Condensed heterocyclic derivative, therapeutic composition which contains it and its application in medicine

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to condensed heterocyclic derivative, represented by formula (I): where ring A represents 5-member monocyclic heteroaryl, containing 1 or 2 heteroatoms, selected from N or S; RA represents lower alkyl group, optionally substituted with hydroxyl group, COW1, COOW1 or CONW2W3, in which W1-W3 independently represent a hydrogen atom or lower alkyl group; m represents integer 0 or 2; ring B represents benzene ring or thiophene ring; RB represents halogen atom, cyano group, lower alkyl group or OW4, in which W4 represents a hydrogen atom or lower alkyl group; n represents integer 0-2; E1 represents an oxygen atom; E2 represents an oxygen atom; U represents a single bond or lower alkelene group; X represents group, represented by Y, -CO-Y, -SO2-Y, -S-L-Y, -O-L-Y, -CO-L-Y, -SO-L-Y, -SO2-L-Y, -S-Z or -O-Z, in which L represents a lower alkylene group optionally substituted with halogen or hydroxy group; Y represents group, represented by Z or -NW7W8, where W7 and W8 independently represent a hydrogen atom, lower alkyl group or Z on condition that W7 and W8 are not simultaneously hydrogen atoms, or W7 and W8 can bind together with adjacent nitrogen atom with formation of cyclic amino group; Z represents cycloalkyl group, optionally condensed with phenyl and optionally substituted with phenyl group, optionally substituted with halogen or alkoxy group; 6-8-member heterocycoalkyl group, which has 1 heteroatom, selected from nitrogen atom or oxygen atom, optionally condensed with phenyl and optionally substituted with phenyl; phenyl group optionally substituted with a substituent, selected from group, consisting of a halogen atom, cyano group, alkyl group, optionally substituted with halogen atom, hydroxy group or alkoxy group, alkoxy group, optionally substituted with halogen atom, hydroxy group, alkoxy group, alkoxy-carbonyl-oxy group or acyloxy group, alkylthio group, carboxy group and alkoxy-carbonyl group; pyridyl; or its pharmaceutically acceptable salt. Invention also relates to pharmaceutical composition possessing antagonistic activity with respect to gonatotropin-releasing hormone, based on the claimed compound.

EFFECT: obtained are novel compounds and based on them pharmaceutical composition, which can be applied in medicine for prevention or treatment of a disease depending on sex hormones, which is selected from group, consisting of benign prostatic hypertrophy, hysteromyoma, endometriosis, premature puberty, prostate cancer, ovarian cancer and breast cancer.

29 cl, 112 tbl, 428 ex

 

The technical field to which the invention relates

This invention relates to a condensed heterocyclic derivative.

More specifically, this invention relates to a condensed heterocyclic derivative, which have antagonistic activity against gonadotropinreleasing hormone and can be used to prevent or treat dependent on sex hormones diseases, such as benign prostatic hypertrophy, hysteromyoma, endometriosis, metrofibroma, premature puberty, amenorrhea, premenstrual syndrome, dysmenorrhea, or the like, or their prodrugs or pharmaceutically acceptable salts, or their hydrate or solvate, and containing pharmaceutical compositions, etc.

The technical field

Gonadotropinreleasing hormone (GnRH, GnRH is also releasing factor, luteinizing hormone: LHRH, hereinafter called the “GnRH) is a peptide consisting of 10 amino acids: pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2which is secreted from the hypothalamus. GnRH, secreted into the portal vein of the pituitary gland, stimulates the production and secretion of gonadotropin hormones of the anterior lobe of the pituitary gland, luteinizing hormone, LH, and follicle-stimulating hormone, FSH, via receptors, which, according to the I, exist in the anterior pituitary, GnRH receptor. These gonadotropins act on the sex gland, ovary and testis, stimulating follicle growth, ovulation and luteinization and spermatogenesis, as well as stimulate the production and secretion of sex hormones, such as estrogen, progesterone and androgen (see non-Patent reference 1). Thus, antagonists, specifically and selectively acting on GnRH receptors, should regulate the activity of GnRH and regulate the production and secretion of gonadotropin and sex hormones, and therefore, it is expected that they are applicable, as agent for the prevention or treatment dependent on sex hormones diseases.

As an agent that inhibits the function of the GnRH receptor, superagonist GnRH receptor was used as agents for treatment related to sex hormone diseases such as prostate cancer, breast cancer and endometriosis, etc. Superagonist bind GnRH GnRH receptors and show initial temporary stimulating the secretion of gonadotropin effect, the so-called “phenomenon of sudden flare-up”, and then suppress this feature, causing a decrease in gonadotropin and negative regulation of GnRH receptor for its suppression. Thus, superagonist GnRH receptor have the problem lies in the fact that the disease is enevitsa temporarily aggravated due to initially stimulated the secretion of gonadotropin. On the other hand, the mechanism of suppression of GnRH receptor antagonists (hereinafter called “antagonists GnRH”) consists of inhibition of binding to GnRH receptors, and therefore, it is expected that they are suppressing effects instantly without the secretion of gonadotropin. In recent years, as antagonists, peptide GnRH antagonists, such as abarelix and cetrorelix, were developed and used to treat prostate cancer, infertility, etc. However, since these peptide antagonists of GnRH had a poor absorptive capacity, they should not be administered subcutaneously or intramuscularly. Thus, it is desirable to develop ones GnRH antagonist that can be administered orally, and local reactivity at injection can be reduced and the dose can be easily adapted (see non-Patent reference 2).

As a condensed pyrimidine derivatives having ones antagonistic activity against GnRH, known compounds described in Patent references 1 and 2. However, any of the compounds described in Patent reference 1 has a 5-membered heterocyclic ring condensed with the pyrimidine ring, and the aryl substituents on 5-membered geterotsiklicheskikh ring. In addition, the compounds described in Patent reference 2, are derived Piri is Idina, condensed with an aromatic 6-membered ring, and do not always have a sufficiently high oral absorption capacity. In Patent reference 3, which was recently published, describes derivatives of pyrimidine fused with 5-membered heterocyclic ring having ones antagonistic activity against GnRH. However, there is no specific description of these compounds, with the exception of the description of the compounds having sulfonamidnuyu or amide group, and no specific description regarding the kinetics in the blood by oral administration.

As compounds having a pyrimidine ring, a condensed 5-membered heterocyclic ring, along with this, various connections are illustrated as an inhibitor of serine proteases in the Patent reference 4, as an inhibitor of factor XA clotting in Patent reference 5, as the herbicide in Patent reference 6, etc. However, these references do not describe or suggest that the compound having a pyrimidine ring, a condensed 5-membered heterocyclic ring of the present invention has an antagonistic activity against GnRH.

Non-patent reference 1: Hyojun Seirigaku (Standard discrimination), Edition 5, Igakusyoin, pp.882-891.

Non-patent reference 2: Sanka to Fujinka (Obstetrics & Gynecology), 2004, Vol.71, No.3, pp.280-285 and 301-307.

Patent reference 1: Avenue International publication no WO 96/2457.

Patent reference 2: Avenue International publication no WO 2005/019188.

Patent reference 3: Avenue International publication no WO 2006/083005.

Patent reference 4: Description of the Publication of U.S. patent No. 2003/0004167.

Patent reference 5: Avenue International publication no WO 00/39131.

Patent reference 6: Newspaper Publishing Japan patent (Tokuhyo) No. H6-510992.

Description of the invention

Tasks that should be solved by this invention

This invention relates to a connection that has an antagonistic activity against GnRH.

Means for solving these problems

The authors of this invention have conducted serious research to solve the above problems. As a result, it was recently discovered that a pyrimidine derivative, a condensed 5-membered heterocyclic ring represented by the following General formula (I), has an excellent antagonistic activity and demonstrates better kinetics in the blood by oral administration in comparison with the pyrimidine derivative, a condensed aromatic 6-membered ring, forming the basis for this invention.

That is, the present invention relates to:

[1] condensed heterocyclic derivative represented by the formula (I):

where ring A represents A 5-membered cyclizes the second unsaturated hydrocarbon or a 5-membered heteroaryl;

RArepresents a halogen atom, a cyano, a nitro-group, optionally substituted lower alkyl group, optionally substituted lower alkenylphenol group, optionally substituted lower alkylamino group, hydroxylaminopurine group, optionally substituted (lower alkyl)sulfonyloxy group, optionally substituted (lower alkyl)sulfinyl group, tetrazolyl group OW1, SW1That COW1, COOW1, NHCOW1, NHCONW2W3NW2W3, CONW2W3or SO2NW2W3in which W1-W3independently represent a hydrogen atom or optionally substituted lower alkyl group, or W2and W3can bind together with the neighboring nitrogen atom with formation of an optionally substituted cyclic amino group;

m represents an integer of 0-3;

ring B is aryl or heteroaryl;

RBrepresents a halogen atom, cyano, optionally substituted lower alkyl group, OW4That COW4, COOW4or CONW5W6in which W4-W6can bind together with the neighboring nitrogen atom with formation of an optionally substituted cyclic amino group;

n represents an integer of 0-2;

E1represents an oxygen atom, a sulfur atom or N-CN;

E2represents the t oxygen atom or NH;

U is the ordinary bond or optionally substituted lower alkylenes group;

X represents a group represented by Y, -CO-Y, -SO2-Y-S-L-Y, -O-L-Y, -CO-L-Y, -COO-L-Y, -SO-L-Y, -SO2-L-Y-S-Z-O-Z or-COO-Z, in which L represents optionally substituted lower alkylenes group;

Y represents a group represented by Z or-NW7W8where W7and W8independently represent a hydrogen atom, optionally substituted lower alkyl group, or Z, provided that W7and W8are not simultaneously hydrogen atoms, or W7and W8can bind together with the neighboring nitrogen atom with formation of an optionally substituted cyclic amino group;

Z represents optionally condensed and optionally substituted cycloalkyl group, optionally condensed and optionally substituted geterotsyklicescoe group, optionally condensed and optionally substituted aryl group or optionally condensed and optionally substituted heteroaryl group;

or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[2] the condensed heterocyclic derivative, such as described above in [1], where the ring A represents A 5-membered heteroaryl ring, or Proletarsk is at or its pharmaceutically acceptable salt, or its hydrate or MES;

[3] the condensed heterocyclic derivative, such as described above in [2], where the 5-membered heteroaryl ring ring a is any of the thiophene rings represented by the formula:

or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[4] the condensed heterocyclic derivative, such as described above in [3], where the 5-membered heteroaryl ring ring a is a thiophene ring represented by the formula:

or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[5] the condensed heterocyclic derivative, such as described above in any of [1]to[4], where RArepresents a halogen atom, optionally substituted lower alkyl group, COOW1or CONW2W3in which W1-W3independently represent a hydrogen atom or optionally substituted lower alkyl group, or W2and W3can bind together with the neighboring nitrogen atom with formation of an optionally substituted cyclic amino group, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[6] the condensed heterocyclic derivative, t is whom as described above in [5], where RArepresents a lower alkyl group substituted with any group selected from the group consisting of hydroxyl group, carboxypropyl and carbamoyl group; carboxypropyl or karbamoilnuyu group, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[7] the condensed heterocyclic derivative, such as described above in any of [1]to[6], where m is 0 or 1, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[8] the condensed heterocyclic derivative, such as described above in [7], where m is 1 and ring a is a thiophene ring, in which RAassociated with the position of A ring represented by the following General formula:

or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[9] the condensed heterocyclic derivative, such as described above in any of [1]to[8], where E1represents an oxygen atom, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[10] the condensed heterocyclic derivative, such as described above in [1]to[9], where E2represents an oxygen atom, or its prodrug or pharmaceutically acceptable the salt, or its hydrate or MES;

[11] the condensed heterocyclic derivative, such as described above in any of [1]to[10], where the ring B represents a benzene ring, thiophene ring or a pyridine ring, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[12] the condensed heterocyclic derivative, such as described above in [11], where the ring B is any one of rings represented by the formula:

or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[13] the condensed heterocyclic derivative, such as described above in [12], where n is 1 or 2 and the ring B is any ring in which RBassociated with the position of the ring, represented by the following formula:

in this formula, RBhas the above value, and when there are two RBthey may be the same or different from each other, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[14] the condensed heterocyclic derivative, such as described above in [12] or [13], where the ring B is any one of rings represented by the formula:

or it is the prodrug or pharmaceutically acceptable salt, or its hydrate or MES;

[15] the condensed heterocyclic derivative, such as described above in any of [1]to[14], where RBrepresents a halogen atom, optionally substituted lower alkyl group, OW4in which W4represents a hydrogen atom or optionally substituted lower alkyl group, or a cyano, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[16] the condensed heterocyclic derivative, such as described above in [15], where RBrepresents a halogen atom or a lower alkyl group which may be substituted by a halogen atom, or OW4where W4represents a hydrogen atom or optionally substituted lower alkyl group, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[17] the condensed heterocyclic derivative, such as described above in [16], where RBrepresents a fluorine atom, a chlorine atom or OW4where W4represents a lower alkyl group, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[18] the condensed heterocyclic derivative, such as described above in any of [1]to[17], where U is an ordinary bond, methylene group and ethylene group, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[19] the condensed heterocyclic derivative, such as described above in any of [1]to[18], where X represents a group represented by Y-S-L-Y, -O-L-Y, -CO-L-Y, -SO2-L-Y-S-Z or-O-Z, where L, Y, and Z are as defined above values, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[20] the condensed heterocyclic derivative, such as described above in [19], where U is the ordinary bond and X represents a group represented by-S-L-Y, -O-L-Y, -CO-L-Y or-SO2-L-Y in which L and Y have the above specified values, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[21] the condensed heterocyclic derivative, such as described above in [19], in which U represents a methylene group and X represents a group represented by Y, in which Y represents-NW7W8where W7and W8independently represent a hydrogen atom, optionally substituted lower alkyl group, or Z, provided that W7and W8are not simultaneously hydrogen atoms, or W7and W8can bind together with the neighboring nitrogen atom with formation of an optionally substituted cyclic aminogroup is s, -S-Z or-O-Z, where Z is defined above, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[22] the condensed heterocyclic derivative, such as described above in [19], in which U represents an ethylene group and X represents Y, provided that Y is Z and Z is defined above, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[23] the condensed heterocyclic derivative, such as described above in any of [1]to[20], in which L represents a C1-3alkylenes group, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[24] the condensed heterocyclic derivative, such as described above in any of [1]to[23], in which Z represents optionally condensed and optionally substituted aryl group, or its prodrug or pharmaceutically acceptable salt, or hydrate or MES;

[25] the pharmaceutical compositions containing as active ingredient a condensed heterocyclic derivative, such as described above in any of [1]to[24], or its prodrug or pharmaceutically acceptable salt, or a hydrate or MES;

[26] the pharmaceutical compositions of such to whom the above-described in [25], which is an antagonist gonadotropinreleasing hormone;

[27] the pharmaceutical compositions, such as described above in [25], which is an agent for prevention or treatment dependent on sex hormones disease control reproduction, contraceptive, inducing ovulation agent, or the agent for preventing postoperative recurrence is dependent on sex hormones on cancer;

[28] the pharmaceutical compositions, such as described above in [27], where dependent on sex hormones disease selected from the group consisting of benign prostate hypertrophy, hysteromyoma, endometriosis, metrofibroma, premature puberty, amenorrhea, premenstrual syndrome, dysmenorrhea, polycystic ovary, systemic lupus erythematosus, hirsutism, low growth, sleep disorders, acne, baldness, Alzheimer's disease, infertility, irritable bowel syndrome, prostate cancer, uterine cancer, ovarian cancer, breast cancer and cancer of the hypophysis;

[29] a pharmaceutical composition, such as described above in [25], and this composition is an oral composition; and a method of regulation of reproduction, contraception, ovulation induction or prevention of postoperative recurrence is dependent on sex hormones RA is a new disease, which provides for the introduction of an effective amount of the composition; the use of this antagonist for the preparation of pharmaceutical compositions; pharmaceutical compositions, which is a combination with at least one drug selected from the group consisting of agonist gonadotropinreleasing hormones, chemotherapeutic agent, a peptide antagonist gonadotropinreleasing hormone, an inhibitor of 5α-reductase inhibitor α-adrenoceptor, aromatase inhibitor, an inhibitor of the production of adrenal androgen and hormonedisrupting agent; and so on

The effects of the invention

Because of the condensed heterocyclic derivative (I) of this invention or its prodrug or pharmaceutically acceptable salt, or a hydrate or MES has an excellent antagonistic activity against GnRH, it may regulate the effect gonadotropinreleasing hormone and regulate the production and secretion of gonadotropin and sex hormones and as a result it can be used as an agent for the prevention or treatment dependent on sex hormones diseases.

The best way to apply this invention in practice

The meaning of the terms used in this description are as follows.

<> The term "5-membered cyclic unsaturated hydrocarbon" denotes a 5-membered hydrocarbon ring having one or two double bonds.

The term "heteroaryl" denotes a monocyclic heteroaryl having 1 or more heteroatoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, such as thiazole, oxazole, isothiazol, isoxazol, pyridine, pyrimidine, pyrazin, pyridazine, pyrrole, furan, thiophene, imidazole, pyrazole, oxadiazole, thiadiazole, triazole, tetrazole, furazan or similar

The term "optionally substituted" means "can be a substitute.

The term "5-membered heteroaryl" denotes a 5-membered monocyclic heteroaryl, such as the above, and illustration can be, for example, thiazole ring, oxazole, isoxazol, pyrrole, furan, thiophene, imidazole, pyrazole, oxadiazole, thiadiazole, triazole and furazan etc.

The term "aryl" denotes phenyl.

The term "halogen atom" means a fluorine atom, chlorine atom, bromine atom or iodine atom.

The term "lower alkyl" denotes an optionally branched alkyl having 1-6 carbon atoms, such as methyl, ethyl propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl or the like,

The term "lower alkenyl" means optionally branched alkenyl having 2 carbon atoms, such as vinyl, allyl, 1-propenyl, Isopropenyl, 1-butenyl, 2-butenyl, 2-methylallyl or similar

The term "lower quinil" means optionally branched quinil having 2-6 carbon atoms, such as ethinyl, 2-PROPYNYL or similar

The term "(lower alkyl)sulfonyl" means sulfonyl, substituted by the above lower alkyl.

The term "(lower alkyl)sulfinil" means sulfinil, substituted by the above lower alkyl.

The term "lower alkylene" means optionally branched alkylene having 1-6 carbon atoms, such as methylene, ethylene, METROTILE, trimethylene, dimethylmethylene, utilitiles, mutilation, propylethylene, isopropylethylene, dimethylethylene, butylamine, ethylmethylamine, pentamethylene, diethylethylene, dimethyltrimethylene, hexamethylene, diethylethylene or similar

The term "C1-3alkylene" means the above lower alkylene having 1-3 carbon atom.

The term "lower alkoxy" denotes an optionally branched alkoxy having 1-6 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentylamine, neopentylene, tert-pentyloxy, hexyloxy or similar

The term "(lower alkoxy)carbonyl" means optionally branched alkoxycarbonyl having 2-7 carbon atoms.

the Ermin "(lower alkyl)thio" means optionally branched, alkylthio, having 1-6 carbon atoms.

The term "cycloalkyl" denotes a monocyclic cycloalkyl having 3-8 carbon atoms, for example, the illustration may be monocyclic cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl etc.

The term "heteroseksualci" denotes a 3-8-membered heteroseksualci having 1 or more heteroatoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, and optionally having 1 or 2 carbonyl group, such as pyrrolidinyl, piperidinyl, oxopiperidine, morpholinyl, piperazinil, oxopiperidine, thiomorpholine, azepane, diazepan, oxazepines, thiazepines, diocletianopolis, atacanli, tetrahydrofuranyl, tetrahydropyranyl or the like In the presence of the sulfur atom, the sulfur atom may be oxidized.

The term "optionally condensed" means "which may be condensed with a ring selected from the group consisting of the above cycloalkyl, the above-mentioned aryl and above heteroaryl. As "condensed cycloalkyl", "condensed geterotsiklicheskie", "condensed aryl" and "condensed heteroaryl" can be, for example, the indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothiophene, benzoxazole, benzothiazole, benzoic oxazolyl, benzothiazolyl, indazoles, benzimidazoles, chinoline, ethenolysis, phthalazine, honokalani, hintline, cinnoline, indolizinyl, naphthyridine, pteridine, indanyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, indolinyl, isoindolyl, 2,3,4,5-tetrahydrobenzo[b]oxepin, 6,7,8,9-tetrahydro-5H-benzocycloheptene, bromanil etc. and the free valence can be located anywhere on the ring.

The term "cyclic amino" refers to a group having at least one nitrogen atom in the ring in the above-mentioned optionally condensed heteroseksualci. For example, the illustration may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinil, 4-morpholinyl, 4-thiomorpholine, 2,3,4,5,6,7-hexahydro-1H-azepin-1-yl, 1-indolinyl, 2-isoindolyl, 3,4-dihydro-1,5-naphthiridine-1(2H)-yl, 1,2,3,4-tetrahydroquinolin-1-yl, 3,4-dihydroquinoline-1(2H)-yl, 3,4-dihydroisoquinoline-2(1H)-yl, octahedrally-1(2H)-yl, octahydronaphthalene-2(1H)-yl, perhydroxyl-1-yl, 2,3-dihydro-4H-1,4-benzoxazin-4-yl, 2,3-dihydro-4H-1,4-benzothiazin-4-yl, 3,4-dihydroquinoxaline-1(2H)-yl, 2,3-dihydro-4H-pyrid[3,2-b][1,4]oxazin-4-yl, 2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl, 1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl, 3,4-dihydro-1,5-benzoxazepin-5(2H)-yl, 2,3-dihydro-4,1-benzothiazepin-1(5H)-yl, 3,4-dihydro-1,5-benzothiazepin-5(2H)-yl, 2,3-dihydro-4,1-benzoxazepin-1(5H)-yl, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-1-yl, 2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-1-yl, 5,6,7,8-t is trihydro-4H-thieno[3,2-b]azepin-4-yl, 3,4,5,6-tetrahydro-1-benzazocin-1(2H)-yl etc.

The term(di)(lower alkyl)amino” denotes an amino, mono - or disubstituted by the above lower alkyl. Two lower alkyl groups in disubstituted amino may be different and two lower alkyl groups may contact together with the neighboring nitrogen atom with formation of cyclic amino group.

The term(di)(lower alkyl)carbarnoyl” means carbarnoyl, mono - or disubstituted by the above lower alkyl. Two lower alkyl groups in the disubstituted carbamoyl can be different and two lower alkyl groups may contact together with the neighboring nitrogen atom with formation of cyclic amino group.

The term “acyl” denotes an optionally branched aliphatic acyl carboxylic acid having 2 to 7 carbon atoms, cycloalkenyl carboxylic acid, heterocollateral carboxylic acid, arylaryl carboxylic acid or heteroaromatic carboxylic acid.

The term “acylamino” denotes amino, substituted by the above acyl.

In the General formula (I) as rings And preferred is a 5-membered heteroaryl, more preferred is a thiophene ring, and a thiophene ring represented by the following formula:

it is especially preferred. As RAsuppose the equipment is a halogen atom, optionally substituted lower alkyl group, COOW1, CONW2W3in which W1- W3independently represent a hydrogen atom or optionally substituted lower alkyl group, or W2and W3can bind together with the neighboring nitrogen atom with formation of an optionally substituted cyclic amino group, or the like, more preferred is a lower alkyl group substituted by a group selected from the group consisting of hydroxyl group, carboxypropyl and carbamoyl group; more preferred is carboxypropyl or carnemolla group; most preferred is carboxypropyl. In the case when m is 2 or more, RAmay be the same or different. As m preferred are 0 or 1, and when m is 1, ring A, with RAon this ring, thiophene ring represented by the following formula:

it is especially preferred. In this case, as RAmore preferred is optionally substituted lower alkyl group, COOW1or CONW2W3in which W1- W3independently represent a hydrogen atom or optionally substituted lower alkyl group, or W2and W3may contact with with the one nitrogen atom with formation of an optionally substituted cyclic amino group.

In the General formula (I) as E1preferred is an oxygen atom. As E2preferred is a nitrogen atom.

In the General formula (I) as ring B preferred is a benzene ring, thiophene ring or a pyridine ring, and more preferred is a benzene ring or thiophene ring. In this case, places the binding rings are preferred binding sites, represented by the following formula:

and more preferably the binding sites represented by the following formula:

where the left link is the link with the nitrogen atom condensed pyrimidine ring, and the right link is the link with the U.

In the case when n is 1 or 2, as a ring with RBon this ring, preferred are a benzene ring, thiophene ring or a pyridine ring represented by the following formula:

left connection from the presented relations, not related to RBis communication with the nitrogen atom on condensed pyrimidine ring, and the right relationship is communication with U. as RBpreferred is a halogen atom, optionally substituted lower alkyl group, OW4 where W4represents a hydrogen atom or optionally substituted lower alkyl group, cyano, or the like, more preferred is a halogen atom, a lower alkyl group which may be substituted by a halogen atom, or OW4and particularly preferred is a fluorine atom, a chlorine atom or OW4where W4denotes a lower alkyl group. In the case when n is 2, two RBmay be the same or different. In addition, in the case where the ring with RBthis ring is a benzene ring, thiophene ring or a pyridine ring represented by the following formula:

left connection from the presented relations, not associated with any one of RB1and RB2is communication with the nitrogen atom condensed pyrimidine ring, and the right link is a link from U, as RB1preferred is a fluorine atom or a chlorine atom as RB2preferred are a fluorine atom, a methoxy group or ethoxypropan and more preferred is a methoxy group.

In the General formula (I), U denotes preferably ordinary bond, methylene group or ethylene group.

In particular, (i) where U is the ordinary relationship, as X is preferred group, represent the run-S-L-Y, -O-L-Y, -CO-L-Y or-SO2-L-Y, where L is optionally substituted lower alkylenes group; Y represents Z or-NW7W8where W7and W8independently represent a hydrogen atom, optionally substituted lower alkyl group, or Z, provided that both are not simultaneously a hydrogen atom, or W7and W8can communicate with each other together with the adjacent nitrogen atom with formation of an optionally substituted cyclic amino group; Z represents an optionally condensed and optionally substituted cycloalkyl group, optionally condensed and optionally substituted geterotsyklicescoe group, optionally condensed and optionally substituted aryl group or optionally condensed and optionally substituted heteroaryl group, (ii) when U is methylene group, X is preferred group represented by Y, provided that Y represents-NW7W8where W7and W8independently represent a hydrogen atom, optionally substituted lower alkyl group, or Z, provided that both are not simultaneously a hydrogen atom, and W7is preferably Z, or W7and W8can bind together with the neighboring nitrogen atom with formation of an optionally substituted is th cyclic amino group, -S-Z or-O-Z, (iii) when U is ethylene group, X is preferred to Y, provided that Y is Z and Z is above a certain value, because they are good kinetics in the blood.

As L is preferred C1-3lower Allenova group.

As Z is preferred optional condensed and optionally substituted heteroaryl group or an optionally condensed and optionally substituted aryl group, and optionally condensed and optionally substituted aryl group is more preferred. In Z as a substituent, which may be optionally substituted heteroaryl group or an optionally substituted aryl group, preferred are a halogen atom, optionally substituted lower alkyl group or optionally substituted lower alkoxygroup, and more preferred are a halogen atom; a lower alkyl group which may be substituted by halogen atom, lower alkoxygroup or hydroxyl group; or a lower alkoxygroup, which may be substituted by halogen atom, lower alkoxygroup or a hydroxyl group.

As a Deputy, who may be optionally substituted cyclic amino group, optionally sameena cycloalkyl group or optionally substituted heterocytolysine group, can be given as an illustration, for example, oxoprop, halogen atom, cyano, hydroxyl group, optionally substituted lower alkyl group, cycloalkyl group, optionally substituted lower alkoxygroup, optionally substituted (lower alkyl)tighrope, carboxypropyl, optionally substituted (lower alkoxy)carbonyl group, carnemolla group, (di)(lower alkyl)carnemolla group, optionally substituted aryl group, alloctype, heteroaryl group, heteroanalogues, alluminare, etc. and can be the same or different two or more groups selected from these groups, provided as a Deputy, who may have optional forms of substituted cyclic amino group NW2W3in RAthe group, aryl group, excluded from the above groups.

As a Deputy, who may be optional substituted aryl group or optionally substituted heteroaryl group, can be cited as an illustration, for example, a halogen atom, a nitro-group, cyano, hydroxyl group, optionally substituted lower alkyl group, cycloalkyl group, optionally substituted lower alkoxygroup, optionally substituted (lower alkyl)tighrope to roxyrama, optionally substituted (lower alkoxy)carbonyl group, carnemolla group, (di)(lower alkyl)carnemolla group, aryl group, alloctype, heteroaryl group, heteroanalogues, alluminare, etc. and can be the same or different two or more groups selected from these groups.

In optional condensed and optionally substituted cycloalkyl group, optionally condensed and optionally substituted geteroseksualnoe group, optionally condensed and optionally substituted aryl group and optionally condensed and optionally substituted heteroaryl group, the above substituents may be the same or different rings in this condensed cyclic structure.

In the case when Z is optionally condensed and optionally substituted cycloalkyl group or optionally condensed and optionally substituted geteroseksualnoe group, as a substituent, which may be of this group, the preferred Deputy is an aryl group or heteroaryl group.

As a Deputy, who may be optionally substituted lower alkyl, optionally substituted lower Allenova, optionally substituted n is SSA Alchemilla, optionally substituted lower Alchemilla, optionally substituted (lower alkyl)sulfonylurea, optionally substituted (lower alkyl)sulfonylurea, optionally substituted lower alkoxygroup, optionally substituted (lower alkyl)tighrope or optionally substituted (lower alkyl)carbonyl group, aryl group or optionally substituted heteroaryl group and the like, can be cited as an illustration of halogen atom, cyano, hydroxyl group, lower alkoxygroup, (lower alkyl)tighrope, amino, (di)(lower alkyl)amino group, carboxypropyl, (lower alkoxy)carbonyl group, carnemolla group, (di)(lower alkyl)carnemolla group, aryl group, heteroaryl group and the like, and may be the same or different two or more groups selected from these groups, provided that RAgroup, aryl group or heteroaryl group, excluded from the above groups.

One example of methods for obtaining a condensed heterocyclic derivative represented by the General formula (I) of the present invention, is shown below.

Method 1

From among the condensed heterocyclic derivative represented by the General formula (I) of the present invention, a compound in which E1is an oxygen atom can be obtained, for example, according to method 1.

Scheme 14

In this formula, R1represents a nitrile group or a (lower alkoxy)carbonyl group, and ring A, ring b and ring B, RA, RB, m, n, E2, U and X have the above specified values.

Method 1-1

Amine compound (1) can be converted by treatment in an inert solvent (e.g. tetrahydrofuran, dichloromethane, a mixed solvent and the like) using a reagent such as phosgene, diphosgene, triphosgene or the like, in the presence of a base (e.g. triethylamine, N,N-diisopropylethylamine, pyridine or the like) usually under cooling on ice at the temperature of reflux distilled for 30 minutes - 1 day isocyanatobenzene (2).

Method 1-2

The connection of urea (4) or condensed heterocyclic derivative (Ia) of this invention can be obtained by reaction of isocyanatobenzene (2) with amine compound (3) in an inert solvent (e.g. tetrahydrofuran, dichloromethane or the like) in the presence or in the absence of a base (e.g. triethylamine, N,N-diisopropylethylamine, pyridine, 4-dimethylaminopyridine or the like) usually under cooling on ice - at reflux distilled (boiling under reflux) for 1 hour to 3 days.

Method 1-3

Condensed heterocyclic production is the ne (Ia) of this invention can be obtained by reaction of the compound of urea (4) in an inert solvent (for example, tetrahydrofuran, dichloromethane, methanol, ethanol, N,N-dimethylformamide, water or the like) in the presence or in the absence of a base (e.g. triethylamine, N,N-diisopropylethylamine, pyridine, 4-dimethylaminopyridine, sodium methoxide, ethoxide sodium, sodium hydride, sodium hydroxide or the like) usually under cooling on ice at the temperature of reflux distilled (boiling under reflux for 5 minutes to 3 days.

Method 2

From among the condensed heterocyclic derivative represented by the formula (I) of the present invention, a compound in which E2is an oxygen atom, can be obtained, for example, by the method 2.

Scheme 15

In this formula, ring A, ring B, RA, RB, m, n, U and X have the above specified values.

Method 2-1

Amide compound (6) can be obtained by exposure of the connection carboxylic acid (5) and amine compounds (3) condensation of getting using the carboxylic acid or the method using a condensing agent which is usually used for this purpose. Method using a carboxylic acid may be, for example, by treating compound carboxylic acid (5) in an inert solvent (dichloromethane, 1,2-dichloroethane or toluene) using a reagent which, as thionyl chloride, oxalicacid or the like, in the presence or in the absence of additives (for example, N,N-dimethylformamide or the like) usually under cooling on ice at the temperature of reflux distilled for 30 minutes - 1 day to become the acid chloride of carboxylic acid and reaction with amine compound (3) in an inert solvent (pyridine, dichloromethane, tetrahydrofuran, water or the like in the presence or in the absence of a base (triethylamine, N,N-diisopropylethylamine, pyridine, 4-dimethylaminopyridine, potassium carbonate, sodium bicarbonate or the like) usually when cooling ice at the temperature of reflux distilled for 1 hour to 3 days. The method using a condensing agent may be carried out, for example, by reaction of the compound carboxylic acid (5) with amine compound (3) in an inert solvent (N,N-dimethylformamide, dichloromethane or tetrahydrofuran) using a condensing agent hydrochloride (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, dicyclohexylcarbodiimide or the like) in the presence of additives (1-hydroxybenzotriazole or the like) in the presence or in the absence of a base (triethylamine, N,N-diisopropylethylamine, pyridine, 4-dimethylaminopyridine or the like) usually under cooling on ice - when the temperature of reflux distilled (boiling under reflux) for 1 hour to 3 days.

How 2-2

Amine the compound (7) can be obtained by reduction of the nitro amide compound (6) by way catalytic reduction or by way of recovery of hydrogen complex compound of the metal, commonly used, or other Way catalytic reduction can be carried out, for example, by treatment of the amide compound (6) in an inert solvent (methanol, ethanol, ethyl acetate, tetrahydrofuran, acetic acid or the like) using a catalyst (palladium powder coal or the like) typically at room temperature at the temperature of reflux distilled for 1 hour to 3 days. Method of recovering hydrogen complex compound of the metal may be, for example, by treatment of the amide compound (6) in an inert solvent (methanol, ethanol, tetrahydrofuran or the like) using a reducing agent (sodium borohydride or the like) in the presence of additives (bromide, Nickel(II), or the like) usually under cooling on ice at room temperature for 30 minutes to 1 day.

Method 2-3

Condensed heterocyclic derivative (Ib) of this invention can be obtained by treating the amide compound (7) in an inert solvent (tetrahydrofuran, dichloromethane, N,N-dimethylformamide or the like) using a reagent such as phosgene, diphosgene, triphosgene, 1,1'-carbonylbis-1H-imidazole or the like in the presence or in the absence of a base (triethylamine, N,N-diisopropylethylamine, pyridine, 4-dimethylaminopyridine, sodium hydride or the like) usually under cooling on ice - when is the temperature of the reflux distilled for 30 minutes 1 day.

Method 2-4

Condensed heterocyclic derivative (IC) of the present invention can be obtained by treating the amide compound (7) in an inert solvent (tetrahydrofuran, N,N-dimethylformamide, methanol or ethanol) using a reagent such as carbon disulphide or the like, in the presence of a base (triethylamine, N,N-diisopropylethylamine, sodium hydride, sodium hydroxide, potassium hydroxide or the like) usually under cooling in an ice - temperature reflux distilled for 1 hour to 3 days.

Method 2-5

Condensed heterocyclic derivative (Id) of the present invention can be obtained by treating the amide compound (7) in an inert solvent (tetrahydrofuran, dichloromethane, N,N-dimethylformamide, methanol, ethanol or the like) using a reagent such as diphenylcarbonate or the like, in the presence of a base (triethylamine, N,N-diisopropylethylamine, sodium hydride, sodium hydroxide, potassium hydroxide or the like) usually under cooling on ice at the temperature of reflux distilled for 1 hour to 3 days.

Method 3

Amine compound (3)used as starting material in the above method 1 or method 2 can also be obtained by reduction of nitro compounds (8), which is commercially available or synthesized according to the method described in the literature or by combining conventional synthetic methods or the like, by the usual method of recovery or the like, for Example, it can be obtained by the following method 3.

Scheme 16

In this formula, the ring B, RB, n, U and X have the above specified values.

Method 3

Amine compound (3) can be obtained by reduction of nitro compounds (8) by way catalytic reduction or by way of recovery of hydrogen complex compound of the metal, which are usually used, or other Way catalytic reduction can be carried out, for example, processing nitrocompounds (8) in an inert solvent (methanol, ethanol, ethyl acetate, tetrahydrofuran, acetic acid or the like) using a catalyst (palladium powder coal powder rhodium on charcoal, platinum powder coal or the like) typically at room temperature at the temperature of reflux distilled for 1 hour to 3 days. Method of recovering hydrogen complex compound of the metal may be, for example, processing nitrocompounds (8) in an inert solvent (methanol, ethanol, tetrahydrofuran or the like) using a reducing agent (sodium borohydride or the like) in the presence of additives (bromide, Nickel(II), or the like) usually under cooling on ice at room temperature for 30 minutes to 1 day.

In addition, when the connection is giving, used or produced in the above way has a functional group which changes in reaction conditions or inhibits the progression of the reaction, of course, this group may be protected by a suitable protective group commonly used qualified in this field specialist, and this protective group can be removed at an appropriate stage.

Condensed heterocyclic derivative represented by the General formula (I) of this invention may be converted into a prodrug, and its carboxyl group, hydroxyl group and/or amino turn reacts with the reagent to obtain prodrugs. In addition, the prodrug of the condensed heterocyclic derivative represented by the General formula (I) of this invention may be a compound that is converted into compound (I) of the present invention under physiological conditions, as described in “Iyakuhin no Kaihatsu” (Development of medicines), Vol.7, Molecular design, pp.163-198, issued by Hirokawa syoten (Hirokawa Book Store).

Condensed heterocyclic derivative represented by the General formula (I), or its prodrug may be transformed into its pharmaceutically acceptable salt in a conventional manner. As examples of such salt can be, for example, salt with inorganic acid, such as chloride-hydrogen acid, nitric to the slot or the like; salt with organic acid, such as acetic acid, methanesulfonate acid or the like; and sodium salt and potassium salt; an additive salt with an organic base, such as N,N'-dibenziletilendiaminom, 2-aminoethanol or similar

Condensed heterocyclic derivative represented by the General formula (I), or its prodrug can be obtained in the form of a hydrate or of MES during cleaning or getting their salts. For the pharmaceutical compositions of this invention can be used, or a condensed heterocyclic derivative or its prodrug, or pharmaceutically acceptable salt or hydrate or MES.

In addition, the condensed heterocyclic derivative represented by the General formula (I), or its prodrug has sometimes tautomers, geometrical isomers and/or optical isomers. For the pharmaceutical compositions of this invention can be used with any of these isomers and their mixture.

Condensed heterocyclic derivative (I) of the present invention has an excellent antagonistic activity against GnRH and may regulate the action gonadotropinreleasing hormone and regulate the production and secretion of gonadotropin and sex hormones. In the condensed heterocyclic derivative (I) of this image is etenia or its prodrug or pharmaceutically acceptable salt, or its hydrate or MES, is extremely useful as an agent for the prevention or treatment dependent on sex hormones diseases, such as benign prostatic hypertrophy, hysteromyoma, endometriosis, metrofibroma, premature puberty, amenorrhea, premenstrual syndrome, dysmenorrhea, polycystic ovary, systemic lupus erythematosus, hirsutism, low growth, sleep disorders, acne, baldness, Alzheimer's disease, infertility, irritable bowel syndrome, prostate cancer, uterine cancer, ovarian cancer, breast cancer and cancer of the hypophysis; regulator of reproduction, contraceptive, inducing ovulation agent or agent for the prevention of postoperative recurrence is dependent on sex hormones cancer or other

The pharmaceutical composition can be prepared by mixing the condensed heterocyclic derivative (I) of this invention or its prodrugs or its pharmaceutically acceptable salt, or hydrate or MES and conventional pharmaceutical carrier.

This pharmaceutical media may be used optionally in combination in accordance with the dosage form, as described below. Examples of the pharmaceutical carrier can be, for example, excipients, such as lactose and the like; the disintegrators such as carboxymethylcellulose or the like; binding agents such as hypromellose or the like; surfactants, such as macrogol, or the like; solvent additives, such as cyclodextrin or the like; acids such as citric acid or the like; stabilizers, such as edetate sodium or the like; pH regulators such as salt of phosphoric acid or the like

Examples of dosage forms of the pharmaceutical compositions of this invention can be, for example, forms for oral administration, such as powders, granules, fine granules, dry syrups, tablets, capsules and the like; forms for parenteral administration, such as injection solutions, compresses (poultice), suppositories and the like, and a form for oral administration is preferred.

Preferred is the preparation of the above ready-made forms so that the dose of a compound represented by the General formula (I) of the present invention, or its pharmaceutically acceptable salt, or hydrate or MES is preferably within the range of 0.1-1000 mg per day per adult human in the case of oral administration and approximately within the range of 0.01-100 mg per day per adult human in the case of parenteral injections in this form.

In addition, farmacevtichnaasociaciya of the present invention may include other medicinal product (other drugs). Examples of such other drugs include a GnRH agonist (for example, leiprorelina acetate, gonadorelin, buserelin, triptorelin, goserelin, nafarelin, histrelin, deslorelin, peterlin, lateralis etc.), chemotherapeutic agent (e.g., ifosfamide, adriamycin, peplomycin, cisplatin, cyclophosphamide, 5-FU, UFT, methotrexate, mitomycin C, mitoxantrone, paclitaxel, datexel and the like), peptide GnRH antagonist (e.g., cetrorelix, ganirelix, abarelix, ozarelix, auralex, degarelix, teverelix and the like), an inhibitor of 5α-reductase (for example, finasteride, dutasteride, and the like), an inhibitor of α-adrenoceptor (e.g., tamsulosin, silodosin, urapidil and the like), an aromatase inhibitor (for example, fadrozole, letrozole, anastrozole, formestane, and the like), an inhibitor of production of adrenal androgen (e.g., liarozole etc.), hormonotherapy agent (for example, an antiestrogen agent, such as tamoxifen, fulvestrant, etc. that contribute to the onset or continuation of the pregnancy agent, such as medroxyprogesterone, etc., androgenic agent, an estrogenic agent and antiandrogenna agent, such as oxendolone, flutamide, nilutamide, bikalutamid and the like), etc.

EXAMPLES

Further, the invention is additionally illustrated in more detail by the following examples and tests. But they do not limit the image is a buy.

Reference example 1

2-Chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)aniline

To a suspension of 1,2,3,4-tetrahydroquinoline (3.12 g) and sodium hydrogen carbonate (2.66 g) in tetrahydrofuran (60 ml) were added successively water (6 ml) and a solution of 4-chloro-3-nitrobenzenesulfonamide (5,4 g) in tetrahydrofuran (30 ml) and the mixture was stirred at room temperature overnight. This reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with water, 1 mol/l chloride-hydrogen acid, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain 1-[(4-chloro-3-nitrophenyl)sulfonyl]-1,2,3,4-tetrahydroquinoline (5.0 g). This substance was dissolved in tetrahydrofuran (45 ml). To the solution was added methanol (45 ml), bromide, Nickel(II) (0.15 g) and sodium borohydride (1,61 g) under cooling on ice and the mixture was stirred at the same temperature for 30 minutes. Then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silicagel the (eluent: n-hexane/ethyl acetate = 3/1) to obtain specified in the connection header (4,33 g).

Reference examples 2-11

Compounds of reference examples 2-11 described in tables 1-2, has been similarly described in reference example 1 using the appropriate starting materials.

Reference example 12

2-Chloro-5-(3,4-dihydroquinoline-1(2H)-ylmethyl)aniline

To a solution of 4-chloro-3-nitrobenzyl alcohol (1 g) in methylene chloride (10 ml) was added triethylamine (1,12 ml) and methanesulfonamide (0.5 ml) under cooling on ice and the mixture was stirred at room temperature for 10 hours. This reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain (4-chloro-3-nitrobenzyl)nelfinavir (1.08 g). This substance was dissolved in a mixture of acetonitrile (4 ml) - ethanol (4 ml). To the solution was added 1,2,3,4-tetrahydroquinolin (1,62 g) and a catalytic amount of sodium iodide and the mixture was stirred at 60°C over night. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 3/1) to obtain 1-(4-chloro-3-nitrobenzyl)-1,2,3,4-tetrahydro the quinoline (1.22 g). This substance was dissolved in tetrahydrofuran (12 ml). To the solution was added methanol (12 ml), bromide, Nickel(II) (44 mg) and borgert sodium (0,46 g) under cooling on ice and the mixture was stirred at the same temperature for 30 minutes. Then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 3/1) to obtain specified in the connection header (0,79 g).

Reference example 13

3-Benzyloxy-6-Chloroaniline

4-Chloro-3-NITROPHENOL (0,13 g) was dissolved in N,N-dimethylformamide (3 ml). To the solution was added potassium carbonate (0.31 g) and benzylbromide (0,14 ml) and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with diethyl ether and the resulting mixture was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was dissolved in tetrahydrofuran (3 ml). To the solution was added methanol (3 ml), bromide, Nickel(II) (8 mg) and sodium borohydride (85 mg) in ohla the Denia on ice and the mixture was stirred at the same temperature for 30 minutes. Then the mixture was stirred at room temperature for 30 minutes. This reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain specified in the title compound (0.15 g).

Reference examples 14-17

Compounds of reference examples 14 to 17 described in table 2 was obtained similarly to the description in reference example 13 using the appropriate starting materials.

Reference example 18

3-(2-Phenylethyl)aniline

A mixture of 3-bromonitromethane (1 g), styrene (1.7 ml), palladium(II) acetate (95 mg), Tris(2-were)phosphine (0.3 g) and N,N-Diisopropylamine (5 ml) was heated under reflux with reflux distilled within 24 hours. This reaction mixture was diluted with diethyl ether and the resulting mixture was washed successively with 1 mol/l chloride-hydrogen acid, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 10/1) to give 3-((E)-2-phenylphenyl)nitrobenzene (0,76 g). To a solution of the obtained 3-((E)-2-phenylphenyl)nitrobenzene (0.26 g) in methanol (10 is l) was added 10% palladium powder coal (50 mg) and the mixture was stirred at room temperature in a hydrogen atmosphere for 2 hours. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure to obtain specified in the connection header (0,22 g).

Reference example 19

Diethyl-2-aminothiophene-3,4, in primary forms

To a mixture of sulfur (6,9 g), atilirovanie (25 g) and ethylcyanoacrylate (24.4 g) in N,N-dimethylformamide (130 ml) was added triethylamine (21.8 g) for 30 minutes at room temperature and the reaction mixture was stirred at 50°C for 2 hours. To the reaction mixture were added water (1 l) and brine (50 ml) and the resulting mixture was extracted with diethyl ether (250 ml) three times. The extracts were dried over anhydrous magnesium sulfate and purified column chromatography on silica gel (eluent: diethyl ether) to obtain specified in the connection header (28,2 g).

Reference example 20

1-(2-Fluoro-6-methoxyphenyl)ethanol

To a solution of 2-fluoro-6-methoxybenzaldehyde (0.5 g) in tetrahydrofuran (20 ml) was added motility (1.15 mol/l solution in diethyl ether, 3.4 ml) at -78°C and the mixture was stirred at the same temperature for 1 hour. Then the mixture was stirred at room temperature for 30 minutes. To the reaction mixture were added saturated aqueous solution of ammonium chloride and the resulting mixture was extracted with diethyl ether. The extract was washed successively with water and salt, R is the target and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain specified in the title compound (0.45 g).

Reference example 21

2-Fluoro-5-[1-(2-fluoro-6-methoxyphenyl)ethoxy]aniline

To a solution of 4-fluoro-3-NITROPHENOL (this compound was synthesized according to the procedure described in International publication WO 97/39064) (0.2 g), 1-(2-fluoro-6-methoxyphenyl)ethanol (0,22 g) and triphenylphosphine (0.4 g) in tetrahydrofuran (1.5 ml) was added diisopropylethylamine (40% solution in toluene, 0,84 ml) at room temperature and the mixture was stirred at room temperature for 2 hours. This reaction mixture was concentrated under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 8/1) to obtain 2-fluoro-5-[1-(2-fluoro-6-methoxyphenyl)ethoxy]-1-nitrobenzene (0.15 g). This substance was dissolved in tetrahydrofuran (3 ml). To the solution was added methanol (3 ml), bromide, Nickel(II) (5 mg) and sodium borohydride (55 mg) under cooling on ice and the mixture was stirred at the same temperature for 30 minutes. Then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and brine and dried over anhydrous self the volume of magnesium. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 3/1) to obtain the specified title compound (0.11 g).

Reference examples 22-29

Compounds of reference examples 22-29, described in tables 3-4, has been similarly described in reference example 13 and reference example 21, using the appropriate starting materials.

