Iap inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

, which can inhibit binding of protein Smac with apoptosis protein inhibitor (IAP).

EFFECT: improved properties of the inhibitor.

4 cl, 198 ex


The text descriptions are given in facsimile form.

1. The compound of formula IVa

where R1means N or C1-C4alkyl;
R2means N or C1-C4alkyl;
R4means cyclohexyl, cyclopentyl or1-C4alkyl;
R5means N;
U represents a group of formula V

where n is 0;
X represents N;
Rc denotes H;
Rd means Ar1-D-Ar2where D is-CH2-, -CF2-, -O-, -C(O)-, -S-, -S(O)-, -S(O)2, 1,3-dioxolane, or-N(Rh), where Rh denotes H, C1-C7alkyl, -CF3, -CH2CH2HE, -C(O)H or-SO2CH3and Ar1and AG2mean substituted or unsubstituted aryl or het, where specified het, which may be substituted stands selected from pyridinyl, pyrimidinyl, tetrazolyl, triazolyl, pyrazolyl, oxazolyl, thiazolyl, 1,2,4-oxadiazolyl, pyrrolyl, imidazolyl, pyrazinyl or triazinyl, as specified aryl means phenyl which may be substituted by one or two halogen;
R6, R7, R6' and R7' each denotes H;
or its pharmaceutically acceptable salt.

2. The compound according to claim 1, where Ar1means pyridinyl or thiazolyl and AG3means phenyl which may be substituted by one or two halogen; or its pharmaceutically acceptable salt.

3. The compound according to claim 1 or 2, where D denotes-CH2-, -CF2-, -O - or-C(O)-, or its pharmaceutically acceptable salt.

4. The compound according to claim 1, selected from the group including:




N-[(1S)-1-cyclohexyl-2-oxo-2-[(2S)-2-[5-(phenylmethyl)-1,2,4-oxadiazol-3-yl]-1-pyrrolidinyl]et the l]-2-(methylamino)-(2S)-propanamide;










N-[(1S)-1-cyclohex the l-2-oxo-2-[(2S)-2-[4-(phenylmethyl)-2-oxazolyl]-1-pyrrolidinyl]ethyl]-2-(methylamino)-(2S)-propanamide;






































< / br> N-[(1S)-2-[(2S)-2-(3-benzoylphenyl)-1-pyrrolidinyl]-1-cyclohexyl-2-oxoethyl]-2-(methylamino)-(2S)-propanamide;











2-(methylamino)-N-[(1S)-2-methyl-1-[[(2S)-2-[3-(methylpentylamino)phenyl]-1-pyrrolidinyl]carbonyl]propyl]-(2S)-propanamide; and

or its pharmaceutically acceptable salt.


Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compounds, which possess agonistic or antagonistic activity of NGF and BDNF neutrophins and represent monomer or dimmer substituted dipeptides, which are analogues of exposed outside parts of loops 1 and 4 of said neutrophins, close to beta-bends of said loops or coinciding with them. Effects in vivo are demonstrated by claimed compounds within dose interval 0.01-10 mg/kg in intraperitoneal introduction.

EFFECT: claimed compounds possess neuroprotective and differentiating activity on cell models, increase concentration of phosphorylated form of tyrosine kinase A and proteins of heat shock Hsp32 and Hsp70 in concentrations10-5-10-9 M, they also possess neuroprotective, antiparkinsonian, anti-stroke, antiischemic, antidepressant, antiamnestic activity on animal models and demonstrate activity on experimental models of Alzheimer's disease.

20 cl, 33 dwg, 23 tbl, 18 ex

FIELD: medicine.

SUBSTANCE: invention refers to inhibitors of enzymes cleaving protein after proline, such as depeptidyl peptidase IV inhibitors, as well as to their pharmaceutical compositions, and methods of application of such inhibitors. Particularly, inhibitors under this invention are improved in comparison with those currently in use in the present art by selecting special classes of side chains in P1 and/or P2 positions of inhibitor which contains carboxylic acid grouping.

