 1H), 7,86 (s, 1H), to 6.67 (s, 1H), 5,51 (s, 1H), 3,94 (s, 3H), and 2.79 (s, 2H), 2,29 (TT, J=11,5, 3.5 Hz, 1H), 1,89-to 1.79 (m, 4H), 1,71-1,20 (m, N).

Example 11(171)

(Z)-2-(7-Dimethylaminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf is 0.42 (chloroform:methanol=10:1).

NMR (CDCl3): δ 11,35 (W, 1H), 7,60 (s, 1H), 6,63 (s, 1H), 5,58 (s, 1H), a 3.87 (s, 3H), of 3.45 (s, 2H), 2,81 (s, 2H), 2,37 was 2.25 (m, 7H), 1,88-to 1.79 (m, 4H), 1,1-1,20 (m, N).

Example 11(172)

(Z)-2-(7-Nitro-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.33 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ 11,42 (W, 1H), with 8.33 (s, 1H), 7,16 (s, 1H), 5,79 (s, 1H), 2,86 (s, 2H), 2,64 (s, 3H), 2,07 (W, 3H), 1.91 a-1,90 (W, 6N), 1,76-1,75 (W, 6N), 1,31 (C, 6N).

Example 11(173)

(Z)-2-(6-Methoxy-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf 0.28 in (chloroform:methanol=10:1).

NMR (CDCl3): δ 11,31 (W, 1H), EUR 7.57 (s, 1H), 6,62 (s, 1H), 5,58 (s, 1H), 3,88 (s, 3H), of 3.75 (s, 2H), 2,80 (s, 2H), 2,47 (s, 3H), 2,29 (TT, J=11,5, 3.5 Hz, 1H), 1,89-to 1.79 (m, 4H), 1,71-1,20 (m, N).

Example 11(174)

(Z)-2-(7-Dimethylaminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.47 (chloroform:methanol=10:1).

NMR (CDCl3): δ 11,99 (W, 1H), 8,02 (d, J=8.5 Hz, 2H), 7,74-7,71 (m, 3H), 6,69 (s, 1H), from 6.22 (s, 1H), 3,91 (s, 3H), 3,49 (s, 2H), 2,89 (s, 2H), 2,31 (C, 6N), to 1.38 (s, 6N).

Example 11(175)

(Z)-2-(7-Nitro-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf 0,89 (chloroform:methanol=50:1).

NMR (CDCl3): δ 11,88 (W, 1H), 8,44 (s, 1H), 8,03 (d, J=8.7 Hz, 2H), 7,76 (d, J=8.7 Hz, 2H), 7,24 (s, 1H), 6,28 (s, 1H), 2.95 and (s, 2H), 2,68 (s, 3H), 1,40 (C, 6N).

Example 11(176)

(Z)-2-(7-Nitro-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclog xalatan-1-he

TLC: Rf 0.25 in (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,25 (SHS, 1H), 8.34 per (s, 1H), 7,16 (s, 1H), 5,65 (s, 1H), 2,87 (s, 2H), 2,65 (s, 3H), 2,34 (TT, J=11,4, 3.3 Hz, 1H), 1.93 and-of 1.65 (m, 5H), 1,58-of 1.18 (m, 11N).

Example 11(177)

(Z)-2-(7-Nitro-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.27 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,17 (SHS, 1H), 8.34 per (s, 1H), 7,16 (s, 1H), 5,62 (s, 1H), 2,86 (s, 2H), 2,65 (s, 3H), of 2.51 (TT, J=9,9, 3,9 Hz, 1H), 1,97-of 1.44 (m, N), of 1.30 (s, 6N).

Example 11(178)

(Z)-2-(7-Methylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.55 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,37 (SHS, 1H), 6,86 (s, 1H), 6,84 (s, 1H), 5,58 (s, 1H), to 3.58 (SHS, 1H), 2,97 (s, 3H), 2,70 (s, 2H), 2,31 (TT, J=12,0, 3.3 Hz, 1H), 2,15 (s, 3H), 1,92-of 1.18 (m, N).

Example 11(179)

(Z)-2-(7-Methylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0,59 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,29 (SHS, 1H), 6,86 (s, 1H), 6,84 (s, 1H), of 5.55 (s, 1H), to 3.58 (SHS, 1H), 2,97 (s, 3H), 2,70 (s, 2H), 2,47 (TT, J=9,9, 3,9 Hz, 1H), 2,15 (s, 3H), 1,97 was 1.43 (m, N), 1.28 (in C, 6N).

Example 11(180)

(Z)-2-(7-Methylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf and 0.61 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,55 (who, 1H), to 6.88 (s, 1H), 6,84 (s, 1H), 5,74 (s, 1H), to 3.58 (SHS, 1H), 2,97 (s, 3H), 2,70 (s, 2H), 2,16 (s, 3H), 2,08-2,02 (m, 3H), 1,94-1,90 (m, 6N), 1,76-1,72 (m, 6N), 1.28 (in C, 6N).

Example 11(181)

(Z)-2-(7-Bromo-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf to 0.39 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,16 (W, 1H), 7,86 (s, 1H), to 6.67 (s, 1H), 5,48 (s, 1H), 3,94 (s, 3H), 2,78 (s, 2H), 2,46 (m, 1H), 1,94-1,50 (m, N), 1,29 (C, 6N).

Example 11(182)

(Z)-2-(6,7-Dicyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.35 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,07 (SHS, 1H), of 8.09 (s, 1H), 7,63 (s, 1H), 5,64 (s, 1H), 2,94 (s, 2H), 2,35 (m, 1H), 1.93 and is 1.75 (m, 5H), 1.56 to 1,20 (m, 11N).

Example 11(183)

(Z)-2-(6,7-Dicyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.37 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,22 (SHS, 1H), 8,10 (s, 1H), 7,63 (s, 1H), 5,78 (s, 1H), 2,94 (s, 2H), 2,12-2,05 (m, 3H), 1.91 a-to 1.87 (m, 6N)and 1.83-1.69 in (m, 6N), 1,31 (C, 6N).

Example 11(184)

(Z)-2-(7-Bromo-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.33 (hexane:ethyl acetate=9:1).

NMR (CDCl3): δ 11,40 (W, 1H), 7,83 (s, 1H),? 7.04 baby mortality (s, 1H), 5,69 (s, 1H), 2,74 (s, 2H), 2,42 (s, 3H), 2.06 to (W, 3H), 1.91 a-1,90 (W, 6N), 1,76-1,75 (W, 6N), 1.28 (in C, 6N).

Example 11(185)

(Z)-2-(6,7-Dicyano-3,3-dimethyl-3,4-dihydro-(2H)-Sochi the Olin-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.30 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 10,98 (SHS, 1H), of 8.09 (s, 1H), 7,63 (s, 1H), ceiling of 5.60 (s, 1H), 2,94 (s, 2H), 2,52 (m, 1H), 1,96-of 1.44 (m, N), 1,31 (C, 6N).

Example 11(186)

(Z)-2-(6,7-dicyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.68 (chloroform:methanol=9:1).

NMR (DMSO-d6): δ 11,77 (SHS, 1H), 9,01 (s, 1H), 8,25 (d, J=8,4 Hz, 2H), 8,17 (s, 1H), of 7.97 (d, J=8,4 Hz, 2H), 6.75 in (s, 1H), 3,09 (s, 2H), 1,30 (C, 6N).

Example 11(187)

(Z)-2-(7-Methylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.50 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,98 (SHS, 1H), 8,01 (d, J=8.7 Hz, 2H), 7,72 (d, J=8.7 Hz, 2H), 6,92 (s, 1H), 6,91 (s, 1H), from 6.22 (s, 1H), 3,66 (SHS, 1H), 2,99 (s, 3H), 2,78 (s, 2H), 2,19 (s, 3H), 1,36 (C, 6N).

Example 11(188)

(Z)-2-(7-Bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf 0,41 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,23 (SHS, 1H), 7,81 (d, J=2.1 Hz, 1H), 7,50 (DD, J=8,1, 2.1 Hz, 1H), 7,05 (d, J=8,1 Hz, 1H), to 5.57 (s, 1H), 2,78 (s, 2H), 2,31 (TT, J=11,4, 3.3 Hz, 1H), 1,92-of 1.65 (m, 5H), 1,58-of 1.18 (m, 11N).

Example 11(189)

(Z)-2-(7-Bromo-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf 0,41 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,22 (W, 1H), 7,83 (s, 1H),? 7.04 baby mortality (s, 1H), of 5.55 (s, 1H), 2,74, 2N), is 2.41 (s, 3H), 2,30 (m, 1H), 1,92-1,20 (m, N).

Example 11(190)

(Z)-2-(6-Chloro-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.34 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,34 (W, 1H), 7,07 (s, 1H), 6.90 to (s, 1H), of 5.55 (s, 1H), 4,33 (W, 1H), 2,98 (d, J=4.5 Hz, 3H), 2,69 (s, 2H), 2,31 (m, 1H), 1,90-of 1.20 (m, 10H), 1.27mm (C, 6N).

Example 11(191)

(Z)-2-(6-Chloro-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.38 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,27 (W, 1H), 7,07 (s, 1H), 6.90 to (s, 1H), 5,52 (s, 1H), 4,33 (W, 1H), 2,98 (d, J=3.5 Hz, 3H), 2,70 (s, 2H), 2,48 (m, 1H), 1,95-of 1.40 (m, N), 1.27mm (C, 6N).

Example 11(192)

(Z)-2-(6-Chloro-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0,41 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,53 (W, 1H), 7,07 (s, 1H), 6,92 (s, 1H), 5,71 (s, 1H), 4,33 (W, 1H), 2,99 (s, 3H), 2,70 (s, 2H), 2.06 to (m, 3H), of 1.92 (m, 6N), a 1.75 (m, 6N), 1.28 (in C, 6N).

Example 11(193)

(Z)-2-(7-Bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf to 0.39 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,14 (SHS, 1H), 7,81 (d, J=1.8 Hz, 1H), 7,50 (DD, J=7,8, 1.8 Hz, 1H), 7,05 (d, J=7.8 Hz, 1H), 5,54 (s, 1H), 2,78 (s, 2H), 2,48 (TT, J=9,9, 3,9 Hz, 1H), 1,97 was 1.43 (m, N), 1.28 (in C, 6N).

Example 11(194)

(Z)-2-(7-Bromo-3,3,6-trimethyl-3,4-dihydro-(2H)-and chinolin-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.60 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ of 11.15 (W, 1H), 7,83 (s, 1H),? 7.04 baby mortality (s, 1H), 5,52 (s, 1H), 2,74 (s, 2H), 2,41 (s, 3H), 2,46 (m, 1H), 1,96 of 1.46 (m, N), 1.28 (in C, 6N).

Example 11(195)

(Z)-2-(7-Nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.57 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ of 11.15 (SHS, 1H), 8,56 (d, J=2.1 Hz, 1H), 8,24 (DD, J=8,7, and 2.1 Hz, 1H), 7,37 (d, J=8.7 Hz, 1H), of 5.68 (s, 1H), 2,94 (s, 2H), 2,53 (TT, J=9,9, 3,9 Hz, 1H), 1,98 of 1.46 (m, N), 1,31 (C, 6N).

Example 11(196)

(Z)-2-(7-Dimethylsulphamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.53 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,51 (SHS, 1H), 8,08 (d, J=1.8 Hz, 1H), to 7.77 (DD, J=7,8, 1.8 Hz, 1H), was 7.36 (d, J=1.8 Hz, 1H), 5,79 (s, 1H), 2,92 (s, 2H), 2,77 (, 6N), 2,10-2,03 (m, 3H), 1,92-of 1.88 (m, 6N), 1,77-1,72 (m, 6N), 1,31 (C, 6N).

Example 11(197)

(Z)-2-(7-Butoxycarbonyl-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.40 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,38 (SHS, 1H), 8,18 (s, 1H), 7,28 (s, 1H), 5,78 (s, 1H), 4,39 (t, J=6.6 Hz, 2H), and 2.83 (s, 2H), 2,10-2,02 (m, 3H), 1.93 and-a 1.88 (m, 6N), 1,84-1,72 (m, 8H), 1,61 is 1.48 (m, 8H), is 1.01 (t, J=7.2 Hz, 3H).

Example 11(198)

(Z)-2-(7-Butoxycarbonyl-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

p> TLC: Rf of 0.38 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,12 (SHS, 1H), 8,15 (s, 1H), 7,28 (s, 1H), 5,59 (s, 1H), 4,39 (t, J=6.6 Hz, 2H), and 2.83 (s, 2H), 2,48 (TT, J=9,9, 3,9 Hz, 1H), 1,96 was 1.43 (m, N), 1,29 (C, 6N), a 1.01 (t, J=7.2 Hz, 3H).

Example 11(199)

(Z)-2-(7-Methylsulfonyl-3,3-dimethyl-3,4-dihydro-(2H)-isoindoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf to 0.39 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,50 (SHS, 1H), 8,17 (d, J=1.8 Hz, 1H), 7,86 (DD, J=7,8, 1.8 Hz, 1H), 7,35 (d, J=7.8 Hz, 1H), of 5.81 (s, 1H), to 4.41 (q, J=5.4 Hz, 1H), 2.91 in (s, 2H), 2,72 (d, J=5.4 Hz, 3H), 2,10-2,03 (m, 3H), 1,92-to 1.87 (m, 6N), 1,77-of 1.73 (m, 6N), 1,31 (C, 6N).

Example 11(200)

(Z)-2-(6-Chloro-7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.33 (ethyl acetate:hexane=5:1).

NMR (CDCl3): δ 11,53 (W, 1H), 7,21 (s, 1H), 7,19 (s, 1H), of 5.68 (s, 1H), 3,99 (s, 3H), 2,74 (s, 2H), 2.06 to (m, 3H), 1.91 a (m, 6N), a 1.75 (m, 6N), 1.28 (in C, 6N).

Example 11(201)

(Z)-2-(7-Methoxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf to 0.39 (hexane:ethyl acetate=6:1).

NMR (CDCl3): δ 11,54 (W, 1H), 7,10 (s, 1H), 6,93 (s, 1H), 5,69 (s, 1H), 3,91 (s, 3H), 2,73 (s, 2H), 2,24 (s, 3H), 2.06 to (W, 3H), 1,92 is 1.91 (W, 6N), 1,75 (W, 6N), 1.28 (in C, 6N).

Example 11(202)

(Z)-2-(7-Methoxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.35 (hexane:ethyl acetate=6:1).

NMR (CDCl3 ): δ 11,34 (W, 1H), to 7.09 (s, 1H), 6,92 (s, 1H), 5,54 (s, 1H), 3,90 (s, 3H), 2,73 (s, 2H), 2,31 (m, 1H), 2,24 (s, 3H), 1,92-of 1.18 (m, N).

Example 11(203)

(Z)-2-(7-Methoxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0.31 in (hexane:ethyl acetate=6:1).

NMR (CDCl3): δ 11,27 (W, 1H), was 7.08 (s, 1H), 6,92 (s, 1H), 5,51 (s, 1H), 3,90 (s, 3H), 2,73 (s, 2H), 2,46 (m, 1H), 2,24 (s, 3H), 1,96-of 1.42 (m, N), 1.27mm (C, 6N).

Examples 12-12(31)

By the same procedure as described in example 1 using the compound obtained in reference example 1, or a corresponding nitrile derivative and 2-methyl-1-phenylpropane-2-ol or a derivative of the alcohol produced the following compounds of the present invention. Additionally, the conversion into the hydrochloride get connection example 12(20) and example 12(24).

Example 12

(Z)-2-(6-Bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.35 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ 11,78 (W, 1H), 7.95 is-a 7.92 (m, 2H), 7,69 (d, J=8.5 Hz, 1H), 7,49-7,38 (m, 5H), 6,28 (W, 1H), 2,87 (s, 2H), 1,37 (C, 6N).

Example 12(1)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(tetrahydropyran-1-yl)Ethan-1-he

TLC: Rf of 0.54 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 11,35 (W, 1H), of 7.70 (m, 1H), 7,41 (m, 1H), 7,30 (m, 1H), 7,19 (m, 1H), 5,63 (W, 1H), of 4.05 (m, 2H), 3.46 in (dt, J=11,5, 3.5 Hz, 2H), 2,86 (s, 2H), 2,54 (m, 1H), 1,90 is 1.70 (m, 4H), 1,31 (C, 6N).

p> Example 12(2)

(Z)-2-(6-Fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.35 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,31 (W, 1H), of 7.70 (DD, J=9,0, 5.5 Hz, 1H), 6,98 (DDD, J=9,0, at 9.0, 2.5 Hz, 1H), to 6.88 (DD, J=9,0, 2.5 Hz, 1H), to 5.57 (s, 1H), 2,82 (s, 2H), 2,28 (m, 1H), 1,95-of 1.20 (m, 10H), 1,29 (C, 6N).

Example 12(3)

(Z)-2-(6-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.40 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ of 11.26 (W, 1H), 7,63 (d, J=9.0 Hz, 1H), 7,26 (DD, J=9,0, 2.5 Hz, 1H), 7,17 (d, J=2.5 Hz, 1H), 5,58 (s, 1H), 2,81 (s, 2H), to 2.29 (m, 1H), 1,95-of 1.20 (m, 10H), 1,29 (C, 6N).

Example 12(4)

(Z)-2-(6-Fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.37 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,22 (W, 1H), of 7.70 (DD, J=9,0, 5.5 Hz, 1H), 6,97 (DDD, J=9,0, at 9.0, 2.5 Hz, 1H), 6.87 in (DD, J=9,0, 2.5 Hz, 1H), of 5.53 (s, 1H), 2,82 (s, 2H), 2,45 (m, 1H), 2.00 in of 1.40 (m, N), 1,29 (C, 6N).

Example 12(5)

(Z)-2-(6-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf is 0.42 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,17 (W, 1H), 7,63 (d, J=8.5 Hz, 1H), 7,25 (DD, J=8,5, 2.0 Hz, 1H), 7,17 (d, J=2.0 Hz, 1H), of 5.55 (s, 1H), 2,80 (s, 2H), 2,45 (m, 1H), 2.00 in of 1.40 (m, N), 1,29 (C, 6N).

Example 12(6)

(Z)-2-(8-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf is 0.42 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,77 (W, 1H), 7,30 (DD, J=7,5, 7.5 Hz, 1H), 6.87 in (d, J=7.5 Hz, 1H), 6,77 (d, J=7.5 Hz, 1H), of 6.20 (s, 1H), 3,92 (s, 3H), and 2.79 (s, 2H), and 2.26 (m, 1H), 1,95-1,10 (m, 10H), of 1.26 (s, 6N).

Example 12(7)

(Z)-2-(6-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.32 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,33 (W, 1H), 7,65 (d, J=8.5 Hz, 1H), 6,80 (DD, J=8,5, 2.5 Hz, 1H), to 6.67 (d, J=2.5 Hz, 1H), of 5.55 (s, 1H), 3,85 (s, 3H), 2,80 (s, 2H), and 2.27 (m, 1H), 1,95-1,10 (m, 10H), 1,29 (C, 6N).

Example 12(8)

(Z)-2-(8-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf and 0.46 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,67 (W, 1H), 7,29 (DD, J=7,5, 7.5 Hz, 1H), 6.87 in (d, J=7.5 Hz, 1H), 6,76 (d, J=7.5 Hz, 1H), 6,17 (s, 1H), 3,91 (s, 3H), 2,78 (s, 2H), 2,42 (m, 1H), 2.00 in of 1.40 (m, N), of 1.26 (s, 6N).

Example 12(9)

(Z)-2-(6-Methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.37 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,25 (W, 1H), 7,65 (d, J=8.5 Hz, 1H), 6,80 (DD, J=8,5, 3.0 Hz, 1H), to 6.67 (d, J=3.0 Hz, 1H), 5,52 (s, 1H), 3,85 (s, 3H), 2,80 (s, 2H), 2,43 (m, 1H), 2.00 in of 1.40 (m, N), 1,29 (C, 6N).

Example 12(10)

(Z)-2-(3,3,4,4-Tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.30 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,63 (W, 1H),7,74-to 7.68 (m, 2H), 7,49-7,25 (m, 4H), 7.03 is-to 6.95 (m, 2H), of 6.26 (s, 1H), 3,92 (s, 3H), 1,31 (W, N).

Example 12(11)

(Z)-2-(3,3,4,4-Tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.58 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,25 (W, 1H), 7,69 (DD, J=7,5, 1.0 Hz, 1H), 7,47-7,37 (m, 2H), 7,29-7,24 (m, 1H), 5,59 (s, 1H), 2,35-of 2.24 (m, 1H), 1,91-to 1.79 (m, 4H), 1,69-of 1.64 (m, 1H), 1,55-1,19 (m, 17H).

Example 12(12)

(Z)-2-(3,3,4,4-Tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.57 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,16 (W, 1H), 7,68 (DD, J=8.0 a, 1.0 Hz, 1H), 7,47-7,37 (m, 2H), 7,29-7,24 (m, 1H), 5.56mm (s, 1H), 2,50-to 2.41 (m, 1H), 1,96-1,90 (m, 2H), 1,83 was 1.43 (m, 10H), 1,26 (W, N).

Example 12(13)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(isoquinoline-1-yl)Ethan-1-he

TLC: Rf of 0.30 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ to 11.79 (W, 1H), 8,86 (d, J=8.0 Hz, 1H), 8,55 (d, J=5.5 Hz, 1H), 7,88-to 7.84 (m, 2H), 7,72-to 7.59 (m, 3H), 7,42 (dt, J=1,0, 7,0 Hz, 1H), 7,33-7,27 (m, 1H), 7,21 (d, J=7.5 Hz, 1H), is 6.54 (s, 1H), 2,94 (2N), of 1.42 (s, 6N).

Example 12(14)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(quinoline-4-yl)Ethan-1-he

TLC: Rf 0,11 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,84 (W, 1H), 8,96 (d, J=4.5 Hz, 1H), 8,42 (d, J=7.5 Hz, 1H), 8,14 (d, J=8.0 Hz, 1H), 7,75-of 7.69 (m, 2H), EUR 7.57 (t, J=8.0 Hz, 1H), 7,51 (d, J=4.5 Hz, 1H), 7,45 (t, J=7.5 Hz, 1H), 7,33-of 7.23 (m, 2N), of 6.02 (s, 1H), 2,97 (s, 2H), USD 1.43 (s, 6N).

Example 12(15)

(Z)-2-(6-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.44 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,63 (W, 1H), 7.68 per-the 7.65 (m, 2H), 7,37 (DDD, J=8,0, to 7.5, 2.0 Hz, 1H), 7,29-7,26 (m, 1H), 7,20 (d, J=2.0 Hz, 1H), 7.03 is-to 6.95 (m, 2H), 6,23 (s, 1H), 3,91 (s, 3H), of 2.86 (s, 2H), 1,36 (C, 6N).

