Phosphatidylinositol-3-kinase inhibitors

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula I , wherein R2 means methyl, Y means carbon or nitrogen, and R1, R3 and R4 have the value specified in the patent claim. Also, the invention refers to a pharmaceutical composition for the use as a pharmaceutical drug having activity of a phosphatidylinositol-3-kinase inhibitor, to the use of the compounds of formula I for preparing the pharmaceutical drug for treating a disease mediated by phosphatidylinositol 3-kinase and to a method for preparing the compounds of formula I .

EFFECT: preparing the compounds of formula I possessing activity of the phosphatidylinositol-3-kinase inhibitor.

10 cl, 5 tbl, 51 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

where R1means (C1-C8)alkylsulphonyl, optionally substituted di(C1-C8-alkyl)amino, (C1-C8)alkylcarboxylic or (C1-C8)alkoxycarbonyl, or
R1means 5 - or 6-membered heterocyclic ring having one or two ring nitrogen heteroatom selected from pyrazinyl, pyrazolyl or thiadiazole, each optionally substituted (C1-C4)alkyl or halogen, or
R1means-CO-NRxRywhere Rxand Rymeans together with the nitrogen to which they are attached, 5-9-membered N-heterocyclic ring selected from tetrahydroaminoacridine or substituted pyrrolidinyl where the Deputy is selected from methylsulfonyl, aminocarbonyl or hydroxyl, or
R1means (C1-C8)alkylaminocarbonyl, optionally substituted at the alkyl group with 1-2 substituents selected from hydroxy, (C1-C8)alkyl, (C1-C8)alkoxy, hydroxyzinesee (C1-C8)alkoxy, di(C1-C8-alkyl)amine, di(C1-C8-alkyl)aminocarbonyl, (C1-C8)alkoxycarbonyl, 5 - or 6-membered heterocyclic ring having one to four ring heteroatoms, selected the group consisting of oxygen or nitrogen, select the frame from oxazolyl, substituted by ethyl, pyrrolyl, replaced by stands, pyrazolyl, optionally substituted (C2-C3)alkyl, tetrazolyl, substituted ethyl, imidazolyl, substituted (C2-C3)alkyl, 1,2,4-oxadiazolyl, substituted ethyl, pyridinyl, optionally substituted stands, pyrrolidinyl, piperidinyl, morpholinyl, 2-oxitetraciclina, 1,2,5-oxadiazolyl, replaced by propylene, or
R2means methyl,
Y represents carbon or nitrogen, and
if R1means unsubstituted (C1-C8)alkylsulphonyl, and Y represents carbon,
R3means halogen, (C1-C8)alkyl, (C1-C8)alkoxy, amino(C1-C8)alkyl, (C1-C8)alkylaminocarbonyl, di(C1-C8-alkyl)amino, (C3-C6)carbocycle selected from cyclopropyl or phenyl, 5 - or 6-membered heterocyclic ring having one or two ring heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, selected from morpholinyl, pyridinyl, thiazolyl replaced by stands, or (C1-C8)alkylamino, optionally substituted di(C1-C8-alkyl)amino, and
R4means hydrogen or (C1-C8)alkyl, otherwise
R3and R4denote each independently hydrogen, halogen, cyano, (C1-C8)alcalali is Anil, (C1-C8)alkylsulfonyl, (C1-C8)alkylsulfonyl, (C1-C8)alkyl, (C1-C8)haloalkyl, (C3)carbocycle representing cyclopropyl, 5 - or 6-membered heterocyclic ring having two ring heteroatoms selected from the group consisting of oxygen and nitrogen, representing morpholinyl or imidazolyl, (C1-C8)alkylamino, or di(C1-C8-alkyl)amino, each optionally substituted amino, hydroxy, di(C1-C8-alkyl)amino or 5 - or 6-membered heterocyclic ring having two ring heteroatoms selected from the group consisting of oxygen or nitrogen, selected from imidazolyl, morpholinyl, pyrrolidinyl, N-methylpiperazine, or (C1-C8)alkoxy, optionally substituted morpholinyl.