EFFECT: compounds of specified formulas I, II and III can have the improved therapeutic index, partially owing to reduced toxicity and improved specificity in relation to target protease.

15 cl, 2 dwg, 6 ex

FIELD: pharmacology.

SUBSTANCE: there is produced synthetic derivative of phthalyl-glycyl-agginyl-piperidide peptide expressing anticoagulant activity estimated by inhibiting amidolytic thrombin activity in system in vitro and double prolongation of rats' blood plasma coagulation as compared with the control values in tests activated partial thromboplastin and thrombin time tests and having formula 1, including pharmaceutically acceptable salts.

EFFECT: new synthetic peptide derivative expressing anticoagulant activity.

1 dwg, 2 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: application describes ACE inhibitor complexes of Perindopril Erbumine with cyclodextrins, polyvinylpyrrolidone or hydroxypropyl cellulose, methods for making thereof, pharmaceutical compositions.

EFFECT: application for treatment of cardiovascular diseases.

19 cl, 23 dwg, 13 ex

FIELD: chemistry.

SUBSTANCE: desired dipeptides are synthesised by reaction of methyl ether N - (9-aminononanoyl)-3-amino-3-phenylpropionic acid and betulonic (3-oxo-lup-20 (29)-en-28) and dihydrobetulonic (3-oxo-lupan-28) acid chloranhydrides.

EFFECT: lupane triterpene dipeptides develop antiviral antiproliferative and immunopotentiating activity.

9 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: present invention refers to bioactive compounds of formula (Ic) , pharmaceutical compositions and application at cancer treatment, where R2-R7, X2, R, Q, G, J, L and M represent values estimated in invention formula and description.

EFFECT: production of compounds which can be used for anticancer medical product.

55 cl, 19 ex

Perindopril // 2339645

FIELD: chemistry.

SUBSTANCE: formula (I) is obtained from protected precursor compound of the formula (II) , where R is carboxy protective group. Method involves protection removal from COOR carboxylic group linked to heterocyclic ring in the formula (II), thus obtaining respective free acid. Protection removal is performed in the presence of an alkali forming pharmaceutically acceptable salt with the indicated free acid and, if necessary, is followed by hydration of pharmaceutically acceptable perindopril salt.

EFFECT: improved method of perindopril obtainment.

15 cl, 1 dwg, 1 tbl, 7 ex

FIELD: organic chemistry of natural compounds.

SUBSTANCE: invention relates to novel compounds, namely, to N'-{N-[3-oxo-lupan-28-oyl]-9-aminononanoyl}-3-amino-3-phenylpropionic acid and its salts of the formula (I) given in the invention description. This compound shows antiviral activity, in particular, anti-HIV activity, and immunostimulating activity. Compounds of the formula (I) are nontoxic and can be obtained from betulin isolated from birch bark as available raw with the high yield.

EFFECT: valuable medicinal properties of compound.

4 tbl, 9 ex

FIELD: chemistry of peptides, microbiology, biotechnology.

SUBSTANCE: L-alanyl-L-glutamine is prepared by incubation of a mixture containing a microorganism able to produce L-alanyl-L-glutamine from L-alanine ester and L-glutamine, L-alanine ester and L-glutamine, and isolation of the end product. Using the invention allows simplifying the process for preparing L-alanyl-L-glutamine. Invention can be used in pharmacy and food processing industry.

EFFECT: improved preparing method of dipeptide.

3 cl, 3 tbl, 1 ex

The invention relates to the field of medicine and relates to new N-pinakamaraming tryptophanase of dipeptides of the formula


where n=1-5;


X=L or D-configuration;


as well as pharmaceutical compositions containing them

FIELD: chemistry.

SUBSTANCE: described is a method of producing 5,6-dihydro-4H-benzo[f]pyrrolo[ 1,2-α][1,4]diazepin-6-one 1, involving moulding a pyrrolodiazepine frame as a result of reduction of nitro-groups of N-(2,5-dioxoalkyl)-2-nitrobenzamides 4, in acetic acid in the presence of iron while carrying out the reaction until boiling and holding for 60 minutes at room temperature.