Example 12(16)

(Z)-2-(6-Chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-chlorophenyl)ethane-1-he

TLC: Rf of 0.38 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,49 (W, 1H), 7,65 (d, J=8.5 Hz, 1H), 7,54-7,51 (m, 1H), 7,42-7,39 (m, 1H), 7,32-7,27 (m, 3H), 7,21 (d, J=2.0 Hz, 1H), to 5.93 (s, 1H), 2,89 (s, 2H), 1,38 (C, 6N).

Example 12(17)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(quinoline-8-yl)ethane-1-he

TLC: Rf to 0.17 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,80 (W, 1H), 9,05 (DD, J=4,0, 2.0 Hz, 1H), 8,19 (DD, J=8,0, 2.0 Hz, 1H), 7,98 (DD, J=7,5, 1.5 Hz, 1H), a 7.85 (DD, J=8,0, 1.5 Hz, 1H), 7,74 (d, J=7.5 Hz, 1H), 7,58 (DD, J=8,0, 7.5 Hz, 1H), 7,44-7,37 (m, 2H), 7,29-7,24 (m, 1H), 7,20 (d, J=7.5 Hz, 1H), 6.35mm (s, 1H), 2,92 (s, 2H), 1,40 (C, 6N).

Example 12(18)

(Z)-2-(6,8-Dichloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf value of 0.52 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,98 (SHS, 1H), 7,93-7,89 (m, 2H), 7,47-7,41 (m, 4H), 7,14 (m, 1H), 6,79 (s, 1H), and 2.83 (s, 2H), 1,33 (C, 6N).

Example 12(19)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-idoxifene is)ethane-1-he

TLC: Rf 0.31 in (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,70 (W, 1H), 7,81 (DD, J=7,5, 2.0 Hz, 1H), to 7.77 (d, J=7.5 Hz, 1H), 7,43-7,27 (m, 3H), 7,20 (d, J=7.5 Hz, 1H), 7,01 (dt, J=1,0, 7.5 Hz, 1H), 6,95 (DD, J=7,5, 1.0 Hz, 1H), 6,55 (s, 1H), 4,15 (kV, J=7,0 Hz, 2H), 2,90 (s, 2H), 1,49 (t, J=7.0 Hz, 3H), 1,36 (C, 6N).

Example 12(20)

Hydrochloride of 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-(adamantane-1-yl)propane-1-it

TLC: Rf of 0.40 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ a 7.92 (d, J=7.5 Hz, 1H), to 7.67 (DD, J=7,5, 7.5 Hz, 1H), 7,42 (DD, J=7,5, 7.5 Hz, 1H), 7,34 (d, J=7.5 Hz, 1H), 5,80 (kV, J=7,0 Hz, 1H), 3,03 (s, 2H), 2,02 (m, 3H), of 1.87 (m, 6N), 1,80-of 1.55 (m, 15 NM).

Example 12 (21)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-chloro-2-methoxyphenyl)Ethan-1-he

TLC: Rf of 0.40 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,70 (W, 1H), 7,73 (d, J=7.5 Hz, 1H), to 7.64 (d, J=8.0 Hz, 1H), 7,41 (t, J=7.5 Hz, 1H), 7,31 (t, J=7.5 Hz, 1H), 7,20 (d, J=7.5 Hz, 1H), 6,99 (DD, J=8,0, 2.0 Hz, 1H), 6,94 (d, J=2.0 Hz, 1H), 6,25 (s, 1H), 3,91 (s, 3H), 2,89 (s, 2H), 1,35 (C, 6N).

Example 12(22)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxy-4-methylthiophenyl)ethane-1-he

TLC: Rf of 0.20 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,70 (W, 1H), 7,74 (d, J=7.5 Hz, 1H), 7,69 (d, J=8.0 Hz, 1H), 7,40 (t, J=7.5 Hz, 1H), 7,30 (t, J=7.5 Hz, 1H), 7,19 (d, J=7.5 Hz, 1H), 6.87 in (DD, J=8,0, 2.0 Hz, 1H), 6,83 (d, J=2.0 Hz, 1H), 6,34 (s, 1H), 3,92 (s, 3H), 2,89 (s, 2H), 2,52 (s, 3H), of 1.35 (s, 6N).

Example 12(23)

(Z)-2-3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxy-4-methylphenyl)ethane-1-he

TLC: Rf of 0.15 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,73 (W, 1H), 7,79 (d, J=8.0 Hz, 1H), 7,72 (d, J=7.5 Hz, 1H), EUR 7.57 (DD, J=8,0, 1.5 Hz, 1H), 7,50 (d, J=1.5 Hz, 1H), 7,44 (t, J=7.5 Hz, 1H), 7,32 (t, J=7.5 Hz, 1H), 7,22 (d, J=7,5 Hz, 1H), 6,14 (s, 1H), 3,98 (s, 3H), is 3.08 (s, 3H), of 2.92 (s, 2H), 1,38 (C, 6N).

Example 12(24)

Hydrochloride of 2-(6-fluoro-3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-phenylpropane-1-it

TLC: Rf of 0.35 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ to 8.14 (d, J=8.0 Hz, 2H), 7,86 (DD, J=8,5, 5.0 Hz, 1H), 7,54 (m, 1H), 7,46 (m, 2H), 7,05 (DDD, J=8,5, an 8.5 and 2.5 Hz, 1H), of 6.96 (DD, J=8,5, 2.5 Hz, 1H), 6,34 (kV, J=6,5 Hz, 1H), 3.04 from (d, J=17,0 Hz, 1H), 2,85 (d, J=17,0 Hz, 1H), 1,79 (d, J=6.5 Hz, 3H), 1,71 (s, 3H), of 1.46 (s, 3H).

Example 12(25)

(Z)-2-(6,7-Dichloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf of 0.23 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ 11,72 (W, 1H), of 7.96-to 7.93 (m, 2H), 7,88 (s, 1H), of 7.48-the 7.43 (m, 3H), 7,33 (s, 1H), 6,24 (s, 1H), 2,85 (s, 2H), 1,36 (C, 6N).

Example 12(26)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-bromo-2-methoxyphenyl)Ethan-1-he

TCX: Rf of 0.29 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,70 (W, 1H), 7,72 (d, J=7.5 Hz, 1H), EUR 7.57 (d, J=8.0 Hz, 1H), 7,41 (t, J=7.5 Hz, 1H), 7,31 (t, J=7.5 Hz, 1H), 7,20 (d, J=7.5 Hz, 1H), 7,15 (DD, J=8,0, 2.0 Hz, 1H), 7,10 (d, J=2.0 Hz, 1H), 6,24 (s, 1H), 3,91 (s, 3H), 2,89 (s, 2H), 1,35 (C, 6N).

Example 12(27)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-bromo-2-harfe who yl)ethane-1-he

TLC: Rf of 0.40 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ to 11.56 (W, 1H), 7,71 (d, J=7.5 Hz, 1H), 7,58 (m, 1H), 7,46-7,41 (m, 3H), 7,31 (t, J=7.5 Hz, 1H), 7,21 (d, J=7.5 Hz, 1H), to 5.93 (s, 1H), 2.91 in (s, 2H), 1,37 (C, 6N).

Example 12(28)

(Z)-2-(6-Bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf is 0.42 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ 11,25 (W, 1H), 7,56 (d, J=8.5 Hz, 1H), 7,42 (DD, J=8,5, 2.0 Hz, 1H), 7,33 (d, J=2.0 Hz, 1H), 5,59 (s, 1H), 2,81 (s, 2H), to 2.29 (m, 1H), 1,89-to 1.79 (m, 4H), 1.69 in (m, 1H), 1,55-1,24 (m, 11N).

Example 12(29)

(Z)-2-(6-Bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf is 0.42 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ 11,16 (W, 1H), 7,56 (d, J=8.5 Hz, 1H), 7,42 (DD, J=8,5, 2.0 Hz, 1H), 7,33 (d, J=2.0 Hz, 1H), of 5.55 (s, 1H), 2,81 (s, 2H), 2,45 (m, 1H), 1,95-of 1.85 (m, 2H), 1,82-of 1.45 (m, 10H), 1,29 (C, 6N).

Example 12(30)

(Z)-2-(6-Bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0,41 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ 11,42 (W, 1H), 7,58 (d, J=8.5 Hz, 1H), 7,42 (DD, J=8,5, 2.0 Hz, 1H), 7,33 (d, J=2.0 Hz, 1H), 5,74 (s, 1H), 2,81 (s, 2H), 2.05 is (W, 3H), 1,90 (W, 6N), 1,74 (W, 6N), 1,29 (C, 6N).

Example 12(31)

(Z)-2-(6-Bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(pyridine-3-yl)ethane-1-he

TLC: Rf 0.25 in (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,82 (W 1H), 9,13 (DD, J=2.0 a, 1.0 Hz, 1H), 8,67 (DD, J=5.0 and 2.0 Hz, 1H), to 8.20 (DDD, J=8.0 a, 2,0, 2,0 Hz, 1H), 7,69 (d, J=8.5 Hz, 1H), 7,50 (DD, J=8,5, 2.0 Hz, 1H), 7,40-7,35 (m, 2H), 6,24 (s, 1H), 2,89 (s, 2H), 1,38 (C, 6N).

Example 13

(Z)-2-(6-Formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To a solution of the compound obtained in example 12 (356 mg)in ether (10 ml) is added dropwise n-utility (1,4 ml; 1.6 M solution in hexane) and after 10 minutes the mixture is heated to 0°C and stirred for 30 minutes. To the reaction mixture is added dropwise dimethylformamide (0,20 ml) at -78°and the mixture is stirred for 30 minutes at 0°C. To the reaction mixture is added saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The residue is purified column chromatography on silica gel (hexane: ethyl acetate=20:1→5:1)to give the compound of the present invention (165 mg)having the following physical data.

TLC: Rf of 0.34 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,75 (W, 1H), 10,07 (s, 1H), 8,01-7,94 (m, 3H), a 7.85 (d, J=8.0 Hz, 1H), 7,74 (s, 1H), of 7.48-7,42 (m, 3H), 6,38 (s, 1H), 2,99 (s, 2H), 1,38 (C, 6N).

Examples 13(1)-13(16)

By the same procedure as described in example 13 using the compound obtained in example 11(7), example 11(70), example 11(81), example 12(26), example 11(119), example 11(153), example 11(154), example 11(156), example 11(168), example 11(170), example 11(181), example 11(184), example 11(188), example 11(189), is the example 11(193) or example 11(194), instead of the compound obtained in example 12, to obtain compounds having the following physical data.

Example 13(1)

(Z)-2-(7-Formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf 0,24 (exac:ethyl acetate=3:1).

NMR (CDCl3): δ 11,82 (W, 1H), 10,08 (s, 1H), 8.34 per (d, J=1.5 Hz, 1H), 7,99-to 7.93 (m, 3H), 7,49-7,40 (m, 4H), 6.42 per (s, 1H), 2,99 (s, 2H), 1,38 (C, 6N).

Example 13(2)

(Z)-2-(7-Formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-1-yl)Ethan-1-he

TCX: Rf 0.31 in (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,76 (W, 1H), 10,00 (s, 1H), 8,48 (m, 1H), they were 8.22 (d, J=1.5 Hz, 1H), 7.95 is-a 7.85 (m, 3H), 7,72 (DD, J=7,0, 1.5 Hz, 1H), 7,55 was 7.45 (m, 3H), 7,42 (d, J=8.0 Hz, 1H), to 6.19 (s, 1H), 3.04 from (s, 2H), 1,44 (, 6N).

Example 13(3)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-formylphenyl)ethane-1-he

TCX: Rf 0.26 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,99 (W, 1H), 10,08 (s, 1H), 8,08 (d, J=8.5 Hz, 2H), 7,95 (d, J=8.5 Hz, 2H), to 7.84 (d, J=7.5 Hz, 1H), 7,46 (t, J=7.5 Hz, 1H), 7,37 (t, J=7.5 Hz, 1H), 7,24 (d, J=7.5 Hz, 1H), 6,34 (s, 1H), 2,93 (s, 2H), 1.39 in (C, 6N).

Example 13(4)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-formyl-2-methoxyphenyl)Ethan-1-he

TCX: Rf 0.26 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,76 (W, 1H), 10,02 (s, 1H), 7,79 (d, J=7.5 Hz, 1H), 7,73 (d, J=7.5 Hz, 1H), 7,51 (DD, J=7,5, 1.0 Hz, 1H), of 7.48 (d, J=1.0 Hz, 1H), 7,43 (t, J=7.5 Hz, 1H), 7,31 t, J=7.5 Hz, 1H), 7,21 (d, J=7.5 Hz, 1H), of 6.20 (s, 1H), with 3.89 (s, 3H), 2.91 in (s, 2H), 1,37 (C, 6N).

Example 13(5)

(Z)-2-(6-Chloro-7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf and 0.28 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,43 (W, 1H), 10,47 (s, 1H), of 8.25 (s, 1H), 7,30 (s, 1H), of 5.83 (s, 1H), 2,87 (s, 2H), 2.06 to (m, 3H), 1,90 (m, 6N), to 1.76 (m, 6N), of 1.30 (s, 6N).

Example 13(6)

(Z)-2-(6-Chloro-7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.36 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,19 (W, 1H), 10,46 (s, 1H), of 8.25 (s, 1H), 7,29 (s, 1H), 5,70 (s, 1H), 2,87 (s, 2H), 2,35 (m, 1H), 1,90-of 1.20 (m, 10H), of 1.30 (s, 6N).

Example 13(7)

(Z)-2-(6-Chloro-7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf of 0.38 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ to 11.11 (W, 1H), 10,45 (s, 1H), 8,24 (s, 1H), 7,29 (s, 1H), to 5.66 (s, 1H), 2,86 (s, 2H), 2,48 (m, 1H), 1,95-of 1.40 (m, N), 1.28 (in C, 6N).

Example 13(8)

(Z)-2-(7-Formyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf is 0.22 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ to 11.52 (W, 1H), 10,45 (s, 1H), to 8.20 (s, 1H), 6,78 (s, 1H), 5,80 (s, 1H), 3,99 (s, 3H), 2,87 (s, 2H), 2.05 is (W, 3H), 1.91 a (W, 6N), 1,75 (W, 6N), of 1.30 (s, 6N).

Example 13(9)

(Z)-2-(7-Formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.64 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,49 (SHS, 1H), 10,06 (s, 1H), they were 8.22 (d, J=1.5 Hz, 1H), of 7.90 (DD, J=7,8, 1.5 Hz, 1H), was 7.36 (d, J=7.8 Hz, 1H), by 5.87 (s, 1H), 2,93 (s, 2H), 2,11-2,04 (m, 3H), 1,94-1,90 (m, 6N), 1,78-of 1.73 (m, 6N), 1,31 (C, 6N).

Example 13(10)

(Z)-2-(7-Formyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.10 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,27 (W, 1H), 10,44 (s, 1H), 8,19 (s, 1H), 6,77 (s, 1H), 5,67 (s, 1H), 3,99 (s, 3H), 2,87 (s, 2H), 2,31 (m, 1H), 1,90-to 1.79 (m, 4H), to 1.70 (m, 1H), 1.56 to 1,20 (m, 11N).

Example 13(11)

(Z)-2-(7-Formyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf 0.21 in (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,20 (W, 1H), 10,44 (s, 1H), 8,19 (s, 1H), 6,77 (s, 1H), 5,64 (s, 1H), 3,99 (s, 3H), 2,87 (s, 2H), 2,47 (m, 1H), 1,94-of 1.45 (m, N), of 1.30 (s, 6N).

Example 13(12)

(Z)-2-(7-Formyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.20 (hexane:ethyl acetate=6:1).

NMR (CDCl3): δ 11,48 (W, 1H), 10,31 (s, 1H), 8,13 (s, 1H), to 7.09 (s, 1H), of 5.84 (s, 1H), 2,86 (s, 2H), 2,70 (s, 3H), 2,07 e 2.06 (W, 3H), 1.93 and-1,92 (W, 6N), 1,75 (W, 6N), of 1.30 (s, 6N).

Example 13(13)

(Z)-2-(7-Formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf to 0.19 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,27 (SHS, 1H), 10,04 (s, 1H), they were 8.22 (d, J=1.5 Hz, 1 is), of 7.90 (DD, J=7,5, 1.5 Hz, 1H), was 7.36 (d, J=7.5 Hz, 1H), 5,73 (s, 1H), 2,93 (s, 2H), 2,34 (TT, J=11,7, 3.3 Hz, 1H), 1,94-of 1.66 (m, 5H), 1,58-1,24 (m, 11N).

Example 13(14)

(Z)-2-(7-Formyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.27 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ of 11.26 (W, 1H), 10,29 (s, 1H), 8,13 (s, 1H), to 7.09 (s, 1H), 5,71 (s, 1H), 2,86 (s, 2H), 2,70 (s, 3H), 2,33 (m, 1H), 1,90-of 1.27 (m, N).

Example 13(15)

(Z)-2-(7-Formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf 0,41 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,19 (SHS, 1H), of 10.05 (s, 1H), 8,21 (d, J=1.5 Hz, 1H), 7,89 (DD, J=7,5, 1.5 Hz, 1H), was 7.36 (d, J=7.5 Hz, 1H), 5,70 (s, 1H), 2,93 (s, 2H), of 2.51 (TT, J=9,9, 3,9 Hz, 1H), 1,98 of 1.46 (m, N), 1,31 (s, 6N).

Example 13(16)

(Z)-2-(7-Formyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf 0.26 (hexane:tracecut=5:1).

NMR (CDCl3): δ 11,18 (W, 1H), 10,29 (s, 1H), 8,13 (s, 1H), was 7.08 (s, 1H), 5,67 (s, 1H), 2,86 (s, 2H), 2,70 (s, 3H), of 2.50 (m, 1H), 1,98-and 1.54 (m, N), of 1.30 (s, 6N).

Example 14

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-AMINOPHENYL)Ethan-1-he

To a suspension of the compound obtained in example 11(54) (312 mg)in acetic acid (10 ml) is added iron powder (1.35 g) at room temperature and the mixture is stirred for 40 minutes at 70°C. the Reaction mixture is try to cool off, add ice and 1 N. hydrochloric acid and the mixture is filtered through celite, the Filtrate is separated. The organic layer is extracted with 2 N. hydrochloric acid. The combined aqueous layer was alkalinized 5 N. aqueous sodium hydroxide solution and extracted with tert-butylmethylamine ether. The extract is washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated, obtaining the compound of the present invention (229 mg)having the following physical data.

TLC: Rf of 0.15 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,67 (W, 1H), 7,86-7,81 (m, 3H), 7,41 (t, J=7.5 Hz, 1H), 7,33 (t, J=7.5 Hz, 1H), 7,20 (d, J=7, 5 Hz, 1H), of 6.71 is 6.67 (m, 2H), 6,29 (s, 1H), was 4.02-3,84 (W, 2N), is 2.88 (s, 2H), 1,34 (C, 6N).

Examples 14(1)-14(15)

By the same procedure as described in example 14, using the compound obtained in example 11(52), example 11(53), example 11(100), examples 11(126)-11(130), example 11(150), example 11(157), example 11(195), example 11(172) or examples 11(175)-11(177)instead of the compound obtained in example 11(54), get the following compounds of the present invention.

Example 14(1)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-AMINOPHENYL)Ethan-1-he

TLC: Rf 0.14 (chloroform:methanol=10:1).

NMR (CDCl3): δ 8,43 (DD, J=8,0, 1.5 Hz, 1H), 7,62-7,56 (m, 2H), of 7.48-to 7.32 (m, 5H), 6.35mm (s, 1H), 2,82 (W, 2H), USD 1.43 (s, 6N).

Example 14(2)

(Z)-2-(3,3-Dimethyl-3,4-dig the draw(2H)-isoquinoline-1-ilidene)-1-(3-AMINOPHENYL)Ethan-1-he

TLC: Rf 0.26 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,80 (W, 1H), 7,82 (d, J=7.5 Hz, 1H), 7,43 (t, J=7.5 Hz, 1H), was 7.36-7,27 (m, 3H), 7.24 to 7,19 (m, 2H), 6,78 (DDD, J=8.0 a, 2,5, 1.0 Hz, 1H), 6,29 (s, 1H), 3,79 (W, 2H), 2,90 (s, 2H), 1,36 (C, 6N).

Example 14(3)

(Z)-2-(7-Amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0.36 and (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,81 (SHS, 1H), 7,97-a 7.92 (m, 2H), 7,46-7,41 (m, 3H), 7,14 (d, J=2.7 Hz, 1H), 7,00 (d, J=7.8 Hz, 1H), 6,77 (DD, J=7,8, 2.7 Hz, 1H), 6,24 (s, 1H), 3,74 (CL, 2H), 2,78 (s, 2H), 1,35 (C, 6N).

Example 14(4)

(Z)-2-(7-Amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.44 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 11,93 (W, 1H), 8,01 (d, J=8.5 Hz, 2H), 7,71 (d, J=8.5 Hz, 2H), 7,11 (d, J=2.5 Hz, 1H), 7,02 (d, J=8.0 Hz, 1H), 6,80 (DD, J=8,0, 2.5 Hz, 1H), 6,18 (s, 1H), of 3.77 (W, 2N), and 2.79 (s, 2H), 1,36 (s, 6N).

Example 14(5)

(Z)-2-(7-Amino-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.58 (ethyl acetate:hexane=1:2).

NMR (CDCl3): δ of 11.26 (W, 1H), 7,11 (s, 1H), 7,06 (s, 1H), 5,51 (s, 1H), 4,06 (W, 2H), 2,69 (s, 2H), and 2.27 (m, 1H), 1,95-of 1.20 (m, 10H), 1.27mm (C, 6N).

Example 14(6)

(Z)-2-(7-Amino-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf to 0.63 (ethyl acetate:hexane=1:2).

NMR (CDCl3): δ11,17 (W, 1H), 7,10 (s, 1H), 7,06 (s, 1H), vs. 5.47 (s, 1H), 4,06 (W, 2H), 2,69 (s, 2H), 2,44 (m, 1H), 2.00 in of 1.40 (m, N), 1.27mm (C, 6N).

Example 14(7)

(Z)-2-(7-Amino-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf of 0.40 (ethyl acetate:hexane=1:2).

NMR (CDCl3): δ 11,90 (W, 1H), 8,00 (d, J=8.5 Hz, 2H), 7,72 (d, J=8.5 Hz, 2H), 7,19 (s, 1H), 7,13 (s, 1H), 6,14 (s, 1H), 4,14 (W, 2H), 2,78 (s, 2H), 1,36 (C, 6N).

Example 14(8)

(Z)-2-(7-Amino-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0,68 (ethyl acetate:hexane=1:2).

NMR (CDCl3): δ 11,43 (W, 1H), 7,12 (s, 1H), 7,07 (s, 1H), 5,65 (s, 1H), 4,08 (W, 2H), 2,69 (s, 2H), 2.05 is (m, 3H), 1,90 (m, 6N), 1,74 (m, 6N), 1.27mm (C, 6N).