Reference example 30

1-[4-Fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-methyl-1-propanone

To concentrated sulfuric acid (10 ml) was added 1-(4-forfinal)-2-methyl-1-propanone (2,92 g) at -20°C and the mixture was stirred at the same temperature for 15 minutes. To this mixture was added a mixture of fuming nitric acid (1.4 ml) and concentrated sulfuric acid (4,2 ml) at -20°C and the mixture was stirred at the same temperature for 20 minutes. To this reaction mixture was added to ice (100 g) and the mixture was heated to room temperature with stirring. This mixture was extracted with ethyl acetate and the extract was washed successively with water three times, saturated aqueous sodium hydrogen carbonate solution twice and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-g is Xan/ethyl acetate = 95/5 - 85/15) to obtain 1-(4-fluoro-3-nitrophenyl)-2-methyl-1-propanone (1.8 g). This substance was dissolved in ethanol (5 ml). To the solution was added 10% palladium on coal in the form of a powder (0.36 g) and the mixture was stirred at room temperature in a hydrogen atmosphere for 2 hours. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 90/10 - 83/17) to obtain 1-(3-amino-4-(forfinal)-2-methyl-1-propanone (1.45 g). This substance was dissolved in tetrahydrofuran (33 ml). To the solution was added 4-dimethylaminopyridine (0,29 g) and di(tert-butyl)dicarbonate (3,49 g) and the mixture was heated under reflux with reflux distilled for 1.5 hours. The reaction mixture was poured into 0.5 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 95/5) to obtain 1-{4-fluoro-3-[N,N-di(tert-butoxycarbonyl)amino]phenyl}-2-methyl-1-propanone (1.8 g). This substance was dissolved in methanol (15 ml). To the solution was added potassium carbonate (1,96 g) and the mixture was stirred at 60°C for 30 minutes. actionnow the mixture was cooled to room temperature. To the mixture was added water and salt solution and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 5/1) to obtain specified in the connection header (1,14 g).

Reference example 31

1-(3-Amino-4-forfinal)-2-(5-fluoro-2-methoxyphenyl)-2-methyl-1-propanone

A mixture of 1-[4-fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-methyl-1-propanone (0.11 g), 2-bromo-4-fernicola (0,057 ml), palladium(II) acetate (4.5 mg), tetrafluoroborate three(tert-butyl)phosphine (5.8 mg) and tert-butoxide sodium (96 mg) in tetrahydrofuran (1 ml) was stirred at 70°C in argon atmosphere for 3 days. To the reaction mixture were added water and the mixture was stirred for 10 minutes. The mixture was poured into 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 10/1) to give 1-[4-fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-(5-fluoro-2-methoxyphenyl)-2-methyl-1-propanone (45 mg). This substance was dissolved chloride in the hydrogen acid (4 mol/l solution in ethyl acetate, 3 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on aminopropiophenone silica gel (eluent: n-hexane/ethyl acetate = 4/1 - 3/1) to obtain the specified title compound (25 mg).

Reference examples 32-35

Compounds of reference examples 32-35, described in tables 4-5, has been similarly described in reference example 31 using the appropriate starting materials.

Reference example 36

3-(1-Feniletilic)aniline

To a mixture of 3-mercaptoquinoline (1 g) and potassium carbonate (1,21 g) in N,N-dimethylformamide (20 ml) was added 1-fenilatilamin (1.2 ml) and the mixture was stirred at room temperature for 2 hours. To the obtained reaction mixture was added water and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 1/1) to obtain the decree of the frame in the title compound (1.78 g).

Reference example 37

The compound of reference example 37, described in table 5, were obtained analogously to the description in reference example 36, using the appropriate starting material.

Reference example 38

3-(1-Methyl-1-feniletilic)aniline

To a mixed solution of water (1.6 ml) concentrated sulfuric acid (1.6 ml) was added 3-nitrothiophene (0.5 g) and the mixture was stirred at room temperature for 1 hour. To the mixture was added a solution of α-methylstyrene (0,38 g) in tetrahydrofuran (1.6 ml) and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into a mixture of ice water and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water, saturated aqueous sodium bicarbonate and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 3/2) to obtain 3-(1-methyl-1-feniletilic)nitrobenzene (0.88 g). This substance was dissolved in tetrahydrofuran (10 ml). To the solution was added methanol (10 ml), bromide, Nickel(II) (35 mg) and sodium borohydride (0,37 g) under cooling on ice and the mixture was stirred at the same temperature for 30 minutes. Then the mixture was stirred at to matnog temperature for 1 hour. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 3/2) to obtain specified in the connection header (0,69 g).

Reference example 39

3-Amino-4-fluoro-N-methyl-N-phenylbenzene

To a solution of 4-fluoro-3-nitrobenzoic acid (2 g) in methylene chloride (50 ml) was added N,N-dimethylformamide (0.01 ml) and oxacillin (6,86 g) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. The solution of this residue in tetrahydrofuran (10 ml) was added to a mixture of N-methylaniline (1.22 g) and sodium bicarbonate (2,72 g) in tetrahydrofuran (20 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with 1 mol/l chloride-hydrogen acid, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain 4-fluoro-3-nitro-N-methyl-N-phenylbenzene (2,95 g). This substance was dissolved in te is rageragerage (50 ml). To the solution was added methanol (50 ml), bromide, Nickel(II) (0.12 g) and sodium borohydride (1.26 g) under cooling on ice and the mixture was stirred at the same temperature for 30 minutes. Then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 1/1) to obtain specified in the connection header (2,33 g).

Reference example 40

The compound of reference example 40, described in table 5, were obtained analogously to the description in reference example 39, using the appropriate starting material.

Reference examples 41-42

Compounds of reference examples 41-42, described in table 5, were obtained analogously to the description in reference example 21 using the appropriate starting materials.

Reference example 43

4-fluoro-2-methoxy-5-nitrobenzenesulfonamide

A mixture of 3-fluoro-4-NITROPHENOL (2,56 g), potassium carbonate (4.5 g) and iodomethane (4,63 g) in N,N-dimethylformamide (15 ml) was stirred at room temperature overnight. P is a promotional mixture was poured into water and the resulting mixture was washed with diethyl ether. The extract was washed twice with water and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain 3-fluoro-4-nitroanisole (2,56 g). This substance was dissolved in 1,2-dichloroethane (13 ml). To the solution was added chlorosulfonic acid (1.3 ml) and the mixture was heated under reflux with reflux distilled for 4 hours. The reaction mixture was diluted with methylene chloride and the resulting mixture was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 2/1) to obtain the specified title compound (0.51 g).

Reference examples 44-69

Compounds of reference examples 44-69 described in tables 6-9, has been similarly described in reference example 1 using the appropriate starting materials.

Reference example 70

Hydrochloride dimethyl-4-amino-5-methylthiophene-2,3-in primary forms

To a methanol (15 ml) was added sodium (0,38 g) under cooling on ice and the mixture was stirred at the same temperature until dissolution of sodium. To the reaction mixture were added ethyl-2-mercaptopropionate (1,81 g) and dimethylfumarate (2.17 g) and the mixture was heated under reflux with reflux distilled for 3 hours. The reaction is mesh was cooled to room temperature. To the mixture was added water (100 ml) and the resulting mixture was washed with diethyl ether. The aqueous layer was cooled on ice and acidified by adding 2 mol/l chloride-hydrogen acid and the resulting mixture was extracted twice with ethyl acetate. The extracts were combined and washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 4/1 - 3/1) to give 5-methyl-4-oxo-2,3-biotoxicological (2,68 g). This substance was dissolved in methanol (8 ml). To the solution was added hydroxylamine hydrochloride (0,92 g) and the mixture was heated under reflux with reflux distilled for 2 hours. The reaction mixture was cooled to room temperature. To the mixture was added ethyl acetate (24 ml) and the resulting mixture was stirred for 10 minutes. Precipitation was collected by filtration and washed with ethyl acetate and dried under reduced pressure to obtain specified in the connection header (0,77 g).

Reference examples 71-72

Compounds of reference examples 71-72, described in table 9, were obtained analogously to the description in reference example 30 using the appropriate starting materials.

Reference examples 73-77

Compounds of reference examples 73-77, described in tables 9-10, received similarly about is itaniu in reference example 31 using the appropriate starting materials.

Reference example 78

4-Bromo-2-(tert-butoxycarbonylamino)-1-torbenson

To a mixture of 1-bromo-4-fluoro-3-nitrobenzene (1.56 g), Nickel bromide(II) (78 mg), methanol (28 ml) and tetrahydrofuran (28 ml) was added sodium borohydride (805 mg) under cooling on ice and the mixture was stirred at the same temperature for 30 minutes. The mixture was stirred at room temperature for 30 minutes and the reaction mixture was poured into a saturated aqueous solution of sodium bicarbonate. The resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain 5-bromo-2-foronline (1.3 g). This substance was dissolved in tetrahydrofuran (30 ml). To the solution was added 4-dimethylaminopyridine (0.26 g) and di(tert-butyl)dicarbonate (3.1 g) and the mixture was heated under reflux with reflux distilled for 1.5 hours. This reaction mixture was poured into 0.5 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue was added methanol (21 ml) and potassium carbonate (2,94 g) and the mixture was heated under reflux with reflux distilled in those who tell 2 hours. To the reaction mixture were added water and the mixture was poured into brine. The resulting mixture was extracted with ethyl acetate and the extract was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 95/5) to obtain specified in the connection header (1,72 g).

Reference example 79

2-(3-Amino-4-forfinal)-1-(2-methoxyphenyl)-2-methyl-1-propanone

A mixture of 1-(2-methoxyphenyl)-2-methyl-1-propanone (0,58 g), 4-bromo-2-(tert-butoxycarbonylamino)-1-fervently (0,94 g), palladium(II) acetate (37 mg), tetrafluoroborate three(tert-butyl)phosphine (47 mg) and tert-butoxide sodium (0,78 g) in tetrahydrofuran (10 ml) was stirred at 60°C in an argon atmosphere overnight. To the reaction mixture were added water and the mixture was stirred for 10 minutes. The mixture was poured into 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with diethyl ether. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 95/5-85/15) to obtain 2-[3-(tert-butoxycarbonylamino)-4-forfinal]-1-(2-methoxyphenyl)-2-methyl-1-propanone (0,91 g). To the obtained 2-[3-(tert-butoxide is ylamino)-4-forfinal]-1-(2-methoxyphenyl)-2-methyl-1-propanone (0.34 g) was added to chloride-hydrogen acid (4 mol/l solution in ethyl acetate, 3 ml) and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the resulting mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to obtain specified in the connection header (0,22 g).

Reference examples 80-81

Compounds of reference examples 80-81, described in table 10 was obtained analogously to the description in reference example 79 using the appropriate starting materials.

Reference example 82

The compound of reference example 82, described in table 11, has been similarly described in reference example 21 using phenol and 4-chloro-3-nitrobenzyl alcohol instead of 4-fluoro-3-NITROPHENOL and 1-(2-fluoro-6-methoxyphenyl)ethanol, respectively.

Reference example 83

2-Chloro-5-(2-phenylethyl)aniline

To a suspension of 4-chloro-3-nitrobenzaldehyde (1 g) and benzyltriphenylphosphonium (2,34 g) in toluene (35 ml) was added sodium hydride (55%, 0.28 g) and the mixture was stirred at room temperature overnight. To the reaction mixture was added 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with methylene chloride. The extract was washed with saline and dried over anhydrous magnesium sulfate and the solvent was removed is under reduced pressure. The residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 10/1) to give 2-chloro-5-((Z)-2-phenylphenyl)-1-nitrobenzene (0,79 g). Obtained 2-chloro-5-((Z)-2-phenylphenyl)-1-nitrobenzene (0.16 g) was dissolved in a mixture of ethanol (6 ml) - methanol (2 ml). To the solution was added 5% powder of rhodium on coal (20 mg) and morpholine (5 mg) and the mixture was stirred at room temperature in hydrogen atmosphere overnight. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 5/1) to obtain the specified title compound (87 mg).

Reference example 84

1-(tert-Butyloxycarbonyl)-5-ethinyl-2-torbenson

A mixture of 4-bromo-2-(tert-butoxycarbonylamino)-1-fervently (0,57 g), trimethylsilylacetamide (0,55 ml), tetrakis(triphenylphosphine)palladium(0) (23 mg) and copper iodide(I) (7 mg) in N,N-Diisopropylamine (5.7 ml) was stirred at 80aboutWith during the night. The reaction mixture was cooled to room temperature and the mixture was diluted with diethyl ether. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 15/1) to obtain 1-(tert-butoxycarbonylamino)-2-fluoro-5-trimethy is similartylenol (0.6 g). This substance was dissolved in tetrahydrofuran (10 ml). To the solution was added Tetra(n-butyl)unmonitored (1 mol/l solution in tetrahydrofuran, 2.4 ml) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 20/1 - 10/1) to obtain the specified title compound (0.34 g).

Reference example 85

2-Bromo-3,4-differenital

To a solution of 3,4-diferente (2 ml) in tetrahydrofuran (50 ml) was added n-utility or 2.67 mol/l solution in n-hexane, 6,95 ml) at -78°C and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added bromine (1,04 ml) and the mixture was stirred at -78°C for 15 minutes. The mixture was stirred while cooling on ice for 1 hour. To the reaction mixture were added saturated aqueous solution of ammonium chloride and the resulting mixture was extracted with diethyl ether. The extract was washed successively with saturated aqueous sodium hydrogen carbonate solution and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 9/1) to obtain specified in the connection header (0,91 g).

Reference example 86

2-Fluoro-5-(2-phenylethyl)aniline

A mixture of 1-(tert-butoxycarbonylamino)-5-ethinyl-2-fervently (0.11 g), odensala (0.1 g), tetrakis(triphenylphosphine)palladium(0) (16 mg) and copper iodide(I) (5 mg) in N,N-Diisopropylamine (2 ml) was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 10/1) to give 1-(tert-butoxycarbonylamino)-2-fluoro-5-phenylethylene (0.14 g). This substance was dissolved in ethyl acetate (3 ml). To the solution was added 10% palladium powder coal (50 mg) and the mixture was stirred at room temperature in a hydrogen atmosphere for 2 hours. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure to obtain 1-(tert-butoxycarbonylamino)-2-fluoro-5-(2-phenylethyl)benzene (0.11 g). To this material was added chloride-hydrogen acid (4 mol/l solution in ethyl acetate, 3 ml) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the resulting mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and rest rytel was removed under reduced pressure. The residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 8/1 - 5/1) to obtain the specified title compound (53 mg).

Reference examples 87-99

Compounds of reference examples 87-99, described in tables 11-13, has been similarly described in reference example 86 using the appropriate starting materials.

Reference example 100

2-Fluoro-4-methoxy-5-(2-phenylethyl)aniline

A mixture of 2-bromo-5-fluoro-4-nitroanisole (0,46 g), phenylacetylene (67 mg), tetrakis(triphenylphosphine)palladium(0) (38 mg) and copper iodide(I) (13 mg) in N,N-Diisopropylamine (5 ml) was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 10/1 - 5/1) to give 5-fluoro-4-nitro-2-phenylethylamine (0.18 g). This substance was dissolved in ethyl acetate (5 ml). To the solution was added 10% palladium powder coal (0.45 g) and the mixture was stirred at room temperature in a hydrogen atmosphere for 3 hours. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 10/1-4/1) with the floor is the group specified in the title compound (87 mg).

Reference example 101

2-Fluoro-5-[2-(2-methoxyphenyl)-1,1-dimethylethyl)aniline

To a mixture of 2-[3-(tert-butoxycarbonylamino)-4-forfinal]-1-(2-methoxyphenyl)-2-methyl-1-propanone (0,59 g) in a mixture of tetrahydrofuran (7.5 ml) - water (0.75 ml) was added sodium borohydride (0.17 g) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 4/1) to give 2-[3-(tert-butoxycarbonylamino)-4-forfinal]-1-(2-methoxyphenyl)-2-methyl-1-propanol (0.54 g). This substance was dissolved in a mixture of ethanol (8 ml) - tetrahydrofuran (3 ml). To the solution was added 2 mol/l chloride-hydrogen acid (0.2 ml) and 10% palladium powder coal (0.27 g) and the mixture was stirred at room temperature in a hydrogen atmosphere for 5 hours. To the reaction mixture were added sodium bicarbonate and the mixture was stirred for 10 minutes. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 7/1) to obtain 2-[3-(tert-butoxycarbonylamino)-4-CFT is henyl]-1-(2-methoxyphenyl)-2-methylpropane (0.15 g). To this material was added chloride-hydrogen acid (4 mol/l solution in ethyl acetate, 3 ml) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the resulting mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to obtain specified in the title compound (0.11 g).

Reference example 102

4-Chloro-3-nitrothiophene

To the concentrated chloride-hydrogen acid (30 ml) was added 4-chloro-3-nitroaniline (5,18 g) under cooling on ice and the mixture was stirred at the same temperature for 5 minutes. To the mixture was added a solution of sodium nitrite (3.1 g) in water (30 ml). This mixture was heated to 50°C. To the mixture was added a solution of O-utilityservice potassium (14.4 g) in water (60 ml) and the mixture was stirred at 50°C for 1 hour. The reaction mixture was cooled to room temperature and the mixture was extracted twice with diethyl ether. The extracts were combined and washed successively with 1 mol/l aqueous solution of sodium hydroxide, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 7/3) the receipt of O-ethyl-S-(4-chloro-3-nitrophenyl)dithiocarbonate (2,96 g). This substance was dissolved in tetrahydrofuran (50 ml). The solution was added to a suspension of sociallyengaged (1,62 g) in tetrahydrofuran (50 ml) while cooling on ice and the mixture was stirred at room temperature for 10 minutes. The reaction mixture was cooled on ice. To the mixture was added water (1.8 ml), 15% aqueous sodium hydroxide solution (1.8 ml) and water (5.4 ml) and the mixture was stirred at room temperature for 30 minutes. Insoluble material was removed by filtration and the filtrate was diluted with ethyl acetate. The resulting mixture was washed successively with 1 mol/l chloride-hydrogen acid, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 9/1-1/9) to obtain the specified title compound (1.28 g).

Reference example 103

5-Benzylthio-2-Chloroaniline

To a solution of 4-chloro-3-nitrothiophene (0.4 g) and benzylbromide (0.3 ml) in N,N-dimethylformamide (6 ml) was added potassium carbonate (0,44 g) and the mixture was stirred at room temperature for 15 minutes. To the reaction mixture were added water and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed when igenom pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 9/1) to obtain 1-benzylthio-4-chloro-3-nitrobenzene (0.54 g). This substance was dissolved in methanol (5 ml) - tetrahydrofuran (5 ml). To the solution was added bromide, Nickel(II) (21 mg) and sodium borohydride (0,22 g) under cooling on ice and the mixture was stirred at the same temperature for 30 minutes. This mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted sequentially with saturated aqueous sodium hydrogen carbonate solution, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 1/1) to obtain specified in the connection header (0,38 g).

Reference example 104

2-Fluoro-5-mercaptoacetic

To a mixture of 5-bromo-2-foronline (4.15 g) methyl-3-mercaptopropionate (2,62 g), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0,63 g) and N,N-diisopropylethylamine (5,64 g) in 1,4-dioxane (80 ml) was added Tris(dibenzylideneacetone)dipalladium(0) (0.3 g) and the mixture was heated under reflux with reflux distilled in an atmosphere of argon overnight. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 2/1 - 5/1 - 2/1) to give 2-fluoro-5-(2-methoxycarbonylethyl)aniline (4,62 g). This substance was dissolved in tetrahydrofuran (120 ml). To the solution was added tert-piperonyl potassium (1 mol/l solution in tetrahydrofuran, of 80.6 ml) at -78°C and the mixture was stirred at the same temperature for 15 minutes. To the reaction mixture was added 1 mol/l chloride-hydrogen acid (81 ml) and the mixture was heated to room temperature and was stirred for 5 minutes. The mixture was poured into ethyl acetate and the organic layer was separated. The organic layer was washed with saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 4/1) to obtain the specified title compound (1.85 g).

Reference example 105

2-Fluoro-6-methoxybenzyloxy alcohol

To a solution of 2-fluoro-6-methoxybenzaldehyde (0,63 g) in tetrahydrofuran (5 ml) was added water (0.5 ml) and sodium borohydride (0.17 g) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water and the resulting mixture was extracted with diethyl ether. The extract was washed with salt solution and the solvent was removed under reduced pressure to obtain specified in the connection header (0,58 g).

Reference examples 106-107

Connection is sulochna examples 106-107, described in table 14, has been similarly described in reference example 105, using the appropriate starting materials.

Reference example 108

2-Fluoro-6-methoxybenzylamine

To a solution of 2-fluoro-6-methoxybenzyloxy alcohol (0,78 g) and triethylamine (of 0.91 ml) in ethyl acetate (12 ml) was added methanesulfonamide (0,43 ml) while cooling on ice and the mixture was stirred at the same temperature for 30 minutes. Insoluble material was removed by filtration and the insoluble material was washed with ethyl acetate (4 ml). The filtrate and washing were combined. To this mixture was added monohydrate of lithium bromide (2,62 g) and the mixture was stirred at 55°C for 2 hours. The reaction mixture was poured into water and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 7/3) to obtain specified in the connection header (0,82 g).

Reference examples 109-110

Compounds of reference examples 109-110, described in table 14 were obtained analogously to the description in reference example 108, using the appropriate starting materials.

Reference example 111

2-(5-fluoro-2-methoxyphenyl is)-2-propanol

To a solution of 5-fluoro-2-methoxybenzaldehyde (1 g) in acetone (4 ml) was added a solution of potassium permanganate (1.54 g) in water (16 ml) and the mixture was heated under reflux with reflux distilled for 4 hours. The reaction mixture was cooled to room temperature. To the mixture was added 2 mol/l aqueous solution of sodium hydroxide (5.2 ml) and insoluble material was removed by filtration. The filtrate was washed with ethyl acetate. The aqueous layer was acidified by adding 2 mol/l chloride-hydrogen acid and the mixture was extracted twice with ethyl acetate. The extracts were combined and washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 1/1 - ethyl acetate) to obtain 5-fluoro-2-methoxybenzoic acid (0.66 g). This substance was dissolved in N,N-dimethylformamide (15 ml). To the solution was added potassium carbonate (0,63 g) and itmean (0,26 ml) and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain methyl 5-fluoro-2-methoxybenzoate (0.7 g). This substance was dissolved in tetrahydrofuran (10 ml). To dissolve is the added iodide Metalmania (3.0 mol/l solution in diethyl ether, 3,82 ml) while cooling on ice and the mixture was stirred at room temperature for 2 hours. To the reaction mixture were added saturated aqueous solution of ammonium chloride and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 1/1) to obtain the specified title compound (0.65 g).

Reference examples 112-113

Compounds of reference examples 112-113, described in table 14, has been similarly described in reference example 111 using the appropriate starting materials.

Reference example 114

2-Fluoro-5-(2-forbesii)aniline

To a solution of 2-fluoro-5-mercaptoquinoline (0,13 g) and 2-ftorangidridy (0,12 ml) in N,N-dimethylformamide (5 ml) was added potassium carbonate (0.25 g) and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with diethyl ether and the resulting mixture was washed successively with 2 times with water and saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 6/1) to receive the drug specified in the title compound (0.17 g).

Reference examples 115-126

Compounds of reference examples 115-126, described in tables 15-16, has been similarly described in reference example 114 using the appropriate starting materials.

Reference example 127

2-Fluoro-5-(1-methyl-1-feniletilic)aniline

To a mixture of water (10 ml) and concentrated sulfuric acid (10 ml) was added sequentially 2-fluoro-5-mercaptoacetic (1.85 g) and a solution of 2-phenyl-2-propanol (1,76 g) in tetrahydrofuran (10 ml) at room temperature and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice water and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water, saturated aqueous sodium bicarbonate and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 6/1 - 3/1) to obtain the specified title compound (1.55 g).

Reference examples 128-141

Compounds of reference examples 128-141, described in tables 16-18, has been similarly described in reference example 127 using the appropriate starting materials.

Reference example 142

4-fluoro-2-methoxy-5-NITROPHENOL

To a solution of 4-fluoro-2-methoxyphenol (1.42 g) and tri is ylamine (1,67 ml) in methylene chloride (20 ml) was added ethylchloride (1,05 ml) and the mixture was stirred at room temperature for 3 days. The reaction mixture was poured into 0.5 mol/l chloride-hydrogen acid and the resulting mixture was extracted with diethyl ether. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue was added concentrated sulfuric acid (7 ml) under cooling on ice and the mixture was stirred at the same temperature for 15 minutes. To the mixture was added dropwise a mixture of fuming nitric acid (0.7 ml) and concentrated sulfuric acid (1 ml) under cooling on ice and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was poured into ice and the resulting mixture was stirred at room temperature for 30 minutes. This mixture was extracted with ethyl acetate. Extract the intermediate was washed successively with 2 times with water and saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 90/10 - 67/33) to obtain 2-ethoxycarbonyl-5-fluoro-4-nitroanisole (0,48 g). To this material was added methanol (8 ml) and sodium hydrogen carbonate (0.31 g) and the mixture was stirred at room temperature for 42 hours. The reaction mixture was poured into 0.5 mol/l chloride-water the native acid and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue is suspended in a mixed solvent (n-hexane/ethyl acetate = 4/1) and was collected by filtration and dried under reduced pressure to obtain specified in the title compound (0.25 g).

Reference examples 143-147

Compounds of reference examples 143-147, described in tables 18-19, had been similarly described in reference example 142 using the appropriate starting materials.

Reference example 148

2 Ethoxy-4-fluoro-5-NITROPHENOL

To a suspension of 4'-fluoro-2'-hydroxyacetophenone (is 3.08 g), cesium carbonate (13,0 g) and sodium iodide (0.6 g) in N,N-dimethylformamide (20 ml) was added bromatan (2,24 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water and the resulting mixture was extracted with diethyl ether. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To a solution of the residue and 4,4'-THIOBIS(6-tert-butyl-o-cresol) (39 mg) in methylene chloride (57.6 ml) was added 3-chloroperbenzoic acid (equal to 4.97 g) under cooling on ice and the mixture was heated under reflux with reflux distilled during the night. The reaction mixture ohla is given on the ice. To this mixture was added a 10% aqueous solution of sodium sulfite and the mixture was stirred for 20 minutes. The organic layer was separated and washed successively three times with water and saline and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was dissolved in methanol (10 ml) - tetrahydrofuran (20 ml). To the solution was added sodium methoxide (28% methanol solution, 5 ml) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into 0.5 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain 2-ethoxy-4-terfenol (3.0 g). Specified in the title compound was obtained analogously to the description in reference example 142 using this material instead of 4-fluoro-2-methoxyphenol.

Reference example 149

The compound of reference example 149, described in table 19, has been similarly described in reference example 20, using the appropriate starting material.

Reference example 150

2-[2-(tert-Butyldimethylsilyloxy)ethoxy]benzyl alcohol

To a suspension of 2-hydroxybenzoato alcohol (0.4 g) and potassium carbonate (0,67 g) in N,N-dimethylformamide (6 ml)was added 2-(tert-butyldimethylsilyloxy)ethylbromide (1,05 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with diethyl ether and the resulting mixture was washed successively with water, 1 mol/ml aqueous solution of sodium hydroxide, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 5/1) to obtain the specified title compound (0.32 g).

Reference example 151

The compound of reference example 151, described in table 19, has been similarly described in reference example 150 using the appropriate starting material.

Reference example 152

2-(tert-Butyldimethylsilyloxy)benzyl alcohol

To a solution of 1,2-benzylimidazole (2 g) and imidazole (1.13 g) in N,N-dimethylformamide (30 ml) was added tert-butyldimethylchlorosilane (2,08 g) and the mixture was stirred at room temperature for 3 days. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with 1 mol/l chloride-hydrogen acid, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 3/2) to obtain specified in the connection header (1,46 g).

The reference in the career 153-154

Compounds of reference examples 153-154, described in table 20, were obtained analogously to the description in reference example 152 using the appropriate starting materials.

Reference example 155

2,3-Debtor-6-(2-methoxyethoxy)benzyl alcohol

To a suspension of 2,3-debtor-6-hydroxybenzaldehyde (0,63 g) and potassium carbonate (0,83 g) in N,N-dimethylformamide (4 ml) was added 2-methoxyethylamine (0.45 ml) and the mixture was stirred at room temperature for 3 days. The reaction mixture was poured into water and the resulting mixture was extracted with diethyl ether. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 85/15 - 60/40) to obtain 2,3-debtor-6-(2-methoxyethoxy)benzaldehyde (0,62 g). This substance was dissolved in tetrahydrofuran (6 ml). To the solution was added water (0.6 ml) and sodium borohydride (0.12 g) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain specified in the connection header (0,61 g).

Silo the examples 156-159

Compounds of reference examples 156-159, described in table 20, were obtained analogously to the description in reference example 155 using the appropriate starting materials.

Reference example 160

1-(2,3-Debtor-6-methoxyphenyl)-1-cyclobutanol

To a solution of 3,4-diferente (2,47 g) in tetrahydrofuran (50 ml) was added n-utility (2,64 mol/l solution in n-hexane, 6.5 ml) at -78°C and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added a solution of cyclobutanone (1 g) in tetrahydrofuran (20 ml) and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture were added saturated aqueous solution of ammonium chloride and the resulting mixture was extracted with diethyl ether. The extract was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 5/1) to obtain specified in the connection header (2,69 g).

Reference example 161

2-Chloro-5-(1-methyl-1-phenylethane)aniline

To a solution of 4-chloro-3-NITROPHENOL (0.5 g), three(n-butyl)phosphine (0,72 ml) and 2-phenyl-2-propanol (0.26 g) in tetrahydrofuran (5 ml) was added 1,1'-azobis(N,N-dimethylformamide) (0.5 g) and the mixture was stirred at 60°C for 20 h the century The reaction mixture was diluted with diethyl ether and the insoluble material was removed by filtration. The filtrate was concentrated under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 10/1) to give 2-chloro-5-(1-methyl-1-phenylethane)-1-nitrobenzene (0,19 g). This substance was dissolved in tetrahydrofuran (3.5 ml). To the solution was added methanol (3.5 ml), bromide, Nickel(II) (11 mg) and sodium borohydride (0.12 g) under cooling on ice and the mixture was stirred at the same temperature for 30 minutes. Then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 3/1) to obtain the specified title compound (0.14 g).

Reference examples 162-166

Compounds of reference examples 162-166 described in table 21 were obtained analogously to the description in reference example 161 using the appropriate starting materials.

Reference examples 167-308

Compounds of reference examples 167-308 described in the table is 22-41, was obtained analogously to the description in reference example 13 and reference example 21 using the appropriate starting materials.

Reference example 309

4-Cyano-2-fluoro-5-(2,3-debtor-6-methoxybenzyloxy)aniline

4-Bromo-2-fluoro-5-(2,3-debtor-6-methoxybenzyloxy)-1-(tert-butoxycarbonylamino)benzene was synthesized in a manner similar to the method described in reference example 78, using 4-bromo-2-fluoro-5-(2,3-debtor-6-methoxybenzyloxy)aniline instead of 5-bromo-2-foranyone. A mixture of this compound (0.24 g) and copper cyanide(I) (90 mg) in N-methyl-2-pyrrolidone (1 ml) was stirred at 220°C (ambient temperature) for 30 minutes. The reaction mixture was poured into water and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 2/1-1/1) to obtain the specified title compound (54 mg).

Referential example 310

4-Fluoro-3-(2,3-debtor-6-methoxybenzyloxy)aniline

A suspension of 4-fluoro-3-hydroxybenzoic acid (0,19 g), 2,3-debtor-6-methoxybenzylamine (0.6 g) and potassium carbonate (0.5 g) in N,N-dimethylformamide (3 ml) was stirred at room temperature for 8 hours. The reaction mixture was poured input and the resulting mixture was extracted with diethyl ether. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was dissolved in tetrahydrofuran (6 ml). To the solution was added methanol (3 ml), water (3 ml) and the monohydrate of lithium hydroxide (0.5 g) and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 1 mol/l chloride-hydrogen acid (15 ml) and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue is suspended in a mixed solvent (eluent: n-hexane/ethyl acetate = 4/1) and was collected by filtration and dried under reduced pressure to obtain 4-fluoro-3-(2,3-debtor-6-methoxybenzyloxy)benzoic acid (0.31 g). This substance was dissolved in 1,4-dioxane (4 ml). To the solution was added triethylamine (0,41 ml) and diphenylphosphoryl (of 0.21 ml) and the mixture was stirred at room temperature for 1 hour. Then the mixture was heated under reflux with reflux distilled for 4 hours. To the reaction mixture was added 1 mol/l aqueous sodium hydroxide solution (4 ml) and the mixture was stirred at room temperature for 1 hour. This reaction mixture was poured into a saturated aqueous solution of hydrocar is onata sodium and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified (eluent: n-hexane/ethyl acetate = 2/1-1/1) to obtain the crude product. To the crude product were added methylene chloride and the insoluble material was removed by filtration. The solvent of the filtrate was removed under reduced pressure to obtain specified in the title compound (70 mg).

Reference examples 311-321

Compounds of reference examples 311-321, described in tables 41-43, has been similarly described in reference example 13 and reference example 21 using the appropriate starting materials.

Reference example 322

The compound of reference example 322, described in table 43, has been similarly described in reference example 160 using the appropriate starting material.

Reference examples 323-324

Compounds of reference examples 323-324, described in table 43, has been similarly described in reference example 161 using the appropriate starting materials.

Reference example 325

2,3-Debtor-6-methoxyphenol

To a solution of 2,3-debtor-6-methoxybenzaldehyde (2.58 g) in methylene chloride (45 ml) was added 3-chloroperbenzoic acid (5,97 g) under cooling on ice and the mixture was heated under reflux at defle the information during the night. The reaction mixture was cooled on ice. To the mixture was added a 10% aqueous solution of sodium sulfite and the mixture was stirred for 20 minutes. The organic layer was separated and washed successively with 2 times with water, saturated aqueous sodium bicarbonate, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was dissolved in a mixture of tetrahydrofuran (15 ml) - methanol (7.5 ml). To the solution was added sodium methoxide (28% methanol solution of 3.75 ml) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 2/3) and column chromatography on aminopropiophenone silica gel (eluent: ethyl acetate/methanol = 9/1 - 3/2) to obtain the specified title compound (1.7 g).

Reference example 326

The compound of reference example 326, described in table 43, has been similarly described in reference example 325, using the appropriate starting material.

Reference example 327

2,debtor-5-nitrobenzyloxy alcohol

To a solution of 2,4-diferentialglea of 2.27 g) in methylene chloride (6 ml) was added concentrated sulfuric acid (6 ml) under cooling on ice and the mixture was stirred for 15 minutes. To the mixture was added fuming nitric acid (1 ml) under cooling on ice and the mixture was stirred at the same temperature for 30 minutes. Then the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate. To the mixture was added water and the organic layer was separated. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution, 2 times with water and saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 7/3) to give 2,4-debtor-5-nitrobenzaldehyde (2,63 g). The obtained 2,4-debtor-5-nitrobenzaldehyde (1 g) was dissolved in tetrahydrofuran (15 ml). To the solution was added sodium borohydride (0.3 g) and the mixture was stirred at room temperature for 5 minutes. To the reaction mixture was added 1 mol/g chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and stop the current was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 1/1) to obtain specified in the connection header (0,76 g).

Reference example 328

The compound of reference example 328, described in table 43, has been similarly described in reference example 327 using the appropriate starting material.

Reference examples 329-331

Compounds of reference examples 329-331, described in table 44, has been similarly described in reference example 21 using 2,3-debtor-6-methoxyphenol or 2,3-debtor-6-(2-methoxyethoxy)phenol and 4-fluoro-3-nitrobenzyl alcohol or 2,4-debtor-5-nitrobenzyl alcohol or 4-fluoro-2-methoxy-5-nitrobenzyl alcohol instead of 4-fluoro-3-NITROPHENOL and 1-(2-fluoro-6-methoxyphenyl)ethanol, respectively.

Reference example 332

2,3-Debtor-6-(2-methoxyethoxy)aniline

To a suspension of 3,4-differenoe (1,43 g) and cesium carbonate (4,89 g) in N,N-dimethylformamide (10 ml) was added 2-methoxyethylamine (0,94 ml) and the mixture was stirred at room temperature for 4 days. The reaction mixture was poured into water and the resulting mixture was extracted with diethyl ether. The extract was washed successively with 1 mol/l aqueous solution of sodium hydroxide, water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was dissolved in tetrahydrofuran (39 ml). To the solution add the Yali n-utility (2,64 mol/l solution in n-hexane, of 3.25 ml) at -78°C and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added dry ice (10 g) and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was acidified by adding 2 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain 2,3-debtor-6-(2-methoxyethoxy)benzoic acid (1.48 g). The obtained 2,3-debtor-6-(2-methoxyethoxy)benzoic acid (0.5 g) was dissolved in 1,4-dioxane (10 ml). To the solution was added triethylamine (0.45 ml) and diphenylphosphoryl (0,61 ml) and the mixture was stirred at room temperature overnight. To the reaction mixture were added ethanol (0,99 g) and the mixture was heated under reflux with reflux distilled for 5 hours. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with 1 mol/l chloride-hydrogen acid, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. To a suspension of the residue in ethanol (10 ml) was added 5 mol/l aqueous solution of sodium hydroxide (4.3 ml) and the mixture was heated under reflux with reflux distilled for 2 hours. The reaction mixture R is bavlyali with ethyl acetate and the resulting mixture was washed twice with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 3/1) to obtain the specified title compound (75 mg).

Reference example 333

The compound of reference example 333, described in table 44, has been similarly described in reference example 332, using the appropriate starting material.

Reference example 334

2-Fluoro-5-[N-(2,6-differenl)-N-methylamino]methyl-4-methoxyaniline

To a solution of 4-fluoro-2-methoxy-5-nitrobenzyl alcohol (0.3 g) in methylene chloride (5 ml) was added triethylamine (0.31 in ml) and methanesulfonamide (0,14 ml) at room temperature and the mixture was stirred for 3 hours. The reaction mixture was diluted with methylene chloride and the mixture of intermediate compounds with water and saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was dissolved in a mixture of acetonitrile (2 ml) - ethanol (2 ml). To the solution was added a catalytic amount of sodium iodide and 2.6-diferencia (0.45 ml) and the mixture was stirred at 60°C over night. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed with water and saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified count the night chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 2/3) to give 5-fluoro-2-[N-(2,6-differenl)amino]methyl-4-nitroanisole (0,41 g). This substance was dissolved in N,N-dimethylformamide (3 ml). To the solution was added sodium hydride (55%, 84 mg) under cooling on ice and the mixture was stirred at the same temperature for 5 minutes. To the reaction mixture was added itmean (0,096 ml) and the mixture was stirred at room temperature overnight. To the reaction mixture were added saturated aqueous solution of ammonium chloride and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 1/1) to give 5-fluoro-2-[N-(2,6-differenl)-N-methylamino]methyl-4-nitroanisole (0.17 g). This substance was dissolved in methanol (3 ml) - tetrahydrofuran (3 ml). To the solution was added bromide, Nickel(II) (5 mg) and sodium borohydride (52 mg) under cooling on ice and the mixture was stirred at the same temperature for 15 minutes. The mixture was stirred at room temperature for 15 minutes. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and brine and dried over b is wodnym magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane - n-hexane/ethyl acetate = 3/2) to obtain the specified title compound (0.12 g).

Reference example 335

The compound of reference example 335, described in table 44, has been similarly described in reference example 334, using the appropriate starting material.

Reference example 336

2-Fluoro-5-[N-(2-fluoro-6-methoxyphenyl)-N-methylamino]methylaniline

To a solution of 4-fluoro-3-nitrobenzoic acid (1,57 g) in methylene chloride (25 ml) was added N,N-dimethylformamide (0,005 ml) and oxacillin (4,32 g) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. A solution of the residue in tetrahydrofuran (5 ml) was added to a suspension of 2-fluoro-6-methoxyaniline (1.2 g) and sodium hydrogen carbonate (2.14 g) in tetrahydrofuran (10 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water and the resulting mixture ekstragirovaniem with ethyl acetate. The extract was washed successively with 1 mol/l chloride-hydrogen acid, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue is suspended in methylene chloride and collected filtrowanie was dried over anhydrous magnesium sulfate to obtain 4-fluoro-3-nitro-N-(2-fluoro-6-methoxyphenyl)benzamide (1.1 g). This substance was dissolved in N,N-dimethylformamide (12 ml). To the solution was added sodium hydride (55%, 172 mg) and itmean (0,76 g) under cooling on ice and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water and the resulting mixture was extracted with ethyl acetate. The extract was washed three times with water and saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain 4-fluoro-3-nitro-N-(2-fluoro-6-methoxyphenyl)-N-methylbenzamide (1,15 g). The obtained 4-fluoro-3-nitro-N-(2-fluoro-6-methoxyphenyl)-N-methylbenzamide (0.3 g) was dissolved in methanol (10 ml) - tetrahydrofuran (10 ml). To the solution was added bromide, Nickel(II) (10 mg) and sodium borohydride (0.11 g) under cooling on ice and the mixture was stirred at the same temperature for 30 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain 3-amino-4-fluoro-N-(2-fluoro-6-methoxyphenyl)-N-methylbenzamide (0.27 g). This substance was dissolved in tetrahydrofuran (8 ml). To the solution was added to the complex of borane-tetrahydrofuran (1 mol/l solution of those is rageragerage, 3,3 ml) and the mixture was heated under reflux with reflux distilled for 2 hours. To the reaction mixture were added methanol while cooling on ice and the mixture was stirred for 10 minutes. The mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 3/1) to obtain the specified title compound (0.11 g).

Reference examples 337-340

Compounds of reference examples 337-340, described in table 45, has been similarly described in reference example 336 using the appropriate starting materials.

Reference examples 341-342

Compounds of reference examples 341-342, described in table 45, has been similarly described in reference example 325 using the appropriate starting materials.

Reference examples 343-344

Compounds of reference examples 343-344, described in table 45, has been similarly described in reference example 21 using 2,3-debtor-6-(2-ethoxyethoxy)phenol or 2,3-debtor-6-[2-(tert-butyldimethylsilyloxy)ethoxy]phenol and 4-fluoro-3-nitrobenzyl alcohol instead of 4-fluoro-3-NITROPHENOL and 1-(2-fluoro-6-methods is Setenil)ethanol, respectively.

Reference example 345

4-Fluoro-3-nitro-2-methoxybenzoic acid

To 4-fluoro-2-methoxybenzoic acid (0.96 g) was added concentrated sulfuric acid (6 ml) under cooling on ice and the mixture was stirred for 15 minutes. To the mixture was added concentrated nitric acid (0.6 ml) under cooling on ice and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture were added ice and the resulting mixture was stirred at room temperature for 10 minutes. The mixture was extracted with ethyl acetate. The extract was washed twice with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. To the residue was added a mixed solvent (n-hexane/ethyl acetate = 2/1) and the insoluble material was collected by filtration and dried under reduced pressure to obtain specified in the connection header (0,78 g).

Reference example 346

The compound of reference example 346 as described in table 46, has been similarly described in reference example 336, using the appropriate starting material.

Example 1

5-Methoxycarbonyl-3-[2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a suspension of the hydrochloride dimethyl-4-aminothiophene-2,3-in primary forms (0.5 g) and triethylamine (from 0.84 ml) in t is traditionale (10 ml) solution was added triphosgene (0,41 g) in tetrahydrofuran (5 ml) and the mixture was stirred at 60°C for 1 hour. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (8 ml). The solution was added to a solution of 2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)aniline (0.64 g) and 4-dimethylaminopyridine (0,49 g) in tetrahydrofuran (8 ml) and the mixture was stirred at 60°C for 2 hours. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with 1 mol/l chloride-hydrogen acid and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was dissolved in methanol (15 ml). To the solution was added sodium methoxide (28% methanol solution of 1.15 ml) and the mixture was stirred at room temperature for 10 minutes. The reaction mixture was diluted with ethyl acetate and the resulting mixture was washed successively with 1 mol/l chloride-hydrogen acid, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 1/1) to obtain the specified title compound (0.65 g).

Connections 2-21

Compounds of examples 2-21 described in tables 47-49, was obtained analogously to example 1 using appropriate starting materials. However, the case of example 6 was used ethanol and ethoxide sodium instead of methanol and sodium methoxide, respectively.

Example 22

5-Carboxy-3-[2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a solution of 5-methoxycarbonyl-3-[2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione (0.2 g) in methanol (12 ml) - tetrahydrofuran (4 ml) was added monohydrate of lithium hydroxide (0.16 g) and the mixture was stirred at 60°C over night. To the reaction mixture was added 1 mol/l chloride-hydrogen acid and the precipitated crystals were collected by filtration. The crystals were washed with water and dried under reduced pressure to obtain specified in the title compound (0.18 g).

Examples 23-29

Connection examples 23-29, described in tables 50-51, was obtained similarly to example 1 and example 22 using the appropriate starting materials.

Example 30

5-Carbarnoyl-3-[2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a solution of 5-carboxy-3-[2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione (14 mg) in tetrahydrofuran (1 ml) was added 1,1'-carbonylbis-1H-imidazole (9 mg) and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 28% aqueous ammonia (0.5 ml) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl is the Etat and the resulting mixture was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: methylene chloride/methanol = 10/1) to obtain the specified title compound (13 mg).

Example 31

5-Methylcarbamoyl-3-[2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

Specified in the title compound was obtained analogously to the description in example 30, using the appropriate starting material.

Example 32

5-(1-Hydroxy-1-methylethyl)-3-[2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a solution of 5-methoxycarbonyl-3-[2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione (0.1 g) in tetrahydrofuran (10 ml) was added methylmagnesium (3 mol/l solution in diethyl ether, to 0.19 ml) while cooling on ice and the mixture was stirred at room temperature overnight. To the reaction mixture were added saturated aqueous solution of ammonium chloride and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 1/1) to obtain the specified title compound (85 mg).

Example 33

5-Hydroxymethyl-3-[2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a solution of 5-methoxycarbonyl-3-[2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione (0.2 g) in tetrahydrofuran (4 ml) was added diisobutylaluminium (1.01 mol/l solution in toluene, 1.5 ml) under cooling on ice and the mixture was stirred for 1 hour. To the reaction mixture were added ethyl acetate and the mixture was stirred for 10 minutes. To the mixture was added 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 1/1) to obtain the specified title compound (0.11 g).

Example 34

5-Formyl-3-[2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a solution of 5-hydroxymethyl-3-[2-chloro-5-(3,4-dihydroquinoline-1(2H)-ylsulphonyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione (77 mg) in N,N-dimethylformamide (2.1 ml) was added manganese dioxide(IV) (0,77 g) and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and the insoluble material was removed by filtration. Phi is Trat washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 1/1) to obtain the specified title compound (32 mg).

Example 35

5-Methoxycarbonyl-3-{2-fluoro-5-[1-(2-fluoro-6-methoxyphenyl)ethoxy]phenyl}thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a mixture of the hydrochloride dimethyl-4-aminothiophene-2,3-in primary forms (90 mg) and triethylamine (0.15 ml) in tetrahydrofuran (3 ml) solution was added triphosgene (74 mg) in tetrahydrofuran (3 ml) and the mixture was stirred at 60°C for 30 minutes. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (3 ml). The solution was added to a solution of 2-fluoro-5-[1-(2-fluoro-6-methoxyphenyl)ethoxy]aniline (0.1 g) and 4-dimethylaminopyridine (88 mg) in tetrahydrofuran (3 ml) and the mixture was stirred at 60°C over night. To the reaction mixture was added 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was dissolved in methanol (5 ml). To the solution was added sodium methoxide (28% methanol solution of 0.21 ml) and the mixture was stirred at room temperature for 15 minutes. To actionnow mixture was added 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 1/2) to obtain the specified title compound (0.14 g).

Examples 36-47

Connection examples 36-47 described in tables 52-53, has been similarly described in example 35 using the appropriate starting materials.

Example 48

5-Carboxy-3-{2-fluoro-5-[1-(2-fluoro-6-methoxyphenyl)ethoxy]phenyl}thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a mixture of 5-methoxycarbonyl-3-{2-fluoro-5-[1-(2-fluoro-6-methoxyphenyl)ethoxy]phenyl}thieno[3,4-d]pyrimidine-2,4(1H,3H)dione (0.12 g) and methanol (3 ml) was added monohydrate of lithium hydroxide (99 mg) and the mixture was stirred at 50°C for 1 hour. The reaction mixture was acidified by adding 1 mol/l chloride-hydrogen acid and the precipitated crystals were collected by filtration. The crystals were washed with water and dried under reduced pressure to obtain specified in the title compound (0.11 g).

Examples 49-60

Connection examples 49-60, described in tables 53-55, was obtained similarly to the description in example 48 using the appropriate starting materials.

Examples 61-65

Connection examples 61-65 described in table 55, was obtained similarly to the description of the example 35 using the appropriate starting materials.

Examples 66-70

Connection examples 66-70 described in tables 55-56, was obtained similarly to the description in example 48 or example 93 using the appropriate starting materials.

Example 71

The compound of example 71, described in table 56, has been similarly described in example 35, using the appropriate starting material.

Example 72

5-methoxycarbonyl-3-[3-(1-phenylethylamine)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a solution of 5-methoxycarbonyl-3-[3-(1-feniletilic)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione (50 mg) in a mixture of acetone (3 ml) - water (0.6 ml) was added sodium hydrogen carbonate (24 mg) and OXONE (registered trademark) (84 mg) and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with ethyl acetate and the extract was washed successively with 1 mol/l chloride-hydrogen acid, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue is suspended in methanol and collected by filtration and dried under reduced pressure to obtain specified in the title compound (45 mg).