EFFECT: simultaneous formation of a pyrrole and a diazepine ring, and high output of end products owing to change in the sequence and conditions of the reaction.

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formulae Ia, Ic, Ig, Ik and pharmaceutically acceptable salts thereof, having activity towards cannabinoid 1 receptor. In formulae

, ,

, ,

R2 is selected from halogen, pyrazinyl, pyridazinyl, pyrimidinyl, pyridinyl, pyridinyl-N-oxide and phenyl; where the said pyrimidinyl, pyridinyl, pyridinyl-N-oxide, pyrazinyl and phenyl are optionally substituted with an amino group; R3 is selected from hydrogen, methylsulphonyl, methlsulphoxide and dimethylaminocarbonyl; R4 is selected from hydrogen, cyano, nitro, carbamimidoyl, tetrazolyl, aminosulphonyl, aminocarbonyl, methylsulphonylamino and methylsulphonyl; R6 is selected from hydrogen, hydroxyethylaminomethyl and methylsulphonylaminomethyl. The invention also relates to a pharmaceutical composition, methods of treating and preventing diseases mediated by the cannabinoid 1 receptor, and use of said compounds in preparing a medicinal agent used to treat such diseases.

EFFECT: improved properties of the derivatives.

12 cl, 1 tbl, 62 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I): or to their pharmaceutically acceptable derivatives selected from a group consisting of pharmaceutically acceptable salts and esters; in which: R1, R2, R3, R4, R5, R6, R7, R8a, R8b, R8c and R8d are such as presented in the patent claim 1. The invention also refers to compounds of formula (I), to a compounds selected from a group, to a pharmaceutical composition, to methods of treating, to a method of decreasing the plasma cholesterol level in a patient, to a method of modulating cholesterol metabolism, catabolism, synthesis, absorption, re-absorption, secretion or excretion in a mammal, to a method of modulating farnesoid X receptor activity, to a compound representing 3-(3,4-difluorobenzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino [4,5-b]indole-5-isopropylcarboxamide, to a composition, to a method of reducing the risk of an onset or a recurrence, to a method of modulating triglyceride metabolism, catabolism, synthesis, absorption, re-absorption, secretions or excretion in a mammal, and also to a method of modulating bile acid metabolism, catabolism, synthesis, absorption, re-absorption, secretions or excretion in a mammal.

EFFECT: preparation of the new biologically active compounds showing possessing nuclear receptor activity.

73 cl, 76 ex, 3 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidine-2,6-diamines of general formula 1, their pharmaceutically acceptable salts and/or hydrates which have serotonin 5-HT6 receptor antagonist properties and can be used in treating or preventing development of various central nervous system diseases, whose pathogenesis is associated with 5-HT6 receptors, particularly Alzheimer's disease, Parkinson's disease, Huntington disease, schizophrenia, other neurodegenerative diseases, cognitive and anxiety disorders and obesity. In general formula (I): R1, R2 and R4, which are optionally identical, independently denote C1-C3 alkyl; R3 and R4, which are optionally identical, denote: a hydrogen atom, optionally substituted C1-C3 alkyl or acetyl; R5 denotes a hydrogen atom or halogen atom.

EFFECT: high treatment efficiency.

13 cl, 12 dwg, 4 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing methyl 7-arylcarbamoyl-6-benzoyl-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidine-5-carboxylates of general formula , where Ar denotes 4-chlorophenyl or 4-methoxyphenyl, which can be used as primary products for synthesis of novel heterocyclic systems in pharmacology. Method involves reaction of methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with 3-methyl-4-phenyl-1H-pyrazole-5-amine in the medium of an inert aprotic solvent.

EFFECT: method is easy to implement and enables to obtain said compounds with high output.

2 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: described are novel substituted naphthyridines of general formula E: (radicals R1 and R3 are described in the claim), pharmaceutically acceptable salts thereof, a pharmaceutical composition containing said compounds, and use of the novel compounds to prepare a medicinal agent for treating or preventing malignant tumours in mammals.