Example 14(9)

(Z)-2-(7-Amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.15 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,29 (W, 1H), 7,02 (d, J=2.5 Hz, 1H), 6,95 (d, J=8.0 Hz, 1H), 6.73 x (DD, J=8,0, 2.5 Hz, 1H), 5,54 (s, 1H), 3,69 (W, 2H), 2,71 (s, 2H), 2,28 (m, 1H), 1,95-of 1.20 (m, 10H), 1.27mm (C, 6N).

Example 14(10)

(Z)-2-(7-Amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.57 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,46 (SHS, 1H),? 7.04 baby mortality (d, J=2.4 Hz, 1H), 6,95 (d, J=8,4 Hz, 1H), 6.73 x (DD, J=8,4, 2.4 Hz, 1H), 5,69 (s, 1H), 3.72 points CL, 2H), 2,71 (s, 2H), 2.05 is (CL, 3H), 1.93 and-1,89 (m, 6N), 1,77-1,72 (m, 6N), 1.27mm (, 6N).

Example 14(11)

(Z)-2-(-Amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.57 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,20 (SHS, 1H), 7,02 (d, J=2.4 Hz, 1H), 6,95 (d, J=7.8 Hz, 1H), 6.73 x (DD, J=7,8, and 2.4 Hz, 1H), 5,51 (s, 1H), 3,69 (CL, 2H), 2,71 (s, 2H), 2,44 (m, 1H), 1,97-of 1.42 (m, N), 1.27mm (C, 6N).

Example 14(12)

(Z)-2-(7-Amino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0.21 in (ethyl acetate:hexane=1:4).

NMR (CDCl3): δ of 11.45 (W, 1H), 7,02 (s, 1H), 6,84 (s, 1H), 5,67 (s, 1H), 3,66 (W, 2H), 2,69 (s, 2H), 2,19 (s, 3H), 2.05 is (W, 3H), 1,92 is 1.91 (W, 6N), a 1.75-1,74 (W, 6N), 1.27mm (C, 6N).

Example 14(13)

(Z)-2-(7-Amino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf 0.31 in (hexane:ethyl acetate=3:2).

NMR (CDCl3): δ 11,91 (W, 1H), 8,01 (d, J=8.7 Hz, 2H), 7,72 (d, J=8.7 Hz, 2H), to 7.09 (s, 1H), 6,91 (s, 1H), 6,17 (s, 1H), 3,71 (W, 2H), 2,78 (s, 2H), 2,22 (s, 3H), 1,36 (C, 6N).

Example 14(14)

(Z)-2-(7-Amino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.37 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,28 (SHS, 1H), 7,01 (s, 1H), 6,84 (s, 1H), of 5.53 (s, 1H), 3,62 (CL, 2H), 2,69 (s, 2H), and 2.27 (TT, J=12,0, 3.3 Hz, 1H), 2,19 (s, 3H), 1,92-of 1.18 (m, N).

Example 14(15)

(Z)-2-(7-Amino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.40 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,19 (SHS, 1H), 7,00 (1H), at 6.84 (s, 1H), 5,49 (s, 1H), 3,62 (CL, 2H), 2,69 (s, 2H), 2,43 (TT, J=9,9, 3.6 Hz, 1H), 2,19 (s, 3H), 1,96-of 1.42 (m, N), 1.27mm (C, 6N).

Example 15

(Z)-2-(6-Carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To a solution of the compound obtained in example 12 (356 mg)in ether (10 ml) is added tert-utility (2.2 ml; 1.5 M solution in pentane) at -78°and after 5 minutes the mixture was bubbled gaseous carbon dioxide. The reaction mixture allow to warm to room temperature, add water and ethyl acetate and the mixture is separated. The organic layer is extracted with water. The combined aqueous layer was subjected to azeotropic distillation with ethanol. To the obtained solid substance add ethanol, filtered and the filtrate concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=1:1)to give the compound of the present invention (19 mg)having the following physical data.

TLC: Rf 0.25 in (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,76 (W, 1H), of 8.06 (DD, J=8,0, 1.5 Hz, 1H), 7,97-a 7.92 (m, 4H), 7,49-7,42 (m, 3H), 6,38 (s, 1H), 2,98 (s, 2H), 1.39 in (C, 6N).

Examples 15(1)-15(4)

By the same procedure as described in example 15, using the compound obtained in example 11(7), example 11(168), example 12(28), example 12(29), example 11(188), example 11(193), example 11(181), example 11(156), example 11(189), example 11(170), example 11(184), example 111(194), the example is 12(30) or example 12(31), instead of the compound obtained in example 12, to obtain the following compounds of the present invention.

Example 15(1)

(Z)-2-(7-Carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf of 0.13 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,84 (W, 1H), to 8.57 (d, J=2.0 Hz, 1H), 8,16 (DD, J=8,0, 2.0 Hz, 1H), 8,00-of 7.96 (m, 2H), of 7.48-7,44 (m, 3H), 7,35 (d, J=8.0 Hz, 1H), gold 6.43 (s, 1H), 2,99 (s, 2H), 1.39 in (C, 6N).

Example 15(2)

(Z)-2-(7-Carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.27 (chloroform:methanol=10:1).

NMR (CDCl3): δ to 11.52 (W, 1H), 8,45 (d, J=1.5 Hz, 1H), 8,12 (DD, J=8,0, 1.5 Hz, 1H), 7,31 (d, J=8.0 Hz, 1H), by 5.87 (s, 1H), 2,92 (s, 2H), 2,08 (W, 3H), 1.93 and (W, 6N), 1.77 in (W, 6N), 1,31 (C, 6N).

Example 15(3)

(Z)-2-(6-Carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.36 (chloroform:methanol=10:1).

NMR (CDCl3): δ 11,25 (W, 1H), 8,01 (DD, J=8,0, 1.5 Hz, 1H), 7,92 (d, J=1.5 Hz, 1H), 7,81 (d, J=8.0 Hz, 1H), 5,69 (s, 1H), 2.91 in (s, 2H), 2,33 (m, 1H), 1.91 a and 1.80 (m, 4H), 1,72 (m, 1H), 1,50-1,20 (m, 11N).

Example 15(4)

(Z)-2-(6-Carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf to 0.39 (chloroform:methanol=10:1).

NMR (CDCl3): δ 11,16 (W, 1H), 8,02 (DD, J=8,5, 1.5 Hz, 1H), 7,92 (d, J=1.5 Hz, 1H), 7,81 (d, J=8.5 Hz, 1H), to 5.66 (s, 1H), 2.91 in (s, 2H), 2,50 (m, 1H), 1,97-1,90 (m, 2H), 1,84-145 (m, 10H), 1,31 (C, 6N).

Example 15(5)

(Z)-2-(7-Carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene.) -1-cyclohexylethyl-1-he

TCX: Rf is 0.24 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,29 (SHS, 1H), 8,45 (d, J=1.8 Hz, 1H), 8,11 (DD, J=7,8, 1.8 Hz, 1H), 7,30 (d, J=7.8 Hz, 1H), 5,73 (s, 1H), 2,92 (s, 2H), 2,35 (m, 1H), 1,95-of 1.65 (m, 5H), 1,54-1,20 (m, 11N).

Example 15(6)

(Z)-2-(7-Carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf of 0.30 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,22 (SHS, 1H), 8,45 (d, J=1.8 Hz, 1H), 8,12 (DD, J=7,8, 1.8 Hz, 1H), 7,30 (d, J=7.8 Hz, 1H), 5,71 (s, 1H), 2,92 (s, 2H), 2,52 (TT, J=9,9, 3.6 Hz, 1H), 1,99-of 1.45 (m, N), is 1.31 (s, 6H).

Example 15(7)

(Z)-2-(7-Carboxy-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf 0,09 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,17 (W, 1H), the 10.40 (W, 1H), 8,54 (s, 1H), 6,85 (s, 1H), 5,67 (s, 1H), 4,13 (s, 3H), 2,89 (s, 2H), 2.49 USD (TT, J=10,0, 4.0 Hz, 1H), 1,94-to 1.87 (m, 2H), 1,83 is 1.48 (m, 10H), of 1.30 (s, 6N).

Example 15(8)

(Z)-2-(7-Carboxy-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.10 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,50 (W, 1H), the 10.40 (W, 1H), 8,55 (s, 1H), 6,85 (s, 1H), of 5.83 (s, 1H), 4,14 (s, 3H), 2,89 (s, 2H), 2.06 to (W, 3H), 1.91 a (W, 6N), 1,75 (W, 6N), 1,31 (C, 6N).

Example 15(9)

(Z)-2-(7-Carboxy-N,3,6-trimethyl-Z,4-dihydro-(2H)-isoch the nolin-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.16 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,29 (W, 1H), to 8.41 (s, 1H), 7,10 (s, 1H), 5,69 (s, 1H), 2,85 (s, 2H), 2,68 (s, 3H), of 2.34 (m, 1H), 1.91 a-1,20 (m, N).

Example 15(10)

(Z)-2-(7-Carboxy-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf 0,07 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,23 (W, 1N), the 10.40 (W, 1H), 8,54 (s, 1H), 6,85 (s, 1H), 5,71 (s, 1H), 4,13 (s, 3H), 2,89 (s, 2H), 2,32 (TT, J=11,5, 3.5 Hz, 1H), 1,89-to 1.79 (m, 4H), to 1.70 (m, 1H), 1.56 to to 1.21 (m, 11N).

Example 15(11)

(2)-2-(7-Carboxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0.25 in (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,51 (W, 1H), to 8.41 (s, 1H), 7,10 (s, 1H), of 5.83 (s, 1H), 2,85 (s, 2H), 2,69 (s, 3H), 2,07-2,05 (W, 3H), 1.93 and-1,92 (W, 6N), 1,76-1,75 (W, 6N), 1,31 (C, 6N).

Example 15(12)

(Z)-2-(7-Carboxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.13 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,22 (W, 1H), 8,42 (s, 1H), 7,10 (s, 1H), to 5.66 (s, 1H), 2,85 (s, 2H), 2,69 (s, 3H), of 2.50 (m, 1H), 1,98-of 1.64 (m, N), 1,31 (C, 6N).

Example 15(13)

(Z)-2-(6-Carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0,08 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ is 11.39 (W, 1H), 7,99 (W, 1H), 7,88 (s, 1H), 7,78 (W, 1H), of 5.82 (s, 1H), 2,86, 2H), 2.06 to (W, 3H), 1.91 a (W, 6N), 1,74 (W, 6N), 1.28 (in C, 6N).

Example 15(14)

(Z)-2-(6-Carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(pyridine-3-yl)ethane-1-he

TLC: Rf 0.31 in (methylene chloride:methanol=10:1).

NMR (CDCl3+ a few drops CD3OD): δ 9,17 (d, J=1.5 Hz, 1H), 8,67 (DD, J=4,5, 1.5 Hz, 1H), 8,27 (DDD, J=8.5 a, 1.5 a, 1.5 Hz, 1H), of 8.06 (DD, J=8,5, 2.0 Hz, 1H), 7,94-to $ 7.91 (m, 2H), 7,44 (DD, J=8,5, and 4.5 Hz, 1H), 6.35mm (s, 1H), 2,98 (s, 2H), of 1.39 (s, 6N).

Examples 16-16(6)

By the same procedure as described in example 5 using the compound obtained in example 12(10), example 11(57), example 11(2), example 11(123), example 11(200), example 11(64) or example 11(32), instead of the compound obtained in example 1(18), obtain the following compounds of the present invention.

Example 16

(Z)-2-(3,3,4,4-Tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-hydroxyphenyl)ethane-1-he

TLC: Rf of 0.60 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 13,65 (s, 1H), 11,29 (W, 1H), 7,81 (d, J=7.5 Hz, 1H), 7,76 (DD, J=8,0, 1.5 Hz, 1H), 7,54-7,49 (m, 1H), 7,44 (DD, J=8,0, 1.5 Hz, 1H), 7,38-7,30 (m, 2H), 6,94 (DD, J=7,0, 1.5 Hz, 1H), 6,83 (dt, J=1,5, 7.5 Hz, 1H), 6.30-in (s, 1H), 1,31 (W, N).

Example 16(1)

(Z)-2-(7-Hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-1-yl)Ethan-1-he

TLC: Rf of 0.44 (ethyl acetate:hexane=1:2).

NMR (CDCl3): δ 11,70 (W, 1H), 8,45 (m, 1H), of 7.90-7,80 (m, 2H), 7.62mm (DD, J=7,0, 1.0 Hz, 1H), 7,50-7,40 (m, 2H), 7,38 (DD, J=8.0 a, 70 Hz, 1H), 7,10 (d, J=2.5 Hz, 1H), 7,00 (d, J=8.5 Hz, 1H), 6,85 (DD, J=8,5, 2.5 Hz, 1H), 6,04 (W, 1H), 5,94 (W, 1H), and 2.79 (s, 2H), 1,34 (C, 6N).

Example 16(2)

(Z)-2-(7-Hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0.14 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,76 (W, 1H), to $ 7.91 (m, 2H), 7,50-7,35 (m, 3H), 7,26 (d, J=2.5 Hz, 1H), 7,05 (d, J=8.5 Hz, 1H), 6,93 (DD, J=8,5, 2.5 Hz, 1H), 6,24 (s, 1H), 5,95 (s, 1H), 2,78 (s, 2H), 1,30 (C, 6N).

Example 16(3)

(Z)-2-(5-Hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0.25 in (hexane:ethyl acetate=2:1).

NMR (DMSO-d6): δ 11.87 per (CL, 1H), 9,80 (s, 1H), 7,98-to 7.93 (m, 2H), 7,52 (d, J=8,4 Hz, 1H), of 7.48-7,40 (m, 3H), 7,18 (t, J=8,4 Hz, 1H), 7,01 (d, J=8,4 Hz, 1H), to 6.39 (s, 1H), 2,81 (s, 2H), 1.28 (in C, 6N).

Example 16(4)

(Z)-2-(6-Chloro-7-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0.28 in (ethyl acetate:hexane=5:1).

NMR (CDCl3): δ 11,38 (W, 1H), 7,39 (s, 1H), 7,14 (s, 1H), 5,70 (s, 1H), ceiling of 5.60 (W, 1H), 2,73 (s, 2H), 2,04 (m, 3H), 1,89 (m, 6N), at 1.73 (m, 6N), 1.28 (in C, 6N).

Example 16(5)

(Z)-2-(7-Hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.18 (ethyl acetate:hexane=1:4).

NMR (CDCl3): δ 11,42 (W, 1H), 7,21 (d, J=2.4 Hz, 1H),? 7.04 baby mortality (d, J=8,1 Hz, 1H), to 6.88 (DD, J=2,4, 8,1 Hz, 1H), 5,71 (s, 1H), 5,16 (W, 1H), 2,75 (s, 2H), 2.05 is (W, 3H), 1.91 a-1,90 (W, 6N), 1,73 (W, 6N), of 1.27 (s, 6 is).

Example 16(6)

(Z)-2-(7-Hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.13 (ethyl acetate:hexane=1:4).

NMR (CDCl3): δ 11,27 (W, 1H), 7,19 (d, J=2.4 Hz, 1H), 7,03 (d, J=8,1 Hz, 1H), 6.89 in (DD, J=2,4, 8,1 Hz, 1H), to 5.57 (s, 1H), 2,75 (s, 2H), 2,28 (m, 1H), 1,92-of 1.18 (m, N).

Examples 17-17(1)

By the same procedure as described in example 9 using the compound obtained in example 11(7), instead of the compound obtained in example 1(68), and bendovervideo acid, or instead of pyridine-3-Voronovo acid is obtained the compound of the present invention.

Example 17

(Z)-2-(7-Phenyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.44 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,88 (W, 1H), 8,01 (d, J=2.0 Hz, 1H), 7,97-7,94 (m, 2H), 7,66 to 7.62 (m, 3H), 7,52-7,40 (m, 6N), 7,30 (d, J=8.0 Hz, 1H), to 6.39 (s, 1H), 2.95 and (s, 2H), 1,40 (C, 6N).

Example 17(1)

(Z)-2-(7-(Pyridin-3-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.32 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11.87 per (W, 1H), 8,90 (d, J=1.5 Hz, 1H), 8,65 (DD, J=5.0 and 1.5 Hz, 1H), 8,00-to $ 7.91 (m, 4H), to 7.64 (DD, J=8,0, 1.5 Hz, 1H), 7,46-7,41 (m, 4H), 7,35 (d, J=7.5 Hz, 1H), 6,38 (s, 1H), 2,96 (s, 2H), 1,41 (, 6N).

Example 18

(Z)-2-(6-(Morpholine-4-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To Rast is switchyard connections obtained in example 12 (180 mg)in toluene (5 ml) is added morpholine (to 0.060 ml) and tert-butyl sodium (70,5 mg) and the mixture Tegaserod. To the mixture add dichlorobis(tri-o-tolylphosphino)palladium(II) (12 mg) and the mixture is stirred for 8 hours at 100°C. To the reaction mixture add dichlorobis(tri-o-tolylphosphino)palladium(II) (12 mg) and the mixture is stirred for 2 hours. The reaction mixture is allowed to cool and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=4:1)to give the compound of the present invention (65 mg)having the following physical data.

TLC: Rf of 0.30 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,81 (SHS, 1H), 7,98-of 7.90 (m, 2H), 7,73 (d, J=8.7 Hz, 1H), 7,45-7,39 (m, 3H), for 6.81 (DD, J=8,7, 2.7 Hz, 1H), 6,65 (d, J=2.7 Hz, 1H), 6,24 (s, 1H), 3,88 (t, J=4.8 Hz, 4H), 3,29 (t, J=4.8 Hz, 4H), and 2.83 (s, 2H), 1,36 (C, 6N).

Example 18(1)

(Z)-2-(7-(Morpholine-4-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

By the same procedure as described in example 18 using compound obtained in example 11(7), instead of the compound obtained in example 12, to obtain the compound of the present invention having the following physical data.

TCX: Rf of 0.44 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11.87 per (CL, 1H), 7,97-of 7.90 (m, 2H), of 7.48-7,41 (m, 3H), 7,32 (d, J=2.4 Hz, 1H), 7,12 (d, J=8,1 Hz, 1H), 7,00 (DD, J=8,1, 2.4 Hz, 1H), and 6.25 (s, 1H), 3,91 (t, J=4.8 Hz, 4H), 3,21 (t, J=4.8 Hz, 4H), 2,82 (who, 2H), 1,35 (C, 6N).

Example 19

(2)-2-(6-Chloro-7-propoxycarbonyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

To n-propanol (5 ml) is added the compound obtained in example 11(153) (198 mg), dichlorobis(triphenylphosphine)palladium(II) (35 mg) and triethylamine (0,14 ml) and in the atmosphere of carbon monoxide, the mixture is stirred over night at 100°C. To the reaction mixture add dichlorobis(triphenylphosphine)palladium(II) (315 mg) and triethylamine (0,84 ml) and the mixture is stirred over night at 100°C. the Reaction mixture was filtered through celite. The filtrate is added to water and the mixture extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:chloroform=3:2→2:3)to give the compound of the present invention (140 mg)having the following physical data.

TCX: Rf 0.31 in (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 11,22 (W, 1H), 8,16 (s, 1H), 7,28 (s, 1H), 5,63 (s, 1H), 4,35 (t, J=6.5 Hz, 2H), and 2.83 (s, 2H), 2,32 (m, 1H), 1,90-1,20 (m, N), 1,29 (C, 6N), of 1.07 (t, J=7.5 Hz, 3H).

Example 20

(Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methylsulfinylphenyl)ethane-1-he

To a solution of the compound obtained in example 11(83) (296 mg)in acetone (4 ml) we use the t suspension oxone (844 mg, the brand name) in a mixture of water/saturated aqueous sodium bicarbonate solution/acetone (2 ml/2 ml/2 ml) and stirred for 45 minutes at 0°C. To the reaction mixture, water is added and the mixture extracted with ethyl acetate. The extract is washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The remainder of the roughly purified column chromatography on silica gel (hexane:ethyl acetate=3:1→1:2). The product is then roughly purified column chromatography on silica gel (chloroform:methanol=100:0→100:1). The product is washed with a mixture of tert-butyl methyl ether/hexane, obtaining the compound of the present invention (20 mg)having the following physical data.

TLC: Rf 0,07 (hexane:ethyl acetate=1:2).

NMR (CDCl3): δ 11,91 (W, 1H), of 8.09 (d, J=8.5 Hz, 2H), to 7.84 (d, J=7.5 Hz, 1H), 7,71 (d, J=8.5 Hz, 2H), 7,46 (t, J=7.5 Hz, 1H), was 7.36 (t, J=7.5 Hz, 1H), 7.23 percent (d, J=7.5 Hz, 1H), of 6.31 (s, 1H), 2,92 (s, 2H), was 2.76 (s, 3H), 1,38 (C, 6N).

Example 21

(Z)-2-(6-Cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To a solution of the compound obtained in example 1(68) (312 mg), N-organic (3 ml) was added copper cyanide(I) (448 mg) at room temperature and the mixture is stirred for 19 hours at 180-190°C. the Reaction mixture allow to cool, add saturated aqueous sodium bicarbonate solution and extragere is by ethyl acetate. The extract is washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=20:1→15:1)to give the compound of the present invention (450 mg)having the following physical data.

TLC: Rf of 0.43 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,75 (W, 1H), 7.95 is-to $ 7.91 (m, 3H), of 7.64 (d, J=8.0 Hz, 1H), 7,53 (s, 1H), 7,49-7,41 (m, 3H), 6,33 (W, 1H), 2,94 (s, 2H), 1,38 (C, 6N).

Example 22

(Z)-2-(7-(1-Hydroxy-1-methylethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To a solution of the compound obtained in example 11(7) (186 mg)in ether (4 ml) is added dropwise n-utility (1,4 ml, 1.5 M solution in hexane) and the mixture is stirred for 90 minutes at 0°C. To the mixture is added dropwise acetone (0,23 ml) and the mixture is stirred for 45 minutes at 0°C. To the reaction mixture are added water and extracted with ethyl acetate. The extract is washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The remainder of the roughly purified column chromatography on silica gel (hexane:ethyl acetate=4:1→25:1) and then washed with ethyl acetate, obtaining the compound of the present invention (91 mg)having the following physical data.

TLC: Rf of 0.6 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,89 (W, 1H), 7,98-7,94 (m, 3H), 7,53 (DD, J=8,0, 2.0 Hz, 1H), 7,47-7,42 (m, 3H), 7,19 (d, J=8.0 Hz, 1H), 6.35mm (s, 1H), 2,88 (s, 2H), 1,80 (W, 1H), 1,64 (C, 6N), 1,36 (C, 6N).

Examples 22(1)-22(2)

By the same procedure as described in example 22, using the compound obtained in example 11(188) or example 11(168), get the following compounds having the following physical data.