Example 73

5-methoxycarbonyl-3-[3-(1-phenylethylamine)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a solution of 5-methoxycarbonyl-3-[3-(1-feniletilic)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione is (50 mg) in a mixture of acetone (3 ml) - water (0.6 ml) was added sodium hydrogen carbonate (77 mg) and OXONE (registered trademark) (0.28 g) and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with ethyl acetate and the extract was washed successively with 1 mol/l chloride-hydrogen acid, water and brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue is suspended in methanol and collected by filtration and dried under reduced pressure to obtain specified in the title compound (48 mg).

Examples 74-76

Connection examples 74-76, described in tables 56-57, has been similarly described in example 35 using the appropriate starting materials.

Example 77

The compound of example 77, described in table 57, has been similarly described in example 73, using the appropriate starting material.

Example 78

The compound of example 78, described in table 57, has been similarly described in example 35, using the appropriate starting material.

Examples 79-82

Connection examples 79-82, described in table 57, has been similarly described in example 48 using the appropriate starting materials.

Example 83

The compound of example 83, described in table 58, received a similar description is in example 73 in example 48, using the appropriate starting material.

Examples 84-87

Connection examples 84-87 described in table 58, has been similarly described in example 48 using the appropriate starting materials.

Example 88

The compound of example 88, described in table 58, has been similarly described in example 35, using the appropriate starting material.

Examples 89-92

Connection examples 89-92, described in tables 58-59, has been similarly described in example 35 using the appropriate starting materials.

Example 93

5-Carboxy-3-[2-fluoro-5-(N-methyl-N-phenylcarbamoyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

A mixture of 5-methoxycarbonyl-3-[2-fluoro-5-(N-methyl-N-phenylcarbamoyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione (0.18 g) and the monohydrate of lithium hydroxide (0.17 g) in a mixture of tetrahydrofuran (6 ml) - methanol (3 ml) - water (3 ml) was stirred at room temperature for 2 hours. The reaction mixture was poured into 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: methylene chloride/methanol = 8/1) to obtain the specified title compound (0.12 g).

Example 94

The compound of example 94, described in table 59, who was alocale similar to the description in example 35 and example 93, using the appropriate starting material.

Examples 95-97

Connection examples 95-97 described in table 59, has been similarly described in example 93 using the appropriate starting materials.

Examples 98-100

Connection examples 98-100, described in tables 59-60, has been similarly described in example 35 using the appropriate starting materials.

Examples 101-103

Connection examples 101-103, described in table 60, was obtained similarly to the description in example 48 using the appropriate starting materials.

Examples 104-108

Connection examples 104-108 described in table 61, was obtained similarly to the description in example 1 using the appropriate starting materials.

Examples 109-201

Connection examples 109-201, described in tables 61-74, was obtained similarly to the description in example 1 and example 48 or example 93 using the appropriate starting materials.

Example 202

5-Carboxy-3-[2-fluoro-5-(1-methyl-1-phenylethylamine)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

5-Methoxycarbonyl-3-[2-fluoro-5-(1-methyl-1-feniletilic)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione was obtained by the method similar to the method described in example 35, using 2-fluoro-5-(1-methyl-1-feniletilic)aniline instead of 2-fluoro-5-[1-(2-fluoro-6-methoxyphenyl)ethoxy]aniline. This compound (0.1 g) was dissolved in methylene chloride (2 ml). To a solution of doba is Lyali 3-chloroperbenzoic acid (92 mg) and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water. To the mixture was added 1 mol/l aqueous solution of sodium thiosulfate and the mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 1/1-1/2) to obtain 5-methoxycarbonyl-3-[2-fluoro-5-(1-methyl-1-phenylethylamine)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione (0.1 g). Specified in the title compound was obtained analogously to the description in example 93 using the obtained 5-methoxycarbonyl-3-[2-fluoro-5-(1-methyl-1-phenylethylamine)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione instead of 5-methoxycarbonyl-3-[2-fluoro-5-(N-methyl-N-phenylcarbamoyl)phenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione.

Examples 203-232

Connection examples 203-232, described in tables 75-79, was obtained similarly to the description in example 202 using the appropriate starting materials.

Example 233

5-Carboxy-3-[2-fluoro-5-(2,3-debtor-6-methoxybenzyloxy)-4-methoxyphenyl]thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a suspension of the hydrochloride dimethyl-4-aminothiophene-2,3-in primary forms (of 0.13 g) and triethylamine (of 0.21 ml) in tetrahydrofuran (5 ml) was added triphosgene (99 mg) under cooling on ice and the mixture was stirred at 60°C for 30 minutes. The reaction mixture razbam the Yali with ethyl acetate and the insoluble material was removed by filtration. The filtrate was concentrated under reduced pressure and the residue was dissolved in tetrahydrofuran (4 ml). This solution was added to a solution of 2-fluoro-5-(2,3-debtor-6-methoxybenzyloxy)-4-methoxyaniline (0.16 g) and 4-dimethylaminopyridine (0.12 g) in tetrahydrofuran (4 ml) and the mixture was stirred at 60°C for 3 days. The reaction mixture was passed through IST ISOLUTE SCX and suirable with ethyl acetate. The eluate was concentrated under reduced pressure and the residue was dissolved in methanol (5 ml). To the solution was added sodium methoxide (28% methanol solution of 0.29 ml) and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture was added 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. A mixture of this residue and monohydrate of lithium hydroxide (0.21 g) in a mixture of tetrahydrofuran (4 ml) - methanol (2 ml) - water (2 ml) was stirred at room temperature for 30 minutes. The reaction mixture was poured into 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column of chromatogra what s on silica gel (eluent: n-hexane/ethyl acetate = 1/2 - the ethyl acetate) to obtain specified in the connection header (0,13 g).

Examples 234-391

Connection examples 234-391 described in tables 79-102, was obtained similarly to the description in example 233 using the appropriate starting materials.

Example 392

The compound of example 392, described in table 102, obtained similarly to the description in example 35 and example 33, using the appropriate starting material.

Examples 393-395

Connection examples 393-395, described in table 102, has been similarly described in example 30 using the appropriate starting materials.

Example 396

5-Carboxy-3-{2-fluoro-5-[2,3-debtor-6-(2-hydroxyethoxy)benzyloxy]phenyl}thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a suspension of the hydrochloride dimethyl-4-aminothiophene-2,3-in primary forms (0.11 g) and triethylamine (0,19 ml) in tetrahydrofuran (5 ml) was added triphosgene (84 mg) under cooling on ice and the mixture was stirred at 60°C for 30 minutes. The reaction mixture was diluted with ethyl acetate and the insoluble material was removed by filtration. The filtrate was concentrated under reduced pressure and the residue was dissolved in tetrahydrofuran (4 ml). This solution was added to a solution of 2-fluoro-5-{2,3-debtor-6-[2-(tert-butyldimethylsilyloxy)ethoxy]benzyloxy}aniline (0.17 g) and 4-dimethylaminopyridine (99 mg) in tetrahydrofuran (4 ml) and this mixture peremeci the Ali at 60°C over night. The reaction mixture was passed through IST ISOLUTE SCX and suirable with ethyl acetate. The eluate was concentrated under reduced pressure and the residue was dissolved in methanol (4 ml). To the solution was added sodium methoxide (28% methanol solution of 0.23 ml) and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture was added 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed with saline and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was dissolved in tetrahydrofuran (4 ml). To the solution was added Tetra(n-butyl)unmonitored (1 mol/l solution in tetrahydrofuran, 1.2 ml) and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with 1 mol/l chloride-hydrogen acid, water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. A mixture of this residue and monohydrate of lithium hydroxide (0.17 g) in a mixture of tetrahydrofuran (5 ml) - methanol (2.5 ml) - water (2.5 ml) was stirred at room temperature for 30 minutes. To the reaction mixture was added 1 mol/l chloride-hydrogen acid and the resulting mixture ex who was regionali with ethyl acetate. The extract was washed successively with water and brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: ethyl acetate) to obtain specified in the connection header (0,13 g).

Examples 397-410

Connection examples 397-410, described in tables 102-104, was obtained similarly to the description in example 396 using the appropriate starting materials.

Examples 411-416

Connection examples 411-416, described in tables 104-105, was obtained similarly to the description in example 233 using the appropriate starting materials.

Example 417

5-Etoxycarbonyl-3-{2-fluoro-5-[2,3-debtor-6-(2-hydroxyethoxy)benzyloxy]phenyl}thieno[3,4-d]pyrimidine-2,4 (1H,3H)dione

To a suspension of 5-carboxy-3-{2-fluoro-5-[2,3-debtor-6-(2-hydroxyethoxy)benzyloxy]phenyl}thieno[3,4-d]pyrimidine-2,4 (1H,3H)dione (0.65 g) in a mixture of ethanol (10 ml) - tetrahydrofuran (5 ml) was added monohydrate p-toluensulfonate acid (24 mg) and the mixture was stirred at 90°C (ambient temperature) during the night. The reaction mixture was concentrated under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 1/2 - 1/4) to obtain the specified title compound (0.39 g).

Example 418

5-Etoxycarbonyl-3-(5-{6-[2-(this is ccarbonate)ethoxy]-2,3-deferasirox}-2-forfinal)thieno[3,4-d]pyrimidine-2,4(1H,3H)dione

To a suspension of 5-etoxycarbonyl-3-{2-fluoro-5-[2,3-debtor-6-(2-hydroxyethoxy)benzyloxy]phenyl}thieno[3,4-d]pyrimidine-2,4 (1H,3H)dione (80 mg) in ethyl acetate (2 ml) was added pyridine (0.036 ml) and ethylchloride (0,021 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was poured into 1 mol/l chloride-hydrogen acid and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and saline and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 1/2) to obtain the specified title compound (38 mg).

Example 419

The compound of example 419, described in table 106, obtained similarly to the description in example 418, using the appropriate starting material.

Examples 420-426

Connection examples 420-426, described in tables 106-107, was obtained similarly to the description in example 233 using the appropriate starting materials.

Example 427

Connection example 427 described in table 107, has been similarly described in example 396, using the appropriate starting material.

Example 428

The compound of example 428, described in table 107, was obtained similarly to the description in example 233 using sootvetstvuyushchego material.

Table 1-46 and tables 47-107 show the chemical structure and1H-NMR-data of the above compounds of reference examples 1-346 and examples 1-428, respectively.

The abbreviations in these tables: “Ref No.”, Ex No.”, “Strc” and “Solv” indicate the Number of the reference example, example, the chemical structure and the solvent for measurement1H-NMR, respectively.

Table 1
Scalp No.Structure1H-NMR (CDCl3) δ ppm:
11,6-of 1.75 (2H, m), 2.49 USD (2H, t, J=6.5 Hz), 3.75 to of 3.85 (2H, m), 4.2V (2H, users), 6.8 or 6.9 (1H, m), of 6.96 (1H, d, J=1,8 Hz), 7,0 is 7.3 (4H, m), 7,7-7,8 (1H, m)
21,5-of 1.65 (2H, m), 1.7 to 1.9 (2H, m), of 2.4-2.5 (2H, m), 3,55-of 3.85 (2H, m), 4,22 (2H, users), 7,0-7,05 (1H, m), to 7.09 (1H, d, J=2.0 Hz), 7,1-7,3 (4H, m), 7,31 (1H, d, J=8,4 Hz)
33,18 (3H, s), 4,22 (2H, users), 6,8-6,85 (1H, m), 6,9 (1H, d, J=2.0 Hz), a 7.1 to 7.15 (2H, m), a 7.2 to 7.35 (4H, m)
4 0,9-1,1 (1H, m), 1,2-1,4 (4H, m), 1,45-of 1.65 (3H, m), 1,7-1,8 (2H, m), is 2.74 (3H, s), 3,65 to 3.8 (1H, m), 4,28 (2H, users), 7,05 and 7.1 (1H, m), 7,2 (1H, d, J=2.2 Hz), 7,34 (1H, d, J=8,5 Hz)
5of 3.28 (3H, s), 4,22 (2H, users), 6,8-6,85 (1H, m), 6,97 (1H, d, J=2.4 Hz), a 7.1 to 7.15 (1H, m), 7,25 of 7.3 (1H, m), and 7.6 to 7.75 (2H, m), 8,25-8,35 (1H, m)
6is 3.21 (3H, s), 4.26 deaths (2H, users), 7,05 and 7.1 (1H, m), 7,14 (1H, d, J=1.9 Hz), 7,2-7,3 (3H, m), of 7.36 (1H, d, J=8.0 Hz), 7,4 was 7.45 (1H, m)
7of 0.94 (6H, d, J=6.6 Hz), as 1.8-1.9 (1H, m), 2,7 (3H, s), is 2.74 (2H, d, J=7.5 Hz), 4,32 (2H, users), to 7.0, and 7.1 (1H, m), 7,16 (1H, d, J=1.7 Hz), 7,37 (1H, d,J=8,2 Hz)
81,6-of 1.75 (2H, m), 2,48 (2H, t, J=6.5 Hz), 3,7-of 3.85 (4H, m), 6.75 in-6,8 (1H, m), 6,85-of 7.25 (6H, m), 7,7-7,8 (1H, m)
9and 3.16 (3H, s), 4.26 deaths (2H, users), 6,8-6,85 (1H, m), 6,92 (1H, d, J=2.4 Hz), 7,0-7,30 (4H, m), 7,32 (1H,d,J=8,2 Hz)
102,32 (3H, s), and 3.16 (3H, s), 4,22 (2H, users), 6.8 or 6.9 (2H, m), 6,92 (1H, d, J=2.4 Hz), 6,95-of 7.25 (3H, m), 7,31 (1H, d, J=8,4 Hz)

Table 2
Ref. Ave No.Structure1H-NMR (CDCl3) δ ppm:
114.26 deaths (2H, users), 6,7-6,9 (1H, m), 7,0 is 7.3 (8H, m)
121,95-of 2.05 (2H, m), of 2.81 (2H, t, J=6.3 Hz), 3,25-3,4 (2H, m), 4,0 (2H, users), 4,34 (2H, s), 6,4-6,5 (1H, m), 6,55 to 6.7 (3H, m), the 6.9 to 7.0 (2H, m), 7,1-7,2 (1H, m)
13as 4.02 (2H, users), 5,0 (2H, s), 6,3-of 6.45 (2H, m), 7,12 (1H, d, J=8.7 Hz), 7,25 was 7.45 (5H, m)
14of 2.36 (3H, s), a 4.03 (2H, users), equal to 4.97 (2H, s), 6,3-of 6.45 (2H, m), 7,13 (1H, d, J=8,8 Hz), 7,15-of 7.3 (3H, m), 7,35 to 7.4 (1H, m)
15is 2.37 (3H, s), was 4.02 (2H, users), 4,96 (2H, s), 6,3-of 6.45 (2H, m), 7,1-7,3 (5H, m)
16Android 4.04 (2H, users), is 5.06 (2H, s), 6,3-6,4 (2H, m), 7,13 (1H, d, J=8.6 Hz), 7,52 (2H, d, J=8.1 Hz), to 7.64(2H, d, J=8.1 Hz)
17of 1.6 (3H, d, J=6.2 Hz), 3,93 (2H, users), 5,15-5,25 (1H, m), 6,15 to 6.3 (2H, m), 7,01 (1H, d, J=8,9 Hz), a 7.2 to 7.35 (5H, m)
18of 2,75 2,95 (4H, m), 6,5-of 6.65 (3H, m), 7,05-to 7.35 (6H, m)

Table 3
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
19(CDCl3) 1,25-1,4 (6H, m), 4,2-of 4.35 (4H, m), 5,95 (2H, s), and 6.6 (1H, s)
20(CDCl3) of 1.56 (3H, d, J=6.9 Hz), 3,32 (1H, d, J=10,7 Hz)to 3.89 (3H, s), 5,2-5,3 (1H, m), 6,65 to 6.75 (2H, m), 7,1-7,2 (1H, m)
21(CDCl3) was 1.69 (3H, d, J=6.6 Hz), 3,6 (2H, users), 3,88 (3H, s), 5,73 (1H, q, J=6.6 Hz), x 6.15 and 6.25 (1H, m), 6,36 (1H, DD, J=7.5 Hz, 2.7 Hz), 6,55 to 6.7 (2H, m), 6,76 (1H, DD, J=10,7 Hz, 9.0 Hz), 7,1-7,2 (1H, m)
22(CDCl3) to 1.59 (3H, d, J=6.5 Hz), 3,62 (2H, users), is 5.18 (1H, q, J=6.5 Hz, 6,1-6,2 (1H, m), and 6.3 (1H, DD, J=7,6 Hz, 2.4 Hz), 6,7-6,8 (1H, m), 7,2-7,4 (5H, m)
23(CDCl3) of 3.69 (2H, users), 3,86 (3H, s), 4.95 points-of 5.05 (2H, m), 6,3-6,4 (1H, m), 6,44 (1H, DD, J=7,6 Hz, 3.1 Hz), 6,65 is 6.8 (2H, m), to 6.88 (1H, DD, J=10,7 Hz and 8.9 Hz), 7,25-to 7.35 (1H, m)
24(CDCl3) of 1.73 (3H, d, J=6.6 Hz), to 3.64 (2H, users), 5,62 (1H, q, J=6.6 Hz), x 6.15 and 6.25 (1H, m), 6,36 (1H, DD, J=7,6 Hz, 2.7 Hz), 6,7-6,9 (3H, m), 7,15-of 7.25 (1H, m)
25(CDCl3) of 1.74 (3H, d, J=6,7 Hz), 3,63 (2H, users), to 5.93 (1H, q, J=6,7 Hz), 6,1-6,2 (1H, m), 6,33 (1H, DD, J=7,6 Hz, 2.6 Hz), 6,76 (1H, DD, J=10.5 Hz, 9.1 Hz), 7,05-to 7.15 (1H, m), 7,2-7,3 (2H, m)
26(CDCl3in ) 1.6 (3H, d, J=6.5 Hz), to 3.64 (2H, users), 5,52 (1H, q, J=6.5 Hz), 6,1-6,2 (1H, m), and 6.3 (1H, DD, J=7,6 Hz, 2.9 Hz), 6,78 (1H, DD, J=10,7 Hz, 9.1 Hz), 7,0-to 7.15 (2H, m), 7,15-of 7.3 (1H, m), 7,35-7,45 (1H, m)

Table 4
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
27 (CDCl3) of 1.53 (3H, d, J=6.3 Hz), 3,6 (2H, users), 3,88 (3H, s), to 5.57 (1H, q, J=6.3 Hz), 6,05-x 6.15 (1H, m), of 6.29 (1H, DD, J=7.5 Hz, 3.0 Hz), 6,7-to 6.95 (3H, m), 7,15-of 7.25 (1H, m), 7.3 to 7.4 (1H, m)
28(CDCl3) was 1.58 (3H, d, J=6.4 Hz), 3,63 (2H, users), to 5.57 (1H, q, J=6.4 Hz), 6,05-x 6.15 (1H, m), and 6.25 (1H, DD, J=7.5 Hz, 2.7 Hz), 6,76 (1H, DD, J=10.5 Hz, 9.1 Hz), 7,15-of 7.25 (2H, m), 7,34 (1H, DD, J=7,7 Hz, 1.5 Hz), 7,46 (1H, DD, J=7.5 Hz, 1.6 Hz)
29(CDCl3) of 1.57 (3H, d, J=6.5 Hz), to 3.64 (2H, users), 5,14 (1H, q, J=6.5 Hz), 6,05-x 6.15 (1H, m), of 6.29 (1H, DD, J=7,3 Hz, 3.1 Hz), 6,78 (1H, DD, J=10,8 Hz and 8.8 Hz), 7,15-to 7.35 (4H, m)
30(CDCl3) to 1.21 (6H, d, J=6,8 Hz)of 1.55 (9H, s), 3,5-3,6 (1H, m), 6,74 (1H, users), 7,1-7,2 (1H, m), and 7.6 to 7.7(1H, m), 8,65 was 8.8 (1H, m)
31(CDCl3) of 1.57 (6H, s)to 3.38 (3H, s), 3,6-3,7 (2H, m), 6,63 (1H, DD, J=9,3 Hz, 4,7 Hz), 6,65 to 6.75 (1H, m), 6,8-6,95 (2H, m), 7,15-of 7.25 (2H, m)
32(CDCl3) was 1.58 (6H, s), 3.5 to 3.8 (2H, m), 6,7-6,8 (2H, m), 7,06 (1H, DD, J=8.7 Hz, 1.8 Hz), 7,2-7,4 (5H, m)
33(CDCl3) was 1.58 (6H, s)to 3.41 (3H, s), of 3.5-3.7 (2H, m), 6,65 to 6.75 (2H, m), 6.8 or 6.9 (1H, m), of 7.0, and 7.1 (1H, m), 7,15-of 7.3 (2H, m), 7,46 (1H, DD,J=7.5 Hz, 1.4 Hz)
34(CDCl3) and 1.63 (6H, s), 3,6-of 3.75 (2H, m), 6,65 to 6.75 (1H, m), 6,8-6,85 (1H, m), 6,85-to 6.95 (1H, m), 7,2-7,3 (3H, m), 7,45-of 7.55 (1H, m)

Table 5
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
35(CDCl3) of 1.57 (6H, s), 3,6-of 3.75 (2H, m), 6,7-to 7.35 (7H, m)
36(DMSO-d6) of 1.52 (3H, d, J=7,0 Hz), 4,47 (1H, q, J=7.0 Hz), 5,11 (2H, s), 6,35 to 6.5 (2H, m), 6,55 and 6.6 (1H, m)6,91 (1H, t, J=7,7 Hz), 7,15 to 7.4 (5H, m)
37(DMSO-d6) to 4.33 (2H, s), 5,19 (2H, s), 6,4-6,55 (2H, m), 6,6-of 6.65 (1H, m), 6,95-7,0 (1H, m), 7.3 to 7.4 (1H, m), 7,45 is 7.5 (2H, m)
3839(CDCl3) 3,47 (3H, s)to 3.64 (2H, users), 6,45-6,55 (1H, m), 6,7 (1H, DD, J=10,7 Hz, 8.6 Hz), 6.87 in (1H, DD, J=8.6 Hz, 2.3 Hz), 7,0-7,05 (2H, m), 7,1-7,2 (1H, m), 7,2-7,3 (2H, m)
40(CDCl3) 3,47 (3H, s), 3,98 (2H, users), 6,4-6,5 (1H, m), 6,85 (1H, d, J=1,8 Hz), of 6.96 (1H, d, J=8,3 Hz), to 7.0, and 7.1 (2H, m), 7,1-7,2 (1H, m), 7,2-7,3 (2H, m)
41(CDCl3) 4,0 (2H, users), 5,3 (1H, q, J=6.3 Hz), x 6.15 and 6.25 (1H, m), 6,34 (1H, d, J=2,8 Hz), 7,05 (1H, d, J=8,9 Hz), 7,35-of 7.55 (5H, m)
42(CDCl3) to 3.92 (3H, s)to 3.99 (2H, users), 5,95 (1H, q, J=6.2 Hz), x 6.15 and 6.25 (1H, m), 6,33 (1H, d, J=2.7 Hz), 6,9-7,1 (3H, m), 7.3 to 7.4 (1H, m), 7,51 (1H, d, J=7,7 Hz)

Table 6
Ref. Ave. No.Structure(Solvent)1H-NMR δ ppm:
43(CDCl3) 4,18 (3H,c), a 7.0 (1H,d, J=11.8 Hz), 8,83 (1H, d, J=7,8 Hz)
44(CDCl3) 3,88 (3H, c), 4,25 (2H, c), of 7.0, and 7.1 (1H, m), a 7.1 to 7.15 (1H, m), 7.23 percent (1H, d, J=1,8 Hz), 7,25 of 7.3 (1H, m), between 7.4 to 7.5 (1H, m), 7,65 is 7.7 (1H, m), 7,9-of 7.95 (1H, m), 10,61 (1H, c)
45(CDCl3) of 1.07 (3H, t, J=7,1 Hz), 3,6 (2H, q, J=7,1 Hz)to 4.23 (2H, c), 6,89 (1H, DD, J=8,3 Hz, 1.8 Hz), of 6.96 (1H, d, J=1,8 Hz), 7,05 and 7.1 (2H, m), 7,25 to 7.4 (4H, m)
46(CDCl3) 3,14 (3H, c), the 4.29 (2H, c), 6,83 (1H, DD, J=8,5 Hz, 1.9 Hz), 6,92 (1H, d, J=1.9 Hz), 7,01 (1H, DD, J=8,2 Hz, 2.5 Hz), 7,34 (1H, d, J=8,2 Hz), 7,38 (1H, d, J=8,5 Hz)
47(CDCl3) 3,15-of 3.25 (3H, m), the 4.29 (2H, c), 6,75-6,9 (2H, m), to 6.95 (1H, DD, J=8,1 Hz, 2.3 Hz), 7,06 (1H, d, J=2.3 Hz), 7,25 to 7.4 (2H, m)
48(CDCl3) 3,23 (3H, c), 4,28 (2H, c), at 6.84 (1H, DD, J=8.0 Hz, 2.3 Hz), 6,92 (1H, d, J=2.3 Hz), 7,15 to 7.2 (2H, m), 7,31 (1H, d, J=8.6 Hz), 8,5-8,55 (2H, m)
49(CDCl3) a 3.15 (3H, c), 4,25 (2H, c, PC 6.82 (1H, DD, J=8,5 Hz, 2.1 Hz)and 6.9 (1H, d, J=2.1 Hz), 7,05 and 7.1 (2H, m), 7,25-to 7.35 (3H, m)
50(CDCl3) of 3.28 (3H, c), of 3.84 (3H, c), 4,25 (2H, users), 6,9-7,05 (3H, m), 7,3-7,5 (3H, m), 7,8-7,9 (1H, m)

Table 7
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
51(CDCl3) a 3.15 (3H, c), and 3.8 (3H, c)to 4.23 (2H, c), 6.8 or 6.9 (3H, m), 6,92 (1H, d, J=2.0 Hz), 7,0-7,05 (2H, m), 7,31 (1H, d, J=8,2 Hz)
52(CDCl3) a 3.75 (3H, c), 4,27 (2H, c), 6,55 to 6.7 (3H, m), 6,74 (1H, c), of 7.0, and 7.1 (1H, m), 7,1-7,2 (2H, m), 7,28(1H, d, J=7.9 Hz)
53(CDCl3) to 3.67 (3H, c), 4,22 (2H, c), 6,75-6,8 (1H, m), 6,85-to 6.95 (1H, m), 6,98 (1H, c), of 7.0, and 7.1 (2H, m), 7,14(1H, d, J=2.4 Hz), 7,24 (1H, d, J=8.6 Hz), and 7.5 (1H, DD, J=7,7 Hz to 1.6 Hz)
54(CDCl3) of 3.77 (3H, c)to 4.23 (2H, c), of 6.31 (1H, c), 6,75-6,85 (2H, m), the 6.9 to 7.0 (3H, m), 7,07 (1H, d, J=2.4 Hz), 7,27 (1H,d, J=8.0 Hz)
55(CDCl3) a 3.2 (3H, c), of 3.48 (3H, c), is 4.21 (2H, users), 6,75-6,85 (1H, m), 6,9-to 6.95 (1H, m), of 6.99 (1H, DD, J=8,3 Hz, 2.0 Hz),? 7.04 baby mortality (1H, d, J=2.0 Hz), 7,25-to 7.35 (3H, m)
56(CDCl3) and 3.16 (3H, c), of 3.77 (3H, c), 4,24 (2H, c), and 6.6 and 6.7 (1H, m), 6,7-6,8 (1H, m), 6.8 or 6.9 (2H, m)6,94 (1H, d, J=2.4 Hz), 7,15-of 7.25 (1H, m), and 7.3 (1H, d, J=8.1 Hz)
57(CDCl3) 3,2-of 3.25 (3H, m), 4.26 deaths (2H, users), the 6.9 to 7.0 (1H, m), of 7.0, and 7.1 (2H, m), a 7.1 to 7.15 (1H, m), 7,25-to 7.35 (3H, m)
58(CDCl3) 3,17 (3H, c), 4,25 (2H, users), 6,83 (1H, DD, J=8,3 Hz, 2.1 Hz), 6,85-7,05 (4H, m), a 7.2 to 7.35 (2H, m)

Table 8
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
59(CDCl3) a 3.15 (3H, c), 4,27 (2H, users), PC 6.82 (1H, DD, J=8,2 Hz, 2.2 Hz), 6,91 (1H, d, J=2.2 Hz), 6,95-7,05 (2H, m), 7,05-to 7.15 (2H, m), 7,31 (1H, d, J=8,2 Hz)
60(CDCl3) a 3.15 (3H, c), 4,25 (2H, c), PC 6.82 (1H, DD, J=8,5 Hz, 2.1 Hz)and 6.9 (1H, d, J=2.1 Hz), 7,05 and 7.1 (2H, m), 7,25-to 7.35 (3H, m)
61(CDCl3) 3,18 (3H, c), 4,25 (2H, c), 7,03 (1H, DD, J=8,5 Hz, 2.0 Hz), and 7.1 (1H, d, J=2.0 Hz), 7,2-7,4 (5H, m)
62(CDCl3) 3,17 (3H, c), 4,24 (2H, c), PC 6.82 (1H, DD, J=8,4 Hz, 1.9 Hz), 6.89 in (1H, d, J=1.9 Hz), 7,1-7,2 (4H, m), 7,3-to 7.35 (1H, m)
63(CDCl3) 3,19 (3H, c), the 4.29 (2H, c), of 7.0, and 7.1 (1H, m), 7,1-7,2 (2H, m), 7,2-of 7.25 (1H, m), of 7.36 (1H, d, J=8.0 Hz), the 7.43 (1H, d, J=2.2 Hz)
64(DMSO-d6) of 3.12 (3H, c), 5,59 (2H, c), a 6.5 and 6.6 (1H, m), 6,7-6,8 (2H, m), 7,05 to 7.2 (3H, m), 7,2-7,4 (3H, m)
65(CDCl3) 3,2-of 3.25 (3H, m), 3,91 (2H, users), 6,95-to 7.15 (5H, m), a 7.2 to 7.35 (2H, m)
66(CDCl3) a 3.2 (3H, c), and 3.5 (3H, c), 3,86 (2H, c), 6,8-6,85 (1H, m), 6,9-to 6.95 (1H, m), 7,0-7, (3H, m), 7,25-to 7.35 (2H, m)

Table 9
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
67(CDCl3) to 3.33 (3H, s), of 3.46 (2H, users), to 3.58 (3H, s), 3,81 (3H, s), of 6.73 (1H, d, J=12,6 Hz), 6,8-6,95 (2H, m), 7,15-of 7.3 (3H, m)
68(CDCl3) to 3.35 (3H, s), 3,51 (2H, users), and 3.7 (3H, s), to 6.67 (1H, d, J=and 12.2 Hz), 7,15-of 7.3 (6H, m)
69(CDCl3) 3,18 (3H, s), 3,88 (2H, s), 6,85-to 6.95 (2H, m), 7,0-7,05 (1H, m), a 7.1 to 7.15 (2H, m), a 7.2 to 7.35 (3H, m)
70(DMSO-d6), and 2.27 (3H, in), 3.75 (3H, s), and 3.8 (3H, s)
71(CDCl3) to 1.21 (3H, t, J=7,1 Hz), 3,01 (2H, q, J=7,1 Hz), to 7.0, and 7.1 (1H, m), 7,42 (1H, d, J=8.6 Hz), 7,55 and 7.6 (1H, m), 8,75 cent to 8.85 (1H, m)
72(CDClsub> 3) to 1.21 (6H, d, J=6.8 Hz), 3,5-3,6 (1H, m), 7,05 (1H, users), the 7.43 (1H, d, J=8.5 Hz), 7,55 and 7.6 (1H, m), 8,78 (1H, users)
73(CDCl3) to 4.17 (2H, users), 4,22 (2H, s), a 7.2 to 7.35 (7H, m), 7,35 to 7.4 (1H, m)

Table 10
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
74(CDCl3) 1,5 (6H, d, J=7,1 Hz), 4,0-4,2 (3H, m), 7,15 to 7.4 (8H, m)
75(CDCl3) of 1.57 (6H, s), 3,98 (2H, users), of 6.65 (1H, DD, J=8,4 Hz, 2.1 Hz), of 6.99 (1H, d, J=2.1 Hz), 7,03 (1H, d, J=8,4 Hz), 7,2-7,4 (5H, m)
76(CDCl3) was 1.58 (6H, s), 3,42 (3H, s), of 3.94 (2H, users), 6,65 to 6.75 (1H, m), 6,8 (1H, DD, J=8.6 Hz, 2.0 Hz), 6,98 (1H, d, J=8.6 Hz), to 7.0, and 7.1 (1H, m), to 7.15 (1H, d, J=2.0 Hz), 7,2-7,3 (1H, m), between 7.4 to 7.5 (1H, m)
77(CDCl3) and 1.63 (6H, s), 4,0 (2H, users), 6,76 (1H, DD, J=8,5 Hz, 1.9 Hz), 6,85-to 6.95 (1H, m), 7,01 (1H, d, J=85 Hz), 7,15 of 7.3 (3H, m), 7,45-of 7.55 (1H, m)
78(CDCl3) of 1.53 (9H, s), 6,7 (1H, users), 6,93 (1H, DD, J=11.0 cm Hz, 8.5 Hz), 7,05 and 7.1 (1H, m), with 8.33 (1H, users)
79(CDCl3) is 1.51 (6H, s), of 3.5-3.9 (5H, m), 6,35-of 6.45 (1H, m), 6,6 to 6.75 (2H, m), 6.75 in-6,9 (2H, m), the 6.9 to 7.0 (1H, m), 7,2-7,3 (1H, m)
80(CDCl3) and 1.54 (6H, s), and 3.72 (2H, users), 6,6 to 6.75 (2H, m), the 6.9 to 7.0 (1H, m), 7,2-7,3 (2H, m), 7,35-7,45 (1H, m), 7.5 to at 7.55 (2H, m)
81(CDCl3) of 1.57 (6H, s), 3,61 (3H, s), 6,55-of 6.65 (2H, m), 6,65 to 6.75 (1H, m), 6.8 or 6.9 (2H, m), 7,15-of 7.25 (1H, m)

Table 11
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
82(CDCl3) 4,07 (2H, s), 4,96 (2H, s), 6,74 (1H, DD, J=8.0 Hz, 1.9 Hz), 6,85 (1H, d, J=1.9 Hz), the 6.9 to 7.0 (3H, m), a 7.2 to 7.35 (3H, m)
83img src="https://img.russianpatents.com/1078/10788801-s.jpg" height="18" width="39" /> (CDCl3) of 2.75 and 2.9 (4H, m), of 3.95 (2H, users), a 6.5 and 6.6 (2H, m), 7,1-to 7.35 (6H, m)
84(CDCl3) of 1.53 (9H, s), 2,99 (1H, s), of 6.68 (1H, users), 6,95-7,05 (1H, m), 705-7,15 (1H, m), 8,25-8,35 (1H, m)
85(CDCl3) 3,88 (3H, s), 6,55-of 6.65 (1H, m), 7,05-to 7.15 (1H, m)
86(CDCl3) of 2.75 and 2.9 (4H, m)to 3.64 (2H, users), 6,45-6,55 (1H, m), 6,55-of 6.65 (1H, m), 6.8 or 6.9 (1H, m), 7,1-7,3 (5H, m)
87(CDCl3) 2,7-2,8 (2H, m), 2,8-2,9 (2H, m), 3,63 (2H, users), 3,83 (3H, s), 6,45-6,55 (1H, m), 6,6-of 6.65 (1H, m), 6.8 or 6.9 (3H, m), 7,05 and 7.1 (1H, m), 7,15-of 7.25 (1H, m)
88(CDCl3) of 2,75 2,85 (2H, m), 2,85-2,95 (2H, m)to 3.64 (2H, users), 6,45-6,55 (1H, m), 6,55-of 6.65 (1H, m), 6.8 or 6.9 (1H, m), 6,95-of 7.25 (4H, m)
89(CDCl3) of 2.7 and 2.9 (4H, m), the 3.65 (2H, users), with 3.79 (3H, s), 6,45-6,55 (1H, m), 6,55-of 6.65 (1H, m), 6,65-6,8 (3H, m), 6,8-6,95 (1H, m), 7,15-of 7.25 (1H, m)

Table 12
Ref. Ave No.Structure(Solvent)1H NMR δ ppm:
90(CDCl3) 2,7-to 2.85 (4H, m), 3,55 of 3.75 (2H, usher.), with 3.79 (3H, s), 6,45-6,55 (1H, m), 6,55-of 6.65 (1H, m), 6.75 in-to 6.95 (3H, m), 7,0-to 7.15 (2H, m)
91(CDCl3) of 2.75 and 2.9 (4H, m), the 3.65 (2H, users), 6,4-6,5 (1H, m), 6,55-of 6.65 (1H, m), 6,8-6,95 (4H, m), 7,15-of 7.3 (1H, m)
92(CDCl3) of 2.7 and 2.9 (4H, m), the 3.65 (2H, users), 6,4-6,5 (1H, m), 6,5-6,6 (1H, m), 6,8-7,0 (3H, m), 7,05-to 7.15 (2H, m)
93(CDCl3) to 2.3 (3H, s), 2,7-2,8 (2H, m), 2,8-2,9 (2H, m), 6,45-6,55 (1H, m), 6,55-of 6.65 (1H, m), 6,85-to 6.95 (1H, m), 7,05 to 7.2 (4H, m)
94(CDCl3) of 2.33 (3H, s), 2,7-2,9 (4H, m), 6,45-6,55 (1H, m), 6,55-of 6.65 (1H, m), 6,85-to 6.95 (1H, m), 6,95-7,05 (3H, m)and 7.1-of 7.25 (1H, m)
95(CDCl3) 2,32 (3H), of 2.7 and 2.9 (4H, m), 6,45-6,55 (1H, m), 6,55-of 6.65 (1H, m), 6,8-6,95 (1H, m), 7,0-to 7.15 (4H, m)
96(CDCl3) 2,6-2,7 (2H, m), 2,85-2,95 (2H, m), 3,5-of 3.75 (2H, usher.), with 3.79 (3H, s), 6,5-6,6 (3H, m), and 6.6 and 6.7 (1H, m), 6.8 or 6.9 (1H, m), 7,13 (1H, t, J=8,5 Hz)
97(CDCl3) 2,7-2,8 (2H, m), 2,8-2,9 (2H, m), 3,5-of 3.75 (2H, usher.), with 3.79 (3H, s), 6,45-6,55 (1H, m), 6,55-of 6.65 (1H, m), 6,7-6,9 (4H, m)

Table 13
Ref. Ave No.Structure(Solvent)1H NMR δ ppm:
98(CDCl3) 2,7-2,8 (2H, m), 2,8-2,9 (2H, m), of 3.5-3.9 (5H, m), 6,45-6,55 (1H, m), 6,55-of 6.65 (2H, m), 6,65 to 6.75 (1H, m), 6,85-to 6.95 (1H, m)
99(CDCl3) 2,65 is 2.75 (2H, m), 2,85-2,95 (2H, m), 3,35 to-3.9 (5H, m), 6,45-6,55 (2H, m), 6,6-of 6.65 (1H, m), 6.8 or 6.9 (1H, m), the 6.9 to 7.0 (1H, m)
100(CDCl3) of 2.75 and 2.9 (4H, m), 3,05-the 3.65 (2H, usher.), and 3.72 (3H, s), 6,5-of 6.65 (2H, m), 7,15-of 7.3 (5H, m)
101(CDCl3) to 1.25 (6H, s), of 2.86 (2H, s), 3.45 points-of 3.85 (5H, m), and 6.6 and 6.7 (1H, m), 6,7-6,9 (5H, m), 7,1-7,2 (1H, m)
102(DMSO-d6) 5,8-6,8 (1H, usher.), to 7.64 (2H, users), of 8.06 (1H, users)
103(DMSO-d6) to 4.15 (2H, s), lower than the 5.37 (2H, s), and 6.5 (1H, DD, J=8,2 Hz, 2.2 Hz), 6,77 (1H, d, J=2.2 Hz), was 7.08 (1H, d, J=8,2 Hz), 7,2-7,4 (5H, m)
104(CDCl3) to 3.34 (1H, s), 3,71 (2H, users), 6,55-of 6.65 (1H, m), 6,7-of 6.75 (1H, m), at 6.84 (1H, DD, J=10,8 Hz and 8.3 Hz)
105(CDCl3) 2,3 (1H, t, J=6.8 Hz), with 3.89 (3H, s), 4,7-4,8 (2H, m), 6,65 to 6.75 (2H, m), 7,15-of 7.3 (1H, m)

Table 14
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
106(CDCl3) of 2.23 (1H, t, J=6.4 Hz), of 3.84 (3H, s), 4,66 2H, d, J=6.4 Hz), 6.75 in-6,85 (1H, m), the 6.9 to 7.0 (1H, m), of 7.0, and 7.1 (1H, m)
107(CDCl3) to 2.35 (1H, t, J=7.0 Hz), a 3.87 (3H, s), 4.75 V to 4.8 (2H, m), 6,55-of 6.65 (1H, m), of 7.0, and 7.1 (1H, m)
108(CDCl3) 3,91 (3H, s), 4,55 with 4.65 (2H, m), 6,65 to 6.75 (2H, m), 7,2-7,3 (1H, m)
109(CDCl3) a 3.87 (3H, s), and 4.5 (2H, s), 6.75 in-6,85 (1H, m), 6,95-7,0 (1H, m), of 7.0, and 7.1 (1H, m)
110(CDCl3) to 3.89 (3H, s), 4,55-4,6 (2H, m), 6,55 and 6.6 (1H, m), 7,0-to 7.15 (1H, m)
111(CDCl3) to 1.59 (6H, s)to 3.89 (3H, s), of 4.05 (1H, s), 6,8-6,95 (2H, m), of 7.0, and 7.1 (1H, m)
112(CDCl3) of 1.66 (3H, s)to 1.67 (3H, s), 3,93 (3H, s)5,08 (1H, s), 6,65 to 6.75 (2H, m), 7,1-7,2 (1H, m)
113(CDCl3) to 1.67 (3H, s), by 1.68 (3H, s), 3,91 (3H, s), 5,04 (1H, s), and 6.6 and 6.7 (1H, m), 6,95-7,05 (1H, m)

Table 15
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
114(CDCl3) 4,0 (2H, s)to 4.33 (2H, s), 6,55 to 6.7 (2H, m), 6.8 or 6.9 (1H, m), 6,95-to 7.35 (4H, m)
115(DMSO-d6) to 4.1 (2H, s), and 5.2 (2H, s), 6,4-6,5 (1H, m), 6,7-6,8 (1H, m), 6,9 (1H, DD, J=11.3 Hz, 8.6 Hz), a 7.2 to 7.35 (5H, m)
116(CDCl3) 3,68 (2H, users), of 4.05 (2H, s), 6,65 to 6.75 (1H, m), 6.75 in-6,9 (4H, m)and 7.1-of 7.25 (1H, m)
117(DMSO-d6) of 2,75 2,85 (2H, m), 3,05 is 3.15 (2H, m), a total of 5.21 (2H, s), 6,45-6,55 (1H, m), 6.75 in-6,85 (1H, m), the 6.9 to 7.0 (1H, m), 7,15-to 7.35 (5H, m)
118(CDCl3) 3,66 (2H, users), of 3.77 (3H, s), 4,05 of 4.1 (2H, m), and 6.6 and 6.7 (2H, m), 6,7-of 6.75 (1H, m), 6.75 in-6,9 (2H, m), 7,1-7,2 (1H, m)
119(CDCl3) 3.5 to 3.8 (5H, m), 4,05 of 4.1 (2H, m), 6,45-6,55 (1H, m),6,65 to 6.75 (1H, m), 6.8 or 6.9 (2H, m), 6,95-7,05 (1H, m)
120(CDCl3) 3,62 (2H, users), 4,1 (2H, s), 6,45-6,55 (1H, m), 6,6-of 6.65 (1H, m), 6,7-of 6.75 (1H, m), of 7.0, and 7.1 (1H, m), a 7.2 to 7.35 (5H, m)
121(CDCl3) 3,66 (2H, users), 3,82 (3H, s)4,06 (2H, s), 6,65 and 6.7 (1H, m), of 6.75 (1H, DD, J=8,5 Hz, 2.2 Hz), 6.8 or 6.9 (3H, m), a 7.1 to 7.15 (1H, m), 7,15-of 7.25 (1H, m)

Table 16
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
122(CDCl3) of 3.69 (2H, s), 4,32 (2H, s), 6,7-6,8 (1H, m), 6.8 or 6.9 (2H, m), 7,05-to 7.15 (1H, m), 7,25 of 7.3 (2H, m)
123(CDCl3) 3,68 (2H, s), of 4.12 (2H, s), and 6.6 and 6.7 (1H, m), 6,7-6,8 (1H, m), 6.8 or 6.9 (1H, m)and 7.1 to 7.2 (3H, m), 7.3 to 7.4 (1H, m)
124(CDCl3) of 3.69 (2H, s), of 3.96 (2H, s), 6,6-of 6.65 (1H, m), 6,7-of 6.75 (1H, m), 6.8 or 6.9 (1H, m), 7,05 and 7.1 (1H, m), 7,15-of 7.25 (3H, m)
125 (CDCl3) 3,68 (2H, users), to 3.99 (2H, s), 6,6-of 6.65 (1H, m), 6,7-of 6.75 (1H, m), 6,8-7,0 (4H, m), 7,15-of 7.25 (1H, m)
126(CDCl3) 3,68 (2H, users), with 3.79 (3H, s)to 4.01 (2H, s), and 6.6 and 6.7 (1H, m), 6,7-6,8 (2H, m), 6,8-to 6.95 (3H, m)
127(CDCl3) to 1.67 (6H, s), 3,55 (2H, users), 6,45-6,55 (2H, m), 6.75 in-6,85 (1H, m), 7,15-of 7.25 (1H, m), 7,25-to 7.35 (2H, m), 7,35-7,45 (2H, m)
128(DMSO-d6) of 1.66 (6H, s), 5,07 (2H, s), 6,1-6,2 (1H, m), 6,4-6,55 (2H, m), 6.75 in-6,9(1H, m), 6,95-to 7.35 (4H, m)
129(DMSO-d6) to 1.61 (6H, s), 5,09 (2H, s), 6,2-6,3 (1H, m), 6,45-6,55 (2H, m), 6,85-6,9 (1H, m), of 7.0, and 7.1 (1H, m), 7,15 to 7.4 (3H, m)

Table 17
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
130(CDCl3) to 1.82 (3H, s)and 1.83 (3H, s), 3,55 (2H, IRS), 3,81 (3H, s), 6,45-of 6.65 (3H, m), 6,65 is 6.8 (2H, m), 7,1-7,2 (1H, m)
131(CDCl3) 1,68 (6H, s), of 3.57 (2H, users), a 3.9 (3H, s), 6,4-6,55 (2H, m), 6,7-6,8 (2H, m), 6,8-6,95 (2H, m)
132(CDCl3) from 1.8 to 1.85 (6H, m)to 3.58 (2H, users), 6,45-6,6 (2H, m), 6.75 in-6,85 (3H, m), 7,1-7,2 (1H, m)
133(CDCl3) to 1.82 (3H, s)and 1.83 (3H, s)and 3.59 (2H, users), with 3.79 (3H, s), 6,4-6,5 (1H, m), 6,55-of 6.65 (2H, m), 6.75 in-6,85 (1H, m), 6,95-7,05 (1H, m)
134(CDCl3) 1,71 (6H, s), of 3.54 (2H, users), to 3.92 (3H, s), 6,4-6,5 (2H, m), 6,7-6,85 (2H, m), to 6.95 (1H, d, J=8.1 Hz), 7,0-7,05 (1H, m), 7,2-7,3 (1H, m)
135(CDCl3) 1,72 (6H, s), 3,55 (2H, users), 6,45 to 6.5 (2H, m), 6,7-6,8 (1H, m), 6,95-7,0 (1H, m), of 7.0, and 7.1 (2H, m), 7,15-of 7.25 (1H, m)
136(CDCl3) to 1.8 (6H, s), 3,52 (2H, s), 6,4-6,5 (2H, m), 6,7-6,8 (1H, m), 7,05 to 7.2 (3H, m), 7,4 was 7.45 (1H, m)
137 (CDCl3) of 1.65 (6H, s), 3,6 (2H, s), 6,45-6,55 (2H, m), 6.75 in-6,85 (1H, m), 7,15-of 7.3(3H, m), 7,35 to 7.4 (1H, m)

Table 18
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
138(CDCl3) of 1.65 (6H,s)to 3.58 (2H, users), 6,45-6,55 (2H, m), 6,79 (1H, DD, J=11.0 cm Hz and 8.2 Hz), 6,85-to 6.95 (1H, m), 7,05 to 7.2 (2H, m), 7,2-7,3 (1H, m)
139(CDCl3) to 1.67 (6H, s)to 3.58 (2H, users), a 3.9 (3H, s), 6,4-6,55 (2H, m), 6.75 in-6,85 (1H, m), 6.87 in (1H, d, J=8.5 Hz), of 6.99 (1H, d, J=2.6 Hz), 7,2 (1H, DD, J=8,5 Hz, 2.6 Hz)
140(CDCl3) 1,8-of 1.95 (1H, m), 2,3-2,5 (3H, m), 2,55-to 2.65 (2H, m), of 3.56 (2H, s), 6,35 to 6.5 (2H, m), 6.75 in-6,85 (1H, m), 6,95-7,0 (2H, m), 7,1-7,2 (1H, m), 7,2-7,3 (2H, m)
141(CDCl3) to 2.1-2.3 (4H, m), 3,51 (2H, users), 3,65 of 3.75 (2H, m), 4,0-4,1 (2H, m), 6,2-of 6.25 (1H, m), 6,3 to 6.35 (1H, m), 6,7-6,8 (1H, m), 7,15-to 7.35 (5H, m)
142(DCl 3) 4,0 (3H, s), of 5.55 (1H, s), 6,74 (1H, d, J=11.7 Hz), to 7.67 (1H, d, J=7,3 Hz)
143(CDCl3) 2,32 (3H, s), of 5.26 (1H, s), 7,06 (1H, d, J=11.0 in Hz)of 7.48 (1H, d, J=6,1 Hz)
144(CDCl3) of 1.26 (3H, t, J=7.5 Hz), 2,7 (2H, q, J=7.5 Hz), of 5.99 (1H, s), 7,06 (1H, d, J=11.3 Hz), of 7.48 (1H, d, J=5.8 Hz)
145(CDCl3) to 5.35 (1H, d, J=3,7 Hz), 7,05-to 7.15 (1H, m), 7,79 (1H, DD, J=8,8 Hz and 7.1 Hz)