2. The compound according to claim 1, where
R1means (C1-C8)alkylsulphonyl, optionally substituted di(C1-C8-alkyl)amino, (C1-C8)alkylcarboxylic or (C1-C8)alkoxycarbonyl,
or R1means 5 - or 6-membered heterocyclic ring having one or two ring nitrogen heteroatom selected from pyrazinyl, pyrazolyl or thiadiazole, each optionally substituted (C1-C4)alkyl or halogen, or
R1means-CO-NRxRywhere R and Rymeans together with the nitrogen to which they are attached, 5-9-membered N-heterocyclic ring selected from tetrahydroaminoacridine or substituted pyrrolidinyl where the Deputy is selected from methylsulfonyl, aminocarbonyl or hydroxyl, or
R1means (C1-C8)alkylaminocarbonyl, optionally substituted at the alkyl group with 1-2 substituents selected from hydroxy, (C1-C8)alkyl, (C1-C8)alkoxy hydroxyzinesee (C1-C8)alkoxy, di(C1-C8-alkyl)amine, di(C1-C8-alkyl)aminocarbonyl, (C1-C8)alkoxycarbonyl, 5 - or 6-membered heterocyclic ring having one to four ring heteroatoms, selected the group consisting of oxygen or nitrogen, is selected from oxazolyl, substituted ethyl, pyrrolyl, replaced by stands, pyrazolyl, optionally substituted (C2-C3)alkyl, tetrazolyl, substituted ethyl, imidazolyl, substituted (C2-C3)alkyl, 1,2,4-oxadiazolyl, substituted ethyl, pyridinyl, optionally substituted stands, pyrrolidinyl, piperidinyl, morpholinyl, 2-oxitetraciclina, 1,2,5-oxadiazolyl, replaced by propylene,
R2means methyl,
Y represents carbon or nitrogen, and
if R1means unsubstituted (C1-C8 )alkylsulphonyl, and Y represents carbon,
R3means halogen, (C1-C8)alkyl or 5 - or 6-membered heterocyclic ring having one or two ring heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, selected from morpholinyl, pyridinyl, thiazolyl replaced by stands, or (C1-C8)alkylamino, optionally substituted di(C1-C8-alkyl)amino, and
R4means hydrogen or (C1-C8)alkyl, otherwise
R3and R4denote each independently hydrogen, halogen, cyano, (C1-C8)alkylsulfanyl, (C1-C8)alkylsulfonyl, (C1-C8)alkylsulfonyl, (C1-C8)alkyl, (C3)carbocycle representing cyclopropyl, 5 - or 6-membered heterocyclic ring having two ring heteroatoms selected from the group consisting of oxygen and nitrogen, representing morpholinyl or imidazolyl, (C1-C8)alkylamino, or di(C1-C8-alkyl)amino, each optionally substituted amino, hydroxy, di(C1-C8-alkyl)amino or 5 - or 6-membered heterocyclic ring having two ring heteroatoms selected from the group consisting of oxygen or nitrogen, selected from imidazolyl, morpholinyl, pyrrolidinyl, N-methylpiperazine, or (C1-C8)ALCO is si, optionally substituted by morpholinyl.

3. The compound according to claim 1 or 2, where
R1means (C1-C4)alkylsulphonyl, optionally substituted di(C1-C4)-alkyl)amino, (C1-C4)alkylcarboxylic or (C1-C4)alkoxycarbonyl, or R1means 5 - or 6-membered heterocyclic ring having one or two ring nitrogen heteroatom selected from pyrazinyl, pyrazolyl or thiadiazole, each optionally substituted C1-C4)alkyl or halogen, or
R1means-CO-NRxRywhere Rxand Rymeans together with the nitrogen to which they are attached, 5-9-membered N-heterocyclic ring selected from tetrahydroaminoacridine or substituted pyrrolidinyl where the Deputy is selected from methylsulfonyl, aminocarbonyl or
hydroxyl, or R1means (C1-C4)alkylaminocarbonyl, optionally substituted at the alkyl group with 1-2 substituents selected from hydroxy, (C1-C8)alkyl, (C1-C8)alkoxy, hydroxyzinesee (C1-C8)alkoxy, di(C1-C8-alkyl)amine, di(C1-C8-alkyl)aminocarbonyl, (C1-C8)alkoxycarbonyl, 5 - or 6-membered heterocyclic ring having one to four ring heteroatoms, selected the group consisting of CI is the oxygen or nitrogen, selected from oxazolyl, substituted ethyl, pyrrolyl, replaced by stands, pyrazolyl, optionally substituted (C2-C3)alkyl, tetrazolyl, substituted ethyl, imidazolyl, substituted (C2-C3)alkyl, 1,2,4-oxadiazolyl, substituted ethyl, pyridinyl, optionally substituted stands, pyrrolidinyl, piperidinyl, morpholinyl, 2-oxitetraciclina, 1,2,5-oxadiazolyl, replaced by propylene,
R2means methyl, Y represents carbon or nitrogen, and
if R1means unsubstituted (C1-C4)alkylsulphonyl, and Y represents carbon,
R3means halogen, (C1-C4)alkyl or 5 - or 6-membered heterocyclic ring having one or two ring heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, selected from morpholinyl, pyridinyl, thiazolyl replaced by stands, and R4means hydrogen or (C1-C4)alkyl, otherwise
R3and R4denote each independently hydrogen, halogen, cyano, (C1-C4)alkylsulfanyl, (C1-C4)alkylsulfonyl, (C1-C4)alkylsulfonyl, (C1-C4)alkyl, (C3)carbocycle representing cyclopropyl, 5 - or 6-membered heterocyclic ring having two ring heteroatoms selected from the group consisting of acid is kind and nitrogen, representing morpholinyl or imidazolyl, (C1-C4)alkylamino, or di(C1-C4-alkyl)amino, each optionally substituted amino,
hydroxy, di(C1-C4-alkyl)amino or 5 - or 6-membered heterocyclic ring having two ring heteroatoms selected from the group consisting of oxygen or nitrogen, selected from imidazolyl, morpholinyl, pyrrolidinyl, N-methylpiperazine, or (C1-C4)alkoxy, optionally substituted morpholinyl.