Example 22(1)

(Z)-2-(7-(1-Hydroxy-1-methylethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf 0.26 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,36 (W, 1H), 7,86 (d, J=2.0 Hz, 1H), of 7.48 (DD, J=8,0, 2.0 Hz, 1H), 7,14 (d, J=8.0 Hz, 1H), to 5.66 (s, 1H), 2,82 (s, 2H), 2,32 (TT, J=11,5, 3.5 Hz, 1H), 1,90 to 1.76 (m, 5H), 1,71-1,20 (m, N).

Example 22(2)

(Z)-2-(7-(1-Hydroxy-1-methylethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf 0.31 in (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,59 (W, 1H), 7,87 (d, J=2.0 Hz, 1H), 7,47 (DD, J=8,0, 2.0 Hz, 1H), 7,14 (d, J=8.0 Hz, 1H), 5,80 (s, 1H), 2,81 (s, 2H), 2.06 to (W, 3H), 1,92 (W, 6N), 1,80 (s, 1H), 1,75 (W, 6N), and 1.63 (s, 6N), of 1.29 (s, 6N).

Example 23

(Z)-2-(6-Acetyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To a solution of the compound obtained in example 12 (356 mg)in ether (10 ml) is added dropwise n-utility (1.8 ml; 1.6 M solution in hexane), stirred for 30 minutes at 0°and then h is cut the mixture bubbled carbon dioxide. The reaction mixture is stirred for 20 minutes at 0°add dropwise methylmagnesium (3,00 ml, 0.9 M solution in tetrahydrofuran) and the mixture is stirred for 2 hours at 0°C. To the reaction mixture tetrahydrofuran, water and ethyl acetate and extracted with ethyl acetate. The combined organic layer is washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=10:1→3:1)to give the compound of the present invention (84 mg)having the following physical data.

TLC: Rf of 0.27 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,74 (W, 1H), 7,97-to 7.93 (m, 2H), to $ 7.91-7,88 (m, 2H), 7,80 (s, 1H), of 7.48-7,42 (m, 3H), 6,37 (s, 1H), 2,97 (s, 2H), 2,65 (s, 3H), of 1.37 (s, 6N).

Example 24

(Z)-2-(7-Gidroksimetil-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

The compound obtained in example 13(1) (209 mg), dissolved in formic acid (4 ml)solution was added hydroxylamine hydrochloride (62 mg) and the mixture is stirred for 1 hour at 100°C. the Reaction mixture allow to cool, add to ice 2 N. aqueous sodium hydroxide solution and then extracted with ethyl acetate. The extract is washed with water and saturated aqueous solution of the m sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=3:1)to give the compound of the present invention (84 mg)having the following physical data.

TLC: Rf 0,49 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,83 (SHS, 1H), to 8.20 (s, 1H), 8,03 (d, J=1.5 Hz, 1H), 7,98-to 7.93 (m, 2H), to 7.64 (DD, J=8,1, 1.5 Hz, 1H), of 7.48-the 7.43 (m, 3H), 7,41 (SHS, 1H), 7,25 (d, J=8,1 Hz, 1H), 6.35mm (s, 1H), 2,92 (s, 2H), 1,37 (, 6N).

Examples 24(1)-24(10)

By the same procedure as described in example 24, using the compound obtained in example 13, example 13(8), example 13(10), example 13(9), example 13(11), example 13(13), example 13(12), example 13(15), example 13(14) or example 13(16)instead of the compound obtained in example 13(1), obtain the following compounds of the present invention.

Example 24(1)

(Z)-2-(6-Gidroksimetil-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.51 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,78 (SHS, 1H), 8,15 (s, 1H), 7,97-a 7.92 (m, 2H), to 7.84 (d, J=8,1 Hz, 1H), 7,53 (DD, J=8,1, 1.5 Hz, 1H), 7,50-7,40 (m, 4H), 6,34 (s, 1H), 2,92 (s, 2H), 1,37 (C, 6N).

Example 24(2)

(Z)-2-(7-Gidroksimetil-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.30 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,54 (W, 1H), 8,49 (s, 1H), 8,08 (s, 1H), 7,55 (W, 1H), of 6.68 (s, 1H), of 5.75 (s, 1 is), 3,91 (s, 3H), 2,82 (s, 2H), 2.05 is (W, 3H), 1.91 a (W, 6N), 1,74 (W, 6N), of 1.30 (s, 6N).

Example 24(3)

(Z)-2-(7-Gidroksimetil-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.45 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,31 (W, 1H), 8,49 (s, 1H), 8,08 (s, 1H), 7,38 (W, 1H), of 6.68 (s, 1H), 5,61 (s, 1H), 3,91 (s, 3H), and 2.83 (s, 2H), to 2.29 (m, 1H), 1,88-to 1.79 (m, 4H), 1.70 to 1,20 (m, N).

Example 24(4)

(Z)-2-(7-Gidroksimetil-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.16 (hexane:ethyl acetate=4:1).

Example 24(5)

(Z)-2-(7-Gidroksimetil-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.57 (hexane:ethyl acetate=1:1).

Example 24(6)

(Z)-2-(7-Gidroksimetil-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.34 (hexane:ethyl acetate=2:1).

Example 24(7)

(Z)-2-(7-Gidroksimetil-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.56 (hexane:ethyl acetate=3:1).

Example 24(8)

(Z)-2-(7-Gidroksimetil-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf 0.31 in (hexane:ethyl acetate=2:1).

Example 24(9)

(Z)-2-(7-Guide is oksiminomyetil-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.47 (hexane:ethyl acetate=3:1).

Example 24(10)

(Z)-2-(7-Gidroksimetil-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf to 0.39 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,22 (W, 1H), to 8.41 (s, 1H), 8,01 (s, 1H), 7,00 (s, 1H), 5,62 (s, 1H), 2,80 (s, 2H), 2,50 is 2.44 (m, 4H), 1,96-of 1.42 (m, N), 1.28 (in C, 6N).

Example 25

(Z)-2-(6-Aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To the compound obtained in example 24(1) (360 mg), add ethanol (16 ml) and 50% aqueous solution of acetic acid (4 ml), add 10% palladium on coal (30 mg) and in hydrogen atmosphere, the mixture was vigorously stirred for 7 hours. The reaction mixture was filtered through celite. The filtrate is concentrated and subjected to azeotropic distillation with ethanol. The residue is purified column chromatography on silica gel (chloroform:methanol=19:1→4:1)to give the compound of the present invention (240 mg)having the following physical data.

TLC: Rf is 0.22 (chloroform:methanol=4:1).

NMR (CDCl3): δ 11,82 (SHS, 1H), 7,97-to $ 7.91 (m, 2H), 7,79 (d, J=7.8 Hz, 1H), 7,46-7,40 (m, 3H), 7,28 (sm, J=7.8 Hz, 1H), 7,18 (SHS, 1H), 6,32 (s, 1H), 3,93 (s, 2H), 2,89 (s, 2H), 1,36 (C, 6N).

Examples 25(1)-25(10)

By the same procedure as described in example 25, using the compound obtained in example 24 examples 24(2)-24(5), example 24(7, example 24(6) or examples 24(8)-24(10)instead of the compound obtained in example 24(1), obtain the following compounds of the present invention.

Example 25(1)

(Z)-2-(7-Aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.15 (hexane:ethyl acetate:Isopropylamine=10:2:1).

NMR (CDCl3): δ up 11,86 (W, 1H), 7,98-7,94 (m, 2H), to 7.77 (s, 1H), 7,46-7,38 (m, 4H), 7,19 (d, J=7.5 Hz, 1H), 6.35mm (s, 1H), 3,95 (s, 2H), 2,89 (s, 2H), 1,36 (C, 6N).

Example 25(2)

(Z)-2-(7-Aminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.16 (chloroform:methanol=10:1).

NMR (CDCl3): δ to 11.52 (W, 1H), 7,56 (s, 1H), 6,63 (s, 1H), 5,71 (s, 1H), 3,90 (s, 3H), 3,85 (s, 2H), 2,80 (s, 2H), 2.06 to (W, 3H), 1,92 (W, 6N), 1,75 (W, 6N), 1,29 (C, 6N).

Example 25(3)

(Z)-2-(7-Aminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.10 (chloroform:methanol=10:1).

NMR (CDCl3): δ 11,31 (W, 1H), EUR 7.57 (s, 1H), 6,62 (s, 1H), 5,58 (s, 1H), with 3.89 (s, 3H), of 3.84 (s, 2H), 2,81 (s, 2H), 2,29 (TT, J=11,5, 3.5 Hz, 1H), 1,90-to 1.79 (m, 4H), 1.70 to to 1.16 (m, N).

Example 25(4)

(Z)-2-(7-Aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.27 (chloroform:methanol=9:1).

NMR (CDCl3): δ 11,53 (SHS, 1H), to 7.64 (s, 1H), 7,35 (sm, J=7.8 Hz, 1H), 7,14 (d, J=7.8 Hz, 1H), 5,79 (s, 1H), 3,2 (s, 2H), 2,82 (s, 2H), 2,09-2,02 (m, 3H), 1,94-1,90 (m, 6N), 1,77-1,72 (m, 6N), 1,29 (C, 6N).

Example 25(5)

(Z)-2-(7-Aminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf of 0.25 (chloroform:methanol=10:1).

NMR (CDCl3): δ 11,23 (W, 1H), EUR 7.57 (s, 1H), 6,62 (s, 1H), of 5.55 (s, 1H), with 3.89 (s, 3H), of 3.84 (s, 2H), 2,80 (s, 2H), 2,45 (TT, J=10,0, 4.0 Hz, 1H), 1,95-of 1.88 (m, 2H), 1,83 of 1.46 (m, 10H), 1,29 (C, 6N).

Example 25(6)

(Z)-2-(7-Aminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0.28 in (hexane:ethyl acetate:Isopropylamine=10:1:0,5).

NMR (CDCl3): δ to 11.52 (W, 1H), 7,63 (s, 1H), of 6.96 (s, 1H), 5,78 (s, 1H), 3,90 (s, 2H), 2,78 (s, 2H), is 2.37 (s, 3H), 2.06 to (W, 3H), 1.93 and-1,92 (W, 6N), 1,76-1,75 (W, 6N), 1.28 (in C, 6N).

Example 25(7)

(Z)-2-(7-Aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf of 0.23 (chloroform:methanol=9:1).

NMR (CDCl3): δ 11,32 (SHS, 1H), 7,66 (SHS, 1H), 7,34 (DD, J=7,8, 1.8 Hz, 1H), 7,14 (d, J=7.8 Hz, 1H), 5,65 (s, 1H), 3,92 (s, 2H), 2,82 (s, 2H), 2,31 (TT, J=12,0, 3.3 Hz, 1H), 1.93 and-of 1.18 (m, N).

Example 25(8)

(Z)-2-(7-Aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0.28 in (chloroform:methanol=9:1).

NMR (CDCl3): δ 11,24 (SHS, 1H), 7,66 (d, J=1.8 Hz, 1H), 7,34 (DD, J=7,8, 1.8 Hz, 1H), 7,14 (d, J=7.8 Hz, 1H), 5,62 (s, 1H), 3,92 (s, 2H), 2,82 (s, 2H), 2,48 (TT, J=9, 9mm, 3.3 Hz, 1H), 197-1,43 (m, N), 1.28 (in C, 6N).

Example 25(9)

(Z)-2-(7-Aminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf to 0.17 (hexane:ethyl acetate:Isopropylamine=10:1:0,5).

NMR (CDCl3): δ 11,31 (W, 1H), 7,65 (s, 1H), of 6.96 (s, 1H), 5,65 (s, 1H), with 3.89 (s, 2H), 2,78 (s, 2H), a 2.36 (s, 3H), 2,30 (m, 1H), to 1.86 (m, 4H), by 1.68 (m, 1H), 1,50 of 1.28 (m, 11N).

Example 25(10)

(Z)-2-(7-Aminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0,49 (hexane:ethyl acetate:Isopropylamine=10:1:1).

NMR (CDCl3): δ 11,23 (W, 1H), to 7.64 (s, 1H), of 6.96 (s, 1H), 5,61 (s, 1H), with 3.89 (s, 2H), 2,78 (s, 2H), 2,46 (m, 1H), a 2.36 (s, 3H), 1,96 of 1.46 (m, N), 1.28 (in C, 6N).

Example 26

(Z)-2-(7-Cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

The compound obtained in example 24(4) (214 mg)in a mixture with methylene chloride (6 ml) cooled to -78°add anhydrous triftormetilfullerenov acid (0,11 ml) and triethylamine (0,11 ml) and the mixture is stirred for 3 hours at room temperature. To the reaction mixture is added saturated aqueous solution of sodium bicarbonate and the mixture extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The remainder of the roughly purified column chromatography on silica compound is barely (hexane:ethyl acetate=4:1). The product is dissolved in a mixture of ethanol (6 ml) and tetrahydrofuran (3 ml), add borohydride sodium (75 mg) and the mixture is stirred over night. To the reaction mixture, water is added and the mixture extracted with methylene chloride. The extract is dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=4:1)to give the compound of the present invention (52 mg)having the following physical data.

TLC: Rf of 0.23 (hexane:ethyl acetate=4:1).

NMR (CDCl3): δ 11,36 (SHS, 1H), 8,00 (s, 1H), 7,65 (DD, J=7,8, 1.5 Hz, 1H), 7,30 (d, J=7.8 Hz, 1H), USD 5.76 (s, 1H), 2,90 (s, 2H), 2,12-2,04 (m, 3H), 1.93 and-a 1.88 (m, 6N), 1,78-of 1.73 (m, 6N), of 1.30 (s, 6N).

Examples 26(1)-26(2)

By the same procedure as described in example 26, using the compound obtained in example 24(6) or example 24(8), instead of the compound obtained in example 24(4), obtain the following compounds.

Example 26(1)

(Z)-2-(7-Cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.36 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,21 (SHS, 1H), to 7.99 (d, J=1.5 Hz, 1H), 7,65 (DD, J=7,5, 1.5 Hz, 1H), 7,31 (d, J=7.5 Hz, 1H), 5,62 (s, 1H), 2,90 (s, 2H), 2,33 (TT, J=11,4, 3.6 Hz, 1H), 1,94-of 1.66 (m, 5H), 1,52-of 1.18 (m, 11N).

Example 26(2)

(Z)-2-(7-Cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf is 0.42 (hexane:ethyl acetate=2:1).

NMR (CDCl 3): δ 11,12 (SHS, 1H), 7,98 (d, J=1.8 Hz, 1H), 7,65 (DD, J=8,1, 1.8 Hz, 1H), 7,30 (d, J=8,1 Hz, 1H), 5,58 (s, 1H), 2,90 (s, 2H), 2,50 (TT, J=9,9, 3,9 Hz, 1H), 1,97 was 1.43 (m, N), of 1.30 (s, 6N).

Example 27

(Z)-2-(7-(Morpholinyl-4-yl)methyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-1-yl)Ethan-1-he

To tetrahydrofuran (5 ml) is added the compound obtained in example 13(2) (206 mg), added dropwise morpholine (0,065 ml) at room temperature and the mixture is stirred for 2 hours at room temperature. To the reaction mixture add triacetoxyborohydride sodium (167 mg) and the mixture is stirred for 3 hours. To the reaction mixture add triacetoxyborohydride sodium (30 mg) and the mixture is stirred for 1 hour. The reaction mixture was added to cold saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The extract is washed successively with water and saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=1:1→2:3)to give the compound of the present invention (205 mg)having the following physical data.

TLC: Rf to 0.17 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 11,80 (W, 1H), of 8.47 (m, 1H), of 7.90-a 7.85 (m, 2H), of 7.70 (DD, J=7,0, 1.0 Hz, 1H), to 7.64 (s, 1H), 7,55 was 7.45 (m, 3H), 7,40 (DD, J=8,0, 1.5 Hz, 1H), 7,17 (d, J=8.0 Hz, 1H), between 6.08 (s, 1H), 3,68 (t, J=7.5 Hz,, 4H), 3,47, 2H), 2,92 (s, 2H), 2,41 (t, J=7.5 Hz, 4H), of 1.41 (s, 6N).

Examples 27(1)-27(27)

By the same procedure as described in example 27, using the compound obtained in example 13(1), example 13, example 13(8), example 13(9), example 13(11), example 11(119), example 13(12), example 13(5), example 13(13), example 13(7), example 13(14), example 13(15), example 13(14), example 13(6) or example 13(16)instead of the compound obtained in example 13(2), and morpholine, or a corresponding amine derivative have the following connections.

Example 27(1)

(Z)-2-(7-(Morpholine-4-yl)methyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.32 (hexane:ethyl acetate=1:4).

NMR (CDCl3): δ 11.87 per (CL, 1H), 7,99-to 7.93 (m, 2H), 7,75 (SHS, 1H), of 7.48-7,39 (m, 4H), 7,17 (d, J=7.8 Hz, 1H), 6,33 (s, 1H), 3,74 (t, J=4.8 Hz, 4H), 3,55 (s, 2H), 2,88 (s, 2H), 2,48 (t, J=4.8 Hz, 4H), of 1.36 (s, 6N).

Example 27(2)

(Z)-2-(7-(piperidine-1-yl)methyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf is 0.49 (chloroform:methanol=9:1).

NMR (CDCl3): δ 11.87 per (CL, 1H), 7,99-to 7.93 (m, 2H), 7,74 (SHS, 1H), of 7.48-7,39 (m, 4H), 7,16 (d, J=7.8 Hz, 1H), 6,34 (s, 1H), 3,52 (s, 2H), 2,88 (s, 2H), 2,41 (CL, 4H), to 1.60 (quintet, J=5.4 Hz, 4H), of 1.46 (m, 2H), 1,36 (, 6N).

Example 27(3)

(Z)-2-(7-(N-Methyl-N-(2-dimethylaminoethyl)aminomethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf 0,13 (chloroform:methanol=9:1).

I is R (CDCl 3): δ 11.87 per (CL, 1H), 7,99-to 7.93 (m, 2H), 7,76 (SHS, 1H), 7,47-7,38 (m, 4H), 7,16 (d, J=7.8 Hz, 1H), 6,34 (s, 1H), only 3.57 (s, 2H), 2,88 (s, 2H), 2,55 is 2.44 (m, 4H), of 2.28 (s, 3H), of 2.23 (s, 6N), 1,36 (C, 6N).

Example 27(4)

(Z)-2-(7-(N-(2-Hydroxyethyl)-N-methylaminomethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf of 0.40 (chloroform:methanol=9:1).

NMR (CDCl3): δ up 11,86 (SHS, 1H), 7,99-to 7.93 (m, 2H), 7,71 (SHS, 1H), 7,47-7,38 (m, 4H), 7,18 (d, J=7.8 Hz, 1H), 6,32 (s, 1H), to 3.67 (t, J=5.4 Hz, 2H), 3,63 (s, 2H), 2,89 (s, 2H), 2,64 (t, J=5.4 Hz, 2H), 2,42 (m, 1H), of 2.28 (s, 3H), 1,36 (C, 6N).

Example 27(5)

(Z)-2-(7-(N-Cyclohexylamino)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf of 0.36 (chloroform:methanol=9:1).

NMR (CDCl3): δ 11,85 (SHS, 1H), 7,99-to 7.93 (m, 2H), 7,76 (SHS, 1H), 7,47-7,38 (m, 4H), 7,17 (d, J=7.8 Hz, 1H), 6,34 (s, 1H), a 3.87 (s, 2H), 2,88 (s, 2H), 2,53 (m, 1H), 2,01 is 1.91 (m, 2H), 1,82-1,71 (m, 2H), 1,62 (m, 1H), 1,38-1,08 (m, 6N), 1,36 (C, 6N).

Example 27(6)

(Z)-2-(6-(Morpholine-4-yl)methyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf 0.28 in (hexane:ethyl acetate=1:4).

NMR (CDCl3): δ 11,82 (SHS, 1H), 7,97-a 7.92 (m, 2H), 7,78 (d, J=8,4 Hz, 1H), 7,47-7,40 (m, 3H), 7,30 (sm, J=8,4 Hz, 1H), 7,19 (SHS, 1H), 6,32 (s, 1H), 3,74 (t, J=4.8 Hz, 4H), 3,53 (s, 2H), 2,89 (s, 2H), 2,48 (t, J=4,8 Hz, 4H), 1,36 (C, 6N).

Example 27(7)

(Z)-2-(6-Dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf 0.31 in (chloroform:methanol=9:1).

NMR (CDCl3): δ 11,82 (SHS, 1H), 7,98-a 7.92 (m, 2H), 7,78 (d, J=8,4 Hz, 1H), 7,47-7,40 (m, 3H), 7,27 (m, 1H), 7,19 (SHS, 1H), 6,32 (s, 1H), 3.46 in (s, 2H), 2,89 (s, 2H), 2,28 (C, 6N), 1,36 (C, 6N).

Example 27(8)

(Z)-2-(6-Methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf of 0.23 (chloroform:methanol=4:1).

NMR (CDCl3): δ 11,82 (SHS, 1H), 7,98-to $ 7.91 (m, 2H), 7,79 (d, J=8,4 Hz, 1H), 7,47-7,40 (m, 3H), 7,28 (m, 1H), 7,20 (SHS, 1H), 6,32 (s, 1H), 3,80 (s, 2H), 2,89 (s, 2H), 2,50 (s, 3H), 1,36 (C, 6N).

Example 27(9)

(Z)-2-(7-Dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf of 0.53 (hexane:ethyl acetate:Isopropylamine=10:2:1).

NMR (CDCl3): δ 11,88 (W, 1H), 7,98-to 7.95 (m, 2H), 7,74 (d, J=1.5 Hz, 1H), 7,46-7,42 (m, 3H), 7,39 (DD, J=8,0, 1.5 Hz, 1H), 7,17 (d, J=8.0 Hz, 1H), 6,34 (s, 1H), 3,47 (s, 2H), 2,89 (s, 2H), 2,28 (C, 6N), 1,36 (, 6N).

Example 27(10)

(Z)-2-(7-Dimethylaminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf is 0.22 (chloroform:methanol=10:1).

NMR (CDCl3): δ 11,58 (W, 1H), 7,58 (s, 1H), 6,63 (s, 1H), 5,71 (s, 1H), 3,88 (s, 3H), 3.46 in (s, 2H), 2,80 (s, 2H), 2,30 (C, 6N), e 2.06 (W, 3H), 1,92 (W, 6N), 1,74 (W, 6N), 1,29 (C, 6N).

Example 27(11)

(Z)-2-(6-Methoxy-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.35 (hexa is:ethyl acetate:Isopropylamine=10:1:1).

NMR (CDCl3): δ 11,53 (W, 1H), 7,56 (s, 1H), 6,63 (s, 1H), 5,71 (s, 1H), 3,88 (s, 3H), 3,76 (s, 2H), 2,80 (s, 2H), 2,48 (s, 3H), 2.06 to (W, 3H), 1,92 (W, 6N), 1,75 (W, 6N), 1,29 (C, 6N).

Example 27(12)

(Z)-2-(7-Methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf and 0.28 (chloroform:methanol=9:1).