Table 19
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
146(CDCl3) 5,7 (1H,s), 7,35(1H, d, J=9.7 Hz), of 7.75 (1H, d, J=6,7 Hz)
147(CDCl3) 5,73 (1H, s), 7,49 (1H, d, J=9.7 Hz), 7,72 (1H, d, J=6,7 Hz)
148(CDCl3) of 1.53 (3H, t, J=7,0 Hz), is 4.21 (2H, q, J=7.0 Hz), to 5.58 (1H, s)of 6.71 (1H, d, J=11,9 Hz), 7,66 (1H, d, J=7,1 Hz)
149(CDCl3) of 1.57 (3H, d, J=6,9 Hz)and 3.31 (1H, d, J=11.2 Hz), 5,15-5,3 (1H, m), 6,55-of 6.65 (1H, m), 6,95-7,05 (1H, m)
150(CDCl3) 0,1 (6H, s)of 0.91 (9H, s), 3.95 to 4,0 (2H, m), 4,05-to 4.15 (2H, m), and 4.68 (2H, s), 6,85-7,0 (2H, m), 7,2-7,3 (2H, m)
151(CDCl3) 0,1 (6H, s)of 0.91 (9H, s), and 1.54 (3H, d, J=6.4 Hz), 3,14 (1H, d, J=6.4 Hz), 3.95 to 4,0 (2H, m), 4,05-to 4.15 (2H, m), a 5.0 to 5.1 (1H, m), 6,85-7,0 (2H, m), 7,2-of 7.25 (1H, m), 7,25-to 7.35 (1H, m)
152(DMSO-d6) to 0.08 (6H, s), and 0.9 (9H, s)to 4.52 (2H, d, J=5.4 Hz), 4,74 (2H, s), is 5.06 (1H, t, J=5.4 Hz), 7,2-7,3 (2H, m), 7,35-7,45 (2H, m)

Table 20
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
153(DMSO-d6) to 0.12 (3H, s)of 0.14 (3H, s)of 0.95 (9H, s)of 1.34 (3H, d, J=6.6 Hz), 4,8 2H, C), 4,9-5,1 (2H, m), 7,2-7,4 (3H, m), 7,45-of 7.55 (1H, m)
154(DMSO-d6) to 0.08 (6H, s), and 0.9 (9H, s), 4,48 (2H, d, J=5.7 Hz), 4,7 (2H, s), 5,16 (1H, t, J=5.7 Hz), 7,1-to 7.35 (4H, m)
155(CDCl3) 3,35-3,5 (4H, m), 3,7-of 3.75 (2H, m), 4,15 to 4.2 (2H, m), 4,7-4,8 (2H, m), 6,55-of 6.65 (1H, m), 6,95 to 7.1 (1H, m)
156(CDCl3) of 1.23 (3H, t, J=6.9 Hz), to 3.58 (2H, q, J=6.9 Hz), of 3.7-3.8 (2H, m), 4,15-of 4.25 (2H, m), and 4.75 (2H, s), 6,55-of 6.65 (1H, m), 6,95 to 7.1 (1H, m)
157(CDCl3) a 2.0 to 2.15 (2H, m), or 3.28 (1H, t, J=7,1 Hz), the 3.35 (3H, s)and 3.59 (2H, t, J=5.6 Hz), 4,11 (2H, t, J=5.8 Hz), 4,7-4,8 (2H, m), 6,5-6,6 (1H, m), 6,95 to 7.1 (1H, m)
158(CDCl3) 0,1 (6H, s)of 0.91 (9H, s), 3,19 (1H, t, J=6.9 Hz), 3,9-4,0 (2H, m), 4,05-to 4.15 (2H, m), 4,7-4,8 (2H, m), 6,55-of 6.65 (1H, m), 6,95 to 7.1 (1H, m)
159(CDCl3) of 0.05 (6H, s)to 0.89 (9H, s), 1,95-of 2.05 (2H, m), 2,52 (1H, t, J=7.0 Hz), 3,81 (2H, t, J=5.8 Hz), of 4.12 (2H, t, J=6.0 Hz), 4,7-4,8 (2H, m), 6,55-of 6.65 (1H, m), of 7.0, and 7.1 (1H, m)

Table 21
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
160(CDCl3) 1,8-of 1.95 (1H, m), 2,25-2,5 (3H, m), 2,65 is 2.75 (3H, m), 3,82 (3H, s), 6,5-6,6 (1H, m), 6,95-7,05 (1H, m)
161(CDCl3) 1,68 (6H, s), a-3.84 (2H, s), 5,98 (1H, DD, J=8,8 Hz, 2.4 Hz), 6,11 (1H, d, J=2.4 Hz), 6,92 (1H, d, J=8,8 Hz), 7,25 of 7.3 (1H, m), 7.3 to 7.4 (2H, m), between 7.4 to 7.5 (2H, m)
162(CDCl3) of 1.7 and 1.75 (6H, m)to 3.89 (2H, s), 6,1 (1H, DD, J=8.7 Hz, 2.6 Hz), 6,23 (1H, d, J=2.6 Hz), 6,95-to 7.15 (3H, m), 7,2-7,3 (1H, m), 7,45 is 7.5 (1H, m)
163(DMSO-d6) to 0.78 (3H, t, J=7,3 Hz)to 1.59 (3H, s), of 1.8-2.0 (2H, m), 5,16 (2H, s), USD 5.76 (1H, DD, J=8,5 Hz, 2.9 Hz), 6,21 (1H, d, J=2,9 Hz), 6,86 (1H, d, J=8.5 Hz), 7,2-7,3 (1H, m), 7.3 to 7.4 (4H, m)
164(DMSO-d6) to 1.76 (6H, s), 5,16 (2H, s), 5,7-5,8 (1H, m), x 6.15 and 6.25 (1H, m), 6.8 or 6.9 (1H, m), 7,25 was 7.45 (3H, m), and 7.5 and 7.6 (1H, m)
165 (CDCl3) 1,8-2,1 (2H, m), to 2.5-2.7 (4H, m), of 3.56 (2H, users), 5,8-5,9 (1H, m), 6,05 of 6.1 (1H, m), 6,65 and 6.7 (1H, m), 7,2-7,3 (1H, m), 7.3 to 7.4 (2H, m), between 7.4 to 7.5 (2H, m)
166(CDCl3) 1,85-of 1.95 (1H, m), 2,35-2,5 (1H, m), from 2.6 to 2.85 (4H, m)to 3.36 (2H, users), 3,71 (3H, s), 6,05-x 6.15 (1H, m), 6.5 to 6,55 (1H, m), 6,65 to 6.75 (1H, m), of 7.0, and 7.1 (1H, m)

Table 22
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
167(CDCl3) of 1.7 to 1.85 (1H, m), 1,9-2,2 (3H, m), 2,7-2,95 (2H, m), 4,0 (2H, users), 5,2-5,3 (1H, m), 6,35-of 6.45 (2H, m)and 7.1 to 7.4 (5H, m)
168(CDCl3) to 4.01 (2H, users), 5,07 (2H, c), 6,3-of 6.45 (2H, m), 7,0-7,5 (5H, m)
169(CDCl3) of 4.04 (2H, users), 5,0 (2H, c), 6,32 (1H, DD, J=8.7 Hz, 2.8 Hz), 6,38 (1H, d, J=2,8 Hz), 6,95-7,05 (1H, m)and 7.1 to 7.2 (3H, m), 7.3 to 7.4 (1H, m)
170 (CDCl3) is 4.03 (2H, users), of 4.95 (2H, c), 6,32 (1H, DD, J=8,4 Hz, 2.7 Hz), 6,38 (1H, d, J=2.7 Hz), to 7.0, and 7.1 (2H, m), 7,12 (1H, d, J=9.0 Hz), 7,35 to 7.4 (2H, m)
171(CDCl3) of 4.04 (2H, users), to 4.98 (2H, c), of 6.31 (1H, DD, J=8,8 Hz, 2.9 Hz), 6,38 (1H, d, J=2,9 Hz), 7,13 (1H, d, J=8,8 Hz), a 7.2 to 7.35 (3H, m), 7,41 (1H, c)
172(CDCl3) is 3.82 (3H, c), was 4.02 (2H, users), to 4.98 (2H, c), 6,34 (1H, DD, J=9,0 Hz, 2.9 Hz), to 6.39 (1H, d, J=2,9 Hz), 6.8 or 6.9 (1H, m), the 6.9 to 7.0 (2H, m), 7,12 (1H, d, J=9.0 Hz), 7,25-to 7.35 (1H, m)
173(CDCl3in ) 1.6 (3H, d, J=6.2 Hz), 3,93 (2H, users), 5,15-5,25 (1H, m), 6,15 to 6.3 (2H, m), 7,01 (1H, d, J=8,9 Hz), a 7.2 to 7.35 (5H, m)
174(CDCl3in ) 1.6 (3H, d, J=6.2 Hz), 3,93 (2H, users), 5,15-5,25 (1H, m), 6,15 to 6.3 (2H, m), 7,01 (1H, d, J=8,9 Hz), a 7.2 to 7.35 (5H, m)

Table 23
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
175 (CDCl3) 3,86 (3H, s)to 4.01 (2H, users), of 5.05 (2H, s), 6,37 (1H, DD, J=8,8 Hz, 2.9 Hz), 6.42 per (1H, d, J=2,9 Hz), 6,85-7,0 (2H, m), 7,11 (1H, d, J=8,8 Hz), 7,25-to 7.35 (1H, m), 7,4 was 7.45 (1H, m)
176(CDCl3) is 3.82 (3H, s), was 4.02 (2H, users), to 4.92 (2H, s), 6,34 (1H, DD, J=8.6 Hz, 2.7 Hz), 6,38 (1H, d, J=2.7 Hz), 6,85-to 6.95 (2H, m), 7,11 (1H, d, J=8.6 Hz), 7,3-to 7.35 (2H, m)
177(CDCl3) is 4.03 (2H, users), a 5.1 (2H, s), 6.35mm (1H, DD, J=8.7 Hz, 2.8 Hz), 6,4 (1H, d, J=2,8 Hz), 7,13 (1H, d, J=8.7 Hz), 7,2-7,3 (2H, m), 7,35 to 7.4 (1H, m), 7,45-of 7.55 (1H, m)
178(CDCl3) was 4.02 (2H, users), 4,96 (2H, s), of 6.31 (1H, DD, J=8,9 Hz, 2.9 Hz), 6,36 (1H, d, J=2,9 Hz), 7,12 (1H, d, J=8,9 Hz), 7.3 to 7.4 (4H, m)
179(CDCl3) of 4.04 (2H, s), 5,14 (2H, s), 6,34 (1H, DD, J=8,8 Hz, 2.8 Hz), 6,4 (1H, d, J=2,8 Hz), 7,11 (1H, d, J=8,8 Hz), 7,2-of 7.25 (1H, m), of 7.48 (1H, d, J=7.8 Hz), the 7.65 to 7.75 (1H, m), 8,55 to 8.6 (1H, m)
180(CDCl3) 2,1-2,2 (1H, m), 2,2-2,3 (1H, m), of 4.05 (2H, users), 4,2-of 4.35 (2H, m), of 5.24 (1H, t, J=3.6 Hz), to 6.39 (1H, DD, J=8,4 Hz, 2.8 Hz), 6.42 per (1H, d, J=2,8 Hz), 6,85-to 6.95 (2H, m), 7,16 (1H, d, J=8,4 Hz), 7,2-7,3 (2H,m)
181(CDCl3) of 4.04 (2H, s), 5,14 (2H, s), 6,3-of 6.45 (2H, m), 7,11 (1H, d, J=8.6 Hz), 7,2-of 7.25 (1H, m), of 7.48 (1H, d, J=7.8 Hz), the 7.65 to 7.75 (1H, m), 8,55 to 8.6 (1H, m)

Table 24
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
182(DMSO-d6) and 1.54 (3H, d, J=6.3 Hz), of 5.26 (2H, s), of 5.55 (1H, q, J=6.3 Hz)and 6.1 (1H, DD, J=8,9 Hz, 2.9 Hz), 6,34 (1H, d, J=2,9 Hz), of 6.99 (1H, d, J=8,9 Hz), 7,15-of 7.25 (2H, m), 7,25 was 7.45 (2H, m)
183(DMSO-d6) 1,5 (3H, d, J=6.5 Hz), of 5.24 (2H, s), are 5.36 (1H, q, J=6.5 Hz), 6,12 (1H, DD, J=9,0 Hz, 2.8 Hz), 6,34 (1H, d, J=2,8 Hz), 6,98 (1H, d, J=9.0 Hz), to 7.0, and 7.1 (1H, m), 7,15-of 7.25 (2H, m), 7,35-7,45 (1H, m)
184(DMSO-d6) 1,49 (3H, d, J=6.2 Hz), with 5.22 (2H, s), to 5.35 (1H, q, J=6.2 Hz), 6,11 (1H, DD, J=8,8 Hz, 2.8 Hz), 6,33 (1H, d, J=2,8 Hz), 6,97 (1H, d, J=8,8 Hz), 7,1-7,2 (2H, m), 7,35-7,45 (2H, m)
185(DMSO-d6) 1,35-1,5 (1H, m), 1,7-1,
(3H, m), 1,9-of 2.05 (2H, m), of 2,75 2,95 (2H, m), of 5.26 (2H, s), are 5.36 (1H, d, J=9,2 Hz), 6,16 (1H, DD, J=9,0 Hz, 2.8 Hz), 6,38 (1H, d, J=2,8 Hz), 7,01 (1H, d, J=9.0 Hz), 7,1-7,2 (3H, m), 7,2-7,3 (1H, m)
186(DMSO-d6) of 1.66 (3H, d, J=6.6 Hz), 5,3 (2H, s), 5,91 (1H, q, J=6.6 Hz), 6,0 (1H, DD, J=8,8 Hz, 2.8 Hz), of 6.31 (1H, d, J=2,8 Hz), 6,98 (1H, d, J=8,8 Hz), 7,25-to 7.35 (1H, m), between 7.4 to 7.5 (2H, m)
187(DMSO-d6) a 1.45 (3H, d, J=6.3 Hz), 3,86 (3H, s), with 5.22 (2H,s)5,54 (1H, q, J=6.3 Hz), of 6.02 (1H, DD, J=8,5 Hz, 2.9 Hz), 6,28 (1H, d, J=2,9 Hz), 6,85-7,05 (3H, m), 7,2-7,3 (2H, m)
188(DMSO-d6) 1,49 (3H, d, J=6.2 Hz), to 3.73 (3H, s), a total of 5.21 (2H,s), from 5.29 (1H, q, J=6.2 Hz), 6,11 (1H, DD, J=9,0 Hz, 2.9 Hz), 6,34 (1H, d, J=2,9 Hz), 6.75 in-6,85 (1H, m), 6,85-7,0 (3H, m), 7,2-7,3 (1H, m)

Table 25
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
189(DMSO-d6) to 1.47 (3H, d, J=6.4 Hz), and 3.72 (3H, s), 5,19 (2H,s), 5,28 (1H,q, J=6.4 Hz)and 6.1 (1H, DD, J=8.6 Hz, 2.9 Hz), 6,33 (1H, d, J=2,9 Hz), 6,85-6,9 (H, m), to 6.95 (1H, d, J=8.6 Hz), 7,25 of 7.3 (2H, m)
190(DMSO-d6) 0,85-0,95 (3H, m), 1.85 to a 2.0 (1H, m), 2.05 is-2,2 (1H, m), 5,28 (2H, s), lower than the 5.37 (1H,t,J=7.2 Hz), 6,1 (1H,DD, J=8.7 Hz, 2.9 Hz), 6,34 (1H, d, J=2,9 Hz), 6,95 to 7.1 (3H, m), 7,3 was 7.45 (1H, m)
191(DMSO-d6) of 1.55 (3H, d, J=6.2 Hz), 5,28 (2H, s), to 5.57 (1H, q, J=6.2 Hz), 6,03 (1H, DD, J=9,0 Hz, 2.8 Hz), 6,34 (1H, d, J=2,8 Hz), 6,98 (1H, d, J=9.0 Hz), 7,45-of 7.55 (1H, m), the 7.65 to 7.75 (3H, m)
192(DMSO-d6) of 1.52 (3H, d, J=6,4 Hz in), 5.25 (2H, s), of 5.48 (1H, q, J=6.4 Hz), 6,13 (1H, DD, J=8,9 Hz, 2.8 Hz), 6,36 (1H, d, J=2,8 Hz), of 6.99 (1H, d, J=8,9 Hz), 7,55 to 7.75 (4H, m)
193(DMSO-d6) of 1.52 (3H, d, J=6.3 Hz), 5,46 (1H, q, J=6.3 Hz), 6,11 (1H, DD, J=8.7 Hz, 2.9 Hz), 6,34 (1H, d, J=2,9 Hz), 6,98 (1H, d, J=8.7 Hz), to 7.59 (2H, d, J=8,2 Hz), 7,71 (2H, d, J=8,2 Hz)
194(CDCl3) was 4.02 (2H, s), is 5.06 (2H, s), 6,37 (1H, DD, J=8.7 Hz, 2.9 Hz), 6,41 (1H, d, J=2,9 Hz), 6,85-7,0 (2H, m), 7,13 (1H, d, J=8.7 Hz), 7,25 to 7.4 (1H, m)
195 (CDCl3) of 4.04 (2H, s), a total of 5.21 (2H, s), 6,35-of 6.45 (2H, m), to 7.15 (1H, d, J=8,8 Hz), 7,2-7,3(1H, m), 7.3 to 7.4 (2H, m)
196(CDCl3) was 1.58 (3H, d, J=6.4 Hz), of 3.94 (2H, s)5,59 (1H, q, J=6.4 Hz), 6,16 (1H, DD, J=8,8 Hz, 2.8 Hz), 6,23 (1H, d, J=2,8 Hz), 7,01 (1H, d, J=8,8 Hz), 7,15-of 7.25 (2H, m), 7.3 to 7.4 (1H, m), between 7.4 to 7.5 (1H, m)

Table 26
Ref. Ave. No.Structure(Solvent)1H-NMR δ ppm:
197(CDCl3) was 1.58 (3H, d, J=6.5 Hz), of 3.95 (2H, s)to 5.17 (1H, q, J=6.5 Hz), to 6.19 (1H, DD, J=9,0 Hz, 2.9 Hz), 6,27 (1H, d, J=2,9 Hz), 7,03 (1H, d, J=9.0 Hz), 7,15-of 7.3 (3H, m), 7,3-to 7.35 (1H, m)
198(CDCl3) of 1.55 to 1.6 (3H, m), of 3.94 (2H, s), 5,15-5,25 (1H, m), 6,15 to 6.3 (2H, m), 6,95-7,05 (1H, m), a 7.2 to 7.35 (4H, m)
199(CDCl3) 1,85-2,3 (4H, m), 3,65 of 3.75 (1H, m), 3,98 (2H, s), a 4.3 and 4.4 (1H, m), 5,3-5,4 (1H, m), of 6.26 (1H, DD, J=8.6 Hz, 2.7 Hz), of 6.31 (1H, d, J=2.7 Hz), to 7.0, and 7.1 (3H, m), 7,15-of 7.25 (1H, m), 7,25 of 7.3 (1H, m)
200 (CDCl3) and 0.98 (3H, t, J=7.4 Hz), 1,75-of 2.05 (2H, m), 3,91 (2H, s), 4,9-of 4.95 (1H, m), 6,2 (1H, DD, J=8,8 Hz, 2.8 Hz), 6,27 (1H, d, J=2,8 Hz), 7,0 (1H, d, J=8,8 Hz), a 7.2 to 7.35 (5H, m)
201(CDCl3) of 1.74 (3H, d, J=6.6 Hz), of 3.95 (2H, s), the 5.65 (1H, q, J=6.6 Hz), 6,28 (1H, DD, J=8.7 Hz, 2.9 Hz), 6,34 (1H, d, J=2,9 Hz), 6.8 or 6.9 (2H, m), 7,03 (1H, d, J=8.7 Hz), 7,15-of 7.25 (1H, m)
202(CDCl3) to 0.89 (3H, d, J=6,7 Hz)of 1.02 (3H, d, J=6.8 Hz), a 2.0 to 2.15 (1H, m), 4,71 (1H, d, J=6.4 Hz), 6,18 (1H, DD, J=8.7 Hz, 2.8 Hz), of 6.26 (1H, d, J=2,8 Hz), 6,98 (1H, d, J=8.7 Hz), a 7.2 to 7.35 (5H, m)
203(CDCl3) 0,85-1,05 (3H, m), 1,2-1,3 (2H, m), 1,6-1,9 (2H, m), 4,6-the 4.65 (1H, m), 6,1 and 6.25 (2H, m), of 6.96 (1H, d, J=8,9 Hz), a 7.2 to 7.35 (5H, m)
204(CDCl3) to 0.97 (3H, t, J=7,3 Hz), 1,75-2,0 (2H, m), 4,85-of 4.95 (1H, m), 6,18 (1H, DD, J=8.7 Hz, 2.8 Hz), of 6.26 (1H, d, J=8.7 Hz), 7,02 (1H, d, J=2,8 Hz), 7,15-to 7.35 (5H, m)

Table 27
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
205(CDCl3) 1,2-1.55V (7H, m), 1,7-of 1.85 (1H, m), 1,9-2,0 (1H, m), 4.95 points to 5.0 (1H, m), to 6.19 (1H, DD, J=8.7 Hz, 2.7 Hz), of 6.26 (1H, d, J=2.7 Hz), of 6.99 (1H, d, J=8.7 Hz), a 7.2 to 7.35 (5H, m)
206(CDCl3) of 3.07 (2H, t, J=7,1 Hz), 4,0 (2H, s), 4,1 (2H, t, J=7,1 Hz), of 6.26 (1H, DD, J=8.7 Hz, 2.7 Hz), of 6.31 (1H, d, J=2.7 Hz), and 7.1 (1H, d, J=8.7 Hz), a 7.2 to 7.35 (5H, m)
207(CDCl3) to 3.1 (2H, t, J=7.0 Hz), 4,0 (2H, users), 4,11 (2H, t, J=7.0 Hz), of 6.26 (1H, DD, J=8.7 Hz, 2.8 Hz), of 6.31 (1H, d, J=2,8 Hz), 7,0-to 7.15 (3H, m), 7,15-of 7.3 (2H, m)
208(CDCl3) of 1.27 (3H, d, J=5.8 Hz), of 2,75 2,85 (1H, m), 3,0-3,1 (1H, m), 3,98 (2H, s), 4,4-4,55 (1H, m), 6,2 to 6.35 (2H, m), to 7.09 (1H, d, J=8,9 Hz), 7,15-to 7.35 (5H, m)
209(CDCl3) 0,99 (3H, t, J=7.4 Hz), 1,8-of 2.05 (2H, m), of 3.94 (2H, s), 5.25 to 5.35 (1H, m), 6,21 (1H, DD, J=8,9 Hz, 2.9 Hz), 6,28 (1H, d, J=2,9 Hz), 7,0-to 7.15 (3H, m), 7,15-of 7.3 (1H, m), 7.3 to 7.4 (1H, m)
210(CDCl3) of 1.39 (3H, d, J=7,0 Hz), 3.15 and is 3.25 (1H, m), 3,85-of 4.05 (4H, m), 6,2 to 6.35 (2H, m), 7,09 (1, d, J=8.6 Hz), a 7.2 to 7.35 (5H, m)
211(DMSO-d6) 5,04 (2H, s), to 5.35 (2H, s), from 6.22 (1H, DD, J=8.7 Hz, 3.0 Hz), to 6.43 (1H, d, J=3.0 Hz), 7,07 (1H, d, J=8.7 Hz), 7,1-of 7.25 (3H, m)
212(DMSO-d6) to 5.03 (2H, s), to 5.35 (2H, s), and 6.25 (1H, DD, J=8,5 Hz, 2.8 Hz), of 6.45 (1H, d, J=2,8 Hz), was 7.08 (1H, d, J=8.5 Hz), 7,2-7,4 (3H, m)

Table 28
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
213(DMSO-d6) of 1.36 (6H, s), 3,88 (2H, in), 5.25 (2H, s), 6,11 (1H, DD, J=8,8 Hz, 2.8 Hz), 6,34 (1H, d, J=2,8 Hz), 7,01 (1H, d, J=8,8 Hz), 7,15-of 7.25 (1H, m), 7,25-to 7.35 (2H, m), 7,4 was 7.45 (2H, m)
214(CDCl3) of 1.53 (3H, d, J=6.2 Hz), 3,71 (3H, s), 3,85 (3H, s), 3,91 (2H, s), to 5.57 (1H, q, J=6.2 Hz), 6,2 (1H, DD, J=8,9 Hz, 2.9 Hz), 6,27 (1H, d, J=2,9 Hz), was 6.73 (1H, DD, J=8,8 Hz, 3.1 Hz), 6,8 (1H, d, J=8,8 Hz), 6,93 (1H,d, J=3.1 Hz), 7,0 (1H, d, J=8,9 Hz)
215 (CDCl3) was 1.58 (3H, d, J=6.5 Hz), of 3.77 (6H, s), of 3.94 (2H, users), 5,11 (1H, q, J=6.5 Hz), to 6.22 (1H, DD, J=8,5 Hz, 2.7 Hz), 6,28 (1H, d, J=2.7 Hz), 6,3 to 6.35 (1H, m), 6,45 to 6.5 (2H, m), 7,02 (1H, d,J=8,5 Hz)
216(CDCl3) of 1.56 (3H, d, J=6.4 Hz), 3,86 (3H, s), of 3.95 (2H, s), 5,14 (1H, q, J=6.4 Hz), 6,15 to 6.3 (2H, m), 6,85-to 6.95 (1H, m), of 7.0, and 7.1 (3H, m)
217(CDCl3) was 1.58 (3H, d, J=6.4 Hz), of 5.48 (1H, q, J=6.4 Hz), to 6.22 (1H, DD, J=8.7 Hz, 2.8 Hz), 6,28 (1H, d, J=2,8 Hz), 6,55 to 6.7 (2H, m), 7,02 (1H, d, J=8.7 Hz), 7,25 of 7.3 (1H, m)
218(DMSO-d6) of 5.05 (2H, s), lower than the 5.37 (2H, s), and 6.25 (1H, DD, J=9,0 Hz, 2.8 Hz), 6,46 (1H, d, J=2,8 Hz), to 7.09 (1H, d, J=9.0 Hz), 7,47 (1H, DD, J=8.7 Hz, 2.6 Hz), 7,55 (1H, d, J=8.7 Hz), 7,6 (1H, d, J=2,6 Hz)
219(DMSO-d6) to 5.03 (2H, s), to 5.35 (2H, s), and 6.25 (1H, DD, J=8.7 Hz, 2.8 Hz), of 6.45 (1H, d, J=2,8 Hz), was 7.08 (1H, d, J=8.7 Hz), 7,25-to 7.35 (1H, m), 7,45 is 7.5 (1H, m), 7,55 and 7.6 (1H, m)

220
Table 29
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
(CDCl3in ) 1.6 (3H, d, J=6.4 Hz), of 3.56 (2H, users), of 5.26 (1H, q, J=6.4 Hz), 6,15 to 6.3 (3H, m), the 6.9 to 7.0 (1H, m), 7,2-7,4 (5H, m)
221(CDCl3) of 1.52 (3H, d, J=6.3 Hz), a 3.87 (3H, s), of 3.94 (2H, users), of 5.55 (1H, q, J=6.3 Hz), 6,18 (1H, DD, J=8,8 Hz, 2.8 Hz), of 6.26 (1H, d, J=2,8 Hz), 6.75 in-6,85 (1H, m), 6,85-to 6.95 (1H, m), 7,01 (1H, d, J=8,8 Hz), 7,06 (1H, DD,J=9,2 Hz, 3.1 Hz)
222(CDCl3) is 1.51 (3H, d, J=6.3 Hz), a 3.87 (3H, s), 3,93 (2H, users), 5,54 (1H, q, J=6.3 Hz), 6,17 (1H, DD, J=8,8 Hz, 3.0 Hz), and 6.25 (1H, d, J=3.0 Hz), 6,55-of 6.65 (2H, m), 7,01 (1H, d, J=8,8 Hz), 7,25-to 7.35 (1H, m)
223(CDCl3) of 1.46 (3H, t, J=7,0 Hz)of 1.55 (3H, d, J=6.3 Hz), 3,9 (2H, users), 4,05-to 4.15 (2H, m), 5,6-the 5.65 (1H, m), 6,2 (1H, DD, J=8,9 Hz, 2.9 Hz), 6,28 (1H, d, J=2,9 Hz), 6,8-6,95 (2H, m), 7,0 (1H, d, J=8,9 Hz), 7,15-of 7.25 (1H, m), 7.3 to 7.4 (1H, m)
224(CDCl3) was 1.69 (3H, d, J=6.6 Hz), 3,85-of 3.95 (5H, m), 5,7-5,8 (1H, m), 6,28 (1H, DD, J=8,8 Hz, 2.5 Hz), 6.35mm (1H, d, J=2.5 Hz), and 6.6 and 6.7 (2H, m), 7,0 (1H, d, J=8,8 Hz), 7,1-7,2 (1H, m)
225 (CDCl3) to 1.59 (3H, d, J=6.4 Hz), 5,23 (1H, q, J=6.4 Hz), x 6.15 and 6.25 (2H, m), 6,83 (1H, d, J=8.0 Hz), 7,2-7,4 (5H, m)
226(DMSO-d6) of 3.84 (3H, s)to 4.92 (2H, s), 5,31 (2H, s), 6,2-of 6.25 (1H, m), to 6.43 (1H, d, J=2.7 Hz), 6.8 or 6.9 (1H, m), 6,93 (1H, d, J=8,2 Hz), 7,06 (1H, d, J=8.6 Hz), 7,35-7,45 (1H, m)

Table 30
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
227(DMSO-d6) of 1.65 (3H, d, J=6,7 Hz), free 5.01 (2H, s), 5,85 to 6.0 (2H, m), 6,0-x 6.15 (2H, m), 6.75 in-6,85 (1H, m), 7,25 was 7.45 (3H, m)
228(CDCl3) was 1.58 (3H, d, J=6.4 Hz), to 3.64 (2H, s), 5,16 (1H, q, J=6.4 Hz), 6,1-x 6.15 (1H, m), of 6.29 (1H, DD, J=7,6 Hz, 3.0 Hz), 6.75 in-6,85 (1H, m), the 6.9 to 7.0 (1H, m), 7,0-to 7.15 (2H, m), a 7.2 to 7.35 (1H, m)
229(CDCl3) is 1.51 (3H, d, J=6.4 Hz), 3,86 (3H, s), the 5.45 to 5.55 (1H, m), 6,05-x 6.15 (1H, m), 6,25 to 6.3 (1H, m), 6,7-6,85 (2H, m), 6,85-to 6.95 (1H, m), 7,05 and 7.1 (1H, m)
230 (CDCl3) 4,06 (2H, s), and 5.2 (2H, s), 6,3-of 6.45 (2H, m), 7,14 (1H, d, J=9.0 Hz), 7,4 was 7.45 (1H, m), and 7.6 to 7.75 (3H, m)
231(CDCl3) 3,44 (3H, s), 3.75 to 3,8 (2H, m)4,06 (2H, s), 4,15 to 4.2 (2H, m), 5,09 (2H, s), 6,34 (1H, DD, J=8.7 Hz, 2.8 Hz), 6,47 (1H, d, J=2,8 Hz), 6,85-7,0 (2H, m), to 7.09 (1H, d, J=8.7 Hz), 7,2-7,3 (1H, m), 7,4-7,45 (1H, m)
232(CDCl3) 3,71 (2H, s), 3,83 (3H, s), 5,0-of 5.05 (2H, m), 6,3 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), 6,55-of 6.65 (1H, m), 6,85-to 6.95 (1H, m), 7,05 to 7.2 (1H, m)
233(CDCl3) was 1.69 (3H, d, J=6,7 Hz), 3,62 (2H, s), 3,86 (3H, s), 5,71 (1H, q, J=6,7 Hz), x 6.15 and 6.25 (1H, m), 6,3-6,4 (1H, m), 6,5-6,6 (1H, m), 6,7-6,8 (1H, m), 6,95-7,05 (1H, m)

Table 31
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
234(CDCl3) 2,49 (3H, s), was 4.02 (2H, users), 5,07 (2H, s), 6,3-of 6.45 (2H, m), 7,12 (1H, d, J=8.7 Hz), 7,15-of 7.25 (1H, m), 7,25-to 7.35 (2H, m), 7,44 (1H, d, J=7,4 Hz)
235 (CDCl3) to 3.73 (2H, users), a 5.0 to 5.1 (2H, m), and 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,8-6,95 (2H, m), 7,1-7,2 (1H, m)
236(CDCl3) 3,74 (2H, users), to 4.98 (2H, s), 6,2-6,3 (1H, m), 6,35-of 6.45 (1H, m), 6,85-7,0 (2H, m), 7,25 to 7.4 (1H, m)
237(CDCl3) 3,74 (2H, users), of 5.05-5,1 (2H, m), and 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), 7,05-to 7.15 (1H, m)
238(CDCl3) 3,71 (2H, users), 3,86 (3H, s), of 5.03 (2H, s), from 6.25 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), 6,8-7,0 (3H, m), 7,25-to 7.35 (1H, m), 7,4 was 7.45 (1H, m)
239(CDCl3) of 1.41 (3H, t, J=7.0 Hz), 4,08 (2H, q, J=7.0 Hz), 5,04 (2H, s), from 6.25 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), 6,8-7,0 (3H, m), 7,2-7,3 (1H, m), 7,4 was 7.45 (1H, m)
240(CDCl3) 3,71 (2H, s), of 5.05 (2H, s), 6,25 to 6.3 (1H, m), 6,35 to 6.7 (2H, m), 6,85-to 6.95 (1H, m), 7,1-7,2 (1H, m), 7,2-7,3 (1H, m), 7.3 to 7.4 (1H, m), 7.5 to at 7.55 (1H, m)
241(CDCl3) 2,39 (6H, s), 3,71 (2H, users), of 4.95 (2H, s), 6,3 to 6.35 (1H, m), 6,4-of 6.45 (1H, m),6,85-to 6.95 (1H, m)of 7.0, and 7.1 (2H, m), 7,1-7,2 (1H, m)

Table 32
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
242(CDCl3) to 3.73 (2H, users), of 5.05-of 5.15 (2H, m), and 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), 7,45 and 7.6 (2H, m)
243(CDCl3) to 2.2-2.3 (3H, m), 3,71 (2H, users), of 5.05-5,1 (2H, m), 6,3-6,4 (1H, m), 6,4-6,5 (1H, m), 6,85-to 6.95 (1H, m), 7,05-to 7.15 (2H, m)
244(CDCl3) of 3.95 to 4.0 (3H, m), 5,02 (2H, s), from 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), 6,95 to 7.1 (2H, m), 7,15-of 7.25 (1H, m)
245(CDCl3) 3,74 (2H, users), 5,09 (2H, s), 6,2-6,3 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), 7,2-of 7.25 (1H, m), between 7.4 to 7.5 (2H, m)
246(CDCl3) 3,7 (2H, users), 3,83 (3H, s), 5,0 (2H, s), 6,25 to 6.3 (1H, m), 6,35-of 6.45 (1H, m), 's 6.75 to 7.0 (3H, m), 7,15 to 7.2 (1H, m)
247(CDCl3) 3,4-4,0 (5H, m), 5,02 (2H, s), from 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6.75 in-6,85 (1H, m), 6,85-to 6.95 (1H, m), 6,95-7,05 (2H, m)
248(CDCl3) 3,7 (2H, users), 5,04 (2H, s), from 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (2H, m), 7,3 was 7.45 (1H, m)

Table 33
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
249(CDCl3) 3,2-4,0 (5H, m), to 4.98 (2H, s), from 6.25 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), 6.75 in-6,9 (2H, m), 7,2-of 7.25 (1H, m), 7,4 was 7.45 (1H, m)
250(CDCl3) and 3.72 (2H, users), 5,07 (2H, s), 6,25 to 6.3 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), 7,25 to 7.4 (3H, m), 7,55 and 7.6 (1H, m)
251(CDCl3) 3,4-4,0 (5H, m), 5,07 (2H, s), 6,3-6,4 (1H, m), 6,4-6,5 (1H, m), 6,85-to 6.95 (1H, m), 7,17 (1H, d, J=9.0 Hz), 7,35 (1H,d,J=9.0 Hz)
252(CDCl ) 5,07 (2H, s), from 6.25 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), 6,85-to 6.95 (1H, m)and 7.1-of 7.25 (1H, m), 7,55-the 7.65 (1H, m), 7,8-a 7.85 (1H, m)
253(CDCl3) to 3.73 (2H, users), is 5.18 (2H, s), 6,2-6,3 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), of 7.0, and 7.1 (1H, m), 7,4-of 7.55 (1H, m), and 7.6 to 7.7 (1H, m)
254(CDCl3) to 2.2-2.3 (3H, m), 3,71 (2H, users), 5,02 (2H, s), from 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6.75 in-6,95 (2H, m), 7,1-7,2 (1H, m)
255(CDCl3) to 2.06 (3H, s), 3,83 (3H, s), 4.95 points-of 5.05 (2H, m), and 6.5 (1H, d, J=7,7 Hz), 6,55-of 6.65 (1H, m), of 6.75 (1H, d, J=11.2 Hz), 7,05-to 7.15 (1H, m)

Table 34
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
256(CDCl3) to 2.06 (3H, c), 3,86 (3H, c), 4,95-of 5.05 (2H, m), of 6.52 (1H, d, J=8.0 Hz), 6,65-6,8 (3H, m), 7,25-to 7.35 (1H, m)
257(CDCl3) is 2.37 (3H, c), 3,71 (2H, users), of 5.05-of 5.15 (2H, m), 6,3-6,4 (1H, m), 6,4-6,5 (1H, is), 6,85-7,0 (2H, m), 7,2-7,3 (1H, m)
258(CDCl3) 3,7 (2H, users), 3,85 (3H, c), 5,0-of 5.05 (2H, m), 6,3 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), 6,65 and 6.7 (1H, m), 6,85-to 6.95 (1H, m), 7.3 to 7.4 (1H, m)
259(CDCl3) 2,32 (3H, c), 5,0 (2H, c), and 6.25 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), 6,85-7,0 (2H, m), 7,05 and 7.1 (1H, m), 7,2-7,3 (1H, m)
260(CDCl3) to 3.92 (3H, c), a 5.1 (2H, c), 6,25 to 6.3 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (2H, m), 7,1-7,2 (1H, m), 7,2-7,3 (1H, m)
261(CDCl3) a 3.9 (3H, c), of 5.05-5,1 (2H, m), 6,25 to 6.3 (1H, m), 6.35mm (1H, m), 6,8-7,0 (2H, m), of 7.0, and 7.1 (2H, m)
262(CDCl3) a 1.08 (2H, t, J=7.4 Hz), 2,47 (2H, q, J=7.4 Hz), 3,85 (3H, c), 4,95-of 5.05 (2H, m), 6,53 (1H, d, J=8.0 Hz), 6,65-6,8 (3H, m), 7,25-to 7.35 (1H, m)
263(CDCl3) a 1.08 (3H, t, J=7,6 Hz), 2,47 (2H, q, J=7,6 Hz), 3,83 (3H, c), 5,0-of 5.05 (2H, m), 6,51 (1H, d, J=7,7 Hz), 6,55-of 6.65 (1H, m), 6,77 (1H, d, J=11.5 Hz), 7,05-to 7.15 (1H, m)

Table 35
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
264(CDCl3) a 3.83 (3H, s), a 5.1 (2H, s), 6,3-6,4 (1H, m), 6,4-of 6.45 (1H, m), 6.75 in-6,85 (1H, m), 6,85-to 6.95 (1H, m), a 7.1 to 7.15 (1H, m)
265(CDCl3) of 3.84 (3H, s), 5,12 (2H, s), 6,3-6,4 (1H, m), 6,4-of 6.45 (1H, m), for 6.81 (1H, d, J=9.3 Hz), 6,85-to 6.95 (1H, m), 7,42 (1H, d,J=9,3 Hz)
266(CDCl3) 2,2-of 2.25 (3H, m), 3,82 (3H, s), 5,0-of 5.05 (2H, m), 6,3-6,4 (1H, m), 6,4-6,5 (1H, m), 6,62 (1H, d, J=8.5 Hz), 6,85-to 6.95 (1H, m), 7,05-to 7.15 (1H, m)
267(CDCl3) 3,7 (2H, users), to 4.98 (2H, s), 6,25 to 6.3 (1H, m), 6,35-of 6.45 (1H, m), 6.8 or 6.9 (1H, m), 7,25 was 7.45 (5H, m)
268(CDCl3) 0,011 (3H, s)0,016 (3H, s)0,86 (9H, s), 3.75 to of 3.85 (1H, m), of 3.85 to 4.0 (3H, m), of 5.05-of 5.15 (1H, m), 6,2-6,3 (2H, m), 7,0 (1H, d, J=9.0 Hz), 7,2-7,4 (5H, m)
269(DMSO-d6) 006 (6H, C)to 0.89 (9H, s), rate 4.79 (2H, s), of 5.03 (2H, s), 5,32 (2H, s), 6,21 (1H, DD, J=8,5 Hz, 2.8 Hz), to 6.43 (1H, d, J=2,8 Hz), 7,06 (1H, d, J=8.5 Hz), 7,2-7,5 (4H, m)
270(DMSO-d6) of 0.07 (6H, s), and 0.9 (9H, s), 4.72 in (2H, s), 4,99 (2H, s), with 5.3 (2H, s), 6,2 (1H, DD, J=8.6 Hz, 2.8 Hz), to 6.43 (1H, d, J=2,8 Hz), 7,05 (1H, d, J=8.6 Hz), 7,2-7,4 (4H, m)

Table 36
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
271(CDCl3) 0,116 (3H, s), 0,12 (3H, s)to 0.92 (9H, s), a 1.5-1.6 (3H, m)to 3.92 (2H, s), 3.95 to of 4.05 (2H, m), 4,05-to 4.15 (2H, m), the 5.65 (1H, q, J=6.4 Hz), to 6.19 (1H, DD, J=8,9 Hz, 2.9 Hz), and 6.3 (1H, d, J=2,9 Hz), 6,8-7,0 (3H, m), 7,15-of 7.25 (1H, m), 7.3 to 7.4 (1H, m)
272(DMSO-d6) of 0.11 (3H, s), 0,12 (3H, s)of 0.91 (9H, s), of 1.52 (3H, d, J=6.3 Hz), 4.75 V-4,9 (2H, m), with 5.22 (2H, s), 5,5-of 5.55 (1H, m), 6,0-6,1 (1H, m), of 6.29 (1H,d, J=2,8 Hz)and 6.9 (1H, d, J=8.6 Hz), 7,2-7,3 (2H, m), 7.3 to 7.4 (2H, m)
273(CDCl3) and 0.09 (6H, s), and 0.9 (9H, s), 3.95 to of 4.05 (5H, m), 4,05-to 4.15 (2H, m), 5,07 (2H, s), 6,3-6,4 (1H, m), 6.42 per (1H, d, J=2,9 Hz), 6,5-7,0 (2H, m)and 7.1 (1H, d, J=8.7 Hz), 7,2-7,3 (1H, m), 7,4 was 7.45 (1H, m)
274(CDCl3) 0,065 (3H, s)0,067 (3H, s), and 0.9 (9H, s), and 1.54 (3H, d, J=6.2 Hz), 2,0-2,1 (2H, m), 3,8-of 3.95 (5H, m), 4,1-4,2 (2H, m), 5,55-the 5.65 (1H, m), 6,15 to 6.2 (1H, m), 6,27 (1H, d, J=2,8 Hz), 6,85-to 6.95 (2H, m), of 6.99 (1H, d, J=8,9 Hz), 7,15-of 7.25 (1H, m), 7,3-to 7.35 (1H, m)
275(CDCl3) to 0.06 (3H, s)of 0.07 (3H, s), and 0.9 (9H, s), by 1.68 (3H, d, J=6.6 Hz), 2,0-2,1 (2H, m), 3,61 (2H, s), 3,8-3,9 (2H, m), 4,05-to 4.15 (2H, m), 5,65 to 5.8 (1H, m), x 6.15 and 6.25 (1H, m), 6,3-6,4 (1H, m), 6,55 to 6.7 (2H,, m), 6,7-6,8 (1H, m), 7,1-7,2 (1H, m)
276(CDCl3) 0,116 (3H, s), 0,123 (3H, s)of 0.93 (9H,s), 1.69 in (3H, d, J=6.6 Hz), 3,62 (2H, s), 3.95 to 4.2V (4H, m), 5,75 to 5.8 (1H, m), x 6.15 and 6.25 (1H, m), 6,35-of 6.45 (1H, m), and 6.6 and 6.7 (2H, m), 6,7-6,8 (1H, m), 7,1-7,2(1H m)

Table 37
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
277(CDCl3) 3,4-4,0 (2H, usher.), is 4.93 (2H, s), 6,2-of 6.25 (1H, m), 6,35 is 6.4 (1H, m), 6,85-to 6.95 (1H, m), 7,25-to 7.35 (3H, m)
278 (CDCl3) is 2.37 (3H, s), 3.45 points to 4.0 (5H, m), 5,04 (2H, s), 6,3-6,4 (1H, m), 6,4-6,5 (1H, m), 6.75 in-6,8 (1H, m), 6,8-6,95 (2H, m), 7,15-of 7.25 (1H, m)
279(CDCl3) to 1.25 (3H, t, J=7,6 Hz), 2,7 (2H, q, J=7,6 Hz), of 3.5-3.9 (2H, usher.), equal to 4.97 (2H, s), from 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), 7,15-to 7.35 (3H, m), 7,35-7,45 (1H, m)
280(CDCl3) 3,5-of 3.85 (2H, usher.), a 3.87 (3H, s), 4,99 (2H, s), 6,2-6,3 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), 7.3 to 7.4 (2H, m)
281(CDCl3) 3,6-3,9 (2H, usher.), to 5.08 (2H, s), from 6.25 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), and 7.6 to 7.75 (2H, m)
282(CDCl3) to 1.25 (3H, t, J=7,7 Hz)to 2.67 (2H, q, J=7,7 Hz), of 3.5-3.9 (2H, usher.), of 4.95 (2H, s), from 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), 7,1-to 7.35 (4H, m)
283(CDCl3) to 3.38 (3H, s), 3,6-of 3.85 (2H, usher.), of 4.54 (2H, s), of 5.05 (2H, s), from 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), 7,3-to 7.35 (2H, m), 7,35 is 7.5 (2H, m)
284 (CDCl3) to 3.4 (3H, s), 3,55-of 3.85 (2H, usher.), 4,47 (2H, s), to 4.98 (2H, s), 6,25 to 6.3 (1H, m), 6,35-of 6.45 (1H, m), 6.8 or 6.9 (1H, m), 7,25 to 7.4 (4H, m)

(CDCl3) 3,55-3,9 (2H, usher.), of 5.05 (2H, s), 6,2-6,3 (1H, m), 6,35-of 6.45 (1H, m), 6,8-6,95 (2H, m), 6,95 to 7.1 (1H, m)
Table 38
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
285(CDCl3) 3,74 (2H, users), of 5.15 (2H, s), from 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), the 7.65 (1H, t, J=8.0 Hz), of 7.97 (2H, d, J=8.0 Hz)
286(CDCl3) to 2.29 (3H, s), a 2.45 (3H, s), 3.45 points-of 3.95 (5H, m), equal to 4.97 (2H, s), from 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), to 7.09 (1H, d, J=2.2 Hz), 7,21 (1H, d, J=2.2 Hz)
287(CDCl3) 3,55-of 3.85 (2H, usher.), a 3.87 (3H, s), a 5.0 to 5.1 (2H, m), and 6.25 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), 6,8-7,0 (3H, m)
288(CDCl3) 3,5-of 3.85 (2H, usher.), 3,88 (3H, s), to 5.08 (2H, s), 6,3-6,4 (1H, m), 6,4-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), 7,1-7,2 (1H, m), 7,3-to 7.35 (1H, m), between 7.4 to 7.5 (1H, m)
289
290(CDCl3) 3,55-3,9 (2H, usher.), 5,09 (2H, s), from 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), 7.3 to 7.4 (1H, m), 7,45 and 7.6 (2H, m)
291(CDCl3) to 3.73 (2H, users), 3,86 (3H, s), free 5.01 (2H, s), 6,2-6,3 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (1H, m), 7,05-to 7.15 (2H, m)