4. The compound of the formula I

in free form or in salt form,
where R1means (C1-C3)alkylsulphonyl, optionally substituted di(C1-C8-alkyl)amino or (C1-C8)alkoxycarbonyl, or
R1means 5 - or 6-membered heterocyclic ring having one or two ring nitrogen heteroatom selected from pyrazinyl, pyrazolyl or thiadiazole, each optionally substituted (C1-C4)alkyl or halogen, or
R1means (C1-C4)alkylaminocarbonyl, optionally substituted at the alkyl group with 1-2 substituents selected from hydroxy, (C1-C3)alkoxy, di(C1-C2-alkyl)amine, dimethylaminoborane, (C1-C4)alkoxycarbonyl, 5 - or 6-membered heterocyclic ring, imeushih which one to four ring heteroatoms, selected of the group consisting of oxygen or nitrogen, is selected from oxazolyl, substituted ethyl, pyrrolyl, replaced by stands, pyrazolyl, optionally substituted (C2-C3)alkyl, tetrazolyl, substituted ethyl, imidazolyl, substituted (C2-C3)alkyl, 1,2,4-oxadiazolyl, substituted ethyl, pyridinyl, optionally substituted stands, pyrrolidinyl, piperidinyl, morpholinyl, 2-oxitetraciclina, 1,2,5-oxadiazolyl, replaced by propylene, R2means methyl, Y represents carbon or nitrogen, and
if R1means unsubstituted (C1-C3)alkylsulphonyl, and Y represents carbon,
R3means halogen, (C1-C4)alkyl, methoxy, aminomethyl, methylaminomethyl, dimethylamino, (C3-C6)carbocycle selected from cyclopropyl or phenyl, 5 - or 6-membered heterocyclic ring having one or two ring heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, selected from morpholinyl, pyridinyl, thiazolyl replaced by stands, or acylamino, substituted dimethylamino, and
R4means hydrogen or methyl, otherwise
R3and R4denote each independently hydrogen, halogen, cyano, (C1-C4)alkyl, (C3)carbocycle representing cyclopropyl, 5 - or 6-membered heterocycle which ical ring, having two ring heteroatoms selected from the group consisting of oxygen and nitrogen, representing morpholinyl or imidazolyl, acylamino, optionally substituted by hydroxyl.

5. The compound according to claim 4,
where R1means (C1-C3)alkylsulphonyl or 5 - or 6-membered heterocyclic ring having one or two ring nitrogen heteroatom selected from pyrazinyl, pyrazolyl or thiadiazole, each optionally substituted (C1-C4)alkyl or halogen, or
R1means (C1-C4)alkylaminocarbonyl, optionally substituted at the alkyl group with 1-2 substituents selected from hydroxy, (C1-C3)alkoxy, di(C1-C2-alkyl)amine, dimethylaminoborane, (C1-C4)alkoxycarbonyl, 5 - or 6-membered heterocyclic ring having one to four ring heteroatoms, selected the group consisting of oxygen or nitrogen, is selected from oxazolyl, substituted ethyl, pyrrolyl, replaced by stands, pyrazolyl, optionally substituted (C2-C3)alkyl, tetrazolyl, substituted ethyl, imidazolyl, substituted (C2-C3)alkyl, 1,2,4-oxadiazolyl, substituted ethyl, pyridinyl, optionally substituted stands, pyrrolidinyl, piperidinyl, morpholinyl, 2-oxitetraciclina, 1,2,5-oxadiazol the Nile, replaced by propylene,
R2means methyl,
Y represents carbon or nitrogen, and
if R1means unsubstituted (C1-C3)alkylsulphonyl, and Y represents carbon,
R3means halogen, (C1-C4)alkyl, methoxy, aminomethyl, methylaminomethyl, dimethylamino, (C3-C6)carbocycle selected from cyclopropyl or phenyl, 5 - or 6-membered heterocyclic ring having one or two ring heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, selected from morpholinyl, pyridinyl, thiazolyl replaced by stands, and
R4means hydrogen or methyl, otherwise
R3and R4denote each independently hydrogen, halogen, (C1-C4)alkyl, (C3)carbocycle representing cyclopropyl, 5 - or 6-membered heterocyclic ring having two ring heteroatoms selected from the group consisting of oxygen and nitrogen, representing morpholinyl or imidazolyl, acylamino, optionally substituted by hydroxyl.