NMR (CDCl3): δ 11,54 (SHS, 1H), to 7.64 (d, J=1.5 Hz, 1H), was 7.36 (DD, J=7,5, 1.5 Hz, 1H), 7,13 (d, J=7.5 Hz, 1H), 5,79 (s, 1H), 3,79 (s, 2H), 2,82 (s, 2H), 2,50 (s, 3H), 2,09-2,03 (m, 3H), 1,94-1,90 (m, 6N), 1,77-1,72 (m, 6N), 1.28 (in C, 6N).

Example 27(13)

(Z)-2-(6-Methoxy-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf is 0.24 (chloroform:methanol=10:1).

NMR (CDCl3): δ 11,24 (W, 1H), EUR 7.57 (s, 1H), 6,62 (s, 1H), 5,54 (s, 1H), 3,88 (s, 3H), of 3.75 (s, 2H), 2,80 (s, 2H), 2,49-to 2.40 (m, 4H), 1,95-to 1.87 (m, 2H), 1,82 of 1.46 (m, 10H), 1,29 (C, 6N).

Example 27(14)

(Z)-2-(6-Chloro-7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.16 (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ to 11.52 (W, 1H), 7,73 (s, 1H), 7,18 (s, 1H), USD 5.76 (s, 1H), only 3.57 (s, 2H), 2,78 (s, 2H), 2,34 (C, 6N), was 2.05 (m, 3H), 1.91 a (m, 6N), 1,74 (m, 6N), 1.28 (in C, 6N).

Example 27(15)

(Z)-2-(7-Methylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.18 (chloroform:methanol=50:1).

NMR (CDCl3): δ 11,53 (W, 1H), 759 (s, 1H), of 6.96 (s, 1H), 5,77 (s, 1H, in), 3.75 (s, 2H), 2,77 (s, 2H), by 2.55 (s, 3H), of 2.38 (s, 3H), 2.06 to (W, 3H), 1.93 and-1,92 (W, 6N), 1,76-1,75 (W, 6N), 1.28 (in C, 6N).

Example 27(16)

(Z)-2-(7-Dimethylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf 0.21 in (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ to 11.56 (W, 1H), 7,53 (s, 1H), of 6.96 (s, 1H), of 5.75 (s, 1H), 3,41 (s, 2H), 2,77 (s, 2H), 2,39 (s, 3H), and 2.27 (s, 6N), e 2.06 (W, 3H), 1.93 and-1,92 (W, 6N), 1,76-1,75 (W, 6N), 1.28 (in C, 6N).

Example 27(17)

(Z)-2-(6-Chloro-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.35 (water:methanol:chloroform=1:10:100).

NMR (CDCl3): δ of 11.45 (W, 1H), 7,79 (s, 1H), 7,20 (s, 1H), of 5.81 (s, 1H), 3,94 (s, 2H), and 2.79 (s, 2H), 2,53 (s, 3H), of 2.06 (m, 3H), 1.91 a (m, 6N), 1,74 (m, 6N), 1.28 (in C, 6N).

Example 27(18)

(Z)-2-(7-Methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.21 (chloroform:methanol=9:1).

NMR (CDCl3): δ 11,31 (SHS, 1H), to 7.67 (SHS, 1H), was 7.36 (DD, J=7,5, 1.5 Hz, 1H), 7,13 (d, J=7.5 Hz, 1H), to 5.66 (s, 1H), 3,79 (s, 2H), 2,82 (s, 2H), 2.49 USD (s, 3H), 2,31 (TT, J=11,4, 3.6 Hz, 1H), 1,94-of 1.64 (m, 5H), 1,54-1,18 (m, 11N).

Example 27(19)

(Z)-2-(6-Chloro-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf of 0.47 (water:methanol:chloroform=1:10:100).

NMR (CDCl3): δ 11,19 (W, 1H), 7,71 (s, 1H), 7,19 (s, 1H), 5,59 (s, 1H), ,87 (s, 2H), and 2.79 (s, 2H), 2,52 (s, 3H), 2,47 (m, 1H), 1,95-of 1.40 (m, N), 1.28 (in C, 6N).

Example 27(20)

(Z)-2-(6-Chloro-7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf is 0.24 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,24 (W, 1H), 7,73 (s, 1H), 7,18 (s, 1H), 5,58 (s, 1H), 3,55 (s, 2H), 2,78 (s, 2H), 2,48 (m, 1H), 2,33 (C, 6N), 1,95-of 1.40 (m, N), 1.28 (in C, 6N).

Example 27(21)

(Z)-2-(7-Methylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.20 (chloroform:methanol=20:1).

NMR (CDCl3): δ 11,31 (W, 1H), to 7.61 (s, 1H), of 6.96 (s, 1H), 5,63 (s, 1H, in), 3.75 (s, 2H), 2,77 (s, 2H), 2,54 (s, 3H), is 2.37 (s, 3H), 2,34-of 2.26 (m, 1H), 1,90-to 1.79 (m, 4H), 1,71 (m, 1H), 1,55 of 1.28 (m, 11N).

Example 27(22)

(Z)-2-(7-Methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf and 0.28 (chloroform:methanol=9:1).

NMR (CDCl3): δ 11,24 (SHS, 1H), 7,65 (d, J=1.8 Hz, 1H), 7,34 (DD, J=7,8, 1.8 Hz, 1H), 7,13 (d, J=7.8 Hz, 1H), 5,62 (s, 1H), 3,78 (s, 2H), 2,82 (s, 2H), 2.49 USD (s, 3H), 2,47 (m, 1H), 1,97 was 1.43 (m, N), of 1.28 (s, 6N).

Example 27(23)

(Z)-2-(7-Dimethylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf is 0.22 (hexane:ethyl acetate=1:2).

NMR (CDCl3): δ 11,34 (W, 1H), 7,55 (s, 1H), 6,95 (s, 1H), 5,62 (s, 1H), 3,39 (s, 2H), 2,77 (s, 2H), of 2.38 (s, 3H), 2,30 (m, 1H), and 2.27 (s, 6N), 1,89-to 1.79 (m, 4H), to 1.70 (m, 1H), 1,54 of 1.28 (m, 11N).

p> Example 27(24)

(Z)-2-(6-Chloro-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.43 (water: methanol:chloroform=1:10:100).

NMR (CDCl3): δ 11,27 (W, 1H), 7,71 (s, 1H), 7,19 (s, 1H), 5,62 (s, 1H), a 3.87 (s, 2H), and 2.79 (s, 2H), of 2.51 (s, 3H), 2,31 (m, 1H), 1,90-of 1.20 (m, 10H), 1.28 (in C, 6N).

Example 27(25)

(Z)-2-(6-Chloro-7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf 0,59 (water:methanol:chloroform=1:10:100).

NMR (CDCl3): δ 11,31 (W, 1H), 7,74 (s, 1H), 7,18 (s, 1H), 5,62 (s, 1H), 3,55 (s, 2H), and 2.79 (s, 2H), 2,33 (C, 6N), 2,32 (m, 1H), 1,90-of 1.20 (m, 10H), 1.28 (in C, 6N).

Example 27(26)

(Z)-2-(7-Methylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf of 0.27 (chloroform:methanol=10:1).

NMR (CDCl3): δ 11,23 (W, 1H), to 7.61 (s, 1H), of 6.96 (s, 1H), ceiling of 5.60 (s, 1H, in), 3.75 (s, 2H), 2,77 (s, 2H), 2,54 (s, 3H), 2,46 (m, 1H), is 2.37 (s, 3H), 1,96-of 1.44 (m, N), 1.27mm (C, 6N).

Example 27(27)

(Z)-2-(7-Dimethylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf of 0.29 (hexane:ethyl acetate=1:2).

NMR (CDCl3): δ 11,27 (W, 1H), 7,55 (s, 1H), 6,95 (s, 1H), 5,58 (s, 1H), 3,40 (s, 2H), 2,77 (s, 2H), 2,48 (m, 1H), of 2.38 (s, 3H), and 2.27 (s, 6N), 1,96-of 1.44 (m, N), 1.28 (in C, 6N).

Example 28

(Z)-2-(6-Hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-femilet the n-1-it

To a solution of the compound obtained in example 13 (85 mg)in methanol (4 ml) and tetrahydrofuran (1 ml) add borohydride sodium (20 mg) at 0°after 10 minutes, add water to the mixture and the mixture is extracted with ethyl acetate. The extract is dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=3:1→1:1)to give the compound of the present invention (90 mg)having the following physical data.

TLC: Rf of 0.34 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,81 (W, 1H), of 7.96-to 7.93 (m, 2H), 7,82 (d, J=8.0 Hz, 1H), 7,46-7,41 (m, 3H), 7,32 (d, J=8.0 Hz, 1H), 7.23 percent (s, 1H), 6,33 (s, 1H), 4,76 (sm, 2H), 2,90 (s, 2H), 1,86 (PCs, 1H), 1,36 (C, 6N).

Examples 28(1)-28(13)

By the same procedure as described in example 28, using the compound obtained in example 13, the examples 13(5)-13(16), or the compound obtained in example 13, to obtain the following compounds of the present invention.

Example 28(1)

(Z)-2-(7-Hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf 0,12 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,83 (W, 1H), 7,97-7,94 (m, 2H), 7,83 (s, 1H), 7,47-7,42 (m, 4H), 7,22 (d, J=7.5 Hz, 1H), 6.35mm (s, 1H), of 4.77 (s, 2H), 2,90 (s, 2H), 1,80 (W, 1H), 1,36 (C, 6N).

Example 28(2)

(Z)-2-(6-Chloro-7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.38 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,46 (W, 1H), 7,83 (s, 1H), 7,20 (s, 1H), 5,78 (s, 1H), a 4.83 (s, 2H), 2,82 (s, 2H), 2.06 to (m, 3H), 1.91 a (m, 6N), 1,74 (m, 6N), 1,29 (C, 6N).

Example 28(3)

(Z)-2-(6-Chloro-7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.29 (ethyl acetate:hexane=1:3).

NMR (CDCl3): δ 11,25 (W, 1H), to 7.84 (s, 1H), 7,19 (s, 1H), 5,65 (s, 1H), 4,82 (d, J=6.0 Hz, 2H), 2,80 (s, 2H), 2,31 (m, 1H), 1,90-of 1.20 (m, 10H), 1,29 (C, 6N).

Example 28(4)

(Z)-2-(6-Chloro-7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf 0.31 in (ethyl acetate:Texan=1:3).

NMR (CDCl3): δ 11,16 (W, 1H), 7,83 (s, 1H), 7,17 (s, 1H), 5,61 (s, 1H), to 4.81 (s, 2H), and 2.79 (s, 2H), 2,46 (m, 1H), 1,95-of 1.40 (m, N), 1.27mm (C, 6N).

Example 28(5)

(Z)-2-(7-Hydroxymethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.44 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,50 (W, 1H), to 7.64 (s, 1H), 6,65 (s, 1H), 5,72 (s, 1H), 4.72 in (d, J=6.0 Hz, 2H), 3,92 (s, 3H), 2,82 (s, 2H), 2,18 (t, J=6.0 Hz, 1H), 2.06 to (W, 3H), 1.91 a (W, 6N), 1,75 (W, 6N), 1,29 (C, 6N).

Example 28(6)

(Z)-2-(7-Hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.50 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,51 (SHS, 1H), 7,71 (SHS, 1H), 7,40 (DD, J=7,8, 1.8 Hz, 1H), 7,17 (d, J=7,8 G is, 1H), 5,80 (s, 1H), and 4.75 (d, J=5.4 Hz, 2H), and 2.83 (s, 2H), 2,09-2,03 (m, 3H), 1,94-1,90 (m, 6N), 1,78-1,72 (m, 6N), 1,29 (C, 6N).

Example 28(7)

(Z)-2-(7-Hydroxymethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.10 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,29 (W, 1H), to 7.64 (s, 1H), 6,65 (s, 1H), 5,58 (s, 1H), 4,71 (d, J=6.0 Hz, 2H), 3,91 (s, 3H), 2,82 (s, 2H), 2,29 (TT, J=11,5, 3.5 Hz, 1H), 2,16 (t, J=6.0 Hz, 1H), 1,89-of 1.78 (m, 4H), 1.69 in (m, 1H), and 1.56-1,20 (m, 11N).

Example 28(8)

(Z)-2-(7-Hydroxymethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf 0,41 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,21 (W, 1H), to 7.64 (s, 1H), 6,65 (s, 1H), of 5.55 (s, 1H), 4,71 (d, J=6,5 Hz, 2H), 3,91 (s, 3H), 2,82 (s, 2H), 2,45 (m, 1H), 2,16 (t, J=6,5 Hz, 1H), 1,95-of 1.88 (m, 2H), 1,82 of 1.46 (m, 10H), 1,29 (, 6N).

Example 28(9)

(Z)-2-(7-Hydroxymethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf to 0.17 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ 11,50 (W, 1H), 7,69 (s, 1H), 6,99 (s, 1H), 5,78 (s, 1H), and 4.75 (d, J=5.7 Hz, 2H), and 2.79 (s, 2H), 2,39 (s, 3H), 2.06 to (W, 3H), 1,92 is 1.91 (W, 6N), 1,76-1,75 (W, 6N), 1.28 (in C, 6N).

Example 28(10)

(Z)-2-(7-Hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf 0,49 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,30 (SHS, 1H), 7,72 (SHS, 1H), 7,39 (DD, J=7,8, 1.8 Hz, 1H), 7,17 (d, J=78 Hz, 1H), to 5.66 (s, 1H), 4,74 (s, 2H), and 2.83 (s, 2H), 2,30 (TT, J=11,4, 3.6 Hz, 1H), 1.93 and-of 1.18 (m, N).

Example 28(11)

(Z)-2-(7-Hydroxymethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf 0.21 in (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,29 (W, 1H), of 7.70 (s, 1H), 6,98 (s, 1H), 5,64 (s, 1H), 4,74 (d, J=5,1 Hz, 2H), and 2.79 (s, 2H), is 2.37 (s, 3H), 2,30 (m, 1H), 1,92 to 1.76 (m, 4H), 1.69 in (m, 1H), 1,55 of 1.28 (m, 11N).

Example 28(12)

(Z)-2-(7-Hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf 0.21 in (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,22 (SHS, 1H), 7,71 (SHS, 1H), 7,39 (DD, J=7,8, 1.8 Hz, 1H), 7,16 (d, J=7.8 Hz, 1H), 5,62 (s, 1H), 4,74 (s, 2H), and 2.83 (s, 2H), 2,46 (TT, J=9, 9mm, 3.3 Hz, 1H), 1,99-of 1.42 (m, N), 1.28 (in C, 6N).

Example 28(13)

(Z)-2-(7-Hydroxymethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf of 0.34 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,21 (W, 1H), of 7.70 (s, 1H), 6,98 (s, 1H), 5,61 (s, 1H), 4,74 (d, J=4,8 Hz, 2H), and 2.79 (s, 2H), 2,46 (m, 1H), is 2.37 (s, 3H), 1,96 is 1.86 (m, 2H), 1,84-of 1.56 (m, 10H), 1.28 (in C, 6N).

Examples 29-29(11)

By the same procedure as described in example 8 using the compound obtained in example 2(3), or compounds obtained in example 14, example 14(2), example 14(3), example 14(10), example 14(3) or 14(10), and acetylchloride or the corresponding halide derivative, receive the following compounds the Oia of the present invention.

Example 29

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(1-phenolsulfonephthalein-4-yl)Ethan-1-he

TCX: Rf of 0.47 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,29 (W, 1H), 7,81-to 7.77 (m, 2H), of 7.64-7,51 (m, 4H), 7,40 (t, J=7.5 Hz, 1H), 7,31-7,26 (m, 1H), 7,17 (d, J=7.5 Hz, 1H), 5,54 (s, 1H), 3,88-of 3.85 (m, 2H), 2,84 (s, 2H), 2,41 is 2.33 (m, 2H), 2,24-2,14 (m, 1H), 1,97 to 1.76 (m, 4H), 1,29 (C, 6N).

Example 29(1)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(1-ethylsulfonyl-4-yl)Ethan-1-he

TCX: Rf 0.26 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,32 (W, 1H), 7,69 (d, J=7.5 Hz, 1H), 7,41 (t, J=7.5 Hz, 1H), 7,30 (t, J=7.5 Hz, 1H), 7,19 (d, J=7.5 Hz, 1H), 5,62 (s, 1H), 3,88-a-3.84 (m, 2H), 3,01-of 2.86 (m, 6N), 2,46 to 2.35 (m, 1H), 1,99-of 1.93 (m, 2H), 1,89-of 1.78 (m, 2H), 1,38 (t, J=7.0 Hz, 3H), 1,31 (C, 6N).

Example 29(2)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(1-propylsulfonyl-4-yl)Ethan-1-he

TCX: Rf of 0.34 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,32 (W, 1H), 7,69 (d, J=7.5 Hz, 1H), 7,41 (t, J=7.5 Hz, 1H), 7,30 (t, J=7.5 Hz, 1H), 7,19 (d, J=7.5 Hz, 1H), 5,62 (s, 1H), a 3.87-a 3.83 (m, 2H), 2,93-and 2.83 (m, 6N), 2,44 to 2.35 (m, 1H), 1,99-1,75 m, 6N), 1,31 (C, 6N), of 1.06 (t, J=7.5 Hz, 3H).

Example 29(3)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(1-butylsulfonyl-4-yl)Ethan-1-he

TCX: Rf of 0.10 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,33 (W, 1H), 7,69 (DD, J=7,5, 1.0 Hz, 1H), 7,41 (dt, J=1,0, 7.5 Hz, 1H), 7,30 dt, J=1,0, 7.5 Hz, 1H), 7,19 (DD, J=7,5, 1.0 Hz, 1H), 5,62 (s, 1H), a 3.87-a 3.83 (m, 2H), 2.95 and-and 2.83 (m, 6N), 2,45-of 2.34 (m, 1H), 2.00 in of 1.93 (m, 2H), 1,90 to 1.76 (m, 4H), 1,51-of 1.40 (m, 2H), 1,31 (C, 6N), is 0.96 (t, J=7.5 Hz,, 3H).

Example 29(4)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(1-octylaniline-4-yl)Ethan-1-he

TLC: Rf is 0.22 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,33 (W, 1H), 7,69 (d, J=7.5 Hz, 1H), 7,41 (t, J=7.5 Hz, 1H), 7,30 (t, J=7.5 Hz, 1H), 7,19 (d, J=7.5 Hz, 1H), 5,61 (s, 1H), a 3.87-a 3.83 (m, 2H), 2,94-2,82 (m, 6N), 2,44-of 2.34 (m, 1H), 1,98-of 1.93 (m, 2H), 1,87 to 1.76 (m, 4H), 1,44-1,22 (m, N), 0,88 (PCs, 3H).

Example 29(5)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-acetylaminophenol)ethane-1-he

TCX: Rf 0,09 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,80 (W, 1H), 7,94 (d, J=8.5 Hz, 2H), 7,83 (d, J=7.5 Hz, 1H), 7,58 (d, J=8.5 Hz, 2H), 7,43 (t, J=7.5 Hz, 1H), 7,37-to 7.32 (m, 2H), 7,21 (d, J=7.5 Hz, 1H), of 6.31 (s, 1H), 2,90 (s, 2H), of 2.21 (s, 3H), 1,36 (C, 6N).

Example 29(6)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-acetylaminophenol)ethane-1-he

TCX: Rf 0,12 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,83 (W, 1H), 7,87-of 7.82 (m, 3H), of 7.69 (d, J=8.0 Hz, 1H), 7,46-to 7.32 (m, 4H), 7,22 (d, J=7.5 Hz, 1H), of 6.31 (s, 1H), 2.91 in (s, 2H), of 2.21 (s, 3H), of 1.37 (s, 6N).

Example 29(7)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-methylaminophenol)ethane-1-he

TCX: Rf is 0.24 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ up 11,86 (W, 1H), 7,82 (d, J=5 Hz, 1H), 7,78-7,73 (m, 2H), of 7.48-7,40 (m, 3H), of 7.36 (t, J=7.5 Hz, 1H), 7,21 (d, J=7.5 Hz, 1H), 6,54 (W, 1H), 6,29 (s, 1H), to 3.02 (s, 3H), 2.91 in (s, 2H), 1,37 (C, 6N).

Example 29(8)

(Z)-2-(7-Acetylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf of 0.23 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,81 (W, 1H), of 7.96-to $ 7.91 (m, 3H), of 7.64 (DD, J=8,0, 2.0 Hz, 1H), 7,45-7,39 (m, 4H), 7,17 (d, J=8.0 Hz, 1H), 6,29 (s, 1H), 2,84 (s, 2H), of 2.23 (s, 3H), 1,33 (C, 6N).

Example 29(9)

(Z)-2-(7-Acetylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.38 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,48 (W, 1H), 7,78 (d, J=2.0 Hz, 1H), 7.62mm (DD, J=8,0, 2.0 Hz, 1H), 7,27 (W, 1H), 7,13 (d, J=8.0 Hz, 1H), 5,74 (s, 1H), and 2.79 (s, 2H), 2,22 (s, 3H), 2.05 is (W, 3H), 1.91 a (W, 6N), 1,74 (W, 6N), of 1.28 (s, 6N).

Example 29(10)

(Z)-2-(7-Methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TCX: Rf 0.14 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,80 (W, 1H), of 7.96-a 7.92 (m, 2H), to 7.64 (d, J=2.0 Hz, 1H), 7,47-7,42 (m, 3H), 7,35 (DD, J=8,0, 2.0 Hz, 1H), 7,22 (d, J=8.0 Hz, 1H), 6,54 (W, 1H), 6,27 (s, 1H), 3,06 (s, 3H), 2,88 (s, 2H), 1,36 (, 6N).

Example 29(11)

(Z)-2-(7-Methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.20 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,46 (W, 1H), 7,51 (d, J=2.0 Hz, 1H), 7,34 (DD, J=8,0, 2.0 Hz, 1H), 7,18 (d, J=8.0 Hz, 1H), 6,46 (W, 1H), 5,72 (s, 1H), 3,05 (C, H), of 2.81 (s, 2H), 2.06 to (W, 3H), 1,90 (W, 6N), 1,74 (W, 6N), 1,29 (C, 6N).

Example 30

(Z)-2-(6-Methylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

A solution of the compound obtained in example 15 (100 mg)in tetrahydrofuran (3 ml) is cooled with ice, add triethylamine (0,09 ml) and horizontallayout (0,08 ml) and the mixture is stirred for 30 minutes at room temperature. Aggregated mass which is formed is filtered off. It chilled with ice to a solution of 40% aqueous solution of methylamine (0,120 ml) in tetrahydrofuran (2 ml) is added thus obtained filtrate and the mixture is stirred at room temperature over night. The reaction mixture was concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=1:1)to give the compound of the present invention (92 mg)having the following physical data.

TLC: Rf and 0.46 (ethyl acetate).