Table 39
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
292(CDCl3) to 2.3 (3H, s), 3,55 to-3.9 (5H, m), 4,99 (2H, s), from 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,8-6,95 (2H, m), 6,95-7,05 (1H, m)
293(CDCl3) 3,5-of 3.95 (8H, m), to 4.98 (2H, s), from 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,85-to 6.95 (2H, m), 7,05 (1H, d, J=2.4 Hz)
294(CDCl3) 3,5-of 3.95 (5H, m)5,0 (2H, s), 6,2-6,3 (1H, m), 6,35-of 6.45 (1H, m), 6.75 in-6,85 (1H, m), 6,85-to 6.95 (1H, m), 695-7,05 (1H, m)
295(CDCl3) a 3.75 (3H, s), 3,85 (3H, s), of 5.05-of 5.15 (2H, m), the 6.5 to 7.3 (5H, m)
296(CDCl3) 3,2-3,6 (2H, usher.), of 3.75 (3H, s), 3,82 (3H, s), of 5.05-of 5.15 (2H, m), 6,53 (1H, d, J=9.0 Hz), 6,55 to 6.7 (2H, m), 7,05-to 7.15 (1H, m)
297(CDCl3) to 3.41 (3H, s), 3,6-4,0 (4H, m), 4,05-to 4.15 (2H, m), of 5.05-5,1 (2H, m), and 6.25 to 6.35 (1H, m), 6,45-6,55 (1H, m), 6,6-of 6.65 (1H, m), 6.8 or 6.9 (1H, m), 7,05-to 7.15 (1H, m)
298(CDCl3) to 1.19 (3H, t, J=7.0 Hz), of 3.56 (2H, q, J=7.0 Hz), of 3.7-3.8 (2H, m), 4,05-to 4.15 (2H, m), of 5.05-5,1 (2H, m), and 6.25 to 6.35 (1H, m), 6,45-6,55 (1H, m), 6,6-of 6.65 (1H, m), 6.8 or 6.9 (1H, m), 7,05-to 7.15 (1H, m)

Table 40
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
299(CDCl3) of 3.5-3.9 (8H, m)5,0 (2H, s), from 6.25 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), 6.75 in-6,9 (3H, m), 7,03 (1H, d, J=2.3 Hz)
300 (CDCl3) to 2.29 (3H, s), 3.45 points-of 3.95 (5H, m), 4,99 (2H, s), from 6.25 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), 6,79 (1H, d, J=8,3 Hz), 6.8 or 6.9 (1H, m), was 7.08 (1H, DD, J=8,3 Hz, 1.8 Hz), 7.23 percent (1H, d,J=1,8 Hz)
301(CDCl3) 1,95-2,1 (2H, m), 3,29 (3H, s)to 3.49 (2H, t, J=6,1 Hz)4,06 (2H, t, J=6,1 Hz), 5,0-of 5.05 (2H, m), and 6.25 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), 6,55-of 6.65 (1H, m), 6,85-to 6.95 (1H, m), 7,05-to 7.15 (1H, m)
302(CDCl3) 3,1-3,7 (2H, usher.), 3,81 (3H, s), 3,83 (3H, s), 5,07 (2H, s), to 6.39 (1H, d, J=8,8 Hz), of 6.66 (1H, d, J=12.1 Hz), 6.75 in-6,85 (1H, m), the 6.9 to 7.0 (1H, m), 7,2-of 7.25 (1H, m)
303(CDCl3) of 1.41 (3H, t, J=7.0 Hz), 3,1-3,7 (2H, usher.), a 3.83 (3H, s)to 4.01 (2H, q, J=7.0 Hz), is 5.06 (2H, s), 6.42 per (1H, d, J=8.6 Hz), to 6.67 (1H, d, J=12.1 Hz), 6.75 in-6,85 (1H, m), the 6.9 to 7.0 (1H, m), 7,2-7,3 (1H, m)
304(CDCl3) of 1.34 (3H, t, J=7.0 Hz), 3,1-3,7 (2H, usher.), of 3.84 (3H, s), of 3.96 (2H, q, J=7.0 Hz), of 5.05-of 5.15 (2H, m), 6,53 (1H, d, J=9.0 Hz), only 6.64 (1H, d, J=11,9 Hz), 6,65 to 6.75 (2H, m), 7,2-7,3 (1H, m)
305(CDCl3) to 1.35 (3H, t, J=7.0 Hz), 3,1-3,7 (2H, ush the R.), is 3.82 (3H, s), of 3.96 (2H, q, J=7.0 Hz), of 5.05-of 5.15 (2H, m), of 6.52 (1H, d, J=9.0 Hz), 6,55 to 6.7 (2H, m), 7,05-to 7.15 (1H, m)

Table 41
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
306(CDCl3) 3,55 (2H, users), 3,83 (3H)of 5.05-of 5.15 (2H, m), 6,5-of 6.65 (2H, m), 6.75 in-6,85 (1H, m), 7,05 to 7.2 (1H, m)
307(CDCl3) 3.5 to 3.8 (2H, usher.), of 3.84 (3H, s), of 5.05-of 5.15 (2H, m), 6,5-of 6.65 (2H, m), 7,0 (1H, d, J=10.4 Hz), 7,05 to 7.2 (1H, m)
308(CDCl3) and 3.72 (2H, users), of 3.84 (3H, s), of 5.05-of 5.15 (2H, m), 6,5-of 6.65 (2H, m), 7,05 to 7.2 (2H, m)
309(CDCl3) of 3.85 (3H, s)to 4.23 (2H, users), 5,1-of 5.15 (2H, m), 6,47 (1H, d, J=7,2 Hz), 6,6-of 6.65 (1H, m), 7,1-7,2 (2H, m)
310(CDCl3) of 3.53 (2H, users), 3,83 (3H, s), 5,1-of 5.15 (2H, m), x 6.15 and 6.25 (1H, m), 6,45 to 6.5 (1H, m), 6,55-of 6.65 (1H, m), 6.8 or 6.9 (1H, m), 7,05 to 7.2 (1H, m)
311(CDCl3) 3,1-3,7 (2H, usher.), 3,76 (3H, s), a 5.1 (2H, s), of 6.52 (1H, d, J=8.7 Hz), only 6.64 (1H, d, J=12.0 Hz), 6,85-to 6.95 (2H, m), 7,25-to 7.35 (1H, m)
312(CDCl3) of 3.77 (3H, in), 5.25 (2H, s), 6,55 (1H, d,J=8,9 Hz), of 6.66(1H,d, J=12.0 Hz), 7,15-of 7.25 (1H, m), 7.3 to 7.4 (2H, m)

Table 42
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
313(CDCl3) 3,55 (2H, users), 5,12 (2H, s), 6,45-6,6 (1H, m), 6.75 in-6,85 (1H, m), 6,85-7,0 (2H, m), 7,25 to 7.4 (1H, m)
314(CDCl3) 3,57 (2H, users), 5,28 (2H, s), 6,5-6,6 (1H, m), 6.75 in-6,85 (1H, m), 7,2-7,3 (1H, m), 7.3 to 7.4 (2H, m)
315(CDCl3) 3,1-3,7 (2H, usher.), 3,76 (3H, s), 3,82 (3H, s), 5,1-of 5.15 (2H, m), 6,27 (1H, DD, J=8,3 Hz, 2.6 Hz), 6.48 in (1H, d, J=2.6 Hz), 6,55-of 6.65 (1H, m), of 6.73 (1H, d, J=8,3 Hz), 7,05-to 7.15 (1H, m)
316 (CDCl3) of 3.43 (3H, s), of 3.7-3.8 (5H, m), 4,1-to 4.15 (2H, m), 5,1-5,2 (2H, m), 6,55 to 6.7 (3H, m), 7,0-to 7.15 (1H, m)
317(CDCl3) to 1.21 (3H, t, J=6.8 Hz), 3,2-of 3.85 (9H, m), 4,05 to 4.2 (2H, m), 5,1-5,2 (2H, m), 6,55 to 6.7 (3H, m), 7,0-to 7.15 (1H, m)
318(CDCl3) 3,44 (3H, s), 3.5 to 3.8 (4H, m), 4,05-to 4.15 (2H, m), 5,15-5,2 (2H, m), 6,55-of 6.65 (1H, m), 6,65-6,85 (2H, m), 7,0-to 7.15 (1H, m)
319(CDCl3) to 1.21 (3H, t, J=7,0 Hz)and 3.59 (2H, q, J=7.0 Hz), 3.75 to of 3.85 (2H, m), 4,1-to 4.15 (2H, m), 5,15-5,2 (2H, m), 6,55 to 6.7 (2H, m), 6,7-6,8 (1H, m), 7,05-to 7.15 (1H, m)
320(CDCl3) to 0.04 (6H, s)of 0.87 (9H, s)to 3.92 (2H, t, J=5,1 Hz), of 4.05 (2H, t, J=5,1 Hz), a 5.0 to 5.1 (2H, m), and 6.25 to 6.35 (1H, m), 6,4-of 6.45 (1H, m), and 6.6 and 6.7 (1H, m), 6.8 or 6.9 (1H, m), 7,0-to 7.15 (1H, m)

Table 43
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
321 (CDCl3) of 0.01 (6H, s)0,86 (9H, s), 1,9-2,0 (2H, m), 3,74 (2H, t, J=6,1 Hz), 4,07 (2H, t, J=6.0 Hz), 5,0-of 5.05 (2H, m), and 6.25 to 6.35 (1H, m), 6,35-of 6.45 (1H, m), 6,55-of 6.65 (1H, m), 6,8-6,95 (1H, m), 7,05-to 7.15 (1H, m,)
322(CDCl3) 1,85-of 1.95 (1H, m), of 2.21 (1H, s), 2,3-2,5 (3H, m), 2,65-2,8 (2H, m), 6.8 or 6.9 (2H, m), 7,15-of 7.25 (1H, m)
323(CDCl3) of 1.85 to 2.0 (1H, m), 2,2-to 2.35 (1H, m), 2,7-to 2.85 (4H, m)to 3.58 (2H, users), 6,05-x 6.15 (1H, m), 6,2-6,3 (1H, m), 6,7-6,85 (3H, m), 7,15-of 7.25 (1H, m)
324(CDCl3) from 1.8 to 1.85 (6H, m), 3,2-3,9 (2H, usher.), 6,0-6,05 (1H, m), 6,2-of 6.25 (1H, m), 6,65 to 6.75 (1H, m), 6.8 or 6.9 (2H, m), 7,15-of 7.3 (1H, m)
325(CDCl3) 3,88 (3H, s), 5,5-5,6 (1H, m), 6,5-6,7 (2H, m)
326(CDCl3) a 3.5 (3H, s), 3,65 of 3.75 (2H, m), 4,1-to 4.15 (2H, m), 6,5-of 6.65 (1H, m), 6,65 and 6.7 (1H, m), 7,38(1H, s)
327(CDCl3) to 4.81 (2H, s), to 7.0, and 7.1 (1H, m), 8,25-8,35 (1H, m)
328 (CDCl3) of 3.95 (3H, s), 4,69 (2H, s), 6,72 (1H, d, J=12,5 Hz), 8,17 (1H, d, J=8.7 Hz)

Table 44
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
329(CDCl3) 3,59 (2H, users), 3,83 (3H, c), to 5.08 (2H, c), 6,55 and 6.6 (1H, m), 6,7-6,9 (2H, m), 6,97 (1H, DD, J=9.8 Hz, 6.8 Hz)
330(CDCl3) of 3.42 (2H, users), to 3.73 (3H, c), 3,82 (3H, c), 5,07 (2H, c), 6,5-of 6.65 (2H, m), 6.75 in-6,85 (1H, m), of 6.96 (1H, d, J=9.8 Hz)
331(CDCl3) to 3.45 (3H, c), of 3.7-3.8 (2H, m), 4,05-to 4.15 (2H, m), 5,04 (2H, c), 6,55-of 6.65 (1H, m), 6,7-6,85 (2H, m), 6,85-to 6.95 (1H, m), 7,0-7,05 (1H, m)
332(CDCl3) 3,44 (3H, c), 3,7-of 3.75 (2H, m)to 3.99 (2H, users), 4,05-to 4.15 (2H, m), 6,35-6,55 (2H, m)
333(CDCl3) 3,8-of 3.95 (5H, m), 6,4-6,5 (2H, m)
334 (CDCl3) of 2,75 2,85 (3H, m), 3,39 (2H, users), the 3.65 (3H, c), 4,17 (2H, c), 6,56 (1H, d, J=12.9 Hz), 6.75 in-6,95 (4H, m)
335(CDCl3) 2,78 (3H, c), is 3.41 (2H, users), to 3.67 (3H, c), 4,22 (2H, c), 6,56 (1H, d, J=12,8 Hz), 6,95-7,0 (1H, m), 7,13 (1H, d, J=10.4 Hz), 7,25 of 7.3 (2H, m)
336(CDCl3) 2,7-2,8 (3H, m), the 3.65 (2H, users), 3,86 (3H, c), of 4.05 (2H, c), and 6.6 and 6.7 (3H, m), 6.8 or 6.9 (2H, m), 6,95-7,05 (1H, m)

Table 45
Ref. Ave No.Structure(Solvent)1H-NMR δ ppm:
337(CDCl3) of 2.75 to 2.8 (3H, m), 3,68 (2H, users), 4,1 (2H, s), and 6.6 and 6.7 (1H, m), 's 6.75 to 7.0 (5H, m)
338(CDCl3) 2,73 (3H, s), 3,2-4,0 (2H, usher.), 4,19 (2H, s), 6.75 in-6,85 (1H, m), 6,85-to 6.95 (1H, m), 6,95-7,05 (2H, m), 7,25 of 7.3 (2H, m)
339(CDCl3) of 2.75 to 2.8 (3H, m), to 3.67 (2H, users), 3,83 (3H, s)4,08 (2H, s), 6,45-6,55 (1H, m), and 6.6 and 6.7 (1H, m), 6.75 in-to 6.95 (3H, m)
340(CDCl3) of 2.75 to 2.8 (3H, m), 3,42 (3H, s), 3,6-of 3.85 (4H, m), 4,05-to 4.15 (4H, m), 6.5 to 6,55 (1H, m), and 6.6 and 6.7 (1H, m), 6,7-6,85 (1H, m), 6,85-7,0 (2H, m)
341(CDCl3) is 1.31 (3H, t, J=7,0 Hz)to 3.67 (2H, q, J=7.0 Hz), 3,7-of 3.75 (2H, m), 4,1-to 4.15 (2H, m), 6,5-of 6.65 (1H, m), 6,65 to 6.75 (1H, m), of 7.75(1H,s)
342(CDCl3) to 0.15 (6H, s)of 0.95 (9H, s), 3,85-of 3.95 (2H, m), 4,0-4,1 (2H, m), 6,5-of 6.65 (1H, m), 6,65 to 6.75 (1H, m), of 7.36 (1H, s)
343(CDCl3) to 1.24 (3H, t, J=7.0 Hz), 3,6 (2H, q, J=7.0 Hz), 3.75 to of 3.85 (2H, m), 4,05-to 4.15 (2H, m), of 5.05 (2H, s), 6,55-of 6.65 (1H, m), 6,7-6,85 (2H, m), 6,85-to 6.95 (1H, m), 6,95-7,05 (1H, m)
344(CDCl3) and 0.09 (6H, s), and 0.9 (9H, s), 3.95 to 4,0 (2H, m), 4,0-4,1 (2H, m), of 5.03 (2H, s), 6,55-of 6.65 (1H, m), 6,7-6,85 (2H, m), 6,85-7,0 (2H, m)

Table 46
Ref. Ave No.Structure (Solvent)1H-NMR δ ppm:
345(DMSO-d6) of 3.97 (3H, s), and 7.4 (1H, d, J=a 13.9 Hz), of 8.47 (1H, d, J=8,8 Hz), 13,0-of 13.7(1H, user.)
346(CDCl3) of 2,75 2,85 (3H, m), 3,39 (2H, users), the 3.65 (3H, s), 3,81 (3H, s)to 4.16 (2H, s), 6,45-6,55 (1H, m), 6,56 (1H, d, J=a 12.7 Hz), 6.75 in-6,85 (1H, m), 6.89 in (1H, d, J=10.3 Hz)

Table 47
Ave. No.Structure(Solvent)1H-NMR δ ppm:
1(CDCl3) of 1.6 and 1.75 (2H, m), 2,45 of 2.6 (2H, m), 3,7-of 3.85 (2H, m), of 3.94 (3H, s), PC 6.82 (1H, s), 7,0-to 7.15 (2H, m), 7,15-of 7.25 (1H, m), 7,49 (1H, DD, J=8,4 Hz, 2.0 Hz), 7,54 (1H, d, J=8,4 Hz), and 7.6 (1H, d, J=2.0 Hz), 7,7 one-7.8 (1H, m), for 9.47 (1H, s)
2(CDCl3) of 1.6 and 1.75 (2H, m), 2,4-2,6 (2H, m), of 3.7-3.8 (1H, m), 3,8-3,9 (1H, m), PC 6.82 (1H, d, J=5,2 Hz), 7,0-to 7.15 (2H, m), 7,15-of 7.25 (1H, m), 7,46 (1H, DD, J=8,3 Hz, 2.1 Hz), 7,54 (1H, d, J=8,3 Hz), the 7.65 (1H, d, J=2.1 Hz), 7,7-7,8 (2H, m), 9,65 (1H, s)
3 (CDCl3) of 1.6 and 1.75 (2H, m), 2,4-2,6 (2H, m), of 3.7-3.9 (2H, m), 6.89 in (1H, d, J=5.8 Hz), 7,0-to 7.15 (2H, m), 7,15-of 7.25 (1H, m), 7,32 (1H, d, J=5.8 Hz), 7,46 (1H, DD, J=8,4 Hz, 2.1 Hz), 7,55 (1H, d, J=8,4 Hz), to 7.64 (1H, d, J=2.1 Hz), 7,75 one-7.8(1H, m), 9,54(1H, users)
4(CDCl3) of 1.6-1.8 (2H, m), 2,4-2,6 (2H, m), 3,65 to 3.8 (4H, m), 3,8-3,9 (1H, m), 7,0-to 7.15 (2H, m), 7,15-of 7.25 (1H, m), 7,49 (1H, DD, J=8,4 Hz, 1.9 Hz), 7,55 (1H, d, J=8,4 Hz), to 7.59 (1H, d, J=1.9 Hz), of 7.75 (1H, d, J=7.5 Hz), to $ 7.91 (1H, s)
5(CDCl3) 1,95-of 2.05 (2H, m), of 2,75 2,85 (2H, m), 3,3-to 3.35 (2H, m), 4,48 (2H, s), and 6.5 (1H, d, J=8,4 Hz), 6,55-of 6.65 (1H, m), for 6.81 (1H, d, J=5.6 Hz), the 6.9 to 7.0 (2H, m), a 7.2 to 7.35 (3H, m), 7,51 (1H, d, J=8,4 Hz), 9,94 (1H, users)
6(CDCl3) to 1.38 (3H, t, J=7,1 Hz), 1,6-of 1.75 (2H, m), 2,4-2,6 (2H, m), 3,7-of 3.85 (2H, m)to 4.41 (2H, q, J=7,1 Hz), PC 6.82 (1H, s), 7,0-to 7.15 (2H, m), 7,15-of 7.25 (1H, m), 7,47 (1H, DD, J=8,5 Hz, 2.2 Hz), 7,53 (1H, d, J=8,5 Hz), and 7.6 (1H, d, J=2.2 Hz), 7,7-7,8 (1H, m), 9,11 (1H, s)
7(CDCl3) of 1.2 and 1.35 (2H, m), 1,75-1,9 (2H, m), 2,4-by 2.55 (2H, m), 3,2-4,3 (2H, usher.), 6,87 (1H, d, J=5.3 Hz), and 7.1 to 7.2 (3H, m), 7,25-to 7.35 (2H, m), 7,63 (1H, d, J=8.5 Hz), 7,69 (1H, DD, J=8,5 Hz, 1.9 Hz), 7,78 (1H, d, J=1.9 Hz), 9,5-10,2 (1H, user.)

Table 48
Ave. No.Structure(Solvent)1H-NMR δ ppm:
8(CDCl3) a 3.2 (3H, c), 6,87 (1H, d, J=5.4 Hz), a 7.1 to 7.15 (2H, m), a 7.2 to 7.35 (4H, m), 7,54 (1H, DD, J=8,4 Hz, 2.0 Hz), and 7.6 (1H, d, J=2.0 Hz), to 7.64 (1H, d, J=8,4 Hz), 9,5-11,0 (1H, user.)
9(CDCl3) of 0.9 to 1.8 (10H, m), 2,77 (3H, c), of 3.7-3.8 (1H, m), 6.87 in (1H, d, J=5.7 Hz), and 7.3 (1H, d, J=5.7 Hz), 7,69 (1H, d, J=8.1 Hz), 7,8-7,9 (2H, m), 9,5-10,5 (1H, user.)
10(DMSO-d6) 3,26 (3H, c), 7,19 (1H, d, J=5.7 Hz), 7,22 (1H, d, J=5.7 Hz), 7,25 of 7.3 (1H, m), 7,45-of 7.55 (1H, m), a 7.62 (1H, DD, J=8,5 Hz, 2.1 Hz), 7,8-7,9 (2H, m), of 8.04 (1H, d, J=2.1 Hz), 8,3 an 8.4 (1H, m), 12,54 (1H, c)
11(DMSO-d6) and 3.16 (3H, c), 7,05 (1H, d, J=7.8 Hz), 7,15 was 7.45 (4H, m), and 7.5 and 7.6 (1H, m), 7,75 and 8.1 (3H, m), 12,55 (1H, c)
12(DMSO-d6) 0,8-0,9 (6H, m), 1,75-of 1.95 (1H, m), 2,6-2,8 (5H, m), 7,15-of 7.25 (2H, m), 7,8-of 7.95 (2H, m), with 8.0 and 8.1 (1H, m), of 12.53 (1H, c)
13(DMSO-d6) of 1.6 and 1.75 (2H, m), 2,4-by 2.55 (2H, m), 3,7-of 3.85 (2H, m), to 6.95 (1H, d, J=3.1 Hz), 7,05-of 7.25 (3H, m), 7,52 (1H, DD, J=8,5 Hz, 2.0 Hz), 7,56 (1H, d, J=8.1 Hz), 7,78 (1H, d, J=8.5 Hz), of 8.04 (1H, d, J=2.0 Hz), charged 8.52 (1H, d, J=3.1 Hz), 11,53 (1H, c)
14(CDCl3) 1,75-1,9 (2H, m), 2,55-2,7 (2H, m), 3.75 to of 3.95 (2H, m), 6,9 (1H, d, J=5.5 Hz), 7,05-of 7.25 (4H, m), 7,29 (1H, d, J=5.5 Hz), 7,74 (1H, d,J=8,2 Hz), 10,17 (1H, c)

Table 49
Ave., No.Structure(Solvent)1H-NMR δ ppm:
15(DMSO-d6) 1,6-1,7 (2H, m), of 2.4-2.5 (2H, m), of 3.7-3.8 (2H, m), 7,05 and 7.1 (2H, m)and 7.1-of 7.25 (3H, m), 7,45-the 7.65 (4H, m), 7,74 (1H, d, J=1.0 Hz), 12,37 (1H, c)
16(DMSO-d6) 3,18 (3H, c), of 7.0, and 7.1 (1H, m), 7,15-of 7.25 (3H, m), 7,35 to 7.4 (2H, m), and 7.6 (1H, DD, J=8,5 Hz, 2.3 Hz), 7,87 (1H, d, J=8.5 Hz), of 7.96 (1H,d,J=2.3 Hz), 12,54 (1H, c)
17(DMSO-d6) and 2.26 (3H, c)and 3.15 (3H, c), 6,8-6,95 (2H, m), 7,057,25 (4H, m)and 7.6 (1H, DD, J=8,4 Hz, 2.3 Hz), 7,8-7,9 (2H, m), 12,54 (1H, c)
18(DMSO-d6) to 5.1 (2H, c), 7,14 (1H, DD, J=9,0 Hz, 2.9 Hz), 7,18 (1H, d, J=5.6 Hz), 7,22 (1H, d, J=5.6 Hz), 7,25 (1H, d, J=2,9 Hz), 7,3-7,5 (5H, m), 7,53 (1H, d, J=9.0 Hz), 12,48 (1H, c)
19(DMSO-d6) of 1.85 to 2.0 (2H, m), 2,7-2,8 (2H, m), 3,3-3,4 (2H, m), 3,81 (3H, c), and 4.5 (2H, c), 6,4-6,5 (2H, m), 6,85-to 6.95 (2H, m), 7,2 (1H, c), 7,31 (1H, DD, J=8,2 Hz, 2.1 Hz), and 7.4 (1H, d, J=2.1 Hz), 7,56 (1H, d, J=8,2 Hz), to 11.61 (1H, c)
20(DMSO-d6) 7,05 of 7.3 (7H, m), 7,75-7,9 (2H, m), 7.95 is-with 8.05 (1H, m), 10,48 (1H, c), 12,56 (1H, c)
21(DMSO-d6) 7,0-of 7.3 (7H, m), 7,55 to 7.7 (2H, m), 7,75-a 7.85 (2H, m), 10,4 (1H, c), and 12.4 (1H, c)

Table 50
Ave., No.Structure(Solvent)1H-NMR δ ppm:
22(DMSO-d6) 1,6-1,7 (2H, m), 2,4-by 2.55 (2H, m), of 3.7-3.8 (2H, m), 7,05-of 7.25 (3H, m, 7,39 (1H, s), 7,55 (1H, d, J=8,2 Hz), and 7.6 (1H, DD, J=8,5 Hz, 2.4 Hz), 7,83 (1H, d, J=8.5 Hz), of 8.09 (1H, d, J=2.4 Hz), a 12.03 (1H, s), 14,23 (1H, s)
23(DMSO-d6) 5,11 (2H, s), 7,19 (1H, DD, J=9,0 Hz, 2.9 Hz), 7,3 was 7.45 (5H, m), 7,45 is 7.5 (2H, m), EUR 7.57 (1H, d, J=9.0 Hz), 12,04 (1H, s), accounted for 14.45 (1H, users)
24(DMSO-d6) of 1.85 to 2.0 (2H, m), 2,7-2,8 (2H, m), 3,3-3,4 (2H, m)to 4.52 (2H, s), 6,44 (1H, d, J=8,2 Hz), 6,45 to 6.5 (1H, m), 6,85-to 6.95 (2H, m), of 7.36 (1H, d, J=8,2 Hz), 7,38 (1H, s)of 7.48 (1H, d, J=2.1 Hz), to 7.61 (1H, d, J=8,2 Hz), 12,0 (1H, s), accounted for 14.45 (1H, users)
25(DMSO-d6) of 2.33 (3H, s), 5,09 (2H, s), 7,15-of 7.3 (4H, m), 7,35 (1H, d, J=2.7 Hz), 7,41 (1H, s), the 7.43 (1H, d, J=7,7 Hz), 7,58 (1H, d, J=9.0 Hz), 12,04 (1H, s), 14,44 (1H, s)
26(DMSO-d6) 2,32 (3H, s), 5,07 (2H, s), 7,1-to 7.35 (6H, m), 7,41 (1H, s), EUR 7.57 (1H, d, J=8.7 Hz), 12,04 (1H, s), accounted for 14.45 (1H, users)
27(DMSO-d6) of 5.24 (2H, s), 7,2 (1H, DD, J=8,8 Hz, 3.0 Hz), 7,35 (1H, d, J=3.0 Hz), 7,41 (1H, s), to 7.59 (1H, d, J=8,8 Hz), 7,69 (2H, d, J=8,2 Hz), 7,78 (2H, d, J=8,2 Hz), 12,04 (1H, s), 14,43 (1H, s)
28 (DMSO-d6) a 1.5-1.6 (3H, m), the 5.45 to 5.55 (1H, m), of 7.0, and 7.1 (1H, m), 7.23 percent (1H, DD, J=6,1 Hz, 2.9 Hz), of 7.25 and 7.5 (7H, m), 11,95 compared to 12.1 (1H, m), 14,42 (1H, s)

Table 51
Ave., No.Structure(Solvent)1H-NMR δ ppm:
29(DMSO-d6) to 2.85 to 3.0 (4H, m), 7,15-to 7.35 (8H, m), 7,38 (1H, s), 7,41 (1H, t, J=7,7 Hz), 11,92 (1H, s), 14,94 (1H, users)
30(DMSO-d6) 1,6-1,7 (2H, m), 2,4-by 2.55 (2H, m), 3,7-of 3.85 (2H, m), 7,0-7,2 (3H, m), 7,24 (1H, s), 7,56 (1H, d, J=8,3 Hz), to 7.59 (1H, DD, J=8,5 Hz, 2.1 Hz), 7,81 (1H, d, J=8.5 Hz), 8,05-of 8.15 (2H, m), of 9.55 (1H, s), 11,81 (1H, s)
31(CDCl3) of 1.65 and 1.75 (2H, m), 2,4-2,6 (2H, m), 2,99 (3H, d, J=4,7 Hz), of 3.7-3.9 (2H, m)6,91 (1H, s), 6,95-to 7.15 (2H, m), 7,15-of 7.25 (1H, m), 7.5 to the 7.65 (3H, m), 7,7-7,8 (1H, m), 8,91 (1H, s), of 10.05-10,15 (1H, m)
32(CDCl3) of 1.55 (6H, s), 1,6-of 1.75 (2H, m), 2,4-by 2.55 (2H, m), of 3.7-3.9 (2H, m), 6,04 (1H, s), of 6.49 (1H, s), 7,0-to 7.15 (2H, m), 7,15-of 7.25 (2H, m), 7.5 to at 7.55 (1H, m), 55-7,6 (2H, m), 7,76 (1H, d, J=8,3 Hz), to 8.41 (1H, s)
33(DMSO-d6) of 1.6 and 1.75 (2H, m), 2,45 is 2.55 (2H, m), 3,7-of 3.85 (2H, m), 4.95 points-of 5.05 (2H, m), of 5.99 (1H, t, J=5.5 Hz), was 6.73 (1H, s), 7,05-to 7.15 (2H, m), 7,15-of 7.25 (1H, m), and 7.5 and 7.6 (2H, m), 7,78 (1H, d, J=8.5 Hz), of 7.97 (1H, d, J=2.3 Hz), 11,41 (1H, s)
34(DMSO-d6) of 1.6 and 1.75 (2H, m), 2,45 is 2.55 (2H, m), of 3.7-3.8 (2H, m), 7,05-to 7.15 (2H, m), 7,15-of 7.25 (1H, m), and 7.5 and 7.6 (3H, m), 7,82 (1H, d, J=8.5 Hz), of 8.09 (1H, d, J=2.1 Hz), 10,5-10,55 (1H, m), 11,88(1H, s)

Table 52
Ave., No.Structure(Solvent)1H-NMR δ ppm:
35(DMSO-d6) of 1.64 (3H, d, J=6.5 Hz), 3,8-3,9 (6H, m), 5,79 (1H, q, J=6.5 Hz), 6,7-6,8 (1H, m), 6,85-to 6.95 (2H, m), 6,95-7,05 (1H, m), 7,15-of 7.25 (2H, m), 7,25-to 7.35 (1H, m), 11,63 (1H,c)
36(DMSO-d6) a 3.83 (3H, c), 3,85 (3H, c), 4,99 (2H, c), 6,85-7,0 (2H, m), 7,1-7,2 (2H, m), 7,21 (1H, c), 7,25-to 7.35 (1H, m), between 7.4 to 7.5 (1H, m), 11,68 (1H, c)
37 (DMSO-d6) a 3.75 (3H, c), 3,85 (3H, c), 4,99 (2H, c), 6,85-7,0 (2H, m), 7,1-7,2 (2H, m), 7,25-to 7.35 (1H, m), between 7.4 to 7.5 (1H, m), the 7.65 (1H, c), 12,64 (1H, c)
38(DMSO-d6) and 1.54 (3H, d, J=6.3 Hz), 3,8-of 3.85 (3H, m), 5,46 (1H, q, J=6.3 Hz), the 6.9 to 7.0 (1H, m), 7,05 and 7.1 (1H, m), 7,15 was 7.45 (7H, m), 11,63 (1H, c)
39(DMSO-d6) to 1.7 (3H, d, J=6.8 Hz), 3,8-of 3.85 (3H, m), 5,7-5,8 (1H, m), the 6.9 to 7.0 (1H, m), 7,05-to 7.15 (3H, m), 7,15-of 7.3 (2H, m), 7,35 is 7.5 (1H, m), 11,63(1H, c)
40(DMSO-d6) 1,71 (3H, d, J=6.6 Hz), 3,82 (3H, c), 5,95-6,05 (1H, m), 6.8 or 6.9 (1H, m), 7,0-7,05 (1H, m), 7,15-of 7.3 (2H, m), 7.3 to 7.4 (1H, m), 7,45 is 7.5 (2H, m), 11,63 (1H, c)
41(DMSO-d6) was 1.58 (3H, d, J=6.3 Hz), 3,8-of 3.85 (3H, m), to 5.66 (1H, q, J=6.3 Hz), the 6.9 to 7.0 (1H, m), 7,05-to 7.15 (1H, m), 7,15-of 7.3 (4H, m), 7.3 to 7.4 (1H, m), 7,45-of 7.55 (1H, m), 11,63 (1H, c)
42(DMSO-d6) was 1.69 (3H, d, J=6.4 Hz), 3,7-of 3.75 (3H, m), 5,7-5,8 (1H, m), the 6.9 to 7.0 (1H, m), 7,05-to 7.15 (3H, m), 7,2-7,3 (1H, m), 7,35 is 7.5 (1H, m), 7,6-the 7.65 (1H, m), 12,59 (1H, c)

Table 53
Ave., No.Structure(Solvent)1H-NMR δ ppm:
43(DMSO-d6) 1,71 (3H, d, J=6.6 Hz), 3,74 (3H, c), 5,95-6,05 (1H, m), 6.8 or 6.9 (1H, m), 6,95-7,05 (1H, m), 7,2-7,3 (1H, m), 7.3 to 7.4 (1H, m), between 7.4 to 7.5 (2H, m), 7,6-the 7.65 (1H, m), 12,59 (1H, c)
44(DMSO-d6) of 1.64 (3H, d, J=6,7 Hz), of 3.7-3.8 (3H, m), 3,8-3,9 (3H, m), 5,75-to 5.85 (1H, m), 6,7-6,8 (1H, m), 6,85-to 6.95 (2H, m), 6,95-7,05 (1H, m), 7,15-of 7.25 (1H, m), 7,25-to 7.35 (1H, m), 7,63 (1H,S), to 12.58 (1H,S)
45(DMSO-d6) is 1.51 (3H, d, J=6.3 Hz), 3,8-3,9 (6H, m), 5,6-5,7 (1H, m), 6.8 or 6.9 (1H, m), the 6.9 to 7.0 (1H, m), of 7.0, and 7.1 (2H, m), 7,15-of 7.3 (3H, m), 7.3 to 7.4 (1H, m), and 11.6 (1H, s)
46(DMSO-d6) of 1.57 (3H, d, J=6.3 Hz), 3,8-of 3.85 (3H, m), 5,6-5,7 (1H, m), 6.8 or 6.9 (1H, m), 7,05 and 7.1 (1H, m), 7,15-of 7.3 (2H, m), 7.3 to 7.4 (2H, m), 7,45 is 7.5 (1H, m), and 7.5 and 7.6 (1H, m), of 11.61 (1H, s)
47(DMSO-d6) and 1.54 (3H, d, J=6.2 Hz), 3.75 to of 3.85 (3H, m), the 5.45 to 5.55 (1H, m), 6,95-7,05 (1H, m), 7,05-to 7.15 (1H, m), 7,15-of 7.25 (2H, m), 7,3 was 7.45 (3H, m), 7,49(1H, s), of 11.61 (1H, s)
48(DMSO-d6) of 1.65 (3H, d, J=6.5 Hz), 3,8-3,9 (3H, m), 5,75-to 5.85 (1H, m), 6,7-6,8 (1H, m), 6,85-7,0 (2H, m), 7,05 and 7.1 (1H, m), a 7.2 to 7.35 (2H, m), 7,37 (1H, d, J=3.6 Hz), 12,01 (1H, c), 14,43 (1H, s)
49(DMSO-d6) of 3.85 (3H, c), 5,0 (2H, c), to 6.88 (1H, t, J=8.7 Hz), to 6.95 (1H, d, J=8.7 Hz), 7,15-of 7.25 (2H, m), 7,3-7,5 (3H, m), 12,06 (1H, c), 14,43 (1H, s)
50(DMSO-d6) of 3.85 (3H, c), 5,0 (2H, c), to 6.88 (1H, t, J=8.6 Hz), to 6.95 (1H, d, J=8.6 Hz), 7,1-7,2 (1H, m), 7,2-of 7.25 (1H, m), 7.3 to 7.4 (1H, m), between 7.4 to 7.5 (1H, m), 7,94 (1H, c), 13,04 (1H, c), 13,93 (1H, s)

Table 54
Ave., No.Structure(Solvent)1H-NMR δ ppm:
51(DMSO-d6) a 1.5-1.6 (3H, m), 5,4-5,5 (1H, m), 6,95-7,05 (1H, m), 7,1-7,2 (1H, m), 7,2-7,4 (5H, m), 7,4 was 7.45 (2H, m), 11,95 a 12.05 (1H, m), 14,42 (1H, s)
52(DMSO-d6) to 1.7 (3H, d, J=6.6 Hz), USD 5.76 (1H, q, J=6.6 Hz), 7,0-7,2(4H, m), 7,25-to 7.35 (1H, m), 7,35 is 7.5 (2H, m), 11,95 a 12.05 (1H, m), 14,42 (1H, s)
53(DMSO-d6) of 1.65 and 1.75 (3H, m), 6,03 (1H, q, J=6.6 Hz), 6,85-to 6.95 (1H, m), 7,05-to 7.15 (1H, m), 7,25 to 7.4 (3H, m), between 7.4 to 7.5 (2H, m), 11,95 a 12.05 (1H, m), 14.4V (1H, s)
54(DMSO-d6) 1,55-1,65 (3H, m), the 5.65 (1H, q, J=6.5 Hz), 7,0-7,05 (1H, m), 7,15-of 7.25 (3H, m), 7,25 to 7.4 (3H, m), 7,45-of 7.55 (1H, m), 11,95 a 12.05 (1H, m), 14,42 (1H, s)
55(DMSO-d6) of 1.65 and 1.75 (3H, m), 5,7-5,8 (1H, m), 6,95 to 7.2 (4H, m), 7,2-7,5 (2H, m), to 7.93 (1H, d, J=7,2 Hz), 12,98 (1H, s), 13,85-14,0 (1H, m)
56(DMSO-d6) 1,72 (3H, d, J=6.6 Hz), 6,0-6,1 (1H, m), 6,85-to 6.95 (1H, m), 7,05 and 7.1 (1H, m), 7,25 to 7.4 (2H, m), 7,45 is 7.5 (2H, m), 7,92 (1H, d,J=11,1 Hz), 12,98 (1H, users), 13,85-14,0 (1H, m)
57(DMSO-d6) of 1.65 (3H, d, J=6.6 Hz), 3,8-3,9 (3H, m), 5,79 (1H, q, J=6.6 Hz), 6,7-6,8 (1H, m), 6,85-to 6.95 (2H, m), of 7.0, and 7.1 (1H, m), a 7.2 to 7.35 (2H, m), a 7.85-8,0 (1H, m), 12,98 (1H, users), 13,85-14,05 (1H, m)
58(DMSO-d6) 1,52 (H, d, J=6.3 Hz), 3,8-3,9 (3H, m), 5,64 (1H, q, J=6.3 Hz), 6,85-7,0 (2H, m), 7,0-to 7.15 (2H, m), 7,2-7,4 (4H, m), 11,95 to 12.0 (1H, m), 14,41 (1H, s)

Table 55
Ave., No.Structure(Solvent)1H-NMR δ ppm:
59(DMSO-d6) 1,45-of 1.65 (3H, m), 5,55-5,8 (1H, m), 6,8-in 7.7 (8H, m), 11,98 (1H, c), 14,39 (1H, c)
60(DMSO-d6) 1,45-of 1.65 (3H, m), of 5.4 to 5.6 (1H, m), 6,95 and 7.6 (8H, m), 11,99 (1H, c), 14,39 (1H, c)
61(DMSO-d6) of 1.56 (3H, c), of 1.57 (3H, c), 3,82 (3H, c), 7,15 was 7.45 (8H, m), 7,8-7,9 (1H, m), 11,68(1H, s)
62(DMSO-d6) a 1.5-1.6 (6H, m)to 3.34 (3H, c), 3,82 (3H, c), at 6.84 (1H, d, J=8,2 Hz), to 7.0, and 7.1 (1H, m), 7,1-7,3 (3H, m), 7.3 to 7.4 (1H, m), and 7.5 and 7.6 (1H, m), 7,8-7,9 (1H, m), 11,63 (1H, c)
63(DMSO-d6) to 1.59 (3H, c), and 1.6 (3H, c), 3,82 (3H, c), 7,05-to 7.15 (1H, m), 7,19 (1H, c), 7,2-7,4 (3H, m), between 7.4 to 7.5 (1H, m), the 7.65 to 7.75 (1H, m), of 7.9 to 8.0 (1H, m), 1,7(1H, c)
64(DMSO-d6) of 1.57 (3H, c), was 1.58 (3H, c), 3,82 (3H, c), 7,06 (1H, d, J=8,4 Hz), 7,1-of 7.25 (3H, m), 7,25-to 7.35 (1H, m), 7,35-7,45 (2H, m), 7,8-7,9 (1H, m), 11,68(1H, c)
65(DMSO-d6) and 1.54 (6H, c), and 3.31 (3H, c), 3,82 (3H, c), 6.8 or 6.9 (1H, m), of 7.0, and 7.1 (1H, m), 7,15-of 7.25 (2H, m), 7,3 was 7.45 (2H, m), 7,8-7,9 (1H, m), 11,63 (1H, s)
66(DMSO-d6) of 1.55 to 1.6 (6H, m), 7,25 was 7.45 (8H, m), of 7.9 to 8.0 (1H, m), 12,0 (1H, c), 14,29 (1H, c)

Table 56
Ave., No.Structure(Solvent)1H-NMR δ ppm:
67(DMSO-d6) of 1.55 (3H, s), and 1.56 (3H, s)to 3.33 (3H, s), at 6.84 (1H, d, J=8,2 Hz), to 7.0, and 7.1 (1H, m), 7,15-of 7.3 (2H, m), 7,37 (1H, s), between 7.4 to 7.5 (1H, m), 7.5 to at 7.55 (1H, m), 7,9-of 7.95 (1H, m), 11,99 (1H, s), 14,35 (1H, s)
68(DMSO-d6) to 1.59 (3H, s)of 1.62 (3H, s), to 7.0, and 7.1 (1H, m), 7,25 to 7.4 (4H, m), and 7.5 and 7.6 (1H, m), the 7.65 to 7.75 (1H, m), 7.95 is-with 8.05 (1H, m), 12,01 (1H, s),14,29 (1H, C)
69(DMSO-d6) was 1.58 (3H, s)to 1.59 (3H, s), 7,0-of 7.25 (3H, m), 7,3 was 7.45 (3H, m), 7,45-of 7.55 (1H, m), 7,9-of 7.95 (1H, m), 12,02 (1H, s), 14,29 (1H, s)
70(DMSO-d6) and 1.54 (3H, s), and 1.56 (3H, s), and 3.31 (3H, s), 6.8 or 6.9 (1H, m), of 7.0, and 7.1 (1H, m), 7,26 (1H, t, J=9,2 Hz), 7.3 to 7.4 (2H, m), and 7.5 and 7.6 (1H, m), a 7.85-of 7.95 (1H, m), 11,99 (1H, s), 14,36 (1H, s)
71(DMSO-d6) of 1.55 to 1.6 (3H, m), 3,82 (3H, s), 4,6-4,7 (1H, m), 7,1-7,2 (2H, m), 7,2 was 7.45 (8H, m), 11,49 (1H, s)
72(DMSO-d6) of 1.36 (3H, d, J=7,2 Hz), 3,82 (3H, s), 4,05-to 4.15 (1H, m), 7,15-the 7.65 (10H, m), 11,54 (1H, s)
73(DMSO-d6) of 1.56 (3H, d, J=7,1 Hz), 3,83 (3H, s), 4,71 (1H, q, J=7,1 Hz), 7,18 (1H, s), a 7.2 to 7.35 (5H, m), and 7.6 to 7.7 (3H, m), 7,75 one-7.8 (1H, m), to 11.56 (1H, s)
74(DMSO-d6) is 3.82 (3H, s), of 4.44 (2H, s), 7,1-of 7.25 (2H, m), 7.3 to 7.4 (1H, m), 7,4 was 7.45 (3H, m), 7,45-of 7.55 (2H, m), and 11.5 (1H, s)

Table 57
Ave., No.Structure(Solvent)1H-NMR δ ppm:
75(DMSO-d6) of 1.64 (6H, c), 3,82 (3H, c), 7,05-of 7.25 (4H, m), 7,25 to 7.4 (4H, m), between 7.4 to 7.5 (2H, m), of 11.45 (1H, s)
76(DMSO-d6) of 1.57 (3H, d, J=6.9 Hz), 3,74 (3H, c), of 4.66 (1H, q, J=6.9 Hz), a 7.1 to 7.15 (1H, m), 7,2 was 7.45 (8H, m), to 7.59 (1H, c), to 12.44 (1H, c)
77(DMSO-d6) of 1.56 (3H, d, J=6.8 Hz), 3,76 (3H, c), the 4.65-of 4.75 (1H, m), a 7.2 to 7.35 (5H, m), and 7.6 to 7.75 (4H, m), 7,78 (1H, c), to 12.52 (1H, c)
78(DMSO-d6) 3,74 (3H, c), of 4.44 (2H, c), 7,15-of 7.25 (1H, m), 7.3 to at 7.55 (6H, m), to 7.59 (1H, c), 12,45 (1H, s)
79(DMSO-d6) was 1.58 (3H, d, J=6,9 Hz)and 4.65 (1H, q, J=6.9 Hz), 7,2-7,5 (1 OH, m), 11,93 (1H, c), 14,87 (1H, s)
80(DMSO-d6) of 1.39 (3H, d, J=7,3 Hz), 4,05-to 4.15 (1H, m), 7,2-7,8 (10H, m), 11,95 (1H, c), 14,8 (1H, s)
81(DMSO-d6) to 1.59 (3H, d, J=7,7 Hz), 4.72 in (1H, q, J=7,7 Hz), a 7.2 to 7.35 (5H, m), 7,39 (1H, c), 7,65 was 7.9 (4H, m), 11,96 (1H, c), 14,73 (1H, c)
82(DMSO-d6) of 4.44 (2H, c), 7,25 was 7.45 (3H, m), 7,45-of 7.55 (5H, m), 11,93 (1H, c), 14,87 (1H, c)

Table 58
Ave., No.Structure(Solvent)1H-NMR δ ppm:
83(DMSO-d6) 4,94 (2H, s), 7,35-of 7.55 (4H, m), 7,75-a 7.85 (3H, m), 7.95 is to 8.0 (1H, m), 11,96 (1H, s), 14,75 (1H, s)
84(DMSO-d6) of 1.65 (6H, s), a 7.1 to 7.5 (10H, m), 11,88 (1H, s), 14,84 (1H, s)
85(DMSO-d6) was 1.58 (3H, d, J=7,0 Hz), of 4.66 (1H, q, J=7.0 Hz), 7,15 was 7.45 (9H, m), and 8.0 (1H, s), 12,94 (1H,S), 14,43 (1H,S)
86(DMSO-d6) was 1.58 (3H, d, J=7,0 Hz), 4.72 in (1H, q, J=7.0 Hz), 7,2-7,5 (5H, m), 7,65 one-7.8 (3H, m), to 7.84 (1H, s), 7,98 (1H, s), 12,96 (1H, s), 14,26 (1H, s)
87(DMSO-d6) of 4.45 (2H, s), 7,25 of 7.3 (1H, m), 7.3 to 7.4 (1H, m), 7,45-of 7.55 (5H, m), and 8.0 (1H, s), 12,94 (1H, s), 14,42 (1H, s)
88(DMSO-d6) 4,94 (2H, s), 7,35-7,45 (1H, m), 7,45-of 7.55 (2H, m), 7,7-a 7.85 (3H, m), 7.95 is to 8.0 (2H, m), 12,96 (1H, s), and 14.3 (1H, s)
89(DMSO-d6) 3,37 (3H, s), 3,83 (3H, s), 7,15-of 7.25 (5H, m), 7,25-to 7.35 (2H, m), 7,44 (1H, d, J=8.1 Hz), 7,56 (1H, d, J=1.9 Hz), 11,63 (1H, s)
90(DMSO-d6) 3,37 (3H, s), 3,83 (3H, s), 7,15-to 7.35 (8H, m), 7,53 (1H, DD, J=7,3 Hz, 1.9 Hz), 11,63 (1H, s)

Table 59
Ave., No.Structure(Solvent)1H-NMR δ ppm:
91(DMSO-d6) 3,37 (3H, c), 3,82 (3H, c), and 7.1 to 7.4 (10H, m), 11,46(1H, s)
92 (DMSO-d6) 3,37 (3H, c), 3,74 (3H, c), and 7.1 to 7.4 (9H, m), 7,58 (1H, c), 12,42 (1H, c)
93(DMSO-d6) to 3.38 (3H, c), 7,15 to 7.4 (8H, m), and 7.5 and 7.6 (1H, m), 11,96 (1H, c), 14,34 (1H, c)
94(DMSO-d6) 3,37 (3H, c), 7,15 to 7.4 (7H, m), 7,44 (1H, d, J=8.7 Hz), 7,72 (1H, c)
95(DMSO-d6) to 3.38 (3H, c), 7,15-of 7.25 (3H, m), 7,25-to 7.35 (3H, m), 7,38 (1H, c), and 7.5 (1H, d, J=7.5 Hz), 7,58 (1H, d, J=1.9 Hz), 11,98 (1H, c), 14,33 (1H, s)
96(DMSO-d6) 3,37 (3H, c), 7,15 to 7.4 (10H, m), 11,89 (1H, s), 14,81 (1H, s)
97(DMSO-d6) 3,37 (3H, c), 7,15 to 7.4 (9H, m), to 7.99 (1H, c), and 12.9 (1H, c), 14,37 (1H, c)
98(DMSO-d6) 3,75-of 3.85 (3H, m), 6,3-6,4 (1H, m), 7,05-to 7.15 (1H, m), 7,2 (1H, c), 7,32 (1H, DD, J=7,6 Hz, 2.9 Hz), 7,45-of 7.55 (4H, m), 7,55-the 7.65 (2H, m), 11,66(1H, c)