6. The compound according to claim 4 or 5,
where R1means (C1-C3)alkylsulphonyl or 5 - or 6-membered N-heterocyclic ring having one or two ring nitrogen heteroatom selected from pyrazinyl, pyrazolyl or thiadiazole, each optionally substituted (C1-C4)alkyl or haloge the Ohm, or
R1means (C1-C4)alkylaminocarbonyl, optionally substituted at the alkyl group with 1-2 substituents selected from (C1-C4)alkoxycarbonyl, dimethylaminoborane or 5 - or 6-membered heterocyclic ring having one to four ring heteroatoms, selected the group consisting of oxygen or nitrogen, is selected from oxazolyl, substituted ethyl, pyrrolyl, replaced by stands, pyrazolyl, optionally substituted (C2-C3)alkyl, tetrazolyl, substituted ethyl, imidazolyl, substituted (C2-C3)alkyl, 1,2,4-oxadiazolyl, substituted ethyl,
pyridinyl, optionally substituted stands, pyrrolidinyl, piperidinyl, morpholinyl, 2-oxitetraciclina, 1,2,5-oxadiazolyl, replaced by propylene, R2means methyl, Y represents carbon or nitrogen, and
if R1means unsubstituted (C1-C3)alkylsulphonyl, and Y represents carbon,
R3means halogen, (C1-C4)alkyl or 5 - or 6-membered heterocyclic ring having one or two ring heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, selected from morpholinyl, pyridinyl, thiazolyl replaced by stands, or acylamino, substituted dimethylamino, and
R4means hydrogen or methyl, otherwise
Rsup> 3and R4denote each independently hydrogen, halogen, (C1-C4)alkyl,
(C3)carbocycle representing cyclopropyl, 5 - or 6-membered N-heterocyclic ring having two ring heteroatoms selected from the group consisting of oxygen and nitrogen, representing morpholinyl or imidazolyl, or acylamino, optionally substituted by hydroxyl.

7. The compound according to claim 1 or 4 for use as pharmaceutical agents that have activity against inhibitor of phosphatidylinositol-3-kinase.

8. Pharmaceutical composition comprising as active ingredient the compound according to claim 1 or 4 for use as pharmaceutical agents that have activity against inhibitor of phosphatidylinositol-3-kinase, together with a pharmaceutically acceptable carrier or diluent.

9. The use of compounds according to claim 1 or 4 for the preparation of a pharmaceutical agent for treating diseases mediated by phosphatidylinositol-3-kinase.

10. The method of obtaining the compounds of formula I as defined in claim 1, in free or salt form, which includes:
(i) (a) interactions of the compounds of formula II

where R2, R3, R4and Y have the meanings defined above and X is halogen,
with the compound of the formula III

where R1has the meaning defined above; and
(ii) removing any protective groups, and regeneration educated compounds of formula I in free or salt form.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I), wherein A represents a pyrrole group or a pyrazole group, and X represents a carbon atom or a nitrogen atom; R1 represents a carboxy group; R2 independently represents a group specified in a substitute group α; R3 independently represents phenyl(C1-C6alkyl)group substituted by, phenyl(C1-C6alkyl)group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α); m is equal to 0, 1, 2 or 3, n is equal to 0 or 1; each of R4, R5, R6 and R7 independently represents a hydrogen atom, C1-C6alkyl group or a halogen atom; B represents a substituted naphthyl group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α), or the group represented by formula (II), wherein B1, B2 and α are those as specified in the patent claim. Also, the invention refers to a pharmaceutical composition possessing lipolysis inhibiting activity, to the use of the compounds of formula (I) in preparing a drug preparation for treating hyperlipidemia, dislipidemia, abnormal lipid metabolism, arteriosclerosis or type II diabetes mellitus and to a method of treating or preventing the mentioned diseases.

EFFECT: preparing the compounds of formula (I) possessing lipolysis inhibiting activity.