NMR (CDCl3): δ 11,76 (SHS, 1H), 7,97-a 7.92 (m, 2H), 7,87 (d, J=9.0 Hz, 1H), 7,69-7,63 (m, 2H), of 7.48-7,42 (m, 3H), 6,34 (s, 1H), 6,20 (SHS, 1H), 3,05 (d, J=4,8 Hz, 3H), 2,94 (s, 2H), 1,36 (C, 6N).

Examples 30(1)-30(11)

By the same procedure as described in example 30, using the compound obtained in example 15, or instead of the compounds obtained in examples 15(1)-15(4) or example 15(13), and methylamine or a corresponding amine derivative have the following connections this is about inventions.

Example 30(1)

(Z)-2-(6-Dimethylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.40 (ethyl acetate).

NMR (CDCl3): δ 11,78 (SHS, 1H), 7,97-a 7.92 (m, 2H), 7,86 (d, J=8,1 Hz, 1H), of 7.48-7,41 (m, 3H), 7,37 (DD, J=8,1, 1.5 Hz, 1H), 7,29 (d, J=1.5 Hz, 1H), 6,34 (s, 1H), 3,14 (s, 3H), 3,01 (s, 3H), of 2.92 (s, 2H), 1,37 (, 6N).

Example 30(2)

(Z)-2-(6-Carbarnoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.36 (chloroform:methanol=9:1).

NMR (CDCl3): δ 11,76 (SHS, 1H), 7,98-7,88 (m, 3H), 7,75-of 7.69 (m, 2H), 7,49-7,41 (m, 3H), 6.35mm (s, 1H), 6,12 (SHS, 1H), 5,71 (SHS, 1H), 2.95 and (s, 2H), 1,37 (C, 6N).

Example 30(3)

(Z)-2-(7-Carbarnoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0,07 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,82 (W, 1H), 8,31 (d, J=1.5 Hz, 1H), 7,98-7,94 (m, 2H), 7,83 (DD, J=8,0, 1.5 Hz, 1H), of 7.48-7,42 (m, 3H), 7,31 (d, J=8.0 Hz, 1H), to 6.39 (s, 1H), 6,10 (W, 1H), 5,67 (W, 1H), 2.95 and (s, 2H), 1,37 (, 6N).

Example 30(4)

(Z)-2-(7-Methylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0.14 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,81 (W, 1H), 8,24 (d, J=2.0 Hz, 1H), 7,98-7,94 (m, 2H), 7,78 (DD, J=8,0, 2.0 Hz, 1H), of 7.48-7,41 (m, 3H), 7,28 (d, J=8.0 Hz, 1H), to 6.39 (s, 1H), 6,20 (W, 1H), of 3.07 (d, J=5.0 Hz, 3H), 2,94 (s, 2H), of 1.36 (s, 6N).

Example 30(5)

(Z)-2-(7-Dimethylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoch the nolin-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0,12 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ to 11.79 (W, 1H), of 7.96-to $ 7.91 (m, 3H), 7,49-7,40 (m, 4H), 7,26 (m, 1H), 6,33 (s, 1H), 3,16 (W, 3H), 3.04 from (W, 3H), of 2.93 (s, 2H), 1,37 (C, 6N).

Example 30(6)

(Z)-2-(7-Carbarnoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.34 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,51 (W, 1H), 8,19 (d, J=1.2 Hz, 1H), to 7.77 (DD, J=1,2, 7.5 Hz, 1H), 7,27 (d, J=7.5 Hz, 1H), of 5.84 (s, 1H), 2,89 (s, 2H), 2.06 to (W, 3H), 1,92 is 1.91 (W, 6N), 1,76-1,75 (W, 6N), of 1.30 (s, 6N).

Example 30(7)

(Z)-2-(7-Methylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.40 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,49 (W, 1H), 8,14 (d, J=1.2 Hz, 1H), of 7.70 (DD, J=1,2, 7,8 Hz, 1H), 7.23 percent (d, J=7.8 Hz, 1H), 6,14 (W, 1H), of 5.84 (s, 1H), 3,06 (d, J=7.8 Hz, 3H), 2,87 (s, 2H), 2.06 to (W, 3H), 1,92 is 1.91 (W, 6N), of 1.75 (s, 6N), 1,29 (C, 6N).

Example 30(8)

(Z)-2-(7-Dimethylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.50 (chloroform:methanol=50:1).

NMR (CDCl3): δ of 11.45 (W, 1H), 7,81 (d, J=1.2 Hz, 1H), 7,41 (DD, J=1,2, 7,8 Hz, 1H), 7,20 (d, J=7.8 Hz, 1H), 5,78 (s, 1H), 3.15 in (W, 3H), 3,02 (W, 3H), of 2.86 (s, 2H), 2.05 is (W, 3H), 1,90-1,89 (W, 6N), 1,74 (W, 6N), of 1.30 (s, 6N).

Example 30(9)

(Z)-2-(6-Carbarnoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf 0,12 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,24 (W, 1H), 7,78 (d, J=8.0 Hz, 1H), 7,70-7,66 (m, 2H), 6,14 (W, 1H), of 5.83 (W, 1H), to 5.66 (s, 1H), 2,89 (s, 2H), 2,30 (TT, J=11,5, 3.5 Hz, 1H), 1,90 and 1.80 (m, 4H), to 1.70 (m, 1H), 1,50-1,20 (m, 11N).

Example 30(10)

(Z)-2-(6-Carbarnoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0,12 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ of 11.15 (W, 1H), 7,78 (d, J=8.0 Hz, 1H), 7,69-7,66 (m, 2H), between 6.08 (W, 1H), 5,75 (W, 1H), 5,63 (s, 1H), 2,89 (s, 2H), 2,48 (TT, J=10,0, 4.0 Hz, 1H), 1,95-of 1.88 (m, 2H), 1,82-of 1.45 (m, 10H), 1,29 (C, 6N).

Example 30(11)

(Z)-2-(6-Carbarnoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.13 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,40 (W, 1H), 7,79 (d, J=8.0 Hz, 1H), 7,70-7,66 (m, 2H), 6,05 (W, 1H), of 5.81 (s, 1H), 5,76 (W, 1H), 2,89 (s, 2H), 2.06 to (W, 3H), 1.91 a (W, 6N), 1,75 (W, 6N), of 1.30 (s, 6N).

Example 31

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyano-2-methoxyphenyl)Ethan-1-he

To a suspension of the compound obtained in example 13(4) (423 mg)in formic acid (10 ml) is added hydroxylamine hydrochloride (1,05 g) and the mixture is stirred for 30 minutes at 130°C. the Reaction mixture allow to cool, add ice and water and aggregated mass which is formed is filtered off. Aggregated mass is dissolved in ethyl acetate and the mixture PEFC is therefore washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The remainder of the roughly purified column chromatography on silica gel (hexane:ethyl acetate=5:1→2:1). The product is washed with tert-butylmethylamine ether, obtaining the compound of the present invention (65 mg)having the following physical data.

TLC: Rf of 0.32 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,73 (W, 1H), 7,73-of 7.70 (m, 2H), 7,44 (dt, J=1,0, 7.5 Hz, 1H), 7,34-7,29 (m, 2H), 7.23 percent-7,19 (m, 2H), 6,16 (s, 1H), 3,94 (s, 3H), 2.91 in (s, 2H), 1,37 (C, 6N).

Examples 31(1)-31(3)

By the same procedure as described in example 31, using the compound obtained in example 13(1), example 13(12) or example 13(14)instead of the compound obtained in 13(4), obtain the following compounds of the present invention.

Example 31(1)

(Z)-2-(7-Cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0,49 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,73 (SHS, 1H), 8,11 (d, J=1.5 Hz, 1H), 7,99-to 7.93 (m, 2H), of 7.70 (DD, J=8,1, 1.5 Hz, 1H), 7,51-7,44 (m, 3H), 7,35 (d, J=8,1 Hz, 1H), of 6.31 (s, 1H), 2,97 (s, 2H), 1,37 (C, 6N).

Example 31(2)

(Z)-2-(7-Cyano-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.50 (methylene chloride).

NMR (CDCl3): δ 11,37 (W, 1H), 7,94 (s, 1H), 7,14 (s, 1H), 5,73 (s, 1H), 2,84 (s, 2H), 2.57 m (s, 3H), 2,07 (W, 3H), 1.91 a-1,90 (W, 6N), 1,76 (W, 6N), 1,29 (C, 6N).

Example 31(3)

(Z)-2-(7-Cyano-3,3,6-trimethyl-3,4-dihydro-(2H)-from the quinoline-1-ilidene)-1-cyclohexylethyl-1-he

TCX: Rf of 0.45 (methylene chloride).

NMR (CDCl3): δ 11,21 (W, 1H), 7,92 (s, 1H), 7,14 (s, 1H), 5,58 (s, 1H), 2,84 (s, 2H), 2.57 m (s, 3H), 2,36-of 2.28 (m, 1H), 1,92-of 1.29 (m, N).

Example 32

(Z)-2-(6-Ethinyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To a suspension (methyl bromide)triphenylphosphorane (371 mg) in tetrahydrofuran (3 ml) was added dropwise tert-piperonyl potassium (2.55 ml, 1.0 M in THF) at -78°and the mixture is stirred for 30 minutes at 0°C. To the mixture are added dropwise the compound obtained in example 13 (200 mg)in tetrahydrofuran (5 ml) at -78°and the mixture is stirred for 90 minutes at 0°and within 60 minutes at room temperature. To the reaction mixture is added a mixture of ice-water and extracted with ethyl acetate. The extract is washed successively with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=20:1→10:1)to give the compound of the present invention (127 mg)having the following physical data.

TLC: Rf and 0.46 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,76 (W, 1H), of 7.96-a 7.92 (m, 2H), 7,78 (d, J=8.0 Hz, 1H), 7,47-7,41 (m, 4H), 7,35 (d, J=1.0 Hz, 1H), of 6.31 (s, 1H), up 3.22 (s, 1H), 2,88 (s, 2H), 1,36 (C, 6N).

Examples 32(1)-32(2)

By the same procedure as described in Primera, using the compound obtained in example 13(1) or example 13(3), instead of the compound obtained in example 13, to obtain the following compounds of the present invention.

Example 32(1)

(Z)-2-(7-Ethinyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.48 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ to 11.79 (W, 1H), 7,97-7,94 (m, 3H), 7,54 (DD, J=8,0, 1.5 Hz, 1H), 7,47-7,42 (m, 3H), 7,19 (d, J=8.0 Hz, 1H), of 6.31 (s, 1H), 3,14 (s, 1H), 2,90 (s, 2H), 1,36 (C, 6N).

Example 32(2)

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-ethynylphenyl)ethane-1-he

TLC: Rf to 0.39 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,88 (W, 1H), to $ 7.91 (d, J=8.5 Hz, 2H), 7,82 (d, J=7.5 Hz, 1H), 7,55 (d, J=8.5 Hz, 2H), 7,44 (t, J=7.5 Hz, 1H), 7,35 (t, J=7.5 Hz, 1H), 7,22 (d, J=7.5 Hz, 1H), of 6.31 (s, 1H), 3,17 (s, 1H), 2.91 in (s, 2H), 1,37 (C, 6N).

Example 33

(Z)-2-(6-((E)-2-Carboxyethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To a solution of the compound obtained in example 13 (200 mg)in pyridine (5 ml) is added piperidine (2 drops) at room temperature, added malonic acid (122 mg) and the mixture is stirred for 20 minutes at room temperature, for 30 minutes at 85°With over 3.5 hours at 100°and over night at 80°C. the Reaction mixture allow to cool and diluted with ethyl acetate. About the organic layer is washed successively with a saturated aqueous solution of sodium chloride, water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=2:1→ethyl acetate)to give the compound of the present invention (173 mg)having the following physical data.

TLC: Rf of 0.16 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,76 (W, 1H), 7,97-to 7.93 (m, 2H), 7,87 (d, J=8.0 Hz, 1H), 7,78 (d, J=16.0 Hz, 1H), 7,52 (DD, J=8,0, 1.5 Hz, 1H), of 7.48-7,41 (m, 3H), 7,40 (d, J=1.5 Hz, 1H), is 6.54 (d, J=16.0 Hz, 1H), 6.35mm (s, 1H), of 2.93 (s, 2H), 1,38 (C, 6N).

Example 34

(Z)-2-(6-((E)-2-Methoxycarbonylamino)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To a solution of the compound obtained in example 33 (90 mg)in dimethylformamide (2 ml) is added potassium carbonate (39 mg) and methyliodide (0,033 ml) and the mixture is stirred over night at room temperature. To the reaction mixture, water is added and aggregated mass which is formed is filtered off. Aggregated mass is dissolved in ethyl acetate and washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated, obtaining the compound of the present invention (94 mg)having the following physical data.

TLC: Rf of 0.68 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,76 (W, 1H), of 7.96-to 7.93 (m, 2H), a 7.85 (d, J=8.0 Hz, 1H), 7,69 (d, J=16.0 Hz, 1H), 7,51-7,41 (m, 4H), and 7.6 (s, 1H), of 6.52 (d, J=16.0 Hz, 1H), 6,34 (s, 1H), 3,83 (s, 3H), of 2.92 (s, 2H), 1,38 (C, 6N).

Examples 34(1)-34(2)

By the same procedure as described in example 34 using the compound obtained in example 15 or example 15(1), instead of the compound obtained in example 33, are provided the following compounds of the present invention.

Example 34(1)

(Z)-2-(6-Methoxycarbonyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.43 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,75 (W, 1H), 8,01-7,94 (m, 3H), of 7.90-7,88 (m, 2H), of 7.48-7,41 (m, 3H), 6,37 (s, 1H), 3.96 points (s, 3H), 2.95 and (s, 2H), 1,37 (C, 6N).

Example 34(2)

(Z)-2-(7-Methoxycarbonyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf 0.25 in (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,83 (W, 1H), 8,49 (d, J=2.0 Hz, 1H), 8,10 (DD, J=8,0, 2.0 Hz, 1H), 7,99-of 7.96 (m, 2H), 7,49-7,44 (m, 3H), 7,31 (d, J=8.0 Hz, 1H), 6,40 (s, 1H), 3,98 (s, 3H), 2,96 (s, 2H), 1,37 (C, 6N).

Example 35

(Z)-2-(7-Carboxy-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

To a tetrahydrofuran (1 ml) and methanol (1 ml) is added the compound obtained in example 19 (58 mg), add 2 N. aqueous sodium hydroxide solution (1 ml) and the mixture is stirred over night at room temperature. The reaction mixture is neutralized 1 N. hydrochloric acid and extracted with ethyl is the Etat. The extract was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is washed with a mixture of hexane and ethyl acetate, obtaining the compound of the present invention (45 mg)having the following physical data.

TLC: Rf 0.40 in (water:methanol:chloroform=1:10:100).

NMR (CDCl3): δ 11,24 (W, 1H), 8,35 (s, 1H), 7,33 (s, 1H), to 5.66 (s, 1H), 2,86 (s, 2H), 2,34 (m, 1H), 1,95-of 1.65 (m, 5H), 1.55V is 1.20 (m, 5H), 1,31 (C, 6N).

Examples 35(1)-35(2)

By the same procedure as described in example 35 using the compound obtained in example 11(197) or example 11(198), get the following compounds of the present invention.

Example 35(1)

(Z)-2-(7-Carboxy-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf 0.28 in (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,44 (SHS, 1H), with 8.33 (s, 1H), 7,33 (s, 1H), 5,80 (s, 1H), 2,86 (s, 2H), 2,10-2,03 (m, 3H), 1.93 and-1,89 (m, 6N), 1,77-1,72 (m, 6N), 1,31 (C, 6N).

Example 35(2)

(Z)-2-(7-Carboxy-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TLC: Rf 0.28 in (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,16 (SHS, 1H), 8.34 per (s, 1H), 7,32 (s, 1H), 5,63 (s, 1H), 2,85 (s, 2H), 2,50 (TT, J=9,9, 3,9 Hz, 1H), 1,97-of 1.42 (m, N), 1,31 (C, 6N).

Example 36

(Z)-2-(3,3,4,4-Tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

On t the coy same method, as described in example 3, using 1,3,3,4,4-pentamethyl-3,4-dihydroisoquinoline instead of the compound obtained in reference example 2 and 4-cyanobenzoate instead of 3 cyanobenzaldehyde get compounds of the present invention having the following physical data.

TLC: Rf of 0.48 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,90 (W, 1H), 8,03 (d, J=8.5 Hz, 2H), 7,79 (DD, J=7,5, 1.0 Hz, 1H), 7,72 (d, J=8.5 Hz, 2H), 7,52 (dt, J=1,0, 7.5 Hz, 1H), 7,45 (DD, J=7,5, 1.0 Hz, 1H), 7,34 (dt, J=1,0, 7.5 Hz, 1H), and 6.25 (s, 1H), 1,31 (W, N).

Example 37

(Z)-2-(7-Formylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To a mixture of acetic anhydride (0,50 ml) and formic acid (5 ml) is added the compound obtained in example 14(3) (151 mg), and the mixture is stirred for 1 hour at 70°C. the Reaction mixture allow to cool, add ice, the mixture is neutralized with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=2:1)to give the compound of the present invention (131 mg)having the following physical data.

TLC: Rf 0.21 in (hexane:ethyl acetate=1:1).

NMR (DMSO-d6 ): δ 11,74 (SHS, 1H), 10,26 (SHS, 1H), 8,13 (d, J=1.8 Hz, 1H), 7,89-to 7.84 (m, 2H), 7,74 (DD, J=8,1, 1.8 Hz, 1H), 7,50-the 7.43 (m, 3H), 7,28 (d, J=8,1 Hz, 1H), 7,26 (s, 1H), 6,24 (s, 1H), 2,87 (s, 2H), 1.27mm (, 6N).

Example 37(1)

(Z)-2-(6-Formylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

By the same procedure as described in example 37, using the compound obtained in example 40, instead of the compound obtained in example 14(3), obtain the following compound of the present invention.

TLC: Rf of 0.40 (hexane:ethyl acetate=1:4).

NMR (CDCl3): δ to 11.79 (SHS, 1H), 8,43 (s, 1H), 7,97-a 7.92 (m, 2H), 7,80 (d, J=8,4 Hz, 1H), 7,63 (d, J=2.1 Hz, 1H), 7,47-7,39 (m, 3H), 7,37 (DD, J=8,4, and 2.1 Hz, 1H), 6,27 (s, 1H), 2,89 (s, 2H), 1,36 (C, 6N).

Example 38

(Z)-2-(7-Methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To a suspension of sociallyengaged (77 mg) in tetrahydrofuran (1 ml) add a solution of the compound obtained in example 37 (131 mg)in tetrahydrofuran (4 ml) and the mixture is stirred for 4 hours at room temperature. To the reaction mixture is added saturated aqueous solution of sodium sulfate and filtered through celite. The filtrate is concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=4:1)to give the compound of the present invention (73 mg)having the following physical data.

TLC: Rf 0,41 (hexane:etelaat is=2:1).

NMR (CDCl3): δ 11,85 (SHS, 1H), 7,97-to $ 7.91 (m, 2H), 7,46-7,40 (m, 3H), 7,03 (d, J=8,1 Hz, 1H), 7,03 (d, J=2.4 Hz, 1H), of 6.71 (DD, J=8,1, 2.4 Hz, 1H), and 6.25 (s, 1H), 2.91 in (s, 3H), 2,78 (s, 2H), 1,35 (C, 6N).

Examples 38(1)-38(2)

By the same procedure as described in example 38, using the compound obtained in example 37(1) or 30(4), instead of the compound obtained in example 37, will receive the following compounds of the present invention.

Example 38(1)

(Z)-2-(6-Methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf is 0.69 (hexane:ethyl acetate=1:4).

NMR (CDCl3): δ 11,85 (SHS, 1H), 7,97-to $ 7.91 (m, 2H), 7,66 (d, J=8.7 Hz, 1H), 7,44-7,38 (m, 3H), 6,51 (DD, J=8,7, 2.4 Hz, 1H), 6.35mm (d, J=2.4 Hz, 1H), 6,21 (s, 1H), 4,14 (SHS, 1H), 2.91 in (s, 3H), 2,80 (s, 2H), 1,36 (, 6N).

Example 38(2)

(Z)-2-(7-Methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

TLC: Rf of 0.29 (hexane:ethyl acetate:Isopropylamine=10:2:1).

NMR (CDCl3): δ up 11,86 (W, 1H), 7,98-to 7.95 (m, 2H), to 7.77 (s, 1H), 7,47-7,37 (m, 4H), 7,18 (d, J=8.0 Hz, 1H), 6.35mm (s, 1H), 3,81 (s, 2H), 2,89 (s, 2H), 2,50 (s, 3H), 1,36 (C, 6N).

Example 39

(Z)-2-(6-tert-Butoxycarbonylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To a suspension of the compound obtained in example 15 (965 mg)in tert-butanol (15 ml), add triethylamine (0,460 ml) and diphenylphosphoryl (0,710 ml) and the mixture is stirred is for 3 hours at 100° C. the Reaction mixture allow to cool, diluted with ethyl acetate and then washed successively with water, saturated aqueous sodium bicarbonate and saturated aqueous solution. sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=9:1)to give the compound of the present invention (1.04 g)having the following physical data.

TLC: Rf of 0.58 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,81 (SHS, 1H), of 7.96-to $ 7.91 (m, 2H), 7,74 (d, J=8.7 Hz, 1H), 7,46-7,40 (m, 4H), 7,16 (DD, J=8,7, 2.7 Hz, 1H), 6,64 (SHS, 1H), of 6.26 (s, 1H), 2,87 (s, 2H), and 1.54 (s, N), of 1.35 (s, 6N).

Examples 39(1)-39(4)

By the same procedure as described in example 39, using the compound obtained in example 15(3), example 15(4), example 15(13) or example 15(14)instead of the compound obtained in example 15, to obtain the following compounds of the present invention.

Example 39(1)

(Z)-2-(6-tert-Butoxycarbonylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf to 0.17 (hexane:ethyl acetate=5:1).

NMR (CDCl3): δ 11,30 (W, 1H), 7.62mm (d, J=8.5 Hz, 1H), 7,38 (d, J=2.0 Hz, 1H), 7,12 (DD, J=8,5, 2.0 Hz, 1H), 6,61 (W, 1H), 5.56mm (s, 1H), 2,80 (s, 2H), and 2.26 (m, 1H), 1,89-of 1.78 (m, 4H), by 1.68 (m, 1H), 1,58-1,24 (m, 20N).

Example 39(2)

(Z)-2-(6-tert-Butoxycarbonylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cycloheptyl the an-1-he

TLC: Rf is 0.42 (hexane:ethyl acetate=3:1).

Example 39(3)

(Z)-2-(6-tert-Butoxycarbonylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf is 0.42 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,48 (W, 1H), to 7.64 (d, J=9.0 Hz, 1H), 7,42 (d, J=2.0 Hz, 1H), 7,10 (DD, J=9,0, 2.0 Hz, 1H), 6,60 (W, 1H), 5,71 (s, 1H), 2,80 (s, 2H), 2.05 is (W, 3H), 1.91 a (W, 6N), 1,74 (W, 6N), 1,53 (s, N), of 1.28 (s, 6N).