Table 60
Ave., No.Structure(Solvent)1H-NMR δ ppm:
99(DMSO-d6) 3,75-of 3.95 (6H, m), 6,2 to 6.35 (1H, m), the 6.9 to 7.0 (1H, m), of 7.0, and 7.1 (1H, m), 7,17 (1H, d, J=8.0 Hz), 7,21 (1H, c), 7,31 (1H, DD, J=6,4 Hz, 3.0 Hz), 7,4-of 7.55 (3H, m), 11,64 (1H, c)
100(DMSO-d6) 3,7-of 3.75 (3H, m), 3,85-of 3.95 (3H, m), 6,2 to 6.35 (1H, m), the 6.9 to 7.0 (1H, m),? 7.04 baby mortality (1H, t, J=7,6 Hz), 7,15 to 7.2 (1H, m), 7,25-to 7.35 (1H, m), 7,4-of 7.55 (3H, m), of 7.64 (1H, c), and 12.6 (1H, s)
101(DMSO-d6) 6,3-6,4 (1H, m), 7,1-7,2 (1H, m), 7,35 to 7.4 (2H, m), 7,45-of 7.55 (3H, m), 7,55-the 7.65 (3H, m), 11,95 compared to 12.1 (1H, m), 14,32 (1H, c)
102(DMSO-d6) 3,85-of 3.95 (3H, m), and 6.25 to 6.35 (1H, m), 6,95 to 7.1 (2H, m), 7,15 to 7.2 (1H, m), 7,35 and 7.5 (4H, m), 7,56 (1H, d, J=8,9 Hz), 12,0 compared to 12.1 (1H, m), 14,34 (1H, s)
103(DMSO-d6) 3,85-of 3.95 (3H, m), and 6.25 to 6.35 (1H, m), 6,95 to 7.1 (2H, m), 7,15 to 7.2 (1H, m), 7.3 to 7.4 (1H, m), between 7.4 to 7.5 (2H, m), 7,55 (1H, d, J=9.0 Hz), 7,92 (1H, d, J=4.5 Hz), 13,0 (1H, users), 13,8-13,95 (1H, m)

Table 61
Ave., No.Structure(Solvent)1H-NMR δ ppm:
104(CDCl3) to 3.89 (3H, s), at 6.84 (1H, d, J=5.8 Hz), 7,05 and 7.1 (1H, m), 7,28 (1H, d, J=5.8 Hz), 7,45-of 7.55 (1H, m), to 7.59 (1H, d, J=8.5 Hz), the 7.65 to 7.75 (1H, m), 7,8-a 7.85 (1H, m), a 7.85-8,0 (2H, m), 10,06 (1H, s), is 10.75 (1H, C)
105(CDCl3) of 1.6 and 1.75 (2H, m), 2,45 is 2.55 (2H, m), 3.45 points and 3.6 (1H, m), 3,7-of 3.85 (2H, m), of 6.45 (1H, d, J=0.5 Hz), 7,01 (1H, d, J=7,0 Hz), 7,05-of 7.25 (2H, m), and 7.5 and 7.6 (3H, m), 7,76 (1H, d, J=7,7 Hz), is 10.68 (1H, s)
106(DMSO-d6) 3,74 (3H, s), 3,83 (3H, s), 4,15 to 4.2 (2H, m), 6.75 in-6,85 (1H, m), 7,21 (1H, s), 7,25 to 7.4 (2H, m), between 7.4 to 7.5 (1H, m), 7.5 to at 7.55 (1H, m), 11,65 (1H, s)
107(DMSO-d6) of 3.77 (3H, s), 3,83 (3H, s)to 4.15 (2H, s), 6.75 in-6,9 (2H, m), 7,15-of 7.55 (5H, m), 11,65 (1H,s)
108(CDCl3) and 3.16 (3H, s), to 6.88 (1H, d, J=5.8 Hz), to 7.0, and 7.1 (2H, m), 7,25-to 7.35 (3H, m), and 7.5 and 7.6 (2H, m), and 7.6 to 7.7 (1H, m), 9,5-11,0 (1H, user.)
109(DMSO-d6) 7,1-of 7.25 (3H, m), 7,44 (1H, d, J=8.5 Hz), the 7.5 and 7.6 (1H, m), 7,87 (1H, d, J=8.5 Hz), of 7.9 to 8.0 (2H, m), 8,18 (1H, d, J=2.2 Hz), 11,0-12,0 (1H, usher.), to 12.52 (1H, s)
110(CDCl3) 3,22 (3H, s), 7,05-to 7.15 (3H, m), 7,25-to 7.35 (3H, m), 7,45-of 7.55 (1H, m), 7,71 (1H, s), which 9.22 (1H, s), 14,14 (1H, s)

Table 62
Ave., No.Structure(Solvent)1H-NMR δ ppm:
111(CDCl3) a 1.11 (3H, t, J=7,1 Hz), 3,5-3,6 (1H, m), 3,65 to 3.8 (1H, m), 7,05 and 7.1 (2H, m), 7,13 (1H, c), 7,25-to 7.35 (3H, m), 7,55 (1H, d, J=2.2 Hz), and 7.7 (1H, d, J=8,4 Hz), to 7.77 (1H, DD, J=8,4 Hz, 2.2 Hz), which 9.22 (1H, c), 14,17 (1H, c)
112(CDCl3) to 3.33 (3H, c), and 7.1 (1H, c), 7,15 to 7.2 (1H, m), EUR 7.57 (1H, d, J=8,2 Hz), and 7.6 to 7.75 (4H, m), 8,3 an 8.4 (1H, m), 9,05 (1H, c), 14,09 (1H, c)
113(DMSO-d6) of 1.6 and 1.75 (2H, m), 2,45 is 2.55 (2H, m), 3,7-of 3.85 (2H, m), the 6.9 to 7.0 (1H, m), 7,05-of 7.25 (3H, m), and 7.5 and 7.6 (2H, m), 7,78 (1H, d, J=8.5 Hz), 8,0-with 8.05(1H, m), 8,5-8,55 (1H, m), to 11.52 (1H, s)
114(DMSO-d6) 3,17 (3H, c), 7,05-to 7.15 (2H, m), 7,25 to 7.4 (3H, m), 7,63 (1H, DD, J=8,6 Hz, 2.2 Hz), the 7.85-of 7.95 (3H, m), 12,5-13,5 (1H, usher.), 13,79 (1H, s)
115(DMSO-d6) 3,26 (3H, c), 7,25 of 7.3 (1H, m), 7,45-of 7.55 (1H, m), the 7.65 to 7.75 (1H, m), 7,8-of 7.95 (3H, m), 8,05 and 8.1 (1H, m), 8,3 an 8.4 (1H, m)
116(CDCl3) 3,17 (3H, c), the 6.9 to 7.0 (1H, m), 7,13 (1H, c), 7,29 (1H, d, J=2.5 Hz), 7,39 (1H, d, J=8,4 Hz), 7,51 (1H, d, J=1.2 Hz), 7,7-7,8 (2H, m), 9,12(1H, c), 14,05 (1H, s)
117(CDCl3) of 3.25 (3H, c), 6,75-6,9 (2H, m), 7,13 (1H, c), 7,2-7,3 (1H, m), 7,63 (1H, d, J=2.1 Hz), of 7.75 (1H, d, J=8.6 Hz), 7,8-a 7.85 (1H, m), 9,03 (1H, c), 14,11 (1H, c)

Table 63
Ave., No.Structure(Solvent)1H-NMR δ ppm:
118(CDCl3) 3,22 (3H, c), was 7.08 (1H, c), 7,15-of 7.25 (2H, m), 7,38 (1H, d, J=1.7 Hz), 7,7-7,8 (2H, m), 8,55 to 8.6 (2H, m)
119(DMSO-d6) 3,23 (3H, c), and 3.8 (3H, c), 6,9-to 6.95 (1H, m), 7,35-of 7.55 (3H, m), 7,7-a 7.85 (2H, m), of 7.9 to 8.0 (2H, m), a 12.03 (1H, c), 14,29 (1H, c)
120(DMSO-d6) of 3.12 (3H, c), of 3.73 (3H, c), 6,85-6,9 (2H, m), 6,95-7,0 (2H, m), 7,39 (1H, c), to 7.68 (1H, DD, J=8,4 Hz, 2.3 Hz), the 7.85-of 7.95 (2H, m), a 12.03 (1H, s), and 14.3 (1H, s)
121(DMSO-d6) 3,51 (3H, c), 6,85-to 6.95 (2H, m), 7,15-of 7.25 (2H, m), 7,38 (1H, c), 7,7-7,8 (1H, m), a 7.85-of 7.95 (1H, m), 7.95 is to 8.0 (1H, m), 9,74 (1H, c), 12,02 (1H, c), and 13.5 to 15.0 (1H, user.)
122(DMSO-d6) to 3.67 (3H, c), 6,6 to 6.75 (3H, m), 7,1-7,2 (1H, m), 7,38 (1H, c), to 7.84 (1H, DD, J=8,5 Hz, 2.2 Hz), 7,89 (1H, d, J=8.5 Hz), 8,13 (1H, d, J=2.2 Hz), 10,49 (1H, s), 12,04 (1H, s), 14,22 (1H, s)
123(DMSO-d6) of 3.69 (3H, c), 6,83 (2H, d, J=8,9 Hz), of 6.99 (2H, d, J=8,9 Hz), 7,38 (1H, c), of 7.75 (1H, DD, J=8,5 Hz, 2.0 Hz), 7,88 (1H, d, J=8.5 Hz), to 7.99 (1H, d, J=2.0 Hz), 10,08 (1H, c), a 12.03 (1H, s), 14.24 from (1H, s)
124(DMSO-d6) 3,17 (3H, c), 3,47 (3H, c), the 6.9 to 7.0 (2H, m, 7,15 to 7.2 (1H, m), 7,25-to 7.35 (1H, m), 7,39 (1H, c), 7,71 (1H, DD, J=8,6 Hz, 2.2 Hz), and 7.9 (1H, d, J=8.6 Hz), 8,02 (1H, d, J=2.2 Hz), 12,02 (1H, s), 14,31 (1H, c)

Table 64
Ave., No.Structure(Solvent)1H-NMR δ ppm:
125(DMSO-d6) 3,18 (3H, c), of 3.69 (3H, c), 6,55 to 6.7 (2H, m), 6.8 or 6.9 (1H, m), 7,2-7,3 (1H, m), 7,35 to 7.4 (1H, m), and 7.6 to 7.7 (1H, m), a 7.85-with 8.05 (2H, m), 12,04 (1H, c), 14,26 (1H, c)
126(DMSO-d6) 3,18 (3H, c), 7,1-to 7.35 (3H, m), 7,35-7,45 (2H, m), 7,81 (1H, d, J=2.3 Hz), 7,95 (1H, d, J=8.5 Hz), 8,03 (1H, d, J=2.3 Hz), a 12.03 (1H, s), 14,29 (1H, s)
127(DMSO-d6) 3,19 (3H, c), 6,95-7,05 (2H, m), 7,1-7,2 (1H, m), 7,35-7,45 (2H, m), 7,7-of 7.75 (1H, m), of 7.9 to 8.0 (2H, m), 12,04 (1H, c), 14,27 (1H, s)
128(DMSO-d6) a 3.15 (3H, c), 7,05-of 7.25 (4H, m), 7,38 (1H, c), of 7.69 (1H, DD, J=8,5 Hz, 2.5 Hz), and 7.9 (1H, d, J=2.5 Hz), to 7.93 (1H, d, J=8.5 Hz), a 12.05 (1H, s), 14,29 (1H, s)
129 (DMSO-d6) a 3.15 (3H, c), a 7.1 to 7.15 (2H, m), 7,35-7,45 (3H, m), and 7.7 (1H, DD, J=8.6 Hz, 2.1 Hz), 7,9-of 7.95 (2H, m), a 12.05 (1H, c), of 14.28 (1H, s)
130(DMSO-d6) 3,19 (3H, c), 7,05 and 7.1 (1H, m), 7,2-of 7.25 (1H, m), 7,35-7,45 (3H, m), 7,72 (1H, DD, J=8,5 Hz, 2.1 Hz), of 7.9 to 8.0 (2H, m), 12,06 (1H, s), and 14.3(1H, s)
131(DMSO-d6) and 3.16 (3H, c), of 7.0, and 7.1 (1H, m), 7,25 was 7.45 (3H, m), 7,55 and 7.6 (1H, m), a 7.85-7,9 (1H, m), of 7.97 (1H, d, J=8,5 Hz)and 8.1 (1H, c), 12,06 (1H, s), 14,31 (1H, c)

Table 65
Ave., No.Structure(Solvent)1H-NMR δ ppm:
132(DMSO-d6) of 3.13 (3H, c), of 7.0, and 7.1 (1H, m), 7.3 to 7.4 (2H, m), 7,45-of 7.55 (2H, m), 7,86 (1H, DD, J=8,5 Hz, 2.4 Hz), 7,98 (1H, d, J=8.5 Hz), 8,02 (1H, d, J=2.4 Hz), a 12.03 (1H, c), and 14.3 (1H, c)
133(DMSO-d6) 3,17 (3H, c), 7,2-7,3 (2H, m), 7.3 to 7.4 (3H, m), 7,71 (1H, DD, J=8,5 Hz, 2.1 Hz), and 7.9 (1H, d, J=2.1 Hz), to 7.93 (1H, d, J=8.5 Hz), 12,0 (1H, s), 14,25 (1H, s)
134 (DMSO-d6) a 3.15 (3H, c), 7,06 (1H, d, J=8.5 Hz), 7,35-7,45 (2H, m), 7,76 (1H, d, J=2.4 Hz), the 7.85-7,9 (1H, m), of 7.97 (1H, d, J=8.5 Hz), 8,07 (1H, d, J=2.2 Hz), a 12.03 (1H, c), 14,27 (1H, s)
135(DMSO-d6) and 3.16 (3H, c), 7,05 and 7.1 (2H, m), 7,25 to 7.4 (4H, m), 7,55-the 7.65 (1H, m), 7,7-7,8 (3H, m), 11,95 (1H, c), 14,77 (1H, c)
136(DMSO-d6), and 3.16 (3H, c), 7,05 and 7.1 (2H, m), 7,25 to 7.4 (3H, m), 7,55-the 7.65 (1H, m), 7,7-7,8 (3H, m), 7,98 (1H, c), to 12.95 (1H, c), 14,31 (1H, s)
137(DMSO-d6) and 3.16 (3H, c), 3,47 (3H, c), 6,85-7,0 (2H, m), 7,1-7,2 (1H, m), 7,25-to 7.35 (1H, m), of 7.69 (1H, DD, J=8,4 Hz, 2.1 Hz), the 7.85-of 7.95 (2H, m), to 7.99 (1H, d, J=2.1 Hz), 12,5-13,5 (1H, usher.), 13,83 (1H, users)
138(DMSO-d6) 3,17 (3H, c), 7,1-of 7.25 (2H, m), 7,25-to 7.35 (1H, m), 7,35-7,45 (2H, m), the 7.65 to 7.75 (1H, m), 7,8-7,9 (1H, m), 8,02 (1H, DD, J=6,6 Hz, 2.3 Hz), a 12.03 (1H, c), 14,31 (1H, c)

Table 66
Ave., No.Structure(Solvent)1H-NMR δ ppm:
139(DMSO-d6) and 3.16 (3H, c), 3,47 (3H, c), the 6.9 to 7.0 (2H, m), 7,19 (1H, DD, J=8.0 Hz, 1.5 Hz), 7,3-to 7.35 (1H, m), 7,37 (1H, c), and 7.6 to 7.7 (1H, m), 7,7-7,8 (1H, m), and 8.0 (1H, DD, J=6,6 Hz, 2.5 Hz), 12,02 (1H, s), 14,32 (1H, )
140(DMSO-d6) 1,6-1,7 (2H, m), 2,45 is 2.55 (5H, m), 3.75 to 3,8 (2H, m), 7,05-of 7.25 (3H, m), 7,56 (1H, d, J=8.5 Hz), 7,6-the 7.65 (1H, m), to 7.84 (1H, d, J=8,5 Hz)and 8.1 (1H, d, J=2.4 Hz), 11,94 (1H, c), 14,22 (1H, s)
141(CD3OD) to 3.36 (3H, c), of 3.54 (3H, c)to 4.01 (3H, c), 6,85-to 6.95 (2H, m), 7,15-to 7.35 (4H, m), of 7.69 (1H,d, J=8,4 Hz)
142(DMSO-d6) to 3.3 (3H, c), a 3.87 (3H, c), 7,15 to 7.4 (6H, m), 7,42 (1H, d, J=11.7 Hz), 7,92 (1H, d, J=8,3 Hz), 11,95 (1H, c), 14,39 (1H, c)
143(DMSO-d6) 3,17 (3H, c), 7,05-to 7.15 (2H, m), 7,25 to 7.4 (4H, m), and 7.6 to 7.75 (2H, m), of 7.9 to 8.0 (1H, m), 12,02 (1H, c), 14,29 (1H, c)
144(DMSO-d6) was 4.42 (2H, c), 7,2 was 7.45 (6H, m), 7,86 (1H, d, J=8.5 Hz), and 8.2 (1H, DD, J=8,5 Hz, 2.2 Hz), 8,29 (1H, d, J=2.2 Hz), 12,06 (1H, users), 14,32 (1H, users)
15 (DMSO-d6) 1,4-1,5 (3H, m), 4,9-5,0 (1H, m), 7,15 was 7.45 (6H, m), 7,7-7,8 (1H, m), 8,1-of 8.15 (1H, m), and 8.2 and 8.3 (1H, m), 12,0 compared to 12.1 (1H, m), 14,2-14,35 (1H, m)

/tr>
Table 67
Ave., No.Structure(Solvent)1H-NMR δ ppm:
146(DMSO-d6) of 1.57 (6H, s), 7,25 was 7.45 (7H, m), and 7.5 and 7.6 (1H, m), of 7.9 to 8.0 (1H, m), 11,9 compared to 12.1 (1H, usher.), of 14.2-14.4V (1H, user.)
147(DMSO-d6) of 1.55 (3H, s)of 1.57 (3H, s)to 3.33 (3H, s), 6,8-6,85 (1H, m), of 7.0, and 7.1 (1H, m), 7,2-7,3 (1H, m), 7,3-7,5 (3H, m), 7.5 to at 7.55 (1H, m), 7,94 (1H, d, J=2.4 Hz), 12,0 (1H, s), 14,37 (1H, users)
148(DMSO-d6in ) 1.6 (3H, s)of 1.62 (3H, s), 7,0-to 7.15 (1H, m), 7,25 to 7.4 (3H, m), 7,47 (1H, DD, J=8,7 Hz, 2.0 Hz), EUR 7.57 (1H, d, J=8.7 Hz), the 7.65 to 7.75 (1H, m), 8,01 (1H, d, J=2.0 Hz), a 12.03 (1H, s), and 14.3(1H, users)
149(DMSO-d6) was 4.42 (2H, s), a 7.2 to 7.35 (5H, m), 7,86 (1H, d, J=8.5 Hz), 7,94 (1H, s), 8,15 to 8.3 (2H, m), at 13.84(1H, s)
150(DMSO-d6) of 1.55 (6H, s), 7,25-of 7.55 (8H, m), 7,6-the 7.65 (1H, m), 11,99 (1H, s), of 14.46 (1H, users)
151(DMSO-d6) 1,49 (3H, s), 1,5 (3H, s), 3,66 (3H, s), 6,55-of 6.65 (1H, m), 6.75 in-6,85 (1H, m), 6,95-7,05 (1H, m), of 7.25 and 7.5 (4H, m), and 7.5 and 7.6 (1H, m), 11,99 (1H, s), 14,5 (1H, s)
152(DMSO-d6) 1,536 (3H, s)1,543 (3H, s), 3,61 (3H, s), 6.75 in-6,85 (2H, m), 7.3 to 7.4 (3H, m), 7,45 and 7.6 (2H, m), 11,98 (1H, s), 14,5 (1H, s)

Table 68
Ave., No.Structure(Solvent)1H-NMR δ ppm:
153(DMSO-d6) 1,49 (3H, c), 1,5 (3H, c), 3,66 (3H, c), 6,55-of 6.65 (1H, m), 6.75 in-6,85 (1H, m), 6,95-7,05 (1H, m), 7,25-of 7.55 (4H, m), 7,94 (1H, c), from 12.8 to 13.1 (1H, usher.), 14,01 (1H, c)
154(DMSO-d6) of 5.15 (2H, c), 6,9-7,1 (3H, m), 7,25-to 7.35 (2H, m), and 7.4 (1H, c), 7,55-the 7.65 (1H, m), the 7.65 to 7.75 (2H, m), a 12.05 (1H, c), 14,42 (1H, s)
(DMSO-d6) 2,85-2,95 (4H, m)and 7.1 and 7.6 (9H, m), 12,04 (1H, s), of 14.46 (1H, s)
156(DMSO-d6) of 2.8-3.0 (4H, m), 7,15 was 7.45 (9H, m), a 12.03 (1H, s), of 14.46 (1H, users)
157(DMSO-d6) of 2.8 and 2.9 (4H, m), with 3.79 (3H, c), 6.8 or 6.9 (1H, m), the 6.9 to 7.0 (1H, m)and 7.1-of 7.25 (2H, m), 7,25 was 7.45 (4H, m), 12,02 (1H, c), 14, 48mm (1H, users)
158(DMSO-d6) to 2.85 to 3.0 (4H, m), 7,05 to 7.2 (2H, m), 7,2 was 7.45 (6H, m), a 12.03 (1H, c), of 14.46 (1H, users)
159(DMSO-d6) 2,8-2,95 (4H, m), and 3.72 (3H, c), 6,7-6,85 (3H, m), 7,15-of 7.25 (1H, m), 7,25 was 7.45 (4H, m), 11,95 compared to 12.1 (1H, usher.), 14,35-14,55 (1H, user.)

Table 69
Ave., No.Structure(Solvent)1H-NMR δ ppm:
160(DMSO-d6) of 2,75 2,95 (4H, m), 3,71 (H, c), 6.8 or 6.9 (2H, m), 7,1-7,2 (2H, m), 7,25 was 7.45 (4H, m), 12,01 (1H, users), 14.4V-14,55 (1H, user.)
161(DMSO-d6) to 2.85 to 3.0 (4H, m), 6,95-7,05 (1H, m), 7,05-to 7.15 (2H, m), 7,25 was 7.45 (5H, m), a 12.03 (1H, users), and 14.3 and 14.6 (1H, user.)
162(DMSO-d6) 2,8-2,95 (4H, m), 7,05-to 7.15 (2H, m), 7,2 was 7.45 (6H, m), a 12.03 (1H, users), and 14.3 and 14.6 (1H, user.)
163(DMSO-d6) of 2.28 (3H, c), a 2.8 and 2.9 (4H, m), 7,05-of 7.25 (4H, m), of 7.25 and 7.5 (4H, m), 12,04 (1H, users), 14,47 (1H, users)
164(DMSO-d6), and 2.27 (3H, c), 2,8-2,95 (4H, m), 6,95 to 7.1 (3H, m), 7,1-7,2 (1H, m), 7,25 was 7.45 (4H, m), a 12.03 (1H, users), 14,47 (1H, users)
165(DMSO-d6) to 2.25 (3H, c), 2,8-2,95 (4H, m), 7,05-to 7.15 (4H, m), 7,25 was 7.45 (4H, m), a 12.03 (1H, users), 14,35-14,6 (1H, user.)
166(DMSO-d6) of 1.23 (3H, c), 1,25 (3H, c), 2,85 (2H, c)to 3.67 (3H, c), 6,7-6,8 (2H, m), 6,85-to 6.95 (1H, m), 7,1-7,2 (1H, m), 7,25-to 7.35 (1H, m), 7,35-7,45 (2H, m), and 7.5 and 7.6 (1H, m), 12,0 (1H, s), 14,55 (1H, s)

Table 70
Ave., No.Structure(Solvent)1H-NMR δ ppm:
167(DMSO-d6) 2,65 is 2.75 (2H, m), 2,8-2,9 (2H, m in), 3.75 (6H, s), 6,55 to 6.7 (2H, m), 7,1-7,2 (1H, m), 7,25 was 7.45 (4H, m), 12,0 (1H, s), 14, 48mm (1H, users)
168(DMSO-d6) 2,8-2,95 (4H, m), of 3.77 (3H, s), 6,9-7,1 (3H, m), 7,25 was 7.45 (4H, m), 12,01 (1H, s), of 14.46 (1H, users)
169(DMSO-d6) 2,85-2,95 (4H, m in), 3.75 (3H, s), 6,9-7,05 (1H, m), 7,05 to 7.2 (1H, m), 7,3 was 7.45 (4H, m), 12,01 (1H, s), accounted for 14.45 (1H, users)
170(DMSO-d6) of 2,75 2,85 (2H, m), 2,85-2,95 (2H, m), of 3.77 (3H, s), 6.75 in-6,85 (1H, m), 7,15-to 7.35 (4H, m), 7,37(1H, s), 11,99 (1H, s), of 14.46 (1H, users)
171(DMSO-d6) of 2.75 and 2.9 (4H, m), 3,86 (3H, s), was 7.08 (1H, d, J=and 12.2 Hz), 7,15-to 7.35 (6H, m), 7,38 (1H, s), of $ 11.97 (1H, s), 14,55 (1H, users)
172 (DMSO-d6) to 4.28 (2H, s), a 7.2 to 7.35 (3H, m), 7,35 and 7.5 (4H, m), 7,58 (1H, d, J=8.5 Hz), 7,66 (1H, d, J=2.2 Hz), 12,06 (1H, s), 14,41 (1H, s)
173(DMSO-d6) 4,29 (2H, s), 7,2 was 7.45 (6H, m), EUR 7.57 (1H, d, J=8.5 Hz), to 7.64 (1H, d, J=2.3 Hz), 7,94 (1H, s), 13,03 (1H, s), 13,94 (1H, s)

Table 71
Ave., No.Structure(Solvent)1H-NMR δ ppm:
174(DMSO-d6) was 1.69 (6H, c), 7,0-7,2 (4H, m), 7,25 to 7.4 (5H, m), 11,89 (1H, c), 14,86 (1H, c)
175(DMSO-d6) 4,24 (2H, c), 7,2-7,5 (8H, m), a 7.62 (1H, DD, J=6,7 Hz, 2.2 Hz), a 12.05 (1H, c), 14,41 (1H, s)
176(DMSO-d6) of 1.65 (6H, c)of 7.0, and 7.1 (1H, m), 7,1 was 7.45 (8H, m), 11,88 (1H, c), 14,83 (1H, c)
177(DMSO-d6) of 2.8 and 2.9 (2H, m), 3.15 and is 3.25 (2H, m), 7,15-of 7.55 (8H, m), 7,58 (1H, DD, J=6.8 G is, 2,3 Hz)
178(DMSO-d6) is 4.21 (2H, c), 7,0-to 7.15 (2H, m), 7,3 was 7.45 (3H, m), 7.5 to the 7.65 (2H, m), 12,0 (1H, c), 14,37 (1H, s)
179(DMSO-d6) 3,76 (3H, c), is 4.15 (2H, c), 6,75-6,9 (2H, m), 7,25-to 7.35 (2H, m), 7,35-7,45 (1H, m), 7,45 and 7.6 (2H, m)
180(DMSO-d6) 4,27 (2H, c), 7,15-to 7.5 (10H, m), 11,93 (1H, s), 14,88 (1H, s)

Table 72
Ave., No.Structure(Solvent)1H-NMR δ ppm:
181(DMSO-d6) of 1.65 to 1.7 (6H, m), 3,86 (3H, s), 6.75 in-6,85 (1H, m), 7,0-to 7.15 (3H, m), 7,2-7,3 (2H, m), 7,37 (1H, s), 7,42 (1H, DD, J=6,9 Hz, 2.2 Hz), 11,98 (1H, s), 14,38 (1H, s)
182(DMSO-d6) 3,79 (3H, s)to 4.16 (2H, s), 6.8 or 6.9 (1H, m), 6,95-7,05 (1H, m), 7,2-7,3 (2H, m), 7,3-7,5 (3H, m), to 7.59 (1H, DD, J=7,0 Hz, 2.2 Hz), 12,02 (1H, s), 14,39 (1H, s)
183 (DMSO-d6) was 1.69 (6H, s), 7,0-to 7.35 (6H, m), 7,37 (1H, s), 7,46 (1H, DD, J=6,7 Hz, 2.2 Hz), 11,98 (1H, s), 14,37 (1H, users)
184(DMSO-d6) 4,24 (2H, s), 7,05-of 7.25 (2H, m), 7,25 was 7.45 (4H, m), 7,45-of 7.55 (1H, m), 7,63 (1H, DD, J=6,8 Hz, 2.5 Hz), a 12.03 (1H, s), 14,38 (1H, s)
185(DMSO-d6) of 4.25 (2H, s), to 7.0, and 7.1 (1H, m), 7,15 to 7.2 (2H, m), of 7.25 and 7.5 (4H, m), a 7.62 (1H, DD, J=6,7 Hz, 2.3 Hz), a 12.03 (1H, s), 14,37 (1H, s)
186(DMSO-d6) 4,4 (2H, s), and 7.3 and 7.6 (6H, m), the 7.65 to 7.75 (1H, m), 12,01 (1H, s), 14,37 (1H, s)
187(DMSO-d6) of 1.75 to 1.8 (6H, m), 7,05-to 7.15 (1H, m), 7,15-of 7.3 (4H, m), 7,37 (1H, s), between 7.4 to 7.5 (2H, m), of $ 11.97 (1H, s), 14,37 (1H, s)

Table 73
Ave., No.Structure(Solvent)1H-NMR δ ppm:
188(DMSO-d6) of 1.65 (6H, s), 7,15-of 7.25 (1H, m), 7,25 was 7.45 (6, m)and 7.5 and 7.6 (1H, m), 12,0 (1H, s), 14,38 (1H, s)
189(DMSO-d6) of 1.64 (6H, s), 7,15-to 7.35 (5H, m), 7,37 (1H, s), 7,4 was 7.45 (2H, m), 7,52 (1H, DD, J=7,3 Hz, 2.3 Hz), 11,99 (1H, s), 14,37 (1H, users)
190(DMSO-d6) 1,75-of 1.85 (6H, m), of 3.77 (3H, s), and 6.6 and 6.7 (1H, m), 6,85 (1H, d, J=8.1 Hz), 7,05-to 7.15 (1H, m), a 7.2 to 7.35 (2H, m), 7,37 (1H, s), 7,4 was 7.45 (1H, m), of $ 11.97 (1H, s), 14.4V (1H, users)
191(DMSO-d6) of 1.65 to 1.7 (6H, m), 3,85 (3H, s), 6.75 in-6,85 (1H, m), of 7.0, and 7.1 (2H, m), 7,1-7,2 (1H, m), 7,25-to 7.35 (1H, m), 7,37 (1H, s), and 7.4 (1H, DD, J=7,3 Hz, 2.2 Hz), 11,98 (1H, s), 14,39 (1H, users)
192(DMSO-d6) is 1.81 (6H, s), 6,9-7,05 (2H, m), 7,1-7,2 (1H, m), 7,25 to 7.4 (3H, m), 7,45 is 7.5 (1H, m), of $ 11.97 (1H, s), 14,38 (1H, users)
193(DMSO-d6) from 1.8 to 1.85 (6H, m), 3,76 (3H, s), 6.75 in-6,85 (1H, m), 7,15 was 7.45 (5H, m), 11,98 (1H, s), 14,38 (1H, users)
194(DMSO-d6) 4,29 (2H, s), a 7.2 to 7.35 (2H, m), 7,35-of 7.55 (5H, m), and 7.6 to 7.7 (1H, m), 12,02 (1H, s), 14,38 (1H, users)

Table 74
Ave., No.Structure(Solvent)1H-NMR δ ppm:
195(DMSO-d6) 4,24 (2H, c), of 7.25 and 7.5 (7H, m), 7,6-the 7.65 (1H, m), a 12.03 (1H, c), 14,38 (1H, users)
196(DMSO-d6) to 3.73 (3H, c)to 4.16 (2H, c), 6,75-6,85 (1H, m)and 7.1 and 7.6 (5H, m)
197(DMSO-d6) of 3.77 (3H, c), is 4.15 (2H, c), 6,95-to 7.15 (3H, m), 7,35 is 7.5 (3H, m), 7,6-the 7.65 (1H, m), 12,06 (1H, s), 14,41 (1H, s)
198(DMSO-d6) to be 1.6-1.7 (6H, m), of 7.0, and 7.1 (1H, m), 7,15-of 7.25 (3H, m), 7.3 to 7.4 (3H, m), 7.5 to at 7.55 (1H, m), 12,01 (1H, c), 14.4V (1H, c)
199(DMSO-d6) of 1.66 (3H, c)to 1.67 (3H, c), 3,86 (3H, c), a 7.0 (1H, d, J=2.5 Hz), 7,06 (1H, d, J=8,8 Hz), 7,1-7,2 (1H, m), 7,25-to 7.35 (2H, m), 7,38 (1H, c), between 7.4 to 7.5 (1H, m), 12,01 (1H, c), 14,41 (1H, users)
200 (DMSO-d6) of 1.75 to 1.9 (1H, m), 2,15-2,3 (1H, m), 2.4 to approximately 2.65 (4H, m), 7,0-7,2 (4H, m), a 7.2 to 7.35 (3H, m), 7,37 (1H, c), 7,45 is 7.5 (1H, m), 11,98 (1H, c), 14,41 (1H, users)
201(DMSO-d6) 2,05 was 2.25 (4H, m), 3,5-of 3.65 (2H, m), 3,85-of 3.95 (2H, m), 6,85-to 6.95 (1H, m), 7,15 to 7.4 (8H, m), 11,98 (1H, s), 14,38 (1H, users)

Table 75
Ave., No.Structure(Solvent)1H-NMR δ ppm:
202(DMSO-d6) of 1.73 (6H, s), 7.3 to 7.4 (7H, m), and 7.5 and 7.6 (1H, m), 7,95 (1H, DD, J=6,7 Hz, 2.2 Hz), 12,01 (1H, s), 14,25 (1H, s)
203(DMSO-d6) to 1.7 (6H, s), 6.89 in (1H, s), 7,2-7,4 (6H, m), of 7.5 to 7.7 (3H, m)
204(DMSO-d6) of 4.77 (2H, s), 7,15-of 7.25 (2H, m), 7,25-to 7.35 (3H, m), 7,39 (1H, s), 7,87 (1H, DD, J=8,6 Hz, 2.2 Hz), 7,95 (1H, d, J=8.6 Hz), of 8.09 (1H, d, J=2.2 Hz), 12,08 (1H, s), 14,26 (1H, s)
205(d 6) of 4.77 (2H, s), 7,15-of 7.25 (2H, m), 7,25-to 7.35 (3H, m), 7,8-8,0 (3H, m), 8,08 (1H, d, J=2.3 Hz), 13,78(1H, s)
206(DMSO-d6) was 4.76 (2H, s), 7,05-to 7.15 (2H, m), of 7.36 (1H, s), 7,4-of 7.55 (1H, m), 7,7-7,8 (1H, m), 7.95 is to 8.1 (2H, m), 12,02 (1H, s), 14,26 (1H, s)
207(DMSO-d6) 1,89 (6H, s)of 7.0, and 7.1 (2H, m), of 7.36 (1H, s), between 7.4 to 7.5 (1H, m), and 7.6 to 7.7 (2H, m), with 8.0 and 8.1 (1H, m), 12,0 (1H, s), of 14.28 (1H, s)
208(DMSO-d6) 4,72 (2H, s), 7,15-of 7.25 (2H, m), 7,25-to 7.35 (3H, m), 7,39 (1H, s), 7,7-of 7.95 (4H, m), of $ 11.97 (1H, s), 14,72 (1H, s)

Table 76
Ave., No.Structure(Solvent)1H-NMR δ ppm:
209(DMSO-d6) to 1.86 (6H, c)to 3.35 (3H, s), 6,83 (1H, d, J=8.6 Hz), the 6.9 to 7.0 (1H, m), 7,25-to 7.35 (2H, m), 7,37 (1H, s), 7,4 was 7.45 (1H, m), and 7.5 and 7.6 (1H, m), a 7.85-of 7.95 (1H, m), 12,0 (1H, s), 14,29 (1H, c)
210(DMSO-d6) of 3.46 (3H, c), 4,63 (2H, c), 685-6,95 (2H, m), a 7.2 to 7.35 (2H, m), 7,37 (1H, c), and 7.6 to 7.75 (2H, m), of 7.9 to 8.0 (1H, m), 12,02 (1H, c), 14,26 (1H, c)
211(DMSO-d6) is 1.81 (6H, c), 7,05 to 7.2 (2H, m), 7,3 was 7.45 (3H, m), 7.5 to the 7.65 (2H, m), 7,98 (1H, DD, J=6,7 Hz, 2.3 Hz), 12,01 (1H, c), 14,27 (1H, c)
212(DMSO-d6) to 4.81 (2H, c), 6,95-7,05 (2H, m), 7,1-7,2 (1H, m), 7.3 to 7.4 (2H, m), 7,7-of 7.75 (1H, m), of 7.9 to 8.0 (1H, m), of 8.04 (1H, DD, J=6,8 Hz, 2.6 Hz), a 12.05 (1H, c), 14.24 from (1H, c)
213(DMSO-d6) 4,7-4,8 (2H, m), 7,1-7,3 (3H, m), 7,35-7,45 (2H, m), the 7.65 to 7.75 (1H, m), of 7.9 to 8.0 (1H, m), with 8.05 (1H, DD, J=6,8 Hz, 2.5 Hz), a 12.03 (1H, s), 14,25 (1H, s)
214(DMSO-d6) 1,75-of 1.85 (6H, m), 7,05 to 7.2 (2H, m), 7,3-7,5 (4H, m), of 7.6 to 7.8 (3H, m), 11,91 (1H, s), 14,72 (1H, s)
215(DMSO-d6) 4,74 (2H, c), 7,15 to 7.2 (2H, m), 7,25-to 7.35 (3H, m), 7,37 (1H, c), the 7.65 to 7.75 (1H, m), a 7.85-of 7.95 (1H, m), 8,07 (1H, DD, J=6,6 Hz, 2.5 Hz), 12,04 (1H, c), 14.24 from (1H, c)

Table 77
Ave., No.Structure is round (Solvent)1H-NMR δ ppm:
216(DMSO-d6) 1,72 (6H, c), 7,1-of 7.25 (3H, m), 7,3 was 7.45 (3H, m), and 7.6 to 7.7 (1H, m), 7,7-7,8 (2H, m), 11,92 (1H, s), 14,7 (1H, s)
217(DMSO-d6) 2,85-2,95 (2H, m), 3,65 of 3.75 (2H, m), 7,15-of 7.3 (5H, m), 7,37 (1H, c), 7,7-7,8 (1H, m), 8,1-of 8.15 (1H, m), of 8.27 (1H, DD, J=6,6 Hz, 2.6 Hz), a 12.05 (1H, c), 14,23 (1H, users)
218(DMSO-d6) 3,47 (3H, c), to 4.62 (2H, c), of 6.75 (1H, d, J=8,4 Hz), 6.8 or 6.9 (1H, m), 7.3 to 7.4 (2H, m), the 7.65 to 7.75 (1H, m), 7,8-7,9 (1H, m), 7.95 is-with 8.05 (1H, m), 12,0 (1H, c), 14,27 (1H, users)
219(DMSO-d6) to 3.45 (3H, c), and 4.68 (2H, c), 6,7-of 6.75 (1H, m), 7,35-7,45 (2H, m), the 7.65 to 7.75 (1H, m), a 7.85-8,0 (2H, m), 12,01 (1H, c), 14,25 (1H, users)
220(DMSO-d6) 1,9-2,0 (6H, m)to 3.38 (3H, c), 6,65 is 6.8 (2H, m), 7.3 to 7.4 (2H, m), between 7.4 to 7.5 (1H, m), 7,55 and 7.6 (1H, m), 7.95 is to 8.0 (1H, m), 12,0 (1H, c), of 14.28 (1H, users)
221(DMSO-d6) of 1.85 (6H, c)to 3.34 (3H, c), at 6.84 (1H, DD, J=9 Hz, 5,2 Hz), 7,1-of 7.25 (2H, m), 7,37 (1H, c), 7,4 was 7.45 (1H, m), 7,55-the 7.65 (1H, m), of 7.9 to 8.0 (1H, m), 12,0 (1H, c), 14,29 (1H, users)
222(DMSO-d6) 1,9-2,0 (6H, m)to 3.36 (3H, c), 6,65 and 6.7 (1H, m), 7,35-7,45 (2H, m), 7.5 to the 7.65 (2H, m), 7.95 is to 8.0 (1H, m), 12,0 (1H, c), of 14.28 (1H, users)

Table 78
Ave., No.Structure(Solvent)1H-NMR δ ppm:
223(DMSO-d6) is 4.85 (2H, c), 7,3 was 7.45 (5H, m), the 7.65 to 7.75 (1H, m), 7,8-7,9 (1H, m), 8,05 and 8.1 (1H, m), a 12.03 (1H, c), 14,25 (1H, users)
224(DMSO-d6) to 4.81 (2H, c), 7,05-to 7.15 (1H, m), 7,25 was 7.45 (4H, m), 7,7-7,8 (1H, m), of 7.9 to 8.0 (1H, m), 8,05 and 8.1 (1H, m), a 12.05 (1H, c), 14.24 from (1H, users)
225(DMSO-d6) 1,95 (6H, c), 7,25 was 7.45 (5H, m), 7.5 to the 7.65 (2H, m), 8,03 (1H, DD, J=6,8 Hz, 2.4 Hz), 12,0 (1H, c), of 14.28 (1H, c)
226(DMSO-d6) 1,72 (6H, c), 7,3-7,5 (6H, m), 7,55-the 7.65 (1H, m), 8,01 (1H,DD, J=6,7 Hz, 2.3 Hz), 12,02 (1H, c), 14,25 (1H, c)
227(DMSO-d6) 4,96 (2H, c), 7,35-7,45 (2H, m), 7,45-of 7.55 (2H, m), the 7.65 to 7.75 (1H, m), a 7.85-of 7.95 (1H, m), 8,15 to 8.2 (1H, m), a 12.05 (1H, c), of 14.28 (1H, s)
228(DMSO-d6) of 3.43 (3H, c), 4,6-4,7 (2H, m), 6,85-6,9 (1H, m), 7,1-7,2 (2H, m), 7,37 (1H, c), 7,65 is 7.7 (1H, m), 7,75-a 7.85 (1H, m), of 7.9 to 8.0 (1H, m), 12,04 (1H, c), 14,29 (1H, c)
229(DMSO-d6) 1,72 (3H, c), is 1.73 (3H, c), 7,15-of 7.25 (3H, m), 7,35-7,45 (2H, m), 7,45-of 7.55 (1H, m), and 7.6 (1H, t, J=9.1 Hz), of 7.9 to 8.0 (1H, m), 12,04 (1H, c), of 14.28 (1H, users)

Table 79
Ave., No.Structure(Solvent)1H-NMR δ ppm:
230(DMSO-d6) to 1.86 (6H, c), 6,87 (1H, d, J=8,8 Hz), 7,35-7,45 (4H, m), 7,55-the 7.65 (1H, m), 7.95 is to 8.0 (1H, m), a 12.03 (1H, c), and 14.3 (1H, users)
231(DMSO-d6) 1,8-of 1.95 (1H, m), a 2.0 to 2.15 (1H, m), 2,55-2,7 (2H, m), 3.0 to 3.15 in (2H,m), 6,95-7,05 (2H, m), a 7.2 to 7.35 (4H, m), 7,37 (1H, c), 7,45-of 7.55 (1H, m), of 7.9 to 8.0 (1H, m), 12,0 (1H, c), of 14.28 (1H, users)
232(DMSO-d6) of 2.2 to 2.35 (2H, m), 3,05 is 3.2 (2H, m), 3,8-3,9 (2H, m), 7,2-7,4 (7H, m), 7,45-of 7.55 (1H, m), 7,8-7,9 (1H, m), 12,02 (1H, c), 14,25 (1H, users)
233(DMSO-d6) 3,75-of 3.85 (6H, m), 4,96 (2H, c), 6,85-to 6.95 (1H, m), 7,13 (1H, d, J=11.3 Hz), 7,26 (1H, d, J=7,2 Hz), 7,39 (1H, c), 7,4-of 7.55 (1H, m), 12,0 (1H, s), 14,53 (1H, s)
234(DMSO-d6) a 1.7-2.1 (4H, m), 2,65 and 2.9 (2H, m), the 5.45 is 5.5 (1H, m), 7,1 was 7.45 (7H, m), EUR 7.57 (1H, d, J=9.0 Hz), 12,0 compared to 12.1 (1H, m), accounted for 14.45 (1H, c)
235(DMSO-d6) 5,14 (2H, c), 7,15-to 7.5 (6H, m), 7,55-the 7.65 (2H, m), a 12.05 (1H, c), 14,43 (1H, c)
236(DMSO-d6) 5,14 (2H, c), 7,15-of 7.25 (2H, m), of 7.25 and 7.5 (5H, m), 7,58 (1H, d, J=9.1 Hz), a 12.05 (1H, c), 14,43 (1H, s)

Table 80
Ave., No.Structure(Solvent is) 1H-NMR δ ppm:
237(DMSO-d6) 5,09 (2H, c), 7,15-of 7.3 (3H, m), 7,32 (1H, d, J=2,9 Hz), 7,41 (1H, c), and 7.5 and 7.6 (3H, m), 12,04 (1H, c), 14,44 (1H, c)
238(DMSO-d6) to 5.13 (2H, c), 7,19 (1H, DD, J=9,0 Hz, 3.0 Hz), 7,3-7,5 (5H, m), and 7.5 and 7.6 (2H, m), a 12.05 (1H, c), 14,44 (1H, c)
239(DMSO-d6) 3,76 (3H, c), to 5.08 (2H, c), 6,85-to 6.95 (1H, m), 7,0-7,05 (2H, m), 7,18 (1H, DD, J=9.1 Hz, 3.1 Hz), 7,25-to 7.35 (2H, m), 7,41 (1H, c), EUR 7.57 (1H, d, J=9.1 Hz), 12,04 (1H, c), 14,44 (1H, s)
240(DMSO-d6) a 1.5-1.6 (3H, m), the 5.45 to 5.55 (1H, m), of 7.0, and 7.1 (1H, m), 7.23 percent (1H, DD, J=6,1 Hz, 2.9 Hz), of 7.25 and 7.5 (7H, m), 11,95 compared to 12.1 (1H, m), 14,42 (1H, s)
241(DMSO-d6) a 1.5-1.6 (3H, m), the 5.45 to 5.55 (1H, m), of 7.0, and 7.1 (1H, m), 7.23 percent (1H, DD, J=6,1 Hz, 2.9 Hz), of 7.25 and 7.5 (7H, m), 11,95 compared to 12.1 (1H, m), 14,42 (1H, s)
242(DMSO-d6) is 3.82 (3H, c), 5,04 (2H, c), 6,95-7,0 (1H, m), 7,06 (1H, d, J=7.9 Hz), 7,17 (1H, DD, J=9.1 Hz, 2.9 Hz), 7,3 was 7.45 (4H, m), 7,56 (1H, d, J=9.1 Hz), 12,04 (1H, c), of 14.46 (1H, s)
243(DMSO-d6) 3,76 (3H, c), 5,02 (2H, c), the 6.9 to 7.0 (2H, m), 7,15 to 7.2 (1H, m), and 7.3 (1H, d, J=3.3 Hz), 7,35-7,45 (3H, m), 7,56 (1H, d, J=9.0 Hz), 12,04 (1H, c), of 14.46 (1H, c)