36 cl, 1 dwg, 1 tbl, 69 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (1) and pharmaceutically acceptable salts thereof, which exhibit inhibitory activity on phospholipase A2 enzyme and therefore have prostaglandin and/or leucotriene production suppressing action. In formula X is a halogen atom, cyano group, C1-C3 alkyl group, which can be substituted with halogen atoms, C1-C3 alkoxy group or hydroxy group, C2-C4 alkenyl group, C1-C3 alkoxy group or hydroxy group; Y is a hydrogen atom or C1-C3 alkyl group; Z is C1-C3 alkyl group; G is selected from formulae and , where in formulae (G2) and (G5) R4 is a hydrogen atom or C1-C6 alkyl group which can be substituted with halogen atoms; D is -NR10C(O)-, -C(O)NR10-, -S(O)2NR10- or -N(R11)-; R10 is a hydrogen atom; R11 is a hydrogen atom or C1-C3 alkyl group; A is a single bond, C1-C6 alkylene, which can be substituted with a phenyl group, or C2-C4 alkenylene; Q is a phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, S, optionally substituted with a benzene ring; R5, R6 and R7 all or independently denote a hydrogen atom, a halogen atom, C1-C6 alkyl group which can be substituted with halogen atoms, C1-C6 alkoxy group which can be substituted with halogen atoms, phenyloxy group, phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, where said phenyl group and 5-6-member aromatic heterocyclic group can be substituted with a C1-C3 alkyl group which can be substituted with halogen atoms or a C1-C3 alkoxy group. The invention also relates to specific compounds, a medicinal agent, a pharmaceutical composition, a phospholipase A2 enzyme activity inhibitor and a treatment method.

EFFECT: improved method.

21 cl, 56 tbl, 561 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I or use thereof to prepare a medicine for treating depression, anxiety or both: or pharmaceutically acceptable salts thereof, where m is 0-3; n is 0-2; Ar is: optionally substituted indolyl; optionally substituted indazolyl; azaindolyl; 2,3-dihydro-indolyl; 1,3-dihydro-indol-2-one-yl; optionally substituted benzothiophenyl; benzothiazolyl; benzisothiazolyl; optionally substituted quinolinyl; 1,2,3,4-tetrahydroquinolinyl; quinolin-2-one-yl; optionally substituted naphthalenyl; optionally substituted pyridinyl; optionally substituted thiophenyl or optionally substituted phenyl; R1 is: C1-6alkyl; hetero-C1-6alkyl; halo-C1-6alkyl; halo-C2-6alkenyl; C3-7cycloalkyl; C3-7cycloalkyl-C1-6alkyl; C1-6alkyl-C3-6cycloalkyl-C1-6alkyl; C1-6alkoxy; C1-6alkylsulphonyl; phenyl; tetrahydropyranyl-C1-6alkyl; phenyl-C1-3alkyl, where the phenyl part is optionally substituted; heteroaryl-C1-3alkyl; R2 is: hydrogen or C1-6alkyl; and each Ra and Rb is independently: hydrogen; C1-6alkyl; C1-6alkoxy; halo; hydroxy or oxo; or Ra and Rb together form C1-2alkylene; under the condition that, when m is 1, n is 2, and Ar is an optionally substituted phenyl, then R1 is not methyl or ethyl, and where optionally substituted denotes 1-3 substitutes selected from alkyl, cycloalkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, amino, acylamino, monoalkylamino, dialkylamino, hydroxyalkyl, alkoxyalkyl, pyrazolyl, -(CH2)q-S(O)rRf; -(CH2)q-C(=O)-NRgRh; -(CH2)q-N(Rf)-C(=O)-Ri or -(CH2)q-C(=O)-Ri; where q is 0, r is 0 or 2, each Rf, Rg and Rh is independently hydrogen or alkyl, and each Ri is independently alkyl, and where "heteroaryl" denotes a monocyclic radical having 5-6 ring atoms, including 1-2 ring heteroatoms selected from N or S, wherein the rest of the ring atoms are C atoms, "heteroalkyl" denotes an alkyl radical, including a branched C4-C7-alkyl, where one hydrogen atom is substituted by substitutes selected from a group consisting of -ORa, -NRbH, based on the assumption that the bonding of heteroalkyl radical occurs through a carbon atom, where Ra is hydrogen or C1-6alkyl, Rb is C1-6alkyl. Pharmaceutical compositions based on said compound are also disclosed.

EFFECT: obtaining novel compounds which can be used in medicine to treat depression, anxiety or both.