Example 39(4)

(Z)-2-(6-tert-Butoxycarbonylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(pyridine-3-yl)ethane-1-he

TCX: Rf 0,41 (methylene chloride:methanol=10:1).

NMR (CDCl3): δ 11,84 (W, 1H), 9,14 (d, J=1.5 Hz, 1H), 8,65 (DD, J=5.0 and 1.5 Hz, 1H), 8,21 (DDD, J=8.5 a, 1.5 a, 1.5 Hz, 1H), 7,74 (d, J=8.5 Hz, 1H), 7,49 (d, J=2.0 Hz, 1H), was 7.36 (DD, J=8,5, 5.0 Hz, 1H), 7,17 (DD, J=8,5, 2.0 Hz, 1H), to 6.67 (s, 1H), 6,21 (s, 1H), 2,88 (s, 2H), and 1.54 (s, N), to 1.37 (s, 6N).

Example 40

(Z)-2-(6-Amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To the compound obtained in example 39 (1.04 g), add a solution of 4 N. hydrochloric acid in dioxane (20 ml) and the mixture is stirred for 2 hours at room temperature. To the reaction mixture add methanol until then, until it becomes homogeneous, and the mixture is stirred for 1 hour at 50°C. To the reaction mixture is added saturated aqueous bicarbonate is the atrium and extracted with a mixture of ethyl acetate and tetrahydrofuran. The extract was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate to 3:1→chloroform)to give the compound of the present invention (458 mg)having the following physical data.

TLC: Rf of 0.29 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ 11,84 (SHS, 1H), of 7.96-to $ 7.91 (m, 2H), to 7.64 (d, J=8,4 Hz, 1H), 7,44-7,39 (m, 3H), 6,59 (DD, J=8,4, 2.4 Hz, 1H), 6,46 (d, J=2.4 Hz, 1H), 6,21 (s, 1H), 4.00 points (MS, 2H), 2,78 (s, 2H), 1,35 (C, 6N).

Examples 40(1)-40(4)

By the same procedure as described in example 40, using one of the compounds selected from the obtained in examples 39(1)-39(4)instead of the compound obtained in example 39, receive connections of the present invention.

Example 40(1)

(Z)-2-(6-Amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

TLC: Rf 0,11 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,33 (W, 1H), 7,52 (d, J=8.5 Hz, 1H), 6,55 (DD, J=8,5, 2.5 Hz, 1H), 6.42 per (d, J=2.5 Hz, 1H), 5,50 (s, 1H), 3,94 (W, 2N), of 2.72 (s, 2H), 2,25 (TT, J=11,5, 3.5 Hz, 1H), 1,89-of 1.78 (m, 4H), by 1.68 (m, 1H), 1,58-1,20 (m, 11N).

Example 40(2)

(Z)-2-(6-Amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf 0.14 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,25 (W, 1H), 7,51 (d, J=8.5 Hz, 1H), 6,55 (DD, J=8,5, 2.5 Hz, 1H), 6.42 per (d, J=2.5 Hz, 1H), vs. 5.47 (s, 1H), 3,93 (W, 2H), 2,71, 2H), 2,41 (TT, J=9,5, 4.0 Hz, 1H), 1,94-of 1.88 (m, 2H), 1,82-of 1.45 (m, 10H), 1.28 (in C, 6N).

Example 40(3)

(Z)-2-(6-Amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf 0,12 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,51 (W, 1H), 7,54 (d, J=8.5 Hz, 1H), 6,56 (DD, J=8,5, 2.5 Hz, 1H), 6.42 per (d, J=2.5 Hz, 1H), 5,65 (s, 1H), 3,94 (W, 2H), 2,71 (s, 2H), 2.05 is (W, 3H), 1.91 a (W, 6N), 1,74 (W, 6N), 1.28 (in C, 6N).

Example 40(4)

(Z)-2-(6-Amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(pyridine-3-yl)ethane-1-he

TCX: Rf 0,39 (methylene chloride:methanol=10:1).

NMR (CDCl3): δ up 11,86 (W, 1H), 9,13 (DD, J=2.0 a, 1.0 Hz, 1H), 8,64 (DD, J=4,5, 2.0 Hz, 1H), 8,21 (DDD, J=8.0 a, 2,0, 2,0 Hz, 1H), 7,63 (d, J=8.5 Hz, 1H), 7,35 (DDD, J=8.0 a, 4,5, 1.0 Hz, 1H), is 6.61 (DD, J=8,5, 2.5 Hz, 1H), 6,47 (d, J=2.5 Hz, 1H), 6,16 (s, 1H), 4.04 the (W, 2H), 2,80 (s, 2H), 1,37 (C, 6N).

Example 41

(Z)-2-(7-Dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

To a solution of the compound obtained in example 38 (49 mg)in tetrahydrofuran (2 ml) is added acetic acid (0.10 ml), 35% aqueous solution of formaldehyde (0,14 ml) and triacetoxyborohydride sodium (340 mg) and the mixture is stirred over night at room temperature. The reaction mixture was added to saturated aqueous solution of sodium bicarbonate and the mixture extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride, the tub over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=9:1)to give the compound of the present invention (25 mg)having the following physical data.

TLC: Rf of 0.54 (hexane:ethyl acetate=2:1).

NMR (CDCl3): δ 11,90 (SHS, 1H), 7,97-of 7.90 (m, 2H), 7,46-7,41 (m, 3H), 7,13 (d, J=2.7 Hz, 1H), 7,07 (d, J=8,4 Hz, 1H), at 6.84 (DD, J=8,4, 2.7 Hz, 1H), 6,28 (s, 1H), 3,01 (C, 6N), and 2.79 (s, 2H), 1,35 (C, 6N).

Examples 41(1) - 41(2)

By the same procedure as described in example 41, using the compound obtained in example 11(133) or example 11(134), instead of the compound obtained in example 38, are provided the following compounds of the present invention.

Example 41(1)

(Z)-2-(7-Dimethylamino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he

TLC: Rf 0.26 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ of $ 11.97 (W, 1H), 8,00 (d, J=8.5 Hz, 2H), 7,72 (d, J=8.5 Hz, 2H), 7,30 (s, 1H), 6,66 (s, 1H), 6,14 (s, 1H), 3.96 points (s, 3H), 2,85 (s, 8H), to 1.38 (s, 6N).

Example 41(2)

(Z)-2-(7-Dimethylamino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TLC: Rf of 0.47 (hexane:ethyl acetate=1:1).

NMR (CDCl3): δ to 11.56 (W, 1H), 7,25 (s, 1H), 6,60 (s, 1H), to 5.66 (s, 1H), 3,93 (s, 3H), and 2.83 (s, 6N), was 2.76 (s, 2H), 2.06 to (W, 3H), 1,92 (W, 6N), 1,75 (W, 6N), of 1.30 (s, 6N).

Reference example 9

4-Bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-he

To three is xidu carbon (5 ml) was added 3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-he (200 mg) and N-bromosuccinimide (223 mg), add benzoyl peroxide (24 mg), the mixture is stirred over night at room temperature and refluxed for 1 hour. The reaction mixture allow to cool and aggregated mass which is formed is filtered off. The filtrate is successively washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is washed with a mixture (hexane:ethyl acetate=4:1)to give the compound of the present invention (196 mg)having the following physical data.

TLC: Rf of 0.37 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 8,10 (DD, J=7,5, 1.5 Hz, 1H), 7,54 (DDD, J=7,5, to 7.5, 1.5 Hz, 1H), 7,46 (DDD, J=7,5, to 7.5, 1.5 Hz, 1H), 7,39 (DD, J=7,5, 1.5 Hz, 1H), 5,98 (W, 1H), 5,11 (s, 1H), 1,59 (s, 3H), of 1.37 (s, 3H).

Reference example 10

4-Hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-he

To a mixture of dioxane (100 ml) and water (20 ml) is added the compound obtained in reference example 9 (6,57 g), and sodium acetate (21.2 g) and the mixture refluxed for 3 days. To the reaction mixture is added potassium carbonate (10.6 g) and the mixture is stirred over night at room temperature. The reaction mixture is concentrated and to the residue is added ethyl acetate and the mixture filtered. The aqueous layer of the filtrate is extracted with ethyl acetate. The combined organic layer is washed on Ishenim aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=3:2)to give the compound of the present invention (2 g)having the following physical data.

TCX: Rf and 0.28 (ethyl acetate:hexane=1:1).

Reference example 11

4-tert-Butyldimethylsilyloxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-he

To methylene chloride (10 ml) is added the compound obtained in referential example 10 (1.0 g), and tert-butyldimethylsilyl (784 mg), then add imidazole (708 mg) and the mixture is stirred for 2 hours at room temperature. To the reaction mixture are added methylene chloride (10 ml), dimethylformamide (5 ml) and triethylamine (0.5 ml) and the mixture is stirred over night. The reaction mixture was poured into a mixture of ice-water and extracted with a mixture of hexane and ethyl acetate (1:3). The extract is successively washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=3:1)to give the compound of the present invention (632 mg)having the following physical data.

TCX: Rf 0,61 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 8,02 (DD, J=7,5, 1.5 Hz, 1H), 7,52 (DDD, J=7,5, to 7.5, 1.5 Hz, 1H), 7,45-7,35 (m, 2H), 5,80 (W, 1H)and 4.65 (s, 1H), 1.26 in (s, 3H), of 1.18 (s, 3H), of 0.93 (s, N), of 0.14 (s,3H), 0,00 (s, 3H).

Reference example 12

(Z)-2-(4-tert-Butyldimethylsilyloxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

By the same procedure as described in reference examples 6 to 11 using the compound obtained in reference example 11, instead of the compound obtained in reference example 5, to obtain the compound of the present invention having the following physical data.

TLC: Rf of 0.56 (chloroform:hexane=1:5).

NMR (CDCl3): δ 11,66 (W, 1H), 7,95 (m, 2H), 7,79 (d, J=8.0 Hz, 1H), 7,55-7,30 (m, 6N), 6,32 (s, 1H)and 4.65 (s, 1H), 1,36 (s, 3H)and 1.15 (s, 3H), of 0.95 (s, N), and 0.15 (s, 3H), 0,06 (s, 3H).

Example 42

(Z)-2-(3,3-Dimethyl-4-hydroxy-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

The compound obtained in reference example 12 (810 mg), dissolved in tetrahydrofuran (10 ml), add tetrabutylammonium fluoride (4.0 ml, 1.0 M solution in tetrahydrofuran) at 0°and the mixture is stirred for 3 hours at room temperature. The reaction mixture was poured into a mixture of ice-water and extracted with ethyl acetate. The extract was washed with hydrochloric acid, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=4:1→ 3:2)to give the compound of the present invention (566 mg)having the following physical data.

TLC: Rf value of 0.52 (ethyl acetate:hexane=1:1).

NMR (CDCl3): δ 11,65 (W, 1H), 7,94 (m, 2H), a 7.85 (d, J=8.0 Hz, 1H), 7,60-7,40 (m, 6N), 6,37 (s, 1H), 4,55 (d, J=7.5 Hz, 1H), 2,11 (d, J=7.5 Hz, 1H), 1,37 (s, 3H), of 1.33 (s, 3H).

Example 43

(Z)-2-(3,3-Dimethyl-4-oxo-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

The compound obtained in example 42 (428 mg), dissolved in methylene chloride (40 ml), add pyridineboronic (2793 mg) at room temperature and the mixture is stirred for 6 hours at room temperature. The reaction mixture is filtered. The filtrate is concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=9:1→1:1)to give the compound of the present invention (137 mg)having the following physical data.

TLC: Rf 0.31 in (ethyl acetate:hexane=1:5).

NMR (CDCl3): δ 12,22 (W, 1H), 8,17 (DD, J=7,5, 1.5 Hz, 1H), of 8.06 (m, 1H), 7,97 (m, 2H), 7,76 (DDD, J=7,5, to 7.5, 1.5 Hz, 1H), 7,68 (DDD, J=7,5, to 7.5, 1.5 Hz, 1H), 7,55-7,40 (m, 3H), 6,60 (s, 1H), 1,60 (C, 6N).

Examples 44-44(4)

The transformation into the corresponding salts of the compounds obtained in example 11(80) or 14(8), according to the standard technique get the following compounds of the present invention.

Example 44

Hydrochloride (Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-(adamantane-1-yl)Ethan-1-it

TLC: Rf of 0.25 (ethyl acetate:hexane=1:10).

NMR (CDCl3): δ 7,50 (d, J=8.0 Hz, 1H), 7,35 (DD, J=8,0, 2.0 Hz, 1H), 7,28 (d, J=2.0 Hz, 1H), 4,6 (W, 2H), 2.95 and (s, 2H), 2,09 (m, 3H), of 1.95 (m, 6N), a 1.75 (m, 6N), 1,49 (C, 6N).

Example 44(1)

Methanesulfonate (Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-(adamantane-1-yl)Ethan-1-it

TLC: Rf of 0.25 (ethyl acetate:hexane=1:10).

NMR (CDCl3): δ 7,47 (d, J=8.5 Hz, 1H), 7,39 (DD, J=8,5, 2.0 Hz, 1H), 7,33 (s, 1H), 4,6 (W, 2N), to 3.02 (s, 2H), 2,85 (s, 3H), 2,12 (m, 3H), 1,96 (m, 6N), to 1.76 (m, 6N), 1.55V (C, 6N).

Example 44(2)

Bishydroxamic (Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-(adamantane-1-yl)Ethan-1-it

TLC: Rf 0,68 (ethyl acetate:hexane=1:2).

NMR (CDCl3): δ 7,22 (s, 1H), 6,80 (s, 1H), 2.91 in (s, 2H), 2,12 (m, 3H), of 1.98 (m, 6N), to 1.76 (m, 6N), 1,59 (C, 6N).

Example 44(3)

Mismeasurement (Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-(adamantane-1-yl)Ethan-1-it

TCX: Rf 0,68 (ethyl acetate:hexane=1:2).

NMR (CDCl3): δ 7,58 (s, 1H), 7,30 (s, 1H), 4,94 (W, 6N), 2,99 (s, 2H), 2,85 (C, 6N), is 2.09 (m, 3H), of 1.95 (m, 6N), 1,74 (m, 6N), 1,53 (C, 6N).

Example 44(4)

Methanesulfonate (Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-(adamantane-1-yl)Ethan-1-it

TCX: Rf 0,68 (ethyl acetate:hexane=1:2).

NMR (CDCl3): δ 7,34 (s, 1H), 7,15 (s, 1H), 4,81 (W, 2H), 3.46 in (W, 3H), of 2.86 (s, 2H), and 2.83 (s, 3H), of 2.05 (m, 3H), 1,96 (m, 6N) of 1.73 (m, 6N), of 1.46 (s, 6N).

Example 45

(Z)-2-(6-Cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he

To a solution of the compound obtained in example 30(9) (488 mg)in 1,4-dioxane (10 ml) is added pyridine (0,36 ml), add triperoxonane anhydride (0,32 ml) under ice cooling and the mixture is stirred for 15 minutes. The mixture is dried over anhydrous magnesium sulfate and concentrated. The residue is purified column chromatography on silica gel (hexane:ethyl acetate=15:1→13:1), obtaining the compound of the present invention (305 mg)having the following physical data.

TLC: Rf of 0.44 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,18 (W, 1H), 7,80 (d, J=8.5 Hz, 1H), 7,58 (DD, J=8,5, 1.5 Hz, 1H), of 7.48 (d, J=1.5 Hz, 1H), 5,64 (s, 1H), 2,87 (s, 2H), 2,31 (TT, J=11,5, 3.5 Hz, 1H), 1,89 and 1.80 (m, 4H), to 1.70 (m, 1H), 1,51-1,20 (m, 11N).

Examples 45(1)-45(2)

By the same procedure as described in example 45, using the compound obtained in example 30(10) or 30(11), instead of the compound obtained in example 30(9), gain the following compounds of the present invention.

Example 45(1)

(Z)-2-(6-Cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he

TCX: Rf of 0.45 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,09 (W, 1H), 7,79 (d, J=8.0 Hz, 1H), 7,58 (DD, J=8,0, 1.5 Hz, 1H), 7,47 (d, J=1.5 Hz, 1H), 5,61 (s, 1H), 2,87 (s, 2H), 2,48 (TT, J=10,0, 4.0 Hz, 1H), 1,94-to 1.87 (m, 2H), 1,83-of 1.45 (m, 10H), 129 (, 6N).

Example 45(2)

(Z)-2-(6-Cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he

TCX: Rf of 0.48 (hexane:ethyl acetate=3:1).

NMR (CDCl3): δ 11,34 (W, 1H), 7,81 (d, J=8.0 Hz, 1H), to 7.59 (DD, J=8,0, 1.5 Hz, 1H), of 7.48 (d, J=1.5 Hz, 1H), 5,80 (s, 1H), 2,87 (s, 2H), 2.06 to (W, 3H), 1,90 (W, 6N), 1,74 (W, 6N), of 1.30 (s, 6N).

The pharmaceutical composition 1

The following components were mixed conventional method, dried and extruded, thereby obtain 100 tablets each containing 50 mg of active ingredient.

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-
ilidene)-1-cyclohexylethyl-1-he5.0 g
Calcium salt of carboxymethylcellulose
(disintegrity agent)0.2 g
Magnesium stearate (lubricating agent)0.1 g
Microcrystalline cellulose4.7 grams

The pharmaceutical composition 2

The following components were mixed by a common way. The solution is sterilized by the conventional method, each ampoule was filled with 5 ml portions of the solution and the solution was dried by freezing, while receiving 100 ampoules each containing 20 mg of active ingredient.

(Z)-2-(3,3-Dimethyl-3,4-dihydro-(2H)-isoquinoline-1-
ilidene)-1-cyclohexylethyl-1-he2.0 g
Mannitol20 g
Distilled water1000 ml

1. Derivative 3,4-dihydroisoquinoline of the formula (I)

where R1and R2represent, each independently,

1) hydrogen or

2) C1-4-alkyl or

R1and R2taken together with the carbon atom to which they are attached, form a Cyc1, provided that R1and R2do not represent hydrogen at the same time,

Z represents

1)-CR3R4or

2) -O-,

R3and R4represent, each independently,

1)hydrogen,

2) C1-4-alkyl,

3) hydroxy or

R3and R4taken together with the carbon atom to which they are attached, form a C3-8-cycloalkyl or-C(O)-,

R5and R6represent, each independently

1) hydrogen or

2) C1-4-alkyl or

R5and R6taken together with the carbon atom to which they are attached, form a C3-8-cycloalkyl or 3-8-membered monocyclic heterocyclic ring comprising one heteroatom of oxygen,

Cyc1 performance is made by

1) C3-8-cycloalkyl or

2) 3-8-membered monocyclic heterokonta, including one heteroatom selected from oxygen or nitrogen, Cyc1 may be substituted for R10, R10is

1) C1-4-alkyl, 2) hydroxy, 3) -COOR11, 4) keto or 5) -COR13,

R11represents hydrogen or C1-4-alkyl,

R13are 1) C1-4-alkyl,

R7and R8represent, each independently,

1)hydrogen,

2) C1-4-alkyl,

3) C1-8-alkoxy,

4) hydroxy,

5) cyano,

6) halogen,

7) -COOR14,

8) -CONR15R16,

9) Cyc2A,

10) C2-4-quinil,

11) -NR51R52,

12) nitro,

13) formyl,

14) C2-5 acyl,

15) C1-4-alkyl, substituted hydroxy, C1-4-alkoxy, Susa, -NR51R52or-NR53-Cyc2A,

16) -NR54COR55,

17) -NR56SO2R57,

18) -SO2NR58R59,

19) C2-4-alkenyl, substituted COOR14,

20) -CH=N-OH,

21) -(C1-4-alkylene)-NR60-(C1-4-alkylene)-R61or R14represents hydrogen or C1-4-alkyl, R15and R16represent, each independently, hydrogen or C1-4-alkyl, R51and R52, R58and R59represent, each independently, hydrogen or C1-4-alkyl,

R 53, R54, R56and R60represent, each independently, hydrogen or C1-4-alkyl,

R55represents hydrogen or C1-4-alkyl,

R57represents C1-4-alkyl,

R61is-NR62R63,

R62and R63represent, each independently, hydrogen or C1-4-alkyl, Susa represents a C3-10 monocyclic Carballo or 3-10 membered monocyclic heterokonta containing 1-2 heteroatom selected from oxygen and nitrogen,

hereinafter referred to as "ring", is SUS, but the atom attached to the carbonyl is carbon. As is

1) C3-15 mono-, bi - or tricyclic (condensed) Carballo or

2) 3-10 membered mono - or bicyclic (condensed) heterokonta comprising 1-2 of heteroatom selected from oxygen, nitrogen and sulphur,

SUS and Susa, each independently, may be substituted by 1-3 R17, R17represents 1) a C1-8-alkyl, 2) C2-4-quinil, 3) C1-4-alkoxy, 4) C1-4-alkylthio, 5) hydroxy, (6) halo, 7) nitro, 8) carboxy, 9) formyl, 10) cyano, 11) -NR18R19, 12) phenyl, 13) C1-C4-alkyl or C1-4-alkoxy which can be substituted by 1-3 R21, 14) -COOR27, 15) -COR29, 16) -NR31COR32, 17) -SO2R33, 18) -NR34SO2R35or 19) -SOR64/sup> ,

R18and R19, R31and R34represent, each independently, hydrogen or C1-4-alkyl,

R21represents hydroxy or halogen,

R64represents C1-4-alkyl,

R27, R29, R32, R33and R35present

1) C1-8-alkyl, or 2) phenyl,

SUS represents a benzene ring or thiophene,

(called below the dashed line a), and

(called below the dashed line (b)

represent 1) a bond or (2) double bond.

R91) no or (2) is hydrogen, provided that

1) when the dashed line a represents a bond, the dotted line b represents a double bond and R9no,

2) when the dotted line represents a double bond, the dotted line b represents a bond, and R9is hydrogen and R6no, and

3) excluded 2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he), or its non-toxic salt.

2. The compound according to claim 1, where As represents a benzene ring.

3. The compound according to claim 1, where As represents a thiophene ring.

4. The compound according to claim 2, where Z represents-CR3R4and "ring" represents a C3-15-membered mono-, bi - or critic the practical (condensed) carbocyclic ring.

5. The compound according to claim 2, where Z represents-CR3R4and "the ring" is a 3-10-membered mono - or bicyclic (condensed) heterokonta comprising 1-2 of heteroatom selected from oxygen, nitrogen and sulphur.

6. The compound according to claim 2, where Z represents-O -, and the ring is a C3-15 mono-, bi - or tricyclic (condensed) carbocyclic ring.

7. The compound according to claim 2, where Z represents-O -, and the ring is a C3-10-membered mono - or bicyclic (condensed) ring comprising 1-2 of heteroatom selected from oxygen, nitrogen and sulphur.