Table 81
Ave., No.Structure(Solvent)1H-NMR δ ppm:
244(DMSO-d6) is 5.18 (2H, s), 7,02 (1H, s), 7,16 (1H, DD, J=9,0 Hz, 2.7 Hz), 7,25 to 7.4 (2H, m), and 7.5 and 7.6 (2H, m), 7,8-7,9 (1H, m), 8,58 (1H, d,J=4.5 Hz), and 11.0 to 12.5 (1H, user.)
245(DMSO-d6) 5,11 (2H, s), 7,15 to 7.2 (1H, m), 7,32 (1H, d, J=2,9 Hz), 7,41 (1H, s), 7,45-of 7.55 (4H, m), EUR 7.57 (1H, d, J=8.6 Hz), 12,06 (1H, s), 14,43 (1H, s)
246(DMSO-d6) 5,16 (2H, s), 7,1-of 7.25 (2H, m), 7,31 (1H, d, J=2,9 Hz), between 7.4 to 7.5 (1H, m), 7,56 (1H, d, J=9.0 Hz), the 7.85-of 7.95 (1H, m), an 8.5 and 8.6 (1H, m), 8,69 (1H, s), 11,0-13,0 (1H, user.)
247(DMSO-d6) from 2.1 to 2.25 (2H, m), 4,1-4,2 (1H, m), 4,25 is 4.35 (1H, m), the 5.45 5,55 1H, m), 6,8-6,95 (2H, m), a 7.2 to 7.35 (3H, m), 7,35-7,45 (2H, m), to 7.59 (1H, d, J=8.7 Hz), 12,0 a 12.05 (1H, m), 14,42 (1H, s)
248(DMSO-d6) to 5.2 (2H, s), 7,1-7,2 (2H, m), and 7.3 (1H, d, J=2,9 Hz), between 7.4 to 7.5 (2H, m), 7,56 (1H, d, J=8,8 Hz), 8,55-8,65 (2H, m), 11,0-13,0 (1H, user.)
249(DMSO-d6in ) 1.6 (3H, d, J=6.3 Hz), 5,65-of 5.75 (1H, m), of 7.0, and 7.1 (1H, m), 7,15-of 7.3 (3H, m), 7,3 was 7.45 (2H, m), 7,45-of 7.55 (2H, m), 11,95 compared to 12.1 (1H, m), 14,42 (1H, s)
250(DMSO-d6) a 1.5-1.6 (3H, m), 5,5-5,6 (1H, m), 7,0-to 7.15 (2H, m), 7,2-7,3 (3H, m), 7,35-of 7.55 (3H, m), 11,95 to 12.0 (1H, m), 14,41 (1H, s)

Table 82
Ave., No.Structure(Solvent)1H-NMR δ ppm:
251(DMSO-d6) a 1.5-1.6 (3H, m), 5,45 to 5.6 (1H, m), of 7.0, and 7.1 (1H, m), 7,15-of 7.25 (3H, m), and 7.4 (1H, d, J=4,1 Hz), 7,45-of 7.55 (3H, m), 11,95 a 12.05 (1H, m), 14,42 (1H, s)
252(DMSO-d6) 1,35-1,5 (1H, m), 1,652,05 (5H, m), of 2.8-3.0 (2H, m), 5,45 to 5.6 (1H, m), 7,05 to 7.2 (4H, m), 7,25-to 7.35 (2H, m), 7,39 (1H, d, J=3.8 Hz), 7,52 (1H, d, J=8,8 Hz), 12,02 (1H, s), 14,43 (1H, s)
253(DMSO-d6) of 1.73 (3H, d, J=6.6 Hz), 6,07 (1H, q, J=6.6 Hz), 6.89 in (1H, DD, J=9,0 Hz, 3.0 Hz), 7,15 to 7.2 (1H, m), 7.3 to 7.4 (2H, m), 7,45-of 7.55 (3H, m), 12,0 (1H, c), 14.4V (1H, c)
254(DMSO-d6) of 1.53 (3H, d, J=6.2 Hz), of 5.68 (1H, q, J=6.2 Hz), 6,85-7,0 (2H, m), 7,05 (1H, d, J=8,4 Hz), 7,2 (1H, t, J=3.2 Hz), 7,25 to 7.4 (3H, m), 7,47 (1H, d, J=9.3 Hz), 12,01 (1H, s), accounted for 14.45 (1H, s)
255(DMSO-d6) a 1.5-1.6 (3H, m), 3,7-of 3.75 (3H, m), 5,4-5,5 (1H, m), 6.8 or 6.9 (1H, m), 6,95 to 7.1 (3H, m), 7,2-7,3 (2H, m), and 7.4 (1H, d, J=3,4 Hz), 7,47 (1H, DD, J=9,0 Hz, 1.6 Hz), 11,95 a 12.05 (1H, m), 14,43 (1H, c)
256(DMSO-d6) a 1.5-1.6 (3H, m), of 3.73 (3H, c), 5,4-5,5 (1H, m), 6,85-to 6.95 (2H, m), 7,0-7,05 (1H, m), 7,15-of 7.25 (1H, m), 7,3-7,5 (4H, m), 11,95 a 12.05 (1H, m), 14,44 (1H, c)
257(DMSO-d6) of 0.93 (3H, t, J=7.5 Hz), 1,9-2,05 (1H, m), from 2.1 to 2.25 (1H, m), of 5.55 (1H, t, J=7,3 Hz), 6,95-of 7.25 (4H, m), 7,35 is 7.5 (2H, m), 7,52 (1H, d, J=8.7 Hz), 11,95 a 12.05 (1H, m), 14.4V(1H, s)

Table 83
Ave., No.Structure(Solvent)1H-NMR δ ppm:
258(DMSO-d6) of 0.93 (3H, t, J=7.4 Hz), 1,9-2,05 (1H, m), from 2.1 to 2.25 (1H, m), 5,5-5,6 (1H, m), 6,95-of 7.25 (4H, m), 7,35 is 7.5 (1H, m), 7,52 (1H, d, J=9,2 Hz), 7,95 (1H, d, J=6,7 Hz), 12,99 (1H, s), 13,8-14,0 (1H, m)
259(DMSO-d6) 1,55-1,65 (3H, m), 5,65 to 5.8 (1H, m), the 6.9 to 7.0 (1H, m), 7,2-7,3 (1H, m), 7,35-7,45 (1H, m), 7,45 and 7.6 (2H, m), 7,7-a 7.85 (3H, m), a 12.03 (1H, c), 14,41 (1H, c)
260(DMSO-d6) 1,55-1,65 (3H, m), 5,6-5,7 (1H, m), 7,05-to 7.15 (1H, m), 7,25 of 7.3 (1H, m), and 7.4 (1H, d, J=5.6 Hz), 7,45-of 7.55 (1H, m), 7,55-a 7.85 (4H, m), 11,95 compared to 12.1 (1H, m), 14.4V (1H, s)
261(DMSO-d6) 1,55-1,65 (3H, m), 5,6-5,7 (1H, m), of 7.0, and 7.1 (1H, m), 7,25 (1H, DD, J=6,6 Hz, 3.0 Hz), and 7.4 (1H, d, J=5.3 Hz), 7,45-of 7.55 (1H, m), and 7.6 to 7.7 (2H, m), 7,7-7,8 (2H, m), 11,95 compared to 12.1 (1H, m), 14.4V(1H, s)
262(DMSO-d6) to 5.13 (2H, c), 7,15-of 7.3 (3H, m), 7,34 (1H, d, J=2,9 Hz), and 7.4 (1H, c), 7.5 to the 7.65 (2H,m), a 12.03 (1H, c), 14.4V (1H, c)
263(DMSO-d6) of 5.24 (2H, c), 7,2-the 7.65 (7H, m), 12,02 (1H, s), 14,39 (1H, s)
264(DMSO-d6) 5,12 (2H, c), 7,15-of 7.25 (3H, m), 7,32 (1H, d, J=3.1 Hz), 7.5 to the 7.65 (2H, m), 7,94 (1H, c), from 12.8 to 13.2 (1H, usher.), 13,93 (1H, s)

Table 84
Ave., No.Structure(Solvent)1H-NMR δ ppm:
265(DMSO-d6) to 1.59 (3H, d, J=6.3 Hz), 5,71 (1H, q, J=6.3 Hz), 6,85-to 6.95 (1H, m), 7,2-of 7.25 (1H, m), 7,3 was 7.45 (3H, m), 7,45-of 7.55 (3H, m), 11,95 a 12.05 (1H, m), 14,39 (1H, c)
266(DMSO-d6) of 1.56 (3H, d, J=6.2 Hz), 5,45 to 5.6 (1H, m), of 7.0, and 7.1 (1H, m), 7,2-of 7.55 (7H, m), 11,95 a 12.05 (1H, m), 14,39 (1H, c)
267(DMSO-d6) a 1.5-1.6 (3H, m), 5,45 to 5.6 (1H, m), 7,0-7,05 (1H, m), 7,22 (1H, DD, J=8,9 Hz, 3.0 Hz), 7,35 is 7.5 (6H, m), 11,9 a 12.05 (1H, m), 14,39 (1H, c)
268 (DMSO-d6) of 1.9 to 2.15 (4H, m), 3.75 to of 3.85 (1H, m), 4,1-of 4.25 (1H, m), the 5.45 to 5.55 (1H, m), 6,95 was 7.45 (7H, m), 7,53 (1H, d, J=8,9 Hz), 11,95 a 12.05 (1H, m), 14,42 (1H, c)
269(DMSO-d6) of 0.91 (3H, t, J=7.5 Hz), 1,75-2,0 (2H, m), 5,2-5,3 (1H, m), 6,95-7,05 (1H, m), 7,15-to 7.5 (8H, m), 11,95 a 12.05 (1H, m), 14,39 (1H, s)
270(DMSO-d6) 1,71 (3H, d, J=6.5 Hz), of 5.81 (1H, q, J=6.5 Hz), 7,0-to 7.15 (3H, m), 7,2-of 7.25 (1H, m), 7,35 is 7.5 (2H, m), 7,53 (1H, d, J=9,2 Hz), 11,95 a 12.05 (1H, m), 14,41 (1H, c)
271(DMSO-d6) of 1.65 and 1.75 (6H, m), only 6.64 (1H, DD, J=8.7 Hz, 2.8 Hz), 7,07 (1H, d, J=2,8 Hz), of 7.25 and 7.5 (7H, m), of $ 11.97 (1H, s), 14,42 (1H, c)

Table 85
Ave., No.Structure(Solvent)1H-NMR δ ppm:
272(DMSO-d6) of 0.82 (3H, d, J=6.4 Hz), 0,95-1,05 (3H, m), 2.05 is-to 2.15 (1H, m), a 5.0 to 5.1 (1H, m), 6,95-7,05 (1H, m), 7,15-to 7.5 (8H, m), 11,95 a 12.05 (1H, m), 14.4V (1H, c)
273(DMSO-d6) of 0.91 (3H, t, J=7.4 Hz), 1,25-1,5 (2H, m), a 1.7-1.8 (1H, m), 1.85 to a 2.0 (1H, m), 5,3 to 5.35 (1H, m), 6,95-7,05 (1H, m), 7,15-to 7.5 (8H, m), 11,95 a 12.05 (1H, m), 14,41 (1H, users)
274(DMSO-d6) of 0.91 (3H, t, J=7.4 Hz), 1,75-2,0 (2H, m), 5.25 to 5.35 (1H, m), of 7.0, and 7.1 (1H, m), 7,2-of 7.25 (1H, m), 7.3 to at 7.55 (6H, m), 11,95 a 12.05 (1H, m), 14.4V (1H, s)
275(DMSO-d6) of 0.85 (3H, t, J=7,1 Hz), 1,2-a 1.45 (4H, m), 1,7-of 1.85 (1H, m), 1,9-2,0 (1H, m), 5.25 to 5.35 (1H, m), 6,95-7,05 (1H, m), 7,15-to 7.5 (8H, m), 11,95 a 12.05 (1H, m), 14,41 (1H, s)
276(DMSO-d6) 3,05 (2H, t, J=7.0 Hz), 4,19 (2H, t, J=7.0 Hz), 7,05-to 7.15 (1H, m), a 7.2 to 7.35 (6H, m), and 7.4 (1H, c), 7,54 (1H, d, J=9,2 Hz), a 12.03 (1H, c), accounted for 14.45 (1H, c)
277(DMSO-d6) to 3.09 (2H, t, J=6.8 Hz), 4,19 (2H, t, J=6.8 Hz), 7,05-to 7.35 (5H, m), 7,35-7,45 (2H, m), 7,54 (1H, d, J=8,9 Hz), a 12.03 (1H, s), accounted for 14.45 (1H, s)
278(DMSO-d6) to 1.22 (3H, d, J=6.0 Hz), 2,8-2,9 (1H, m), 2.95 and was 3.05 (1H, m), 4,6-of 4.75 (1H, m), to 7.09 (1H, DD, J=9,0 Hz, 3.0 Hz), 7,15-to 7.35 (6H, m), 7,35-7,45 (1H, m), 7,52 (1H, d, J=9,2 Hz), 12,02 (1H, c), of 14.46 (1H, c)

Table 86
Ave., No.Structure(Solvent)1H - NMR δ ppm:
279(DMSO-d6) of 0.93 (3H, t, J=7.5 Hz), 1,8-of 2.05 (2H, m), vs. 5.47 (1H, t, J=6,1 Hz), 6,95-7,05 (1H, m), 7,15-of 7.25 (3H, m), 7.3 to at 7.55 (4H, m), 11,95 a 12.05 (1H, m), 14,35 accounted for 14.45 (1H, m)
280(DMSO-d6) to 1.32 (3H, d, J=6.9 Hz), 3,15 to 3.3 (1H, m), 4,0-to 4.15 (2H, m), to 7.09 (1H, DD, J=8,9 Hz, 3.1 Hz), 7,15 was 7.45 (7H, m), 7,52 (1H, d, J=8,9 Hz), 12,02 (1H, c), accounted for 14.45 (1H, c)
281(DMSO-d6) of 0.93 (3H, t, J=7.5 Hz), 1,8-of 2.05 (2H, m), of 5.48 (1H, t, J=6.5 Hz), 6,95-7,05 (1H, m), 7,15-of 7.25 (3H, m), 7.3 to 7.4 (1H, m), 7,4-of 7.55 (2H, m), 7,94 (1H, d, J=3,4 Hz), 12,98 (1H, c), 13,93 (1H, c)
282(DMSO-d6) to 1.32 (3H, d, J=6.9 Hz), 3,15 to 3.3 (1H, m), 4,0-to 4.15 (2H, m), 7,05 and 7.1 (1H, m), 7,15 to 7.4 (6H, m), 7,52 (1H, d, J=9.0 Hz), 7,95 (1H, c), 13,0 (1H, c), 13,98 (1H, s)
283(DMSO-d6) of 5.15 (2H, c), 7,15-of 7.3 (4H, is), to 7.35 (1H, d, J=2,8 Hz), 7,46 (1H, c), to 7.59 (1H, d, J=8,8 Hz), 12,19 (1H, s)
284(DMSO-d6) 5,14 (2H, c), 7,2-7,5 (6H, m), and 7.6(1H,d,J=8.7 Hz), 12,11 (1H, s), 14,44 (1H, s)
285(DMSO-d6) 1,4 (6H, c)to 4.01 (2H, c), 7,05-to 7.15 (1H, m), 7,15-of 7.25 (2H, m), 7,3-to 7.35 (2H, m), 7,39 (1H, c), between 7.4 to 7.5 (2H, m), 7,52 (1H, d, J=9,2 Hz), 12,0 (1H, c), 14,44 (1H, c)

Table 87
Ave., No.Structure(Solvent)1H-NMR δ ppm:
286(DMSO-d6) of 1.52 (3H, d, J=6.3 Hz), to 3.67 (3H, c), 3,75-of 3.85 (3H, m), the 5.65 (1H, q, J=6.3 Hz), 6,8-7,0 (4H, m), 7,15-of 7.25 (1H, m), 7,39 (1H, d, J=1.9 Hz), of 7.48 (1H, d, J=8,9 Hz), 11,99 (1H, c), 14,42 (1H, c)
287(DMSO-d6) of 1.55 (3H, d, J=6.3 Hz), and 3.31 (3H, c), 3,7-of 3.75 (3H, m), 5,35-of 5.45 (1H, m), 6,35-of 6.45 (1H, m), 6,5-6,6 (2H, m), of 7.0, and 7.1 (1H, m), 7,2-7,3 (1H, m), 7,39 (1H, d, J=2.0 Hz), 7,45 is 7.5 (1H, m), 11,95 a 12.05 (1H, m), 14,41 (1H, s)
288 (DMSO-d6) a 1.5-1.6 (3H, m), 3,81 (3H, c), 5,4-5,5 (1H, m), 7,0 is 7.3 (5H, m), and 7.4 (1H, d, J=3,9 Hz), of 7.48 (1H, DD, J=8,9 Hz to 1.6 Hz), 11,95 a 12.05 (1H, m), 14,41 (1H, c)
289(DMSO-d6) was 1.58 (3H, d, J=6,4 Hz in), 3.75 (3H, c), 5,55-5,7 (1H, m), 6.75 in-6,9 (2H, m), 6,95-7,05 (1H, m), 7,15-of 7.55 (4H, m), 11,95 a 12.05 (1H, m), 14,42 (1H, s)
290(DMSO-d6) a 1.75 (6H, c), is 6.78 (1H, DD, J=9,0 Hz, 3.0 Hz), 7,0-of 7.55 (7H, m), 11,91 (1H, users), 14,0-14,8 (1H, user.)
291(DMSO-d6) to 0.8 (3H, t, J=7,3 Hz)of 1.65 to 1.7 (3H, m), 1.85 to 2.05 is (2H, m), 6,55-of 6.65 (1H, m), was 7.08 (1H, DD, J=6,6 Hz, 3.0 Hz), 7,25 was 7.45 (7H, m), of $ 11.97 (1H, c), 14,43 (1H, c)
292(DMSO-d6) to 1.83 (6H, c), 6,69 (1H, DD, J=9.1 Hz, 3.1 Hz), 7,06 (1H, d, J=3.1 Hz), 7,3-7,5 (5H, m), to 7.61 (1H, DD, J=7,7 Hz, 1.8 Hz), 11,96 (1H, s), 14,42 (1H, s)

td align="justify"> (DMSO-d6) of 5.15 (2H, c), 7,15 to 7.75 (7H, m), a 12.03 (1H, s), 14,41 (1H, c)
Table 88
Ave., No.Structure(Solvent)1H-NMR δ ppm:
293
294(DMSO-d6) 5,14 (2H, c), of 7.23 (1H, DD, J=8,8 Hz, 3.2 Hz), 7,3 was 7.45 (3H, m), 7,45-of 7.55 (1H, m), to 7.59 (1H, d, J=9.1 Hz), 7,65 is 7.7 (1H, m), a 12.03 (1H, c), 14,41 (1H, c)
295(DMSO-d6) of 1.56 (3H, d, J=6.3 Hz), the 5.45 to 5.55 (1H, m), 6,85-6,9 (1H, m), 6,95-7,05 (2H, m), 7,25 was 7.45 (7H, m), 11,9 (1H, c)
296(DMSO-d6) of 1.56 (3H, d, J=6.4 Hz), and 5.5 (1H, q, J=6.4 Hz), 6,85-6,9 (1H, m), 6,9-7,05 (2H, m), 7,25 to 7.4 (4H, m), 7,4 was 7.45 (2H, m), to 7.99 (1H, c), 12,86 (1H, c), 14,43 (1H, c)
297(DMSO-d6) of 1.52 (3H, d, J=6.0 Hz), of 3.84 (3H, c), 5,6-5,7 (1H, m), 6,85-of 7.55 (7H, m), 11,99(1H, s), 14,42 (1H, s)
298(DMSO-d6) of 1.52 (3H, d, J=6.4 Hz), 3,85 to-3.9 (3H, m), 5,6-5,7 (1H, m), 6.75 in-6,8 (1H, m), 6,85-7,0 (2H, m), 7,15-of 7.25 (1H, m), 7,3 was 7.45 (2H, m), of 7.48 (1H, d, J=9,2 Hz), 12,0 (1H, c), 14,44 (1H, s)
299(DMSO-d6) 1,3-1,4 (3H, m), and 1.54 (3H, d, J=6.3 Hz), 4,05 to 4.2 (2H, m), 5,65-of 5.75 (1H, m), 6,85-7,0 (2H,m), 7,0-7,05 (1H, m), 7,15-to 7.35 (3H, m), 7,39 (1H, d, J=4, 2 Hz), of 7.48 (1H, d, J=9.1 Hz), 11,95 a 12.05 (1H, m), 14,42 (1H, s)

Table 89
Ave., No.Structure(Solvent)1H-NMR δ ppm:
300(DMSO-d6) of 1.66 (3H, d, J=6.6 Hz), 3,85 to-3.9 (3H, m), 5,8-5,9 (1H, m), 6.75 in-6,85 (1H, m), 6,85-7,0 (2H, m), 7,17 (1H, d, J=2.6 Hz), 7,25 to 7.4 (2H, m), of 7.48 (1H, d, J=8.6 Hz), 12,0 (1H, s), 14,42 (1H, s)
301(DMSO-d6) a 1.5-1.6 (3H, m), of 1.95 (3H, s), 5,4-5,5 (1H, m), 6,85-to 6.95 (1H, m), 6,98 (1H, DD, J=5.8 Hz, 2.6 Hz), 7,15 was 7.45 (7H, m), 11,85-11,95 (1H, m), of 14.76 (1H, s)
302(DMSO-d6) of 1.56 (3H, d, J=6.3 Hz), 5,52 (1H, q, J=6.3 Hz), 7,03 (1H, DD, J=9,0 Hz, 3.0 Hz), 7,15-to 7.5 (7H, m), of 7.9 to 8.0 (1H, m), 12,99 (1H, users), 13,95 (1H, s)
303(DMSO-d6) of 3.85 (3H, s), of 5.03 (2H, s), 6,85-7,0 (2H, m), 7,21 (1H, DD, J=8,9 Hz, 3.1 Hz), 7,32 (1H, d, J=3.1 Hz), between 7.4 to 7.5 (2H, m), 7,58 (1H, d, J=8,9 Hz), 12,06 (1H, s), 14,43 (1H, s)
304 (DMSO-d6) of 1.73 (3H, d, J=6,7 Hz), 6,0-6,1 (1H, m), 6,8-6,85 (1H, m), the 6.9 to 7.0 (2H, m), 7.3 to 7.4 (3H, m), 7,45 is 7.5 (2H, m), 11,89 (1H, s), 14,86 (1H, s)
305(DMSO-d6) of 1.73 (3H, d, J=6,7 Hz), equal to 6.05 (1H, q, J=6,7 Hz), 6,8-7,0 (3H, m), 7.3 to 7.4 (2H, m), 7,45 is 7.5 (2H, m), to 7.99 (1H, s), 12,92 (1H, s), 14,43 (1H, s)
306(DMSO-d6) of 1.56 (3H, d, J=5.7 Hz), the 5.45 to 5.55 (1H, m), 7,0-7,5 (8H, m), 11,95 a 12.05 (1H, m), 14.4V (1H, users)

Table 90
Ave., No.Structure(Solvent)1H-NMR δ ppm:
307(DMSO-d6) of 1.52 (3H, d, J=6.2 Hz), of 3.84 (3H, s), 5,55-the 5.65 (1H, m), the 6.9 to 7.0 (1H, m), 7,0-to 7.15 (4H, m), 7,2-7,3 (1H, m), 7,35 to 7.4 (1H, m), 11,98 (1H, s), 14.4V(1H, s)
308(DMSO-d6) 5,2 to 5.35 (2H, m), 7,25 (1H, DD, J=9.1 Hz, 3.0 Hz), 7,38 (1H, d, J=3.0 Hz), 7,41 (1H, s), 7,55-the 7.65 (2H, m), 7,75-7,8 (2H, m), 7,94 (1H, d, J=7,7 Hz), a 12.05 (1H, s), 14,43 (1H, s)
309 (DMSO-d6) 3,26 (3H, s), 3,6-3,7 (2H, m), 4,1-4,2 (2H, m), 5,07 (2H, s), 6,95-7,0 (1H, m), 7,07 (1H, d, J=8.0 Hz), 7,15 to 7.2 (1H, m), 7.3 to 7.4 (2H, m), 7,4 was 7.45 (2H, m), 7,55 (1H, d, J=9.3 Hz), 12,04 (1H, s), of 14.46 (1H, s)
310(DMSO-d6) a 3.83 (3H, s), a 5.0 to 5.1 (2H, m), 6,9-to 6.95 (1H, m), 7,15-of 7.25 (2H, m), 7.3 to 7.4 (2H, m), 7,45-of 7.55 (1H, m), 12,02 (1H, s), 14.4V(1H, s)
311(DMSO-d6) of 1.66 (3H, d, J=6.5 Hz), 3,8-3,9 (3H, m), 5,75-to 5.85 (1H, m), 6,8-7,0 (2H, m), 7,05-to 7.15 (1H, m), 7,2-7,4 (3H, m), 11,95 a 12.05 (1H, m), 14,39 (1H, s)
312(DMSO-d6) 2,48 (3H, s), 5,09 (2H, s), 7,15-of 7.25 (2H, m), 7,34 (1H, d, J=2,9 Hz), 7,35-7,45 (3H, m), 7,49 (1H, d, J=7,2 Hz), 7,58 (1H, d, J=9.0 Hz), 12,04 (1H, s), accounted for 14.45 (1H, s)
313(DMSO-d6) to 5.1 (2H, s), 6,95-7,0 (1H, m), 7,05-to 7.15 (2H, m), 7,3-7,5 (7H, m), 11,88 (1H, s), 14,89 (1H, s)

Table 91
Ave., No.Structure(Solvent)1H-NMR δ ppm:
314 (DMSO-d6) 5,14 (2H, s), 7,2-7,3 (3H, m), 7,35-7,45 (2H, m), 7,55-the 7.65 (1H, m), 12,02 (1H, s), 14,38 (1H, s)
315(DMSO-d6) 5,08 (2H, s), 7,15-of 7.25 (1H, m), 7,25 of 7.3 (1H, m), 7,35 to 7.4 (2H, m), 7,55 to 7.7 (1H, m), 7,7-7,8 (1H, m), 12,0 (1H, s), 14.4V(1H, s)
316(DMSO-d6) to 5.2 (2H, s), 7,2-7,3 (2H, m), 7,35-7,45 (2H, m), 7.95 is-with 8.05 (1H, m), 12,02 (1H, s), 14,38 (1H, s)
317(DMSO-d6) is 3.82 (3H, s), 5,02 (2H, s), 6,95-7,0 (1H, m), 7,06 (1H, d, J=8,2 Hz), 7,1-7,2 (1H, m), 7,24 (1H, DD, J=6.0 Hz, 3.2 Hz), 7,3 was 7.45 (4H, m), 12,01 (1H, s), 14,44 (1H, s)
318(DMSO-d6) is 1.31 (3H, t, J=6.9 Hz), 4.09 to (2H, q, J=6.9 Hz), to 5.03 (2H, s), the 6.9 to 7.0 (1H, m),? 7.04 baby mortality (1H, d, J=8,2 Hz), 7,1-7,2 (1H, m), 7,2-of 7.25 (1H, m), 7,3 was 7.45 (4H, m), 12,01 (1H, s), 14,43 (1H, s)
319(DMSO-d6) 5,08 (2H, s), 7,05 is 7.5 (7H, m), 7,55-the 7.65 (1H, m), 12,01 (1H, s), 14,42 (1H, s)
320 (DMSO-d6) was 2.34 (6H, s)of 5.03 (2H, s), 7,0 was 7.45 (7H, m), 12,0 (1H, s), 14.4V (1H, s)

Table 92
Ave., No.Structure(Solvent)1H-NMR δ ppm:
321(DMSO-d6) to 5.17 (2H, s), 7,2-7,3 (2H, m), 7,35-7,45 (2H, m), 7,74 (1H, d, J=8,2 Hz), of 7.9 to 8.0 (1H, m), 12,02 (1H, s), 14,38 (1H, s)
322(DMSO-d6) to 2.2-2.3 (3H, m), of 5.05-of 5.15 (2H, m), 7,2-7,3 (2H, m), 7,32 (1H, d, J=8.6 Hz), 7,35-7,45 (3H, m), 12,02 (1H, s), 14,39 (1H, s)
323(DMSO-d6) 3,85-of 3.95 (3H, m), 5,07 (2H, s), and 7.1 to 7.4 (7H, m), 12,01 (1H, s), 14,42 (1H, s)
324(DMSO-d6) is 5.18 (2H, s), 7,15-of 7.25 (1H, m), 7,25-to 7.35 (1H, m), 7,35 is 7.5 (3H, m), 7,55 to 7.7 (2H, m), 12,01 (1H, s), 14,41 (1H, s)
325(DMSO-d6) 3,81 (3H, s), 5,02 (2H, s), to 7.0, and 7.1 (1H, m), 7,1-7,2 (2H, m), 72-7,4 (4H, m), 12,01 (1H, s), 14,42 (1H, s)
326(DMSO-d6) a 3.75 (3H, s), to 5.08 (2H, s), the 6.9 to 7.0 (1H, m)and 7.1-of 7.25 (3H, m), 7,27 (1H, DD, J=6,1 Hz, 3.2 Hz), 7.3 to 7.4 (2H, m), 12,02 (1H, s), 14,41 (1H, s)
327(DMSO-d6) 5,14 (2H, s), 7,15-to 7.35 (3H, m), 7,35-7,45 (2H, m), 7,7-7,8 (1H, m), 12,02 (1H, s), 14,39 (1H, s)

Table 93
Ave., No.Structure(Solvent)1H-NMR δ ppm:
328(DMSO-d6) a 3.83 (3H, s), free 5.01 (2H, s), to 7.09 (1H, d, J=8,8 Hz), 7,15 to 7.2 (1H, m), 7,25-to 7.35 (1H, m), 7,3 was 7.45 (3H, m), of 7.48 (1H, d, J=2.6 Hz), 12,02 (1H, s), 14,43 (1H, s)
329(DMSO-d6) 5,12 (2H, s), 7,15-of 7.25 (1H, m), 7,27 (1H, DD, J=6.0 Hz, 3.2 Hz), 7.3 to 7.4 (2H, m), between 7.4 to 7.5 (2H, m), and 7.5 and 7.6 (1H, m), and 7.7 (1H, DD, J=7,4 Hz, 1.6 Hz), 12,01 (1H, s), 14,41 (1H, s)
330(DMSO-d6) of 3.85 (3H, s), a 5.1 (2H, s), a 7.2 to 7.35 (2H, m), 7,35-7,45 (3H, m), 7,63 (1H, is, J=8.7 Hz), 12,01 (1H, s), 14,38 (1H, s)
331(DMSO-d6) to 5.21 (2H, s), a 7.2 to 7.35 (2H, m), 7,35-7,45 (2H, m), 7,53 (1H, t, J=9,2 Hz), 7,8-7,9 (1H, m), 8,02 (1H, d, J=6,1 Hz), 12,02 (1H, s), 14.4V (1H, s)
332(DMSO-d6) to 5.21 (2H, s), 7,15-of 7.25 (1H, m), and 7.3 (1H, DD, J=5.8 Hz, 3.0 Hz), 7,35 is 7.5 (3H, m), the 7.65 to 7.75 (1H, m), 7,89 (1H, DD, J=8.7 Hz, 5.4 Hz), 12,01 (1H, s), 14.4V (1H, s)
333(DMSO-d6) of 2.24 (3H, s), to 5.08 (2H, s), 7,05-to 7.15 (1H, m), 7,15-of 7.3 (2H, m), 7,35-7,45 (3H, m), 12,02 (1H, s), 14.4V (1H, s)
334(DMSO-d6) to 2.13 (3H, s), 3,82 (3H, s), 5,0 (2H, s), 6,85-to 6.95 (1H, m), 7,25 (1H, d, J=10.0 Hz), 7,32 (1H, d, J=6.4 Hz), 7,39 (1H, s), 7,4-of 7.55 (1H, m), 12,01 (1H, s)14,47 (1H, s)

Table 94
Ave., No.Structure(Solvent)1H-NMR δ ppm:
335(DMSO-d6) a 2.12 (3H, c), of 3.84 (3H, c), 4,96 (2H, c), 6,8-7,0 (2H, m), 24 (1H, d, J=10,2 Hz), 7,32 (1H, d, J=6.3 Hz), 7,35 is 7.5 (2H, m), 12,04 (1H, s), 14, 48mm (1H, s)
336(DMSO-d6) a 2.36 (3H, c), 5,1-of 5.15 (2H, m), 7,2-7,3 (3H, m), 7,35-7,45 (2H, m), and 7.5 (1H, DD, J=8.7 Hz, 6.2 Hz), a 12.03 (1H, c), 14.4V (1H, s)
337(DMSO-d6) 3,86 (3H, c), 5,04 (2H, c), a 7.0 (1H, d, J=9.3 Hz), 7,15-of 7.25 (2H, m), 7.3 to 7.4 (2H, m), 7,55-the 7.65 (1H, m), a 12.03 (1H, c), 14,41 (1H, s)
338(DMSO-d6) to 2.3 (3H, c), is 5.06 (2H, c), 7,1 was 7.45 (7H, m), a 12.03 (1H, c), 14,43 (1H, c)
339(DMSO-d6) 3,88 (3H, c)to 5.13 (2H, c), 7,15-of 7.25 (3H, m), 7,27 (1H, DD, J=6.0 Hz, 3.2 Hz), 7.3 to 7.4 (3H, m), 12,02 (1H, c), 14,42 (1H, s)
340(DMSO-d6) of 3.85 (3H, c), 5,11 (2H, c), 7,05 of 7.3 (5H, m), 7.3 to 7.4 (2H, m), 12,02 (1H, c), 14,42 (1H, s)
341(DMSO-d6) to 1.1 (3H, t, J=7.5 Hz), 2,45 of 2.6 (2H, m), 3,82 (3H, c), 5,0 (2H, c), 6,9-to 6.95 (1H, m), 7.23 percent (1H, d, J=10.3 Hz), 7,34 (1H, d, J=6.3 Hz), 7,39 (1H, c), 7,4-of 7.55 (1H, m), a 12.03 (1H, s)14,47 (1H, s)

Table 95
Ave., No.Structure(Solvent)1H-NMR δ ppm:
342(DMSO-d6) of 3.84 (3H, s), a 5.1 (2H, s), 7,13 (1H, DD, J=9,2 Hz, 4.0 Hz), 7,15-of 7.3 (2H, m), 7.3 to 7.4 (2H, m), 7,45-of 7.55 (1H, m), a 12.03 (1H, s)
343(DMSO-d6) of 1.73 (3H, d, J=6,7 Hz), a 2.5 to 2.55 (3H, m), 6,07 (1H, q, J=6,7 Hz), 6,85-to 6.95 (1H, m), 7,15 to 7.2 (1H, m), 7.3 to 7.4 (1H, m), 7,45-of 7.55 (3H, m), 11,89 (1H, s), 14,37 (1H, s)
344(DMSO-d6) 3,86 (3H, s), 5,12 (2H, s), 7,1-7,3 (3H, m), 7.3 to 7.4 (2H, m), of 7.69 (1H, d, J=8.7 Hz), a 12.03 (1H, s), 14,41 (1H, s)
345(DMSO-d6) 2,15-2,2 (3H, m), 3,81 (3H, s), 5,0 (2H, s), at 6.84 (1H, d, J=8.5 Hz), 7,15-of 7.25 (2H, m), 7,25 to 7.4 (3H, m), a 12.03 (1H, s), 14,42 (1H, s)
346(DMSO-d6) 5,08 (2H, s), a 7.1 to 7.5 (9H, m), 12,01 (1H, s), 14,42 (1H, s)
347 (DMSO-d6) to 1.1 (3H, t, J=7.5 Hz), 2,45 is 2.55 (2H, m), of 3.84 (3H, s), equal to 4.97 (2H, s), 6,85-7,0 (2H, m), 7,22 (1H, d, J=10,2 Hz), 7,33 (1H, d, J=6.4 Hz), 7,35 is 7.5 (2H, m), 12,02 (1H, s)14,47 (1H, users)
348(DMSO-d6) 5,11 (2H, s), 7,1-7,3 (2H, m), 7,3 was 7.45 (2H, m), 7.5 to the 7.65 (3H, m), 12,0 (1H, users), 14,41 (1H, users)

Table 96
Ave., No.Structure(Solvent)1H-NMR δ ppm:
349(DMSO-d6) of 2.33 (3H, c), of 3.78 (3H, c), 5,04 (2H, c), 6,8-6,95 (2H, m), 7,1-7,3 (3H, m), 7.3 to 7.4 (2H, m), 12,01 (1H, c), 14,42 (1H, users)
350(DMSO-d6) to 1.19 (3H, t, J=7.5 Hz), 2,68 (2H, q, J=7.5 Hz), 5,07 (2H, c), 7,15 to 7.4 (7H, m), between 7.4 to 7.5 (1H, m), 12,0 (1H, users), 14,3-14,55 (1H, user.)
351(DMSO-d6) of 3.84 (3H, c), 5,09 (2H, c), 7,2-of 7.25 (1H, m), 7,25-to 7.35 (1H, m), 7,35-7,45 (2H, m), 7,58 (1H, d, J=2.7 Hz), to 7.68 (1H, d, J=2.7 Hz), 12,01 (1H, users), 14,41 (1H, users)
352 (DMSO-d6) a 5.25 (2H, c), a 7.2 to 7.35 (2H, m), 7,35-7,45 (2H, m), 7.95 is-with 8.05 (1H, m), of 8.1 to 8.2 (1H, m), 12,01 (1H, users), 14.4V (1H, users)
353(DMSO-d6) to 1.19 (3H, t, J=7,6 Hz), 2,62 (2H, q, J=7,6 Hz), of 5.05 (2H, c), and 7.1 to 7.4 (8H, m), 12,01 (1H, users), 14,43 (1H, users)
354(DMSO-d6) to 3.3 (3H, c), a 4.53 (2H, c)to 5.13 (2H, c), 7,1-7,3 (2H, m), 7,3 was 7.45 (5H, m), 7,45-of 7.55 (1H, m), 12,01 (1H, users), 14,42 (1H, users)
355(DMSO-d6) 3,29 (3H, c), 4,43 (2H, c), 5,09 (2H, c), 7,1-7,2 (1H, m), 7,2 was 7.45 (7H, m), 12,01 (1H, users), 14,42 (1H, users)

Table 97
Ave., No.Structure(Solvent)1H-NMR δ ppm:
356(DMSO-d6) 5,19 (2H, s), 7,15-of 7.25 (1H, m), 7,25 of 7.3 (1H, m), 7,35-7,45 (2H, m), 7,92 (1H, t, J=8.0 Hz), 8,21 (2H, d, J=8.0 Hz), 12,01 (1H, s), 14,38 (1H, users)
357 (DMSO-d6) to 2.25 (3H, s), is 2.44 (3H, s), and 3.7 (3H, s), 5,02 (2H, s), 7,1-of 7.25 (3H, m), 7,25 of 7.3 (1H, m), 7.3 to 7.4 (2H, m), 12,01 (1H, users), 14,3-14,55 (1H, user.)
358(DMSO-d6) of 3.85 (3H, s), 5,09 (2H, s), 7,05-to 7.35 (4H, m), 7,35-7,45 (2H, m), 12,02 (1H, users), 14,39 (1H, users)
359(DMSO-d6) to 3.89 (3H, s), 5,07 (2H, s), 7,15-of 7.3 (2H, m), 7,3-7,5 (4H, m), and 7.6 to 7.7 (1H, m), 12,01 (1H, s), 14.4V(1H, users)
360(DMSO-d6) is 5.18 (2H, s), 7,2 was 7.45 (5H, m), 7.5 to the 7.65 (1H, m), 12,02 (1H, s), 14.4V (1H, users)
361(DMSO-d6) 5,14 (2H, s), 7,15-of 7.3 (2H, m), 7,3 was 7.45 (2H, m), of 7.6 to 7.8 (3H, m), 12,02 (1H, s), 14,39 (1H, s)
362(DMSO-d6) is 3.82 (3H, s), a 5.1(2H, s), 7,15 was 7.45 (5H, m), 7,45-of 7.55 (1H, m), 12,01 (1H, s), 14.4V(1H, s)

Table 98
Ave., No.Structure(Solvent)1H-NMR δ ppm:
363(DMSO-d6), and 2.27 (3H, s), 3,71 (3H, s), of 5.05 (2H, s), 7,05-of 7.25 (3H, m), 7,25 of 7.3 (1H, m), 7.3 to 7.4 (2H, m), 12,02 (1H, s), 14,42 (1H, users)
364(DMSO-d6) 3,76 (3H, s), 3,85 (3H, s), of 5.03 (2H, s), 7,05 of 7.3 (4H, m), 7.3 to 7.4 (2H, m), 12,02 (1H, users), 14,42 (1H, users)
365(DMSO-d6) 3,8-3,9 (3H, m), to 5.08 (2H, s), 7,15-of 7.25 (2H, m), 7,25 was 7.45 (4H, m), 12,02 (1H, users), 14,41 (1H, users)
366(DMSO-d6) 3,79 (3H, s), 3,83 (3H, s)to 4.92 (2H, s), 6,8-7,0 (2H, m), 7,11 (1H, d, J=11.2 Hz), 7,27 (1H, d, J=7,6 Hz), 7,38 (1H, s), between 7.4 to 7.5 (1H, m), 11,99 (1H, users), 14,55 (1H, users)
367(DMSO-d6) of 3.23 (3H, s), 3,55-the 3.65 (2H, m), 4,1-4,2 (2H, m), 5,09 (2H, s), the 6.9 to 7.0 (1H, m), 7,15-of 7.3 (2H, m), 7.3 to 7.4 (2H, m), between 7.4 to 7.5 (1H, m), a 12.03 (1H, users), 14,42 (1H, users)
368(DMSO-d6) of 1.02 (3H, t, J=6.9 Hz), of 3.43 (2H, q, J=6.9 Hz), 3,6-3,7 (2H, m), 4,1-4,2 (2H, m), to 5.08 (2H, s), the 6.9 to 7.0 (1H, m), 7,15-of 7.25 (2H, m), 7.3 to 7.4 (2H, m), between 7.4 to 7.5 (1H, m), 12,02 (1H, s), 14,42 (1H, users)
369(DMSO-d6) 3,71 (3H, s), of 3.77 (3H, s), 4,99 (2H, s), 6,85-to 6.95 (1H, m), 6,95-7,05 (2H, m), 7,1-7,2 (1H, m), 7,2-7,3 (1H, m), 7.3 to 7.4 (2H, m), 12,01 (1H, s), 14,44 (1H, users)

Table 99
Ave., No.Structure(Solvent)1H-NMR δ ppm:
370(DMSO-d6) to 2.25 (3H, c), of 3.78 (3H, c), to 4.98 (2H, c)6,94 (1H, d, J=7.9 Hz), 7,1-7,2 (2H, m), 7,2-7,3 (2H, m), 7.3 to 7.4 (2H, m), 12,01 (1H, users), accounted for 14.45 (1H, users)
371(DMSO-d6) 1,85-of 1.95 (2H, m), and 3.16 (3H, c), 3,39 (2H, t, J=6.2 Hz), 4,08 (2H, t, J=6.2 Hz), is 5.06 (2H, c), 6,85-to 6.95 (1H, m), 7,15-of 7.3 (2H, m), 7,3-7,5 (3H, m), a 12.03 (1H, s), 14,42 (1H, users)
372(DMSO-d6) of 3.78 (3H, c), 3,85 (3H, c), 4,94 (2H, c), of 7.0, and 7.1 (1H, m), 7,1-7,2 (2H, m), a 7.2 to 7.35 (2H, m), of 7.36 (1H, c), 11,96 (1H, users), 14,56 (1H, users)
373(DMSO-d6) of 1.36 (3H, t, J=6.9 Hz), of 3.78 (3H, c), of 4.13(2H, kV, J=6.9 Hz), 4,96 (2H, c), of 7.0, and 7.1 (1H, m), 7,1-7,2 (2H, m), a 7.2 to 7.35 (2H, m), 7,37 (1H, c), of $ 11.97 (1H, users), 14,56 (1H, users)
374(DMSO-d6) to 1.3 (3H, t, J=7.0 Hz), 3,82 (3H, c), 4,08 (2H, q, J=7.0 Hz), 4,94 (2H, c), 6,8-7,0 (2H, m)and 7.1 (1H, d, J=11,6 Hz), 7,26 (1H, d, J=7,6 Hz), 7,35 is 7.5 (2H, m), 11,99 (1H, c), 14,55 (1H, users)
375(DMSO-d6) is 1.31 (3H, t, J=7.0 Hz), with 3.79 (3H, c), 4.09 to (2H, q, J=7.0 Hz), 4.95 points-of 5.05 (2H, m), 6,85-to 6.95 (1H, m), 7,12 (1H, d, J=11.7 Hz), 7.23 percent (1H, d, J=7,3 Hz), 7,38 (1H, c), between 7.4 to 7.5 (1H, m), 11,99 (1H, c), 14,54 (1H, users)
376(DMSO-d6) a 3.83 (3H, c), is 5.18 (2H, c), the 6.9 to 7.0 (1H, m), 7,38 (1H, c), 7,45 and 7.6 (1H, m), 7,7-a 7.85 (1H, m), with 8.0 and 8.1 (1H, m), 12,08 (1H, c), 14,16 (1H, users)

Table 100
Ave., No.Structure(Solvent)1H-NMR δ ppm:
377(DMSO-d6) 3,81 (3H, c), 5,07 (2H, c), 6,9-to 6.95 (1H, m), 7,39 (1H, c), 7,45-of 7.55 (1H, m), 7,55-the 7.65 (2H, m), 12,06 (1H, c), 14,37 (1H, users)
378 (DMSO-d6) is 3.82 (3H, c), to 5.08 (2H, c), the 6.9 to 7.0 (1H, m), 7,39 (1H, c), 7,45 and 7.6 (1H, m), to 7.61 (1H, d, J=6,7 Hz), 7,73 (1H, d, J=9.1 Hz), 12,07 (1H, c), 14,33 (1H, users)
379(DMSO-d6) is 3.82 (3H, c), 5,07 (2H, c), the 6.9 to 7.0 (1H, m), 7,39 (1H, c), 7,45-of 7.55 (1H, m), 7,58 (1H, d, J=6.5 Hz), to 7.84 (1H, d, J=8,8 Hz), 12,07 (1H, c), 14,33 (1H, c)
380(DMSO-d6) 3,81 (3H, c), 5,0 (2H, c), 7,1-of 7.25 (3H, m), 7,29 (1H, d, J=7,4 Hz), 7,39 (1H, c), 7,45 and 7.6 (1H, m), 12,01 (1H, c), 14,54 (1H, s)
381(DMSO-d6) is 3.82 (3H, c)to 5.13 (2H, c), to 7.15 (1H, d, J=11,4 Hz), 7,33 (1H, d, J=7,3 Hz), 7,39 (1H, c), 7,45 and 7.6 (3H, m), 12,01 (1H, c), 14,54 (1H, s)
382(DMSO-d6) 5,12 (2H, c), 7,15-of 7.25 (2H, m), 7,39 (1H, c), of 7.5 to 7.7 (3H, m), 12,06 (1H, c), 14,36 (1H, users)
383(DMSO-d6) of 5.24 (2H, c), 7,39 (1H, c), 7,45-of 7.55 (1H, m), 7,55 to 7.75 (4H, m), 12,06 (1H, c), 14,36 (1H, users)

Table 101
Ave., No.Structure(Solvent)1H-NMR δ ppm:
384(DMSO-d6) of 3.78 (3H, c), 3,81 (3H, c), 4,96 (2H, c), 6,85-7,0 (2H, m), 7,07 (1H, d, J=8,4 Hz), 7,18 (1H, d, J=2.4 Hz), 7,37 (1H, c), 7,4-of 7.55 (1H, m), 11.87 per (1H, c), 14,97 (1H, s)
385(DMSO-d6) a 3.2 (3H, c), 3,5-3,6 (2H, m), 3,81 (3H, c), 4,05-to 4.15 (2H, m), free 5.01 (2H, c), 6,85-to 6.95 (1H, m), 7,13 (1H, d, J=11.2 Hz), 7.23 percent (1H, d, J=7,0 Hz), 7,39 (1H, c), between 7.4 to 7.5 (1H, m), 11,99 (1H, c), 14,52 (1H, C)
386(DMSO-d6) to 1.0 (3H, t, J=7.0 Hz), 3,4 (2H, q, J=7.0 Hz), 3,55-the 3.65 (2H, m), 3,81 (3H, c), 4,05-to 4.15 (2H, m), 5,0 (2H, c), 6,85-to 6.95 (1H, m), 7,13 (1H, d, J=11,4 Hz), 7.23 percent (1H, d, J=7,7 Hz), 7,38 (1H, c), 7,4-7,5 (1H, m), 11,99 (1H, s), 14,53 (1H, users)
387(DMSO-d6) 3,19 (3H, c), 3,5-of 3.65 (2H, m), 4,05 to 4.2 (2H, m), 5,13 (2H, c), the 6.9 to 7.0 (1H, m), 7,38 (1H, c), 7,4-the 7.65 (3H, m), a 12.03 (1H, c), 14,34 (1H, users)
388(DMSO-d6) 0,99 (3H, t, J=7.0 Hz), 3,4 (2H, q, J=7.0 Hz), 3,55-3,7 (2H, m), 4,05 to 4.2 (2H, m), 5,11 (2H, c), the 6.9 to 7.0 (1H, m), 7,38 (1H, c), 7,4-the 7.65 (3H, m), a 12.03 (1H, c), 14,35 (1H, ears is .c)
389(DMSO-d6) of 1.75 to 1.9 (1H, m), 1,9-2,05 (1H, m), to 2.5-2.7 (4H, m), 6,55 and 6.6 (1H, m), 6,9-to 6.95 (1H, m), 7,1-7,2 (1H, m), 7,25 was 7.45 (4H, m), 7,45-of 7.55 (2H, m), 11,96 (1H, c), 14,41 (1H, c)
390(DMSO-d6) is 3.82 (3H, c), to 5.08 (2H, c), the 6.9 to 7.0 (1H, m), of 7.0, and 7.1 (1H, m), 7.3 to 7.4 (2H, m), 7,4-of 7.55 (2H, m), 11,91 (1H, users), 14,82 (1H, users)