EFFECT: compounds inhibit Akt acitivity, in particular, the compounds selectively inhibit one or two isoforms of Akt and can be used in medicine.

5 cl, 14 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds (la) of formula applied as tyrosine kinase c-Met inhibitors. , where: LA is selected from ,

or ; RA is selected from:

or each RA2 and RA6 represents hydrogen; RA3 represents RAr; or RA3, RA4 and carbon atoms whereto attached form 6-members aryl, optionally substituted, in the amount up to 4 by independent groups RAr, or a 5-6-members heterocyclyl or heteroaryl ring containing at least one O, N or S atom; R represents -OH; RA5 represents hydrogen or RAr; LB represents a covalent bond or -N(R*)-; RB represents halogen, NH2 or C1-8aliphatic group, optionally substituted by R; a 6-10-members aryl ring; a 3-7-members carbocyclyl ring, a 5-10-members heteroaryl ring containing 1-4 heteroatoms independently selected from nitrogen, oxygen and sulphur atoms, where each said aryl or heteroaryl ring is optionally substituted, in the amount up to five by independent groups RAr; R represents halogen, -R°, -SR°, Ph, optionally substituted R° or -C(O)OR°; each RAr is independently selected from halogen, -R°, -OR°, -SR°, Ph, optionally substituted in the amount up to five by independent groups -R°, -CN, -N(R°)2 or -C(O)OR°; or two adjacent groups RAr taken together, represent 1,2-methylenedixy or 1,2-ethylenedixy; each R* represents hydrogen; and each R° represents independently hydrogen, an optionally substituted C1-6aliphatic radical or an unsubstituted 5-6-members heteroaryl or heterocyclic ring containing 1-3 heteroatoms independently selected from nitrogen, oxygen and sulphur atoms.

EFFECT: invention refers to pharmaceutically acceptable compositions containing the compounds under the invention, and methods of application of the compositions in treatment of various proliferative disorders.

10 cl, 4 tbl, 548 ex, 9 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: there is described new macrocyclic compound of general formula 1-c:

and its pharmaceutically acceptable acid or base addition salts or its stereoisomers (the radical values are presented in the patent claim).

EFFECT: producing the compounds which are hepatitis type C virus inhibitors and can find application in medicine.

9 cl, 1 tbl, 95 ex

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

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

Heterocompound // 2425832

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

or pharmaceutically acceptable salt thereof, where symbols assume the following values; ring denotes

or , X denotes a single bond, -CH2-, -NR3-, -O-, -S-, R1 denotes a halogen; phenyl; pyridyl; (C3-C8)cycloalkyl; or (C1-C6) alkyl or (C2-C6) alkenyl, each of which can contain a halogen, -CONH2, phenyl or (C3-C8)cycloalkyl as a substitute, R2 denotes CN, -O-(C1-C6)alkyl, -C(=O)H, halogen; or (C1-C6)alkyl, which can be substituted with a halogen or -OH, R3 can form morpholino or 1-pyrrolidinyl together with R1 and nitrogen, and when X denotes a single bond, R1 and R2 can jointly form a 5-member ring and additionally contain -(C1-C6)alkyl as a substitute, R4 denotes the following ring: , , , , , , , , , , or , where any one of the bonds in the ring is linked to an oxazole ring, R5 denotes -H, (C1-C6)alkyl, which can be substituted by not less than one group selected from: -C(=O)NRXRY, -NHRX and -ORX- (C2-C6)alkenyl-; -C(=O)H; -C(=O)NRXRY, RX and RY can be identical or different and denote -H; or (C1-C6)alkyl. The invention also relates to a pharmaceutical composition based on said compounds, having SlP1 agonist activity.

EFFECT: compounds and compositions can be used in medicine for preventing and treating rejection during organ transplant, bone marrow or tissue transplant and autoimmune diseases.

16 cl, 84 tbl, 198 ex