8. The compound according to claim 4, which is a

(1) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(2) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-ethoxycarbonylphenyl)ethane-1-he,

(3) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclopentolate-1-he,

(4) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-were)ethane-1-he,

(5) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-were)ethane-1-he,

(6) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-were)ethane-1-he,

(7) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-chlorophenyl)ethane-1-he,

(8) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-chlorophenyl)ethane-1-he,

(9) (Z)-2-(3,3-dimethy the -3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclobutylmethyl-1-he,

(10) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(11) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-chlorophenyl)ethane-1-he,

(12) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(13) (Z)-2-(3,3,5-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(14) (Z)-2-(3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-it.

(15) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-2-yl)Ethan-1-he,

(16) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methoxyphenyl)Ethan-1-he,

(17) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-methoxyphenyl)Ethan-1-he,

(18) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-forfinal)ethane-1-he,

(19) (Z)-2-(3,3,7-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(20) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-1-yl)Ethan-1-he,

(21) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he,

(22) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-forfinal)ethane-1-he,

(23) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-forfinal)ethane-1-he,

(24) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-2-methyl-1-Penilaian-1-he,

(25) (Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-cycle of the hexane]-1-ilidene)-1-Penilaian-1-he,

(26) (Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-cyclopentane]-1-ilidene-)-1-Penilaian-1-he,

(27) (Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-Cycloheptane]-1-ilidene)-1-Penilaian-1-he,

(28) (Z)-2-(3,3-diethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(29) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-ethoxycarbonylphenyl)ethane-1-he,

(30) (Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-CYCLOBUTANE]-1-ilidene)-1-Penilaian-1-he,

(31) (Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,4'-3,4,5,6-tetrahydropyran]-1-ilidene)-1-Penilaian-1-he,

(32) (Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-1'-methylpiperidin]-1-ilidene)-1-Penilaian-1-he,

(33) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-triptoreline)ethane-1-he,

(34) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-triptoreline)ethane-1-he,

(35) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-triptoreline)ethane-1-he,

(36) (Z)-2-(3,3,6,8-tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(37) (Z)-2-(8-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(38) (Z)-2-(6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(39) (Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,4'-piperidine]-1-ilidene)-1-Penilaian-1-he,

(40) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2,6-di is ethylphenyl)ethane-1-he,

(41) (Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-4'-ethoxycarbonylmethoxy]-1-ilidene)-1-Penilaian-1-he,

(42) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclododecyl-1-he,

(43) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-tert-butylphenyl)ethane-1-he,

(44) (Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-4'-oxocyclohexyl]-1-ilidene)-1-Penilaian-1-he,

(45) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-isopropylphenyl)ethane-1-he,

(46) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclooctylmethyl-1-he,

(47) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(1-methylcyclohexyl)ethane-1-he,

(48) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-ethylphenyl)ethane-1-he,

(49) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-butylphenyl)ethane-1-he,

(50) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(1-phenylcyclohexyl)ethane-1-he,

(51) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-propylphenyl)ethane-1-he,

(52) 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-phenylbutane-1-he,

(53) 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-phenylpentane-1-he

(54) (Z)-CIS-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methylcyclohexyl)ethane-1-he,

(55) (Z)-TRANS-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methylcyclohexyl)ethane-1-he,

p num="3435"> (56) (Z)-TRANS-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-methylcyclohexyl)ethane-1-he,

(57) (Z)-CIS-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-methylcyclohexyl)ethane-1-he,

(58) (Z)-CIS-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methylcyclohexyl)ethane-1-he,

(59) (Z)-TRANS-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methylcyclohexyl)ethane-1-he,

(60) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-trifloromethyl)ethane-1-he,

(61) (Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(62) (Z)-2-(5-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(63) (Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(64) (Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(65) (Z)-2-(6-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(66) (Z)-2-(5-Flor-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(67) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-pativilca[2.2.2]Octan-1-yl)Ethan-1-he,

(68) (Z)-TRANS-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-tert-butylcyclohexyl)ethane-1-he,

(69) (Z)-2-(3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(70) (Z)-2-(Spiro[3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-,1'-cyclohexane]-1-ilidene)-1-Penilaian-1-he,

(71) (Z)-2-(6,7-dimethoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(72) (Z)-2-(Spiro[3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-4,1'-cyclopentane]-1-ilidene)-1-Penilaian-1-he,

(73) 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-cyclopentolate-1-he,

(74) 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-cyclohepten-1-he,

(75) 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-phenylpropane-1-he,

(76) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-cyanophenyl)ethane-1-he,

(77) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(78) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-trifloromethyl)ethane-1-he,

(79) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-cyanophenyl)ethane-1-he,

(80) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-trifloromethyl)ethane-1-he,

(81) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-carboxyphenyl)ethane-1-he,

(82) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-carboxyphenyl)ethane-1-he,

(83) (Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-4'-carboxylicacid]-1-ilidene)-1-Penilaian-1-he,

(84) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-hydroxyphenyl)ethane-1-he,

(85) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-hydroxyphenyl)ethane-1-he,

(86) (Z)--(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-hydroxyphenyl)ethane-1-he,

(87) (Z)-2-(6-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(88) 2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-2-methyl-1-phenylpropane-1-he,

(89) 1-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)cyclopentylamine,

(90) 1-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)cyclohexylaniline,

(91) 4-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-3,4,5,6-tetrahydropyran-4-infinicon,

(92) (Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,1'-4'-hydroxycyclohexyl]-1-ilidene)-1-Penilaian-1-he,

(93) (Z)-2-(Spiro[3,4-dihydro-(2H)-isoquinoline-3,4'-1'-acetylpiperidine]-1-ilidene)-1-Penilaian-1-he,

(94) (Z)-2-(6-phenyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(95) (Z)-2-(6-(pyridin-3-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(96) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-hydroxymethylene)ethane-1-he,

(97) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-hydroxymethylene)ethane-1-he,

(98) (Z)-2-(7-isopropyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(99) (Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(100) (Z)-2-(7-ethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(101) (Z)-2-(7-tert-butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(102) (Z)-2-(7-propyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(103) (Z)-2-(7-butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(104) (Z)-2-(7-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(105) (Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(106) (Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(107) (Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he,

(108) (Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(109) (Z)-2-(7-tert-butyl-3,3-dimethyl-3,4-dihydro-(2H)-izochynolyn-1-ilidene)-1-cyclohexylethyl-1-he,

(110) (Z)-2-(7-tert-butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(111) (Z)-2-(7-tert-butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he,

(112) (Z)-2-(7-tert-butyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(113) (Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(114) (Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(115) (Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he,

(116) (Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he,

(117) (Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(118) (Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(119) (Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(120) (Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cycloheptyl tan-1-he,

(121) (Z)-2-(3,3,7-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(122) (Z)-2-(3,3,7-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(123) (Z)-2-(3,3,7-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he,

(124) (Z)-2-(3,3,7-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(125) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-nitrophenyl)Ethan-1-he,

(126) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-nitrophenyl)Ethan-1-he,

(127) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-nitrophenyl)Ethan-1-he,

(128) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2,5-acid)ethane-1-he,

(129) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2,4-acid)ethane-1-he,

(130) (Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-1-yl)Ethan-1-he,

(131) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(anthracene-9-yl)et is n-1-he,

(132) (Z)-2-(3,3,7-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(133) (Z)-2-(7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(134) (Z)-2-(7-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-1-yl)Ethan-1-he,

(135) (Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(136) (Z)-2-(8-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(137) (Z)-2-(8-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(138) (Z)-2-(7-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(139) (Z)-2-(7-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(140) (Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(141) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-bromophenyl)ethane-1-he,

(142) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methylthiophenyl)ethane-1-he,

(143) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-dimethylaminophenyl)ethane-1-he,

(144) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methylphenyl)ethane-1-he,

(145) (Z)-2-(8-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(146) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-ethanol the n-1-ilidene)-1-(2,4-dichlorophenyl)Ethan-1-he,

(147) (Z)-2-(6-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(148) (Z)-2-(6-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(149) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methylnaphthalene-1-yl)Ethan-1-he,

(150) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-fornatale-1-yl)Ethan-1-he,

(151) (Z)-2-(7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(152) (Z)-2-(Spiro[6-chloro-3,4-dihydro-(2H)-isoquinoline-3,4'-3,4,5,6-tetrahydropyran]-1-ilidene)-1-Penilaian-1-he,

(153) (Z)-2-(Spiro[6-chloro-3,4-dihydro-(2H)-isoquinoline-3,4'-3,4,5,6-tetrahydropyran]-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(154) (Z)-2-(Spiro[6-chloro-3,4-dihydro-(2H)-isoquinoline-3,4'-3,4,5,6-tetrahydropyran]-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(155) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(noradsanta-1-yl)Ethan-1-he,

(156) (Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(noradsanta-1-yl)Ethan-1-he,

(157) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-chloro-4-methylphenyl)ethane-1-he,

(158) (Z)-2-(6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(159) (Z)-2-(6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(160) (Z)-2-(7-bromo-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-eskinol the-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(161) (Z)-2-(5-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(162) (Z)-2-(3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(163) (Z)-2-(3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(164) (Z)-2-(7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(165) (Z)-2-(6-chloro-7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(166) (Z)-2-(6-chloro-7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(167) (Z)-2-(6-chloro-7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(168) (Z)-2-(6-chloro-7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(169) (Z)-2-(7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(170) (Z)-2-(7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(171) (Z)-2-(7-amino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(172) (Z)-2-(7-amino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(173) (Z)-2-(6-chloro-7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(174) (Z)-2-(6-chloro-7-dimethylamino-3,3-d is methyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(175) (Z)-2-(6-chloro-7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(176) (Z)-2-(6-chloro-7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(177) (Z)-2-(7-dimethylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(178) (Z)-2-(7-dimethylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(179) (Z)-2-(7-dimethylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(180) (Z)-2-(7-dimethylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(181) (Z)-2-(7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(182) (Z)-2-(7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(183) (Z)-2-(6-methoxy-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(184) (Z)-2-(6-methoxy-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(185) (Z)-2-(7-dimethylamino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(186) (Z)-2-(7-dimethylamino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(187) (Z)-2-(7-dimethylamino-3,3-dimethyl-3,4-dihyd what about-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(188) (Z)-2-(7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(189) (Z)-2-(7-amino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(190) (Z)-2-(7-amino-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(191) (Z)-2-(7-bromo-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoindoline-1-ilidene)-1-cyclohexylethyl-1-he,

(192) (Z)-2-(7-bromo-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(193) (Z)-2-(7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(194) (Z)-2-(7-bromo-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(195) (Z)-2-(7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)ethane-1-he,

(196) (Z)-2-(7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(197) (Z)-2-(7-dimethylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(198) (Z)-2-(7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(199) (Z)-2-(7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(200) (Z)-2-(7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(201) (Z)-2-(7-cyano-6-methoxy-3,3-DIMET is l-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(202) (Z)-2-(7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(203) (Z)-2-(7-cyano-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(204) (Z)-2-(7-cyano-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(205) (Z)-2-(7-cyano-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(206) (Z)-2-(7-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(207) (Z)-2-(7-dimethylaminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(208) (Z)-2-(7-bromo-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(209) (Z)-2-(7-dimethylaminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(210) (Z)-2-(7-nitro-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(211) (Z)-2-(6-methoxy-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(212) (Z)-2-(7-dimethylaminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(213) (Z)-2-(7-nitro-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(214) (Z)-2-(7-nitro-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-illogicality-1-he,

(215) (Z)-2-(7-nitro-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(216) (Z)-2-(7-methylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(217) (Z)-2-(7-methylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(218) (Z)-2-(7-methylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(219) (Z)-2-(7-bromo-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(220) (Z)-2-(6,7-dicyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(221) (Z)-2-(6,7-dicyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(222) (Z)-2-(7-bromo-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(223) (Z)-2-(6,7-dicyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(224) (Z)-2-(6,7-dicyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(225) (Z)-2-(7-methylamino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(226) (Z)-2-(7-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(227) (Z)-2-(7-bromo-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(228) (Z)-2-(6-chloro-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-and chinolin-1-ilidene)-1-cyclohexylethyl-1-he,

(229) (Z)-2-(6-chloro-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(230) (Z)-2-(6-chloro-7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(231) (Z)-2-(7-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(232) (Z)-2-(7-bromo-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(233) (Z)-2-(7-nitro-3,3-dimethyl-3,4-dihydro-(2H)-athinon-1-ilidene)-1-cyclohepten-1-he,

(234) (Z)-2-(7-dimethylsulphamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(235) (Z)-2-(7-butoxycarbonyl-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he. (236) (Z)-2-(7-butoxycarbonyl-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(237) (Z)-2-(7-methylsulfonyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(238) (Z)-2-(6-chloro-7-methoxy-3,3-dimethyl-3,4-dihydro-(2H)isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(239) (Z)-2-(7-methoxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(240) (Z)-2-(7-methoxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(241) (Z)-2-(7-methoxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(242) (Z)-2-(6-b is ω-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(243) (Z)-2-(6-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(244) (Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(245) (Z)-2-(6-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(246) (Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(247) (Z)-2-(8-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(248) (Z)-2-(6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(249) (Z)-2-(8-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(250) (Z)-2-(6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(251) (Z)-2-(3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he,

(252) (Z)-2-(3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(253) (Z)-2-(3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(254) (Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxyphenyl)Ethan-1-he,

(255) (Z)-2-(6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-chlorophenyl)ethane-1-he,

(256) (Z)-2-(6,8-dichloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(257) (Z)-2-(3,3-dimethyl-3,4-dihyd what about-(2H)-isoquinoline-1-ilidene)-1-(2-ethoxyphenyl)ethane-1-he,

(258) (Z)-2-(3,3-dimethyl-3,4-dihydroisoquinoline-1-yl)-1-(adamantane-1-yl)propane-1-he,

(259) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-chloro-2-methoxyphenyl)Ethan-1-he,

(260) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxy-4-methylthiophenyl)ethane-1-he,

(261) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-methoxy-4-methylphenyl)ethane-1-he,

(262) 2-(6-fluoro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-phenylpropane-1-he,

(263) (Z)-2-(6,7-dichloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(264) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-bromo-2-methoxyphenyl)Ethan-1-he,

(265) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-bromo-2-chlorophenyl)ethane-1-he,

(266) (Z)-2-(6-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(267) (Z)-2-(6-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(268) (Z)-2-(6-bromo-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(269) (Z)-2-(6-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(270) (Z)-2-(7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(271) (Z)-2-(7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-1-yl)Ethan-1-he,

(272) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-Illidan)-1-(4-formylphenyl)ethane-1-he,

(273) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-formyl-2-methoxyphenyl)Ethan-1-he,

(274) (Z)-2-(6-chloro-7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(275) (Z)-2-(6-chloro-7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(276) (Z)-2-(6-chloro-7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(277) (Z)-2-(7-formyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(278) (Z)-2-(7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(279) (Z)-2-(7-formyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(280) (Z)-2-(7-formyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(281) (Z)-2-(7-formyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(282) (Z)-2-(7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(283) (Z)-2-(7-formyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(284) (Z)-2-(7-formyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(285)(Z)-2-(7-formyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(286) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoch the nolin-1-ilidene)-1-(4-AMINOPHENYL)Ethan-1-he,

(287) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-AMINOPHENYL)Ethan-1-he,

(288) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-AMINOPHENYL)Ethan-1-he,

(289) (Z)-2-(7-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(290) (Z)-2-(7-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(291) (Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(292) (Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(293) (Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(294) (Z)-2-(7-amino-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(295) (Z)-2-(7-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(296) (Z)-2-(7-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(297) (Z)-2-(7-amino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(298) (Z)-2-(7-amino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(299) (Z)-2-(7-amino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(300) (Z)-2-(7-amino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(30) (Z)-2-(7-amino-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(302) (Z)-2-(6-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(303) (Z)-2-(7-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(304) (Z)-2-(7-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(305) (Z)-2-(6-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(306) (Z)-2-(6-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(307) (Z)-2-(7-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(308) (Z)-2-(7-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(309) (Z)-2-(7-carboxy-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(310) (Z)-2-(7-carboxy-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(311) (Z)-2-(7-carboxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(312) (Z)-2-(7-carboxy-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(313) (Z)-2-(7-carboxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(314) (Z)-2-(7-carboxy-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(315) (Z)-2-(6-carboxy-3,3-dimethyl-3,4-dihydro-(2H)-from the quinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(316) (Z)-2-(3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(2-hydroxyphenyl)ethane-1-he,

(317) (Z)-2-(7-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-1-yl)Ethan-1-he,

(318) (Z)-2-(7-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(319) (Z)-2-(5-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(320) (Z)-2-(6-chloro-7-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(321) (Z)-2-(7-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(322) (Z)-2-(7-hydroxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(323) (Z)-2-(7-phenyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(324) (Z)-2-(7-(pyridin-3-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(325) (Z)-2-(6-(morpholine-4-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(326) (Z)-2-(7-(morpholine-4-yl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(327) (Z)-2-(6-chloro-7-propoxycarbonyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(328) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-methylsulfinylphenyl)ethane-1-he,

(329) (Z)-2-(6-cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he

(330) (Z)-2-(7-(1-hydroxy-1-methylethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(331) (Z)-2-(7-(1-hydroxy-1-methylethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(332) (Z)-2-(7-(1-hydroxy-1-methylethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(333) (Z)-2-(6-acetyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(334) (Z)-2-(7-gidroksimetil-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(335) (Z)-2-(6-gidroksimetil-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(336) (Z)-2-(7-gidroksimetil-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(337) (Z)-2-(7-gidroksimetil-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(338) (Z)-2-(7-gidroksimetil-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(339) (Z)-2-(7-gidroksimetil-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(340) (Z)-2-(7-gidroksimetil-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(341) (Z)-2-(7-gidroksimetil-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(342) (Z)-2-(7-gidroksimetil-3,3-dimethy the -3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(343) (Z)-2-(7-gidroksimetil-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(344) (Z)-2-(7-gidroksimetil-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(345) (Z)-2-(6-aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(346) (Z)-2-(7-aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(347) (Z)-2-(7-aminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(348) (Z)-2-(7-aminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(349) (Z)-2-(7-aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(350) (Z)-2-(7-aminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(351) (Z)-2-(7-aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(352) (Z)-2-(7-aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(353) (Z)-2-(7-aminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(354) (Z)-2-(7-aminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(355) (Z)-2-(7-aminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(357) (Z)-2-(7-cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(358) (Z)-2-(7-cyano-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(359) (Z)-2-(7-(morpholine-4-yl)methyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(naphthalene-1-yl)Ethan-1-he,

(360) (Z)-2-(7-(morpholine-4-yl)methyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(361) (Z)-2-(7-(piperidine-1-yl)methyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(362) (Z)-2-(7-(N-methyl-N-(2-dimethylaminoethyl)aminomethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(363) (Z)-2-(7-(N-(2-hydroxyethyl)-N-methylaminomethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(364) (Z)-2-(7-(N-cyclohexylamino)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(365) (Z)-2-(6-(morpholine-4-yl)methyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(366) (Z)-2-(6-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(367) (Z)-2-(6-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(368) (Z)-2-(7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(369 (Z)-2-(7-dimethylaminomethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(370) (Z)-2-(6-methoxy-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(371) (Z)-2-(7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(372) (Z)-2-(6-methoxy-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(373) (Z)-2-(6-chloro-7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(374) (Z)-2-(7-methylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(375) (Z)-2-(7-dimethylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(376) (Z)-2-(6-chloro-7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(377) (Z)-2-(7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(378) (Z)-2-(6-chloro-7-methylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(379) (Z)-2-(6-chloro-7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(380) (Z)-2-(7-methylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(381) (Z)-2-(7-methylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(382 (Z)-2-(7-dimethylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(383) (Z)-2-(6-chloro-7-methylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(384) (Z)-2-(6-chloro-7-dimethylaminomethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(385) (Z)-2-(7-methylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(386) (Z)-2-(7-dimethylaminomethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(387) (Z)-2-(6-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(388) (Z)-2-(7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(389) (Z)-2-(6-chloro-7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(390) (Z)-2-(6-chloro-7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(391) (Z)-2-(6-chloro-7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(392) (Z)-2-(7-hydroxymethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(393) (Z)-2-(7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(394) (Z)-2-(7-hydroxymethyl-6-methoxy-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(395) (Z)-2-(7-hydroxymethyl-6-methoxy-3,3-DIMET is l-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(396) (Z)-2-(7-hydroxymethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(397) (Z)-2-(7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(398) (Z)-2-(7-hydroxymethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(399) (Z)-2-(7-hydroxymethyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(400) (Z)-2-(7-hydroxymethyl-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(401) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-acetylaminophenol)ethane-1-he,

(402) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-acetylaminophenol)ethane-1-he,

(403) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(3-methylaminophenol)ethane-1-he,

(404) (Z)-2-(7-acetylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(405) (Z)-2-(7-acetylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(406) (Z)-2-(7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(407) (Z)-2-(7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(408) (Z)-2-(6-methylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(409) (Z)-2-(6-dimethylcarbamoyl-3,3-dimethyl-3,4-Digi the ro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(410) (Z)-2-(6-carbarnoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(411) (Z)-2-(7-carbarnoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(412) (Z)-2-(7-methylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(413) (Z)-2-(7-dimethylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(414) (Z)-2-(7-carbarnoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(415) (Z)-2-(7-methylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(416) (Z)-2-(7-dimethylcarbamoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(417) (Z)-2-(6-carbarnoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(418) (Z)-2-(6-carbarnoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(419) (Z)-2-(6-carbarnoyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(420) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyano-2-methoxyphenyl)Ethan-1-he,

(421) (Z)-2-(7-cyano-3,3-dimethyl-3,4-dihydro-(2H)-athinon-1-ilidene)-1-Penilaian-1-he,

(422) (Z)-2-(7-cyano-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(423) (Z)-2-(7-cyano-3,3,6-trimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-cyclohexylidene-1-he,

(424) (Z)-2-(6-ethinyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(425) (Z)-2-(7-ethinyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(426) (Z)-2-(3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-ethynylphenyl)ethane-1-he,

(427) (Z)-2-(6-((E)-2-carboxyethyl)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(428) (Z)-2-(6-((E)-2-methoxycarbonylamino)-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(429) (Z)-2-(6-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(430) (Z)-2-(7-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(431) (Z)-2-(7-carboxy-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohexylethyl-1-he,

(432) (Z)-2-(7-carboxy-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(adamantane-1-yl)Ethan-1-he,

(433) (Z)-2-(7-carboxy-6-chloro-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-cyclohepten-1-he,

(434) (Z)-2-(3,3,4,4-tetramethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-(4-cyanophenyl)ethane-1-he,

(435) (Z)-2-(7-formylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(436) (Z)-2-(6-formylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoquinoline-1-ilidene)-1-Penilaian-1-he,

(437) (Z)-2-(7-methylamino-3,3-dimethyl-3,4-dihydro-(2H)-isoqu