14 cl, 1 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a 2-aza-bicyclo[3.3.0]octane derivative of formula , with stereogenic centres in a (1S,3S,5S)-configuration, where A is a thiazolyl which is unsubstituted or monosubstituted, where the substitute is independently selected from a group comprising C1-4alkyl, C3-6cycloalkyl and NH2; B is phenyl which is unsubstituted or mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, trifluoromethyl, NHC(O)CH3 and halogen; and R1 is an imidazo[2,1·b]thiazolyl or benzoisoxazolyl group, where said groups are independently unsubstituted or monosubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl; or R1 is a 2,3-dihydrobenzofuranyl group; or a pharmaceutically acceptable salt. The 2-aza-bicyclo[3.3.0]octane derivative of formula (I) is as a medicinal agent having the activity of orexin receptor antagonists.

EFFECT: obtaining novel 2-aza-bicyclo[3,3,0]octane derivatives as orexin receptor antagonists.

8 cl, 1 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-phenylbipyrrolidine carboxamides of formula , where values of R, R1, R2, R3 and R4 are given in claim 1.

EFFECT: compounds have activity which binds to the H3 ligand, which allows use thereof in pharmaceutical compositions for treating sleep disorder.

10 cl, 1 tbl, 4 dwg, 153 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are presented nitrogen-containing heterocyclic compounds presented by the following formula wherein the radical values are specified in the description. These compounds or their pharmaceutically acceptable salts possess strong EP1 activity if introduced in a human or an animal; they are used as an effective component of a pharmaceutical agent, e.g. for preventing and/or treating overactive bladder.

EFFECT: compounds are used as an effective component of the pharmaceutical agent for preventing and/or treating the symptoms including frequent urination, heavy urination demand accompanied by fear of involuntary urination, and urinary incontinence.

24 cl, 145 ex, 5 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula

wherein the cycle A represents a carbocyclic group or a heterocyclic group; R1 means (i) lower alkyl optionally substituted by halogen, (ii) lower alkenyl, (iii) lower alkynyl or (iv) a carbocyclic group; each of R3a, R3b, R3c and R3d independently means hydrogen, halogen, lower alkyl optionally substituted by halogen, lower alkenyl, carbocyclyl - lower alkoxy or a carbocyclic group, or R3a and R3b or R3c and R3d can form C3-C10 cycloalkane ring together with an adjoining carbon atoms and can form oxo; a pharmaceutically acceptable salt or solvate of said compound effective in treating the diseases caused by β-amyloid protein production, secretion and/or fixation.

EFFECT: preparing the pharmaceutically acceptable salt or solvate effective in treating the diseases caused by β-amyloid protein production, secretion and/or fixation.

18 cl, 139 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to particular compounds, which demonstrate inhibiting activity with respect to ERK, whose structure formula is given in description, to their pharmaceutically acceptable salts, based on them pharmaceutical composition and their application for treatment of cancer, mediated by ERK activity.

EFFECT: obtaining compounds, which demonstrate inhibiting activity with respect to ERK.

5 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrimidine derivatives and their pharmaceutically acceptable salts possessing the properties of a mTOR kinase inhibitor. In formula (I): A represents a 6-8-member mono- or bicyclic heterocyclic ring containing 1 to 2 heteroatoms optionally specified in N and O as apexes of the ring and having 0-2 double bonds; and wherein the ring A is additionally substituted by 0 to 2 substitutes RA specified in a group consisting of -ORa, -Rc and -(CH2)1-4-ORa wherein Ra is optionally specified in hydrogen and C1-6alkyl; Rc represents C1-6alkyl; G is specified in a group consisting of -C(O)-, -OC(O)-, -NHC(O)- and -S(O)0-2-; B is specified in a group consisting of phenylene and 5-6-member heteroarylene consisting 1-2 nitrogen heteroatom as apexes of the ring, and substituted by 0 to 1 substitutes RB specified in F, Cl, Br, I and Rp; wherein Rp represents C1-6 alkyl; D is specified in a group consisting of -NR3C(O)NR4R5, -NR4R5, C(O)NR4R5, -NR3C(=N-CN)NR4R5, -NR3C(O)R4, -NR3C(O)OR4 and -NR3S(O)2R4, and wherein the group D and a substitute placed on an adjoining atom in the ring B, optionally combined to form a 5-6-member heterocyclic or heteroaryl ring containing 1 to 3 heteroatoms specified in N, O and S, as apexes of the ring and substituted by the substitute 0-1 RD. The R1-R5 radical values are presented in the patent claim.

EFFECT: invention also refers to a pharmaceutical composition containing said compounds, and to the use of the compounds for preparing a drug for treating a malignant tumour mediated by mTOR kinase activity.