Table 102
Ave., No.Structure(Solvent)1H-NMR δ ppm:
391(DMSO-d6) 1,8-of 1.95 (1H, m), 2,25-2,4 (1H, m), 2,6-2,8 (4H, m), 3,6 (3H, c), 6,65 to 6.75 (1H, m), 7,05-to 7.15 (1H, m), 7,25-to 7.35 (2H, m), 7,35 is 7.5 (1H, m), of 11.7 to 12.2 (1H, usher.), a 14.1-14,8 (1H, user.)
392(DMSO-d6) of 3.78 (3H, c), 3,81 (3H, c), 4,9-5,1 (4H, m), 5,95 (1H, t, J=5.6 Hz), of 6.71 (1H, c), 6,85-to 6.95 (1H, m), 7,05 (1H, d, J=11.2 Hz), 7,17 (1H, d, J=7,4 Hz), 7,4-of 7.55 (1H, m), made 11.32 (1H, s)
393(DMSO-d6) to 3.8 (3H, c), 3,81 (H, c)of 4.95 (2H, c), 6,85-to 6.95 (1H, m)and 7.1 (1H, d, J=11.5 Hz), 7,2-7,3 (2H, m), 7,4-of 7.55 (1H, m), 8,05-of 8.15 (1H, m), 9,65 is 9.75 (1H, m), 11,77 (1H, s)
394(DMSO-d6) was 1.58 (3H, d, J=6.4 Hz), 5,65-of 5.75 (1H, m), 6,85-6,9 (1H, m), 7,2-of 7.25 (2H, m), 7,3 was 7.45 (2H, m), 7,45-of 7.55 (3H, m), 8,05-of 8.15 (1H, m), a 9.6 and 9.7 (1H, m), an 11.7 and 11.8 (1H, m)
395(DMSO-d6) 5,16 (2H, c), 7,19 (1H, DD, J=8,9 Hz, 3.2 Hz), 7,24 (1H, c), 7,35-7,45 (3H, m), of 7.5 to 7.7 (3H, m), 8,11 (1H, d, J=2.1 Hz), 9,65 of 9.7 (1H, m), and 11.8 (1H, c)
396(DMSO-d6) 3,6-of 3.75 (2H, m), Android 4.04 (2H, t, J=4.9 Hz), 4,8-of 4.95 (1H, m), 5,13 (2H, c), 6,9-to 6.95 (1H, m), 7,15-of 7.3 (2H, m), 7.3 to 7.4 (2H, m), between 7.4 to 7.5 (1H, m), 12,01 (1H, c), 14.4V (1H, users)
397(DMSO-d6) 1,75-1,9 (2H, m), 3,45-3,55 (2H, m), 4,1 (2H, t, J=6.2 Hz), 4,9-5,0 (1H, m), is 5.06 (2H, c), 6,85-to 6.95 (1H, m), 7,15-of 7.25 (2H, m), 7.3 to 7.4 (2H, m), between 7.4 to 7.5 (1H, m), 12,02 (1H, s), 14.4V(1H, users)

Table 103
Ave., No.Structure(Solvent)1H-NMR δ ppm:
398 (DMSO-d6) 3,55-the 3.65 (1H, m), of 3.7-3.8 (1H, m), 5,15-5,25 (1H, m), 5.25 to 5.35 (1H, m), 7,0-7,05 (1H, m), 7,2-7,5 (8H, m), 11,95 a 12.05 (1H, m), 14,42 (1H, s)
399(DMSO-d6) br4.61 (2H, s), 5,16 (2H, s), a total of 5.21 (1H, users), 7,15-to 7.5 (7H, m), EUR 7.57 (1H, d, J=8.6 Hz),12,0(1H, s)
400(DMSO-d6) 4,51 (2H, d, J=5,2 Hz), a 5.1 (2H, s), with 5.22 (1H, t, J=5,2 Hz), 7,15 to 7.2 (1H, m), 7,25 was 7.45 (6H, m), EUR 7.57 (1H, d, J=8.6 Hz), a 12.03 (1H, s), 14,44 (1H, s)
401(DMSO-d6) br4.61 (2H, s), of 5.15 (2H, s), 7,15-to 7.5 (6H, m), EUR 7.57 (1H, d, J=9,2 Hz), 7,95 (1H, s), 13,95 (1H, s)
402(DMSO-d6) 3,55-the 3.65 (1H, m), of 3.7-3.8 (1H, m), 5,0-5,4 (2H, m), of 7.0, and 7.1 (1H, m), 7,15-to 7.5 (7H, m), 7,95 (1H, d, J=5,9 Hz), 12,98 (1H, users), 13,95 (1H, s)
403(DMSO-d6) of 1.55 (3H, d, J=6.3 Hz), 3,6-3,8 (2H, m), 3.95 to to 4.15 (2H, m), 4,85-of 4.95 (1H, m), 5,75-5,9 (1H, m), 6,9-7,05 (3H, m), 7,15-to 7.5 (5H, m), 11,95 a 12.05 (1H, m), 14,43 (1H, s)
404 (DMSO-d6) of 1.55 (3H, d, J=6.3 Hz), 3,6-3,8 (2H, m), 3.95 to to 4.15 (2H, m), 4,8-5,0 (1H, usher.), 5,75-to 5.85 (1H, m), 6,9-7,05 (3H, m), 7,15-to 7.35 (3H, m), the 7.43 (1H, d, J=8,9 Hz), of 7.9 to 8.0 (1H, m), from 12.8 to 13.2 (1H, usher.), 13,99 (1H, s)

Table 104
Ave., No.Structure(Solvent)1H-NMR δ ppm:
405(DMSO-d6) of 1.57 (3H, d, J=6.2 Hz), 4,55 with 4.65 (1H, m), 4,65-of 4.75 (1H, m), 5,3 to 5.35 (1H, m), 5,7-5,8 (1H, m), 6,95-7,05 (1H, m), 7,2-7,5 (7H, m), 11,95 a 12.05 (1H, m), 14,42 (1H, s)
406(DMSO-d6) 3,65 of 3.75 (2H, m), 4,0-4,1 (2H, m), to 4.87 (1H, users), 5,12 (2H, s), 6,95-7,0 (1H, m), 7,05 (1H, d, J=8.1 Hz), 7,19 (1H, DD, J=9,0 Hz, 3.0 Hz), 7,25 was 7.45 (4H, m), 7,56 (1H, d, J=9.0 Hz), 12,04 (1H, s), of 14.46 (1H with)
407(DMSO-d6) and 1.54 (3H, d, J=6.3 Hz), 1.85 to 1,95 (2H, m), 3,55-the 3.65 (2H, m), 4,05 to 4.2 (2H, m), of 4.54 (1H, users), 5,65-of 5.75 (1H, m), 6,85-7,0 (2H, m), of 7.0, and 7.1 (1H, m), 7,15 to 7.2 (1H, m), a 7.2 to 7.35 (2H, m), and 7.4 (1H, d, J=4.6 Hz), 7,47 (1H, d, J=9.0 Hz), 11,95 a 12.05 (1H, m), 14,42 (1H, s)
408(DMSO-d6) 1,66 (3, d, J=6.4 Hz), 1.85 to 1,95 (2H, m), 3,5-3,6 (2H, m), 4,05 to 4.2 (2H, m), 5,75-to 5.85 (1H, m), between 6.7 and 7.1 (4H, m), 7,2-7,4 (3H, m), 11,95 a 12.05 (1H, m), 14,35 accounted for 14.45 (1H, m)
409(DMSO-d6) of 1.66 (3H, d, J=6.6 Hz), 3,55-3,8 (2H, m), of 3.85 to 4.0 (1H, m), 4,05 to 4.2 (1H, m), 4,9-of 5.05 (1H, m), 5,9-6,0 (1H, m), 6,7-6,9 (2H, m), of 7.0 to 7.4 (5H, m), 11,95 a 12.05 (1H, m), 14,44 (1H, s)
410(DMSO-d6) of 1.66 (3H, d, J=6.4 Hz), 1,8-of 1.95 (2H, m), 3,5-3,6 (2H, m), 4,0-4,2 (2H, m), and 5.8 (1H, q, J=6.4 Hz), 6,7-6,8 (1H, m), 6,8-7,0 (2H, m), 7,0-7,05 (1H, m), a 7.2 to 7.35 (2H, m), 7,9-of 7.95 (1H, m), 13,93 (1H with)
411(DMSO-d6) of 1.85 to 2.0 (1H, m), 2,2-to 2.35 (1H, m), 2,65-to 2.85 (4H, m), 6.75 in-6,85 (1H, m), of 7.0, and 7.1 (3H, m), 7,24 (1H, t, J=9,3 Hz), 7,3 was 7.45 (2H, m), of $ 11.97 (1H, users), and 13.5 to 15.0 (1H, user.)

Table 105
Ave., No.Structure(Solvent)1H-NMR δ ppm:
412(DMSO-d6) 1,820 (3H, s), 1,823 (3H, s), 6.75 in-6,8 (1H, m), 6,95 to 7.1 (3H, m), 7,15-of 7.25 (1H, m), 7,3 was 7.45 (2H, m), 11,96 (1H, users), 14,43 (1H, users)
413(DMSO-d6) 3,79 (3H, s), of 5.05 was 5.2 (2H, m), 6.8 or 6.9 (1H, m), 7,05 to 7.2 (1H, m), 7,37 (1H, s), and 7.5 and 7.6 (1H, m), the 7.65 to 7.75 (1H, m), 12,02 (1H, s), 14,35 (1H, s)
414(DMSO-d6) 3,79 (3H, s), 3,85 (3H, s), a 5.0 to 5.1 (2H, m), 6.8 or 6.9 (1H, m), 7,05 to 7.2 (2H, m), 7,38 (1H, s), 7,51 (1H, d, J=8.5 Hz), 11,98 (1H, s), 14,54 (1H, users)
415(DMSO-d6) with 3.27 (3H, s), 3,6-3,7 (2H, m), 4,1-4,2 (2H, m)to 5.13 (2H, s), 6,85-to 6.95 (1H, m), 7,05 to 7.2 (1H, m), 7,39 (1H, s), between 7.4 to 7.5 (1H, m), and 7.6 to 7.7 (2H, m), a 12.05 (1H, s), 14,42 (1H, s)
416(DMSO-d6) of 1.05 (3H, t, J=7,1 Hz), of 3.46 (2H, q, J=7,1 Hz), 3,65 of 3.75 (2H, m), 4,1-4,2 (2H, m), 5,14 (2H, s), 6,85-to 6.95 (1H, m), 7,05 to 7.2(1H, m), 7,38(1H, s), between 7.4 to 7.5 (1H, m), 7,55 to 7.7 (2H, m), a 12.05 (1H, s), 14,41 (1H, s)
417(DMSO-d6) of 1.27 (3H, t, J=7,1 Hz), 3,68 (2H, t, J=4,8 Hz), of 4.05 (2H, t, J=4,8 Hz), a 4.3 (2H, q, J=7,1 Hz), 5,12 (2H, s), 6,85-to 6.95 (1H, m)and 7.1-of 7.25 (3H, m), 7,25-to 7.35 (1H, m), between 7.4 to 7.5 (1H, m), 11,63(1H, s)

Table 106
Ave., No. Structure(Solvent)1H-NMR δ ppm:
418(DMSO-d6) of 1.13 (3H, t, J=7,0 Hz)of 1.27 (3H, t, J=7,1 Hz), a 4.03 (2H, q, J=7.0 Hz), 4,25 is 4.35 (4H, m), 4,35 is 4.45 (2H, m), 5,07 (2H, s), the 6.9 to 7.0 (1H, m)and 7.1 to 7.2 (3H, m), 7,25-to 7.35 (1H, m), 7,4-of 7.55 (1H, m), 11,63(1H, s)
419(DMSO-d6) was 1.04 (9H, s)of 1.27 (3H, t, J=7,1 Hz), 4,2-of 4.35 (6H, m), of 5.05 (2H, s), 6,9-7,05 (1H, m), 7,05 to 7.2 (3H, m), 7,25-to 7.35 (1H, m), 7,4-of 7.55 (1H, m), 11,63 (1H, s)
420(DMSO-d6) to 2.7-2.75V (3H, m), 3,71 (3H, s), 4,1-of 4.25 (2H, m), 6,95-to 7.15 (4H, m), 7,38 (1H, s), 7,41 (1H,d, J=8.6 Hz), 11,95 (1H, s), of 14.57 (1H, users)
421(DMSO-d6) 2,73 (3H, s), 3,74 (3H, s), 4,15-of 4.25 (2H, m), was 7.08 (1H, d, J=12,4 Hz), 7,15 to 7.2 (1H, m), of 7.36 (1H, s), 7,4 was 7.45 (2H, m), 7,56(1H,d,J=8.7 Hz), 11,96 (1H, users), 14,61 (1H, users)
422(DMSO-d6) of 2.68 (3H, s), 3,81 (3H, s)to 4.15 (2H, s), 6,7-6,85 (2H, m), of 7.0, and 7.1 (1H, m), 7.3 to 7.4 (2H, m), 7,45-of 7.55 (2H, m), 11,98 (1H, s), accounted for 14.45 (1H, s)
423 (DMSO-d6) to 2.75 (3H, s), 4,22 (2H, s), 6,95-to 7.15 (3H, m), 7,35-7,45 (2H, m), 7,45 is 7.5 (2H, m), 12,02 (1H, s)

Table 107
Ave., No.Structure(Solvent)1H-NMR δ ppm:
424(DMSO-d6) of 2.72 (3H, s), 4,3 (2H, s), 7,15-of 7.25 (1H, m), 7,35 and 7.5 (4H, m), 7,55-the 7.65 (2H, m), a 12.03 (1H, s)
425(DMSO-d6) to 2.7-2.75V (3H, m), 3,23 (3H, s), 3,6-3,7 (2H, m), 4,05 of 4.1 (2H, m), 4,22 (2H, s), 6,7-6,8 (1H, m), of 7.0, and 7.1 (1H, m), 7.3 to 7.4 (2H, m), 7,45-of 7.55 (2H, m), a 12.03 (1H, s), of 14.46 (1H, users)
426(DMSO-d6) to 2.7-2.75V (3H, m), with 3.79 (3H, s), 4.2V (2H, s), 6,7-6,8 (1H, m), 7,0-to 7.15 (1H, m), 7.3 to 7.4 (2H, m), 7,45-of 7.55 (2H, m), 12,02 (1H, s)14,47 (1H, users)
427(DMSO-d6) of 3.7-3.8 (2H, m), Android 4.04 (2H, t, J=4.6 Hz), 4,85-of 4.95 (1H, m)to 5.17 (2H, s), 6,85-to 6.95 (1H, m), 7,05-to 7.15 (1H, m), 7,39(1H, s), between 7.4 to 7.5 (1H, m), and 7.6 to 7.7 (2H, m), a 12.05 (1H, s), 14,44 (1H, s)
428 (DMSO-d6) to 2.7-2.75V (3H, m), of 3.7-3.8 (6H, m), 4,1-4,2 (2H, m), 6,7-of 6.75 (1H, m), 6,95 to 7.1 (2H, m), 7,37 (1H, s), 7,41 (1H, d, J=8,8 Hz), 11,95 (1H, s), of 14.57 (1H, s)

Example test 1

1. Cloning and construction of a vector expressing the GnRH receptor 1 person (GnRHR1)

Using cDNA derived from human pituitary gland (BECTON DICKINSON), as a matrix, a DNA fragment encoding 45-1115 P.N. human GnRHR1 (access Number L03380), which was reported Kakar et al., amplified PCR method and embedded in the multiple cloning site of the plasmid pDNA3.1(+) (Invitrogen). This integrated DNA sequence exactly matches that previously reported sequence.

2. Obtaining cells NEC (primary human kidney), expressing the GnRH receptor 1 person

Expressing the vector with the introduced gene GnRHR1 man was transfusional in cultured cells NECK (medium: MEM, 10% FCS containing antibiotics, non-essential amino acids and pyruvic acid) using lipofectin using Lipofectamine (Invitrogen). After transfection, these cells were cultured for 2 days and used for testing.

3. Analysis of the antagonistic action against GnRH

Antagonistic action of the compounds against human GnRHR1 was evaluated by changing levels of calcium in GnRH-stimulated cells. the donkey remove culture medium of cells NC, transtorno expressing human GnRHR1, cells were washed with 200 ál per well of wash buffer (balanced salt solutions, Henk, 20 mm N-2-hydroxyethylpiperazine-N'-2-econsultancy acid, 1.3 mm calcium chloride, 0.5 mm magnesium chloride, 0.4 mm manganese sulfate). 100 μl of a solution of Ca2+-sensitive dye (FLIPR Calcium Assay Kit (Molecular Devices) was added to the wells and cells were incubated for 1 hour at 37°C, 5% CO2. Then, intracellular calcium levels were determined under the following conditions using a FLEX STATION (Molecular Devices). In this equipment, which was heated to 37°C, 50 μl of test compound diluted in buffer for measurement (wash buffer with 0.1% bovine serum albumin)was added to this hole. After one minute, 50 μl of 5 nm GnRH was added to the wells. The concentration of drug at which 50% of the GnRH-stimulated flow of calcium inhibited (the value of the IC50), was calculated using the logit graph (table 108).

Table 108
Number exampleIC50(nm)
2199
380
17 101
222
2585
31272
4829
9519
14610
19117
20220
23315
36715
41442
42029
The control connection 161
The control connection 23

Sample test 2

Analysis on the oral absorption capacity

1. Preparation of samples for measuring the concentration of drug after intravenous injection into the tail vein

As the experimental animal used hungry during the night the rats Sprague-Dawley (SD) (Charles River, male, 7 weeks of age, weighing 170-210 g). About the in mg of the tested compounds were dissolved by adding 0.2 ml of N,N-dimethylacetamide, 0,798 ml of saline solution and 0.002 ml 2n NaOH and then preparing a solution of 1.0 mg/ml of body weight of the rats was measured and the test compound were injected with intravenous tail vein panettiruling rats at a dose of 1 ml/kg (1 mg/kg). Intravenous injection into the tail vein was performed with a needle for injection of 26 G (gauge) and the use of the syringe 1 ml of the Time points of sampling for blood collection were 2, 15, 60, 120, 240 and 360 minutes after intravenous injection into the tail vein. The blood was centrifuged and plasma was used as a sample for measuring the concentration of drug in the blood.

2. Preparation of samples for measuring the concentration of drug after oral administration

As the experimental animal used hungry during the night the rats Sprague-Dawley (SD) (Charles River, male, 7 weeks of age, weighing 170-210 g). 3 mg of the tested compounds were dissolved by adding 0.2 ml of N,N-dimethylacetamide, 9,794 ml of 0.5% aqueous solution of methylcellulose and 0.006 ml of 2n. NaOH and then preparing a solution of 0.3 mg/ml body Weight of rats was measured and the solution under test compounds were administered orally at the dose of 10 ml/kg (3 mg/kg). Oral administration was performed using a gastric tube for rats and syringe 2.5 ml Time points of sampling for blood collection were 15, 30, 60, 120, 240 and 360 minutes after oral what about the introduction. The blood was centrifuged and plasma was used as a sample for measuring the concentration of drug in the blood.

3. The measurement of the concentration of the medicinal product

To 0,025 ml of plasma obtained in 1) and 2)described above, 0.1 ml of a suitable material internal standard was added in accordance with a conventional method and then perform the deproteinization by adding 0,875 ml of acetonitrile. After centrifugation of 0.005 ml of the supernatant was injectively in LC-MS/MS (VIH using the method of mass spectrometric detection). The concentration of drug in plasma was measured according to the method of LS-MS/MS under the following conditions. To 0.05 ml control plasma were added material internal standard and various test compounds in accordance with the usual method, was performed similar to the above procedures, and then build the calibration curve.

LC

Device: Agilent1100

Column: Cadenza C18, 3 ám and 4.6×50 mm

Mobile phase: 10 mm aqueous ammonium acetate (pH 4.5) / acetonitrile (B) (Time and ratio (A) / (B) shown in table 109).

The column temperature: 40°C

The flow rate: 0.5 ml/min

MS/MS

Instrument: API-4000

Ionization method: ESI (Turbo Ion Spray)

Table 109
Time (min)A(%)B(%)
0,09010
3,09010
4,01090
7,01090
7,19010
to 12.09010

Each area under the curve of drug concentration in plasma from the time when intravenous injection into the tail vein and by oral administration of test compounds were determined using WinNonlin Professional by Pharsight Corporation from the concentration of drug in plasma at each time point obtained in the above manner, and then counted bioavailability (%) based on the following formula.

Bioavailability (%) = {[(area under the curve "concentration of the drug in the plasma - time" oral introduction)/3]/(area under the curve "concentration of the drug in the plasma - time" by intravenous injection into the tail vein)} × 100

When peroral the m introduction the maximum concentration of drug in plasma (C max), bioavailability and concentration of drug in plasma at 360 minutes after injection (C360) are shown in tables 110-112.

Table 110
Test connectionWithmax(ng/ml)
Example 22342
Example 4814460
Example 95322
Example 14617917
Example 19113504
Example 2021308
Example 23324959
Example 27117582
Example 36714120
Example 41425560
Example 42015169
The control connection 1<10
The control connection 2 10

Table 111
Test connectionBioavailability (%)
Example 2211
Example 4865
The control connection 1<1
The control connection 2<1

Table 112
Test connectionC360
Example 146A
Example 202B
Example 233A
Example 271A
Example 367A
Example 414A
Example 420B
The control connection 1 <10
The control connection 2<10
A: > 1000 ng/ml
In: 300 ng/ml 1000 ng/ml

In tables 110-112 Control connection 1 is sulfonamidnuyu compound of example 6(4)described in the above Patent reference 2, and reference compound 2 is sulfonamidnuyu compound of example 31 described in the above Patent reference 2.

As shown above, the condensed heterocyclic derivative of the present invention is more preferable on the kinetics of blood, for example, availability and supportability, when administered orally than the control compounds. For example, a condensed heterocyclic derivative examples 48, 146, 191, 202, 233, 271, 367, 414 and 420 are preferred (excellent) availability than the compound of example 22 with sulfonamidnuyu group, and the compound of example 95, having an amide group, and therefore, is preferable as pharmaceutical compositions for oral administration. In addition, the condensed heterocyclic derivative examples 146, 202, 233, 271, 367, 414 and 420, more preferable examples 146, 233, 271, 367 and 414, maintain the concentration in the blood 6 hours after oral administration and are more preferably the mi on supportability, than the control compounds. Thus, the condensed heterocyclic derivative of the present invention can be used as a long acting drug, essentially no basis for sustained release, such as hydroxyethylcellulose, alkylaryl or similar

Industrial applicability

Condensed heterocyclic derivative (I) of this invention or its prodrug, or pharmaceutically acceptable salt, or a hydrate or MES, has an excellent antagonistic activity against GnRH and therefore can be used as an agent for the prevention or treatment dependent on sex hormones diseases by monitoring the actions gonadotropinreleasing hormone and control the production and secretion of gonadotropin and sex hormones. Thus, this invention can provide an agent for preventing or treating benign prostate hypertrophy, hysteromyoma, endometriosis, metrofibroma, premature puberty, amenorrhea, premenstrual syndrome, dysmenorrhea, polycystic ovary, systemic lupus erythematosus, hirsutism, low growth, sleep disorders, acne, baldness, Alzheimer's disease, infertility, the syndrome is and irritable bowel, prostate cancer, uterine cancer, ovarian cancer, breast cancer and cancer of the hypophysis, a regulator of reproduction, contraception, induce ovulation agent or agent for prevention of postoperative recurrence is dependent on sex hormones on cancer, etc.

1. Condensed heterocyclic derivative represented by the formula (I)

where ring a represents a 5-membered monocyclic heteroaryl containing 1 or 2 heteroatoms selected from N or S;
RArepresents a lower alkyl group, optionally substituted hydroxyl group, COW1, COOW1or CONW2W3in which W1-W3independently represent a hydrogen atom or a lower alkyl group;
m represents the integer 0 or 2
the ring represents a benzene ring or thiophene ring;
RBrepresents a halogen atom, a cyano, a lower alkyl group or OW4in which W4represents a hydrogen atom or a lower alkyl group;
n represents an integer of 0-2;
E1represents an oxygen atom;
E2represents an oxygen atom;
U is the ordinary communication or lower alkylenes group;
X represents a group represented by Y, -CO-Y, -SO2-Y-S-L-Y, -O-L-Y, -CO-L-Y, -SO-L-Y, -SO2-L-Y-S-Z or-O-Z, where L t is made lower alkylenes group, optionally substituted with halogen or hydroxy-group;
Y represents a group represented by Z or-NW7W8where W7and W8independently represent a hydrogen atom, a lower alkyl group or Z, provided that W7and W8are not simultaneously hydrogen atoms, or W7and W8can bind together with the neighboring nitrogen atom with formation of cyclic amino group;
Z represents cycloalkyl group optionally condensed with a phenyl and optionally substituted phenyl group, optionally substituted with halogen or alkoxygroup; 6-8-membered geterotsyklicescoe group having 1 heteroatom selected from a nitrogen atom, or oxygen, optionally condensed with a phenyl and optionally substituted phenyl; phenyl group optionally substituted by a Deputy selected from the group consisting of a halogen atom, ceanography, alkyl groups, optionally substituted by halogen atom, hydroxy-group or alkoxygroup, alkoxygroup, optionally substituted by halogen atom, hydroxy-group, alkoxygroup, alkoxycarbonylmethyl or alloctype, allylthiourea, carboxypropyl and alkoxycarbonyl group; pyridyl;
or its pharmaceutically acceptable salt.

2. Condensed heterocyclic derivative of p is 1, where ring a is thiophene or pyrazole nucleus ring, or its pharmaceutically acceptable salt.

3. Condensed heterocyclic derivative according to claim 2 in which the ring a is any of the thiophene rings represented by the formula

or its pharmaceutically acceptable salt.

4. Condensed heterocyclic derivative according to claim 3 in which the ring a is a thiophene ring represented by the formula

or its pharmaceutically acceptable salt.

5. Condensed heterocyclic derivative according to any one of claims 1 to 4, where RArepresents a lower alkyl group, optionally substituted hydroxy-group, COOW1or CONW2W3in which W1-W3independently represent a hydrogen atom or a lower alkyl group, or its pharmaceutically acceptable salt.

6. Condensed heterocyclic derivative according to claim 4, where m is 1 and ring a is a thiophene ring, in which RAassociated with the position of the ring And represented by the following General formula:

or its pharmaceutically acceptable salt.

7. Condensed heterocyclic derivative according to any one of claims 1 to 6, where the ring is any ring, presented to the formula

or its pharmaceutically acceptable salt.

8. Condensed heterocyclic derivative according to claim 7, where n is 1 or 2 and the ring is any ring in which RBassociated with the position of the ring, represented by the following formula:

in this formula, RBhas the above value, and when there are two RBthey may be the same or different from each other, or its pharmaceutically acceptable salt.

9. Condensed heterocyclic derivative according to any one of claims 1 to 8, wherein RBrepresents a fluorine atom, a chlorine atom or OW4where W4represents a lower alkyl group, or its pharmaceutically acceptable salt.

10. Condensed heterocyclic derivative according to any one of claims 1 to 9, where U is an ordinary bond, methylene group or ethylene group, or its pharmaceutically acceptable salt.

11. Condensed heterocyclic derivative according to any one of claims 1 to 10, where X represents a group represented by Y-S-L-Y, -O-L-Y, -CO-L-Y, -SO2-L-Y-S-Z or-O-Z, where L, Y, and Z are as defined above values, or farmatsevticheskaia salt.

12. Condensed heterocyclic derivative according to claim 11, in which U represents an ordinary bond and X represents a group represented by-S-L-Y, -O-L-Y, -CO-L-Y or-SO2-L-Y in which L and Y have the above specified values, or its pharmaceutically acceptable salt.

13. Condensed heterocyclic derivative according to claim 11, in which U represents a methylene group and X represents a group represented by Y, where Y represents-NW7W8where W7and W8independently represent a hydrogen atom, a lower alkyl group, or Z, provided that W7and W8are not simultaneously hydrogen atoms, or W7and W8can bind together with the neighboring nitrogen atom with formation of cyclic amino group; or-O-Z, where Z is defined above, or its pharmaceutically acceptable salt.

14. Condensed heterocyclic derivative according to claim 11, in which U represents an ethylene group and X represents Y, provided that Y is Z and Z is defined above, or its pharmaceutically acceptable salt.

15. Condensed heterocyclic derivative according to any one of claims 1 to 12, in which L represents a C1-3alkylenes group, or its pharmaceutically acceptable salt.

16. Condensed heterocyclic derivative according to any one of claims 1 to 15, where Z PR is dstanley phenyl group, replaced by Deputy selected from the group consisting of a halogen atom, ceanography, alkyl groups, optionally substituted by halogen atom, hydroxy-group or alkoxygroup, alkoxygroup, optionally substituted by halogen atom, hydroxy-group, alkoxygroup, alkoxycarbonylmethyl or alloctype, allylthiourea, carboxypropyl and alkoxycarbonyl group, or its pharmaceutically acceptable salt.

17. Pharmaceutical composition having antagonistic activity against gonadotropinreleasing hormone containing as active ingredient a condensed heterocyclic derivative according to any one of claims 1 to 16 or its pharmaceutically acceptable salt.

18. The pharmaceutical composition according to 17, where dependent on sex hormones disease selected from the group consisting of benign prostate hypertrophy, hysteromyoma, endometriosis, early puberty, prostate cancer, ovarian cancer and breast cancer.

19. The pharmaceutical composition according to 17, and this composition is an oral composition.

20. The method of prevention or treatment dependent on sex hormones diseases, including the introduction of an effective amount of the condensed heterocyclic, proizvodnjo any one of claims 1 to 16 or its pharmaceutically acceptable salt, where dependent on sex hormones disease selected from the group consisting of benign prostate hypertrophy, hysteromyoma, endometriosis, early puberty, prostate cancer, ovarian cancer and breast cancer.

21. The way the regulation of reproduction and / or prevention of postoperative recurrence is dependent on sex hormones on cancer selected from the group consisting of prostate cancer, ovarian cancer and breast cancer, comprising introducing an effective amount of the condensed heterocyclic derivative according to any one of claims 1 to 16 or its pharmaceutically acceptable salt.

22. The use of the condensed heterocyclic derivative according to any one of claims 1 to 16 or its pharmaceutically acceptable salts for the preparation of a pharmaceutical composition having an antagonistic activity against gonadotropinreleasing hormone.

23. The use of the condensed heterocyclic derivative according to any one of claims 1 to 16 or its pharmaceutically acceptable salts for the preparation of pharmaceutical compositions for the regulation of reproduction and / or prevention of postoperative recurrence is dependent on sex hormones on cancer selected from the group consisting of prostate cancer, cancer aicn the a and breast cancer.



 

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FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to application of thienopyridone derivatives of formula (I), in which B represents CH, represents , or , R represents H, R1 and R2, independently on each other, represent H, linear or branched (C1-C4)alkyl, (C1-C4)cycloalkyl, halogen or together form group -(CH2)n-, where n=1- 4, R3 and R4, independently on each other, represent H, R6 represents H, X represents -O-, or their pharmaceutically acceptable salts for preparation of pharmaceutical composition.

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EFFECT: novel compounds and medicinal agents based on said compounds are obtained, which can be used to treat diseases influenced by inhibition, regulation or modulation of HSP90.

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20 cl, 5 dwg, 193 ex

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EFFECT: high efficiency of using novel compounds in therapy.

32 cl, 3 tbl, 7 dwg, 151 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel compounds of formula where values of radicals are given in the formula of invention, and a pharmaceutically acceptable salt thereof. Said compounds have 17β-hydroxysteroid dehydrogenase enzyme (17β-HSD) inhibiting activity. The invention describes use of the formula (I) compound in treating or preventing diseases or disorders which require inhibition of 17β- hydroxysteroid dehydrogenase enzyme, use of the formula (I) compound to prepare a medicinal agent for treating or preventing diseases or disorders which require inhibition of 17β- hydroxysteroid dehydrogenase enzyme, and a pharmaceutical composition based on the formula (I) compound.

EFFECT: derivatives are highly effective.

18 cl, 7 tbl

FIELD: chemistry.

SUBSTANCE: use of compounds of formula (I): where: X denotes >CR1R2 or, when R6 denotes H, X denotes >SO2; Y denotes >CR1R2; Z denotes >C=O, >CH2, single bond; R1 denotes H, R2 denotes H, -COOH, -OH; or R1 and R2 together denote =O, ethylenedioxy or hydroxyimino group; R3 denotes H, lower alkyl group; R4 denotes two H, =O, hydroxyimino group; R5 denotes H, lower alkyl group, halogen; R6 denotes H, lower alkoxy, COOH; R7 and R8 are identical or different from each other and each denotes H, lower alkyl, halogen; and pharmaceutically acceptable salts thereof and esters for preparing a medicinal agent.

EFFECT: agent having neuroprotective action against hypoxia.

2 tbl, 24 ex, 13 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) and formula (II), their tautomers and pharmaceutically acceptable salts. In formula (I) and in formula (II), X - S; R1 - H; R2 - NR5R6; R3 - 5-6-member heteroaryl with 1 heteroatom, selected from N and S, or phenyl, optionally substituted with one or two substituents, selected from halogen, amino, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenalkyl and C1-C6-halogenalkoxy; R4 - H, C1-C6 alkyl, C1-C6 alkoxy or XR3, where X and R3 are determined above; R5 - H; R6 - H; L - N or CR7, where R7 - H; M - S. Invention also relates to pharmaceutical composition, containing as active component invention compound, to method of inhibiting activity of caseinkinase lε and to method of obtaining compounds of formula (I) or formula (II).

EFFECT: compounds of claimed invention possess properties of casein kinase lε inhibitors.

13 cl, 5 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention describes a neutral semiconductor organic compound of formula (I) , where R1 and R2 denote a hydrogen atom, n is the number links in formula (I) and is an integer between 2 and 1000, terminal groups of the compound R3 and R4 denote a hydrogen atom or a linear or branched alkyl group with 1-20 carbon atoms. The invention also describes use of the said compound as a semiconductor in electronic functional elements.

EFFECT: higher oxidation resistance, which enables use of the compound in transistors and other electronic functional elements.

5 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I): , where R1 is C1-C8alkyl optionally substituted with one to three substitutes selected out of substitute group A; R2 is C1-C6alkyl or C1-C6alkoxyC1-C6alkyl; R3 is C1-C6alkyl or C1-C6alkoxy; or R2 and R3 together with adjoining carbon atoms form optionally substituted non-aromatic 5-10-member carbon ring; R4 is hydrogen; G is group represented by the formula: or the rest as provided in the invention claim; and to pharmaceutical composition, application of claimed compounds, and method of atopic dermatitis prevention or treatment.

EFFECT: novel compounds useful as atopic dermatitis treatment medication and antipruritic medicines.

24 cl, 75 ex, 290 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of formula I. In general formula I A is C or N; B, D and E independently represent CR4, NR5, N, O or S; and a ring containing groups A, B, D, E, selected from thienyl, furan, imidazole, oxazole, isothiazole, thiazole, pyrrol, pyrazole; provided that: b) when A is N, not any of B, D, E can be O or S; and c) when A is C, B is CR4 and one of D or E is N or NR5, when any of D or E cannot be NR5 or N; G is N or C; R1 represents one or more substitutes selected from H, Ra halogen, -OH and -ORa; R2 represents one or more substitutes selected from H, halogen and C1-6-alkyl, and also one of substitutes R2 can be -ORb' , -NRb' Rb', -SRb', -SORb', -SO2Rb', -SO2NRb' Rb'; R3 is H, or Cy, selected from phenyl optionally substituted with one or more substitutes selected from Rc , where Rc independently represents halogen, -ORg', where Rg' independently represents a Rg group, where Rg is C1-6-alkyl; each R4 independently represents H, Re, halogen, -CORe', -CO2Re', -CONRe'Re', -NRe'Re'; R5 independently represents H, Re, -CORe, -CONReRe, -SORe or -SO2Re; each Ra independently represents C1-6-alkyl or halogen- C1-6-alkyl; each R independently represents C1-6-alkyl optionally substituted with one or more substitutes selected from Rd and Rf; each Rb' independently represents H or Rb; each Rc independently represents halogen, -ORg', -CONRg'Rg', -NRg'Rg'; Rd is Cy optionally substituted with one or more Rf substitutes; each Rc independently represents C1-6-alkyl optionally substituted with one or more substitutes selected from Rc and Cy*, or Re is Cy, where any of the groups Cy or Cy* can optionally be substituted with one or more substitutes selected from Rc and Rg ; each Re' independently represents H or Re; each Rf independently represents a halogen, -ORh', -CO2Rh; each Rg independently represents Rd or C1-6-alkyl optionally substituted with one or more substitutes selected from Rd and Rf; each Rg' independently represents H or Rg; each Rh independently represents C1-6-alkyl, halogen-C1-6-alkyl or hydroxy- C1-6-alkyl; each Rh' independently represents H or Rh; and Cy or Cy* given in definitions above is a partially saturated, saturated or aromatic 3-7-member monocyclic carbocyclic ring which optionally contains 1-2 heteroatoms selected from N and O, and where the ring or rings can be bonded to the remaining part of the molecule through a carbon or nitrogen atom.

EFFECT: obtaining formula I compounds with p38-kinase inhibitory properties which can be used in making drugs for treating such diseases as tumour immune and autoimmune diseases etc.

21 cl, 10 dwg, 8 tbl, 57 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel crystalline form of a compound of formula (I), which has P2T antagonist properties and can be used to prevent arterial thrombotic complications in patients suffering from coronary artery disease, cerebrovascular and peripheral vascular diseases. The crystalline form of compound (I) is essentially a pure polymorph II, which is essentially in anhydrous form and which is characterised by X-ray powder diffraction pattern, having characteristic base peaks of high intensity at 5.5°(±0.1°), 13.5°(+0.1°), 18.3°(±0.1°), 22.7°(±0.1°) and 24.3°(±0.1°) 2θ, and has characteristic peaks at 5.5°(±0.1°), 6.8°(±0.1°), 10.6°(±0.1o), 13.5°(±0.1°), 14.9°(±0.1°), 18.3°(±0.1°), 19.2°(±0.1°), 22.7°(+0.1°), 24.3°(±0.1°) and 27.1°(±0.1°) 2θ. The differential scanning calorimetry curve of the said crystalline polymorph has melting onset point in the range of 136-139°C.

EFFECT: invention also relates to a method of producing the disclosed polymorph, according to which a compound of formula (I) is crystallised from chloroform.

9 cl, 6 dwg, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula 2: and to its pharmaceutically acceptable salts and their mixtures, where values of R, M, Q, Z, W, D radicals are described in i.1 of the invention formula. Invention also relates to pharmaceutical compositions, which possess inhibiting activity with respect to Btk, based on formula 2 compounds.

EFFECT: obtained are novel compounds and based on them pharmaceutical compositions which can be applied in medicine for treatment of patients with diseases associated with inhibiting Btk activity and/or B-cell activity.

55 cl, 19 ex

FIELD: chemistry.

SUBSTANCE: in formula I' , R denotes -(C=Q)R2a, CN or Y; Y denotes phenyl, or ; Q denotes O; R2a denotes phenyl, OR5 or N(R5)2; R1 denotes H; Z denotes a bond; R3 and R4 denotes H, halogen, C1-6alkoxy, N(R5)2 or Um-V, where m equals 0 or 1; V denotes H, phenyl, 5-6-member heteroaryl containing up to two nitrogen atoms, 5-6-member heterocyclyl containing up to two heteroatoms selected from N or O, or C1-6aliphatic group; U denotes a C1-6alkylidene chain, where up to two methylene links of the chain may be substituted with -CO2-, -C(O)-, -C(O)NH-, -C(O)NR5; R5 denotes H, C0-6alkykphenyl or C1-6aliphatic group, or two R5 groups, taken together with an atom to which they are bonded are optionally bonded to form a 5-7-member heterocyclic ring containing 1-2 heteroatoms selected from N, O or S; JY is selected from N(R9)2, SR9, OR9, halogen, CN, COOR9, -X-OH, phenyl, -X-phenyl, 5-6-member heteroaryl containing up to two nitrogen atoms, -X-(5-6-member heteroaryl containing up to two nitrogen atoms) or X; X denotes a C1-12aliphatic group; R9 denotes H, C1-6aliphatic group, phenyl, C3-6cycloaliphatic group, 4-6-member heterocyclyl containing up to 2 nitrogen atoms. Invention also relates to a pharmaceutical composition and a method of inhibiting Tec or c-Met kinase activity.

EFFECT: high inhibiting activity towards Tec or c-Met kinase.

16 cl, 11 tbl, 20 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates or tautomers thereof, where substitute M is selected from groups D1 and D2, having structural formulae given below, and R1, E, A and X are as described in the formula of invention. Disclosed also are pharmaceutical compositions which contain these compounds, methods for synthesis of these compounds, intermediate compounds and synthesis methods thereof, as well as use of compounds of formula (I) in preventing or treating diseases mediated by CDK kinases, GSK-3 kinases or Aurora kinases.

EFFECT: high effectiveness of the compounds.

40 cl, 8 dwg, 18 tbl, 84 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: described are new compounds of general formula (I): het-X-AB (I) where het is pentamerous N-heteroaryl, additionally containing one O, S or N atom as a heteroatom with heteroaryl with additional O atom being condensed with a benzene ring, or hexamerous N-heteroaryl; X means S; and where N-atom of N- heteroaryl residue and an X group are separated by one carbon atom; AB means 1,2,3-triazolo[4,5-d] pyrimidine-7-yl radical of general formula (II): where R3 is C1-8alkyl, phenyl, benzyl optionally substituted; R5-H, C1-8alkyl or phenyl.

EFFECT: production of new compounds for preparing a pharmaceutical composition either effective for treating cardiovascular, cancer, autoimmune diseases, stroke, neurodegenerative diseases, cystic fibrosis, or used in antithrombotic therapy.

9 cl, 11 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel 5,7-diamino-substituted pyrazolo[1,5-a]pyrimidines selected from specific compounds, e.g. those given below, which have cyclin-dependent kinase inhibiting properties, such as CDK2. The compounds can be used to treat diseases and conditions associated with CDK, such as proliferative diseases, leukaemia.

.

EFFECT: more effective use of the compounds.

12 cl, 87 tbl, 1057 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel benzotriazole UV ray absorbers of general formula (I): (values of radicals are given in the description), having an absorption spectrum which is shifted towards the long-wave region with considerable optical density to 410-420 nm, as well as a UV radiation stable composition which contains novel UV ray absorbers, and use of the novel compounds as UV radiation stabilisers when applying coating on automobiles.

EFFECT: improved composition.

9 cl, 6 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention describes novel polymorphic modification N-{5-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-2-fluoro-phenyl}-N-methyl-acetamide, methods of its obtaining, its application as medication, its application for preparation of medication and pharmaceutical compositions, including novel polymorphic modification.

EFFECT: obtaining novel polymorphic modification for preparation of medication and pharmaceutical compositions.

30 cl, 2 tbl, 24 ex, 7 dwg

FIELD: chemistry.

SUBSTANCE: present invention relates to novel pyrazole derivatives of formula (I) or pharmaceutically acceptable salts thereof, having tyrosine kinase Trk inhibiting properties and used for treating or preventing malignant growths accompanied by high level of Trk, to a method of producing said derivatives, use thereof to prepare a medicinal agent, pharmaceutical compositions based on said derivatives, a method of inhibiting Trk activity and a method of obtaining antiproliferative action. where A denotes a single bond or C1-2alkylene; where the said C1-2alkylene can be optionally substituted with one R22; ring C is a phenyl or a 5-6-member heterocyclic ring with 1-2 heteroatoms selected from N or S. Values of R1-R7, R22 and n are given in the formula of invention.

EFFECT: obtaining pharmaceutically acceptable salts having tyrosine kinase Trk inhibiting properties and used for treating or preventing malignant growths.

20 cl, 5 dwg, 193 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel acetylenyl-pyrazole-pyrimidine derivatives of general formula (I), having mGluR2 (metabotropic glutamate receptor) antogonist properties). In compounds of general formula (I): either E and J denote N, G denotes C and L denotes N, M denotes CH, or M denotes N, L denotes CH; or L and G denote N, E denotes C, and J and M denote CH; or J, G and L denote N, E denotes C, and M denotes CH; or E and L denote N, J and M denote CH, and G denotes C; R1 denotes H, halogen, CF3, CHF2 or C1-6alkyl; R2 denotes H, halogen, C1-6-alkyl, C1-6-alkoxy, CF3 or CHF2, wherein R1=R2≠H; R3 denotes H; -C(CH3)2OH; linear C1-4-alkyl or C3-4-cycloalkyl, which are possibly substituted with one or more substitutes selected from a group comprising 1-3 F and 1-2 OH; A is selected from a group comprising phenyl or a 5- or 6-member heteroaryl having in the ring 1-2 heteroatoms selected from nitrogen, sulphur or nitrogen and sulphur in the 5-member ring, and 1-2 nitrogen atoms i the 6-member ring, and possibly substituted with 1-3 Ra; Ra denotes halogen; hydroxy; cyano; CF3; NReRf; C1-C6-alkyl, possibly substituted amino or hydroxy; ; C1-6-alkoxy; C3-4-cycloalkyl; CO-NRbRc, SO2-NRbRc; or SO2-Rd-; Rb and RC can be identical or different and are selected from a group comprising H; normal or branched C1-6-alkyl, possibly substituted with one or more substitutes selected from a group comprising F, cyano, hydroxy, C1-6-alkoxy, -NH-C(O)-O-C1-6-alkyl, amino, (C1-6-alkyl)amino, di(C1-6-alkyl)amino, heterocycloalkyl having 6 ring atoms, from which 1-2 heteroatoms are selected from nitrogen or nitrogen and oxygen, or a 6-member heteroaryl with one nitrogen heteroatom in the ring; or a 6-membeer heteroaryl with one nitrogen heteroatom in the ring; or Rb and Rc, together with the nitrogen atom with which they are bonded, can form a heterocyclic ring having 6 members in the ring, from which 1-2 atoms are selected from nitrogen and/or oxygen, and which can be substituted with C1-6-alkyl; Rd denotes OH or C1-6-alkyl; Re and Rf denote H, C1-6-alkyl, possibly substituted hydroxy, -C(O)- C1-6-alkyl; S(O)2-C1-6-alkyl.

EFFECT: compounds can be used in preparing medicinal agents for treating central nervous system (CNS) disorders, such as Huntington's chorea, amyotrophic lateral sclerosis, dementia caused by AIDS, parkinsonism etc.

55 cl, 6 dwg, 321 ex

FIELD: chemistry.

SUBSTANCE: invention describes a compound of structural formula IIIm: or pharmaceutically acceptable salt thereof, where: R81 is selected from a group comprising hydrogen, halogen, possibly substituted C1-6alkyl, possibly substituted C2-6alkenyl, possibly substituted C2-6alkynyl, possibly substituted cycloalkyl, possibly substituted heterocycloalkyl, possibly substituted aryl, possibly substituted heteroaryl, -OH, -NH2, -CN, -NO2, -C(O)OH, -S(O)2NH2, -C(O)NH2, -C(S)NH2, -NHC(O)NH2, -NHC(S)NH2, -NHS(O)2NH2, -OR68, -SR68, -NR69R68, -C(O)R68, -C(S)R68, -C(O)OR68, -C(O)NR69R68, -C(S)NR69R68, -S(O)2NR69R68; -NR69C(O)R68, -NR69C(S)R68, -NR69S(O)2R68, -NR69C(O)NH2, -NR69C(O)NR69R68, -NR69C(S)NH2, -NR69C(S)NR69R68, -NR69S(O)2NH2, -NR69S(O)2NR69R68, -S(O)R68 and -S(O)2R68, R83 is selected from a group comprising hydrogen, fluro and chloro; R112 is selected from a group comprising possibly substituted C2-6alkyl, possibly substituted aryl, possibly substituted heteroaryl and -NR79 R80; R68 is selected from a group comprising possibly substituted C1-6alkyl, possibly substituted C2-6alkenyl, but provided that when R68 is possibly substituted C2-6alkenyl, then one of its alkene carbons is not bonded with N, S, O, S(O), S(O)2, C(O) or C(S) from -OR68, -SR68, -NR69R68, -C(O)R68, -C(S)R68, -C(O)OR68, -C(O)NR69R68, -C(S)NR69R68, -S(O)2NR69R68, -NR69C(O)R68, -NR69C(S)R68, -NR69S(O)2R68, -NR69C(O)NH2, -NR69C(O)NR69R68, -NR69C(S)NH2, -NR69C(S)NR69R68, -NR69S(O)2NH2, -NR69S(O)2NR69R68, -S(O)R68 or -S(O)2R68, possibly substituted C2-6alkynyl, but provided that when R68 is possibly substituted C2-6alkynyl, then one of its alkyne carbons is not bonded with N, S, O, S(O), S(O)2, C(O) or C(S) from -OR68, -SR68, -NR69R68, -C(O)R68, -C(S)R68, -C(O)OR68, -C(O)NR69R68, -C(S)NR69R68, -S(O)2NR69R68, -NR69C(O)R68, -NR69C(S)R68, -NR69S(O)2R68, -NR69C(O)NH2, -NR69C(O)NR69R68, -NR69C(S)NH2, -NR69C(S)NR69R68, -NR69S(O)2NH2, -NR69S(O)2NR69R68, -S(O)R68 or -S(O)2R68, possibly substituted cycloalkyl, possibly substituted heterocycloalkyl, possibly substituted aryl and possibly substituted heteroaryl; R69 is selected from a group comprising hydrogen and possibly substituted C1-6alkyl; and R79 and R80 independently denote hydrogen or possibly substituted C1-6alkyl or R79 and R80 together with the nitrogen atom to which they are bonded form a possibly substituted 5-7-member heterocycloalkyl. Described also is a composition and a set for modulating protein kinase based on said compounds and use of said compounds in preparing a medicinal agent.

EFFECT: novel compounds which are active towards protein kinase are obtained and described.

71 cl, 59 ex

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