33 cl, 13 dwg, 4 tbl, 498 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 3-aza-bicyclo[3.3.0]octane derivatives of formula , where R1 and R2 are hydrogen, C1-4alkyl or fluorine; R3 is a phenyl which is unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, trifluoromethyl, trifluoromethoxy group and halogen; 2,3-dihydrobenzofuranyl; 2,3-dihydrobenzo[1,4]dioxynyl; or isoxazolyl, pyridyl, indazolyl, benzofuranyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, pyrrolo[2,1b]thiazolyl, imidazo[ 1,2-a]pyridinyl or imidazo[2,1-b]thiazolyl, where said groups are unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, halogen and trifluoromethyl; A is or ; R4 is C1-4alkyl or -NR6R7; R6 is hydrogen or C1-4alkyl; R7 is hydrogen or C1-4alkyl; and D is a phenyl which is unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, trifluoromethyl and halogen; or a pharmaceutically acceptable salt of such a compound. 3-aza-bicyclo[3.3.0]octane derivatives or a pharmaceutically acceptable salt thereof are used as a medicinal agent having the activity of orexin receptor antagonists.

EFFECT: novel 3-aza-bicyclo[3,3,0]octane derivatives as nonpeptide antagonists of human orexin receptors.

9 cl, 1 tbl, 85 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new indole compounds of formula:

wherein A means 5-member heteroaryl or heterocyclyl each of which has 1 to 3 heteroatoms specified in N, O and S, R1 means R5 -X-B-X'-, R2 means -(CR8 R9 )p-Y-R7, R3 means hydrogen, C1-C6-alkyl or -(CH2)q-C3-C6-cycloalkyl, R4 means C3-C6-cycloalkyl (the other radical values are presented in cl.1 of the patent claim), their pharmaceutically acceptable salts or isomers which may be used for preventing or treating cell necrosis and necrosis-related diseases.

EFFECT: preparing the compounds to be used for preventing or treating cell necrosis and necrosis-related diseases.

34 cl, 2 tbl, 263 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are presented nitrogen-containing heterocyclic compounds presented by the following formula wherein the radical values are specified in the description. These compounds or their pharmaceutically acceptable salts possess strong EP1 activity if introduced in a human or an animal; they are used as an effective component of a pharmaceutical agent, e.g. for preventing and/or treating overactive bladder.

EFFECT: compounds are used as an effective component of the pharmaceutical agent for preventing and/or treating the symptoms including frequent urination, heavy urination demand accompanied by fear of involuntary urination, and urinary incontinence.

24 cl, 145 ex, 5 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to (aza)indole derivatives of formula

wherein the values T, X1-X3, R1, Q, Y, J are presented in clause 1 of the patent claim.

EFFECT: compounds possess xanthine oxidase inhibitory action that enables using it in a pharmaceutical composition for treating a disease specified in a group consisting of hyperuricemia, gouty tophus, gouty arthritis, renal diseases associated with hyperuricemia and nephrolithiasis.

19 cl, 62 tbl, 332 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 7-substituted indoles of formula I:

or their pharmaceutically acceptable salts wherein the values A1, B1, C1, D1, E1, F1, G1, L are presented in cl. 1 of the patent claim.

EFFECT: compounds inhibit activity of anti-apoptotic protein Mc1-1 that enables using them in pharmaceutical compositions.

5 cl, 7 dwg, 2 tbl, 609 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) or pharmaceutically acceptable salts thereof: where: each of R1, R2, R3, R4 is independently selected from a group consisting of a hydrogen atom, a halogen atom, an aryl, a C5-6 heteroaryl having 1-3 heteroatoms in the ring which are selected from O, S and N, -OR5, -NR5R6, and -NR5COR6, where said aryl or C5-6 heteroaryl, having 1-3 heteroatoms in the ring selected from O, S and N, is unsubstituted or additionally substituted with one or more groups selected from a group consisting of alkyl, alkoxyl and halogen, each of R5 and R6 is independently selected from a group consisting of a hydrogen atom or an alkyl, where said alkyl is unsubstituted or additionally substituted with one or more groups selected from a group consisting of an aryl, haloaryl, hydroxyl and alkoxyl. The invention also relates to a pharmaceutical composition which inhibits protein kinase and contains a compound of formula I, a method of producing the compound of formula I, use of said compounds to produce a medicinal agent for treating disorders associated with protein kinase, and a method of modulating catalytic activity of protein kinase.

EFFECT: improved method.

10 cl, 24 ex

FIELD: chemistry.

SUBSTANCE: invention relates to indole derivatives or pharmaceutically acceptable salts thereof of general formula (1): , where values of R1, R2, m are given in claim 1.

EFFECT: compounds have inhibiting activity on IKKβ, which enables their use as a preventive or therapeutic agent for treating IKKβ mediated diseases.

26 cl, 1 tbl, 29 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical composition for treating diabetes, obesity or metabolic syndrome, which includes therapeutically efficient amount of (5-hydroxyadamantan-2-yl)amide of trans-2'-tret-butyl-2'H-[1,3']bipyrazolyl-4'-carboxylic acid or its pharmaceutically acceptable salts, and pharmaceutically acceptable carrier.

EFFECT: invention also relates to application of said compound for preparation of medication, intended for treatment of said diseases.

2 cl, 1 tbl, 99 ex

Chemical compounds // 2469034

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes compounds of formula (I) wherein: R1 means C1-6alkyl or C3-6cycloalkyl; wherein R1 may be optionally carbon-substituted by one or more R6; R2 means hydrogen; R3 and R4 are carbon substitutes, and each is independently specified in carboxy, carbamoyl, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C1-6alkanoylamino, N-(C1-6alkyl)carbamoyl, N,N-(C1-6alkyl)2carbamoyl, N-(C1-6alkoxy)carbamoyl, phenyl-R9 - or heterocyclyl-R10-; wherein R3 and R4 may be independently carbon-substituted by one or more R11; and wherein provided said heterocyclyl contains -NH - residue, then nitrogen may be optionally substituted by a group specified in R12; m has the value of 0, 1 or 2; wherein the values R3 may be equal or different; p has the value of 0, 1 or 2; wherein the values R4 may be equal or different; the ring A means nitrogen-containing 5- or 6-member heterocyclic group; wherein drawn nitrogen represents = N- and is found in an ortho-position to R1R2NC(O)NH group in formula (I); the ring B means phenyl or heterocyclyl; wherein provided said heterocyclyl contains -NH- residue, then nitrogen may be optionally substituted by a group specified in R14; R5 is specified in hydroxy, C1-6alkoxy or -N(R15)(R16); R6 and R11 are carbon substitutes and each is independently specified in halo, C1-6alkyl or C1-6alkoxy; R15 and R16 are independently specified in hydrogen, C1-6alkyl, C1-6alkoxy, cyclopropyl or cyclopentyl; R12 and R14 mean C1-6alkyl; wherein R14 may be optionally carbon specified by one or more R23; R9 and R10 mean a direct link; and R23 means halo or methoxy; wherein said heterocyclyl means pyridine, imidazole, triazole, thiazole, benzothiazole, imodazolepyridine, dihydroquinoline or thiadiazole, or its pharmaceutically acceptable salt; provided said compound represents other than ethyl ester of 5-[2-[[(ethylamino)carbonyl]amino]pyridin-4-yl]-4-methyl-4H-1,2,4-triazole-3-carboxylic acid or their pharmaceutically acceptable salts. There are also described pharmaceutical compositions on the basis of said compounds, a method for bacterial DNA-hydrase and/or bacterial topoisomerase IV inhibition in a homoiothermal animal, as well as a method of treating an infection in a homoiothermal animal.

EFFECT: there are prepared and described new compounds showing antibacterial activity.

24 cl, 165 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present patent claim discloses sulphonyl-substituted compounds of formula QUIN which are used for the purpose of a method for producing a macrocyclic compound of formula (I)

EFFECT: compounds of formula (I) are effective active agents for treating Hepatitis C viral (HCV) infection.

8 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and a method of producing bis-2,4-dialkyl-1,5,3-dithiazepan-3-yls of general formula (1): R=Me, Et, nPr, nBu, which involves reaction of a prepared mixture of ethane dithiol and aldehyde at 0°C (acetic or propionic or butyric or valeric) with hydrazine hydrate (60%) with molar ratio aldehyde: ethane dithiol: hydrazine=40:20:10 at temperature 0°C and atmospheric pressure for 2-4 hours.

EFFECT: method of producing novel compounds which can be used as antibacterial, antifungal and antiviral agents.

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I), where A is C-R1b; R1a, R1b, R1c, R1d, R1e, R2, R3, R4, R5 and n are as described in claim 1 of the invention, as well as pharmaceutically acceptable salts thereof. Described also is a pharmaceutical composition having activity as glucocorticoid receptor modulators.

EFFECT: novel compounds are obtained and described, which are glucocorticoid receptor antagonists and useful for treating and/or preventing diseases such as diabetes, dyslipidaemia, obesity, hyptension, cardiovascular diseases, adrenal gland malfunction or depression.

24 cl, 210 ex

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