Patent RU-2119917-C1 (RU)
Inventor: FRANSI BART
IPC: A61K31/415
Filed: 1993-06-22
Granted: 1998-10-10
Abstract: FIELD: organic chemistry and chemical technology. SUBSTANCE: invention relates to derivatives of pyrazole of the general formula (I), where g 2 ,g 3  and g 6  are hydrogen; g 4  is chlorine or bromine atom, (C 1 -C 3 )-alkyl, trifluoromethyl or phenyl; g 5  is hydrogen or chlorine atom; W 2 ,W 3 ,W 5  and W 6  are hydrogen or chlorine atom; W 4  is hydrogen, chlorine atom, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-alkoxy or nitro-group; X is direct bond or -(CH 2 ) n -N(R 3 )--alkyl, where R 3 - hydrogen or (C 1 -C 3 )- alkyl; n = 0 or 1; R 4  is hydrogen or (C 1 -C 3 )-alkyl. When X means direct bond then R is a group -NR 1 R 2  where R 1  is hydrogen, (C 1 -C 6 )-alkyl or cyclohexyl and R 2  is (C 1 -C 6 )-alkyl, nonaromatic carbocyclic radical C 3 -C 15  possibly substituted with hydroxyl group, one or some (C 1 -C 5 )-alkyls, (C 1 -C 5 )-alkoxy-group or halogen; group amino-(C 1 -C 4 )-alkyl where amino-group can be substituted with (C 1 -C 3 )-alkyl, cyclohexyl- -(C 1 -C 3 )-alkyl; free phenyl or that substituted with halogen or (C 1 -C 5 )-alkyl; phenyl-(C 1 -C 3 )-alkyl, diphenyl-(C 1 -C 3 )-alkyl, saturated heterocyclic radical taken from pyrrolidinyl, piperidyl, hexahydroazepine, morpholinyl, quinuclidinyl and oxabicycloheptinyl being the latter can be free or substituted with (C 1 -C 3 )-alkyl or benzyl; 1-adamantanylmethyl; (C 1 -C 3 )-alkyl substituted with aromatic heterocycle taken from pyrrolyl, pyridyl or indolyl being the latter can be free or substituted with (C 1 -C 5 )-alkyl; or R 1  and R 2  form with nitrogen atom with which they are bound pyrrolidinyl, piperidyl or morpholinyl; or group R 5  that means phenyl-(C 1 -C 3 )-alkyl that can be free or substituted with  -alkyl; cyclohexyl-(C 1 -C 3 )-alkyl or 2-norbornylmethyl; when X means group (CH 2 ) n (R 3 ) then R means group R 2a  that means nonaromatic carbocyclic radical C 3 -C 15 ; phenyl substituted with halogen; phenyl-(C 1 -C 3 )-alkyl possibly substituted with halogen; indolyl possibly substituted with (C 1 -C 5 )-alkoxy-group; anthracenyl; or group NHR 2b  where R 2b  is cyclohexyl, adamantyl, phenyl that can be free or substituted with one or two halogen atoms, (C 1 -C 5 )-alkyl or (C 1 -C 5 )-alkoxy-group or their acid-additive salts. Compounds of the formula (I) are synthesized by interaction of the corresponding derivatives of 3-pyrazole carboxylic acid with amine of the formula NHR 1 R 2  where R 1  and R 2  are given above, or with primary amine R 3 NH 2  where R 3  has values indicated above. Synthesized intermediate amide is reduced to the corresponding intermediate aminomethyl-derivative which is subjected for interaction with acid R 2a COCl chloroanhydride where R 2a  is indicated above, or with isocyane R 2b N=C=O where R 2b  is indicated above. The end compounds are synthesized also by interaction of the corresponding derivatives of 3-pyrazole carboxylic acid with derivative of diphenylphosphorylazide and an intermediate amine is obtained. The latter is treated if necessary with alkylating agent to obtain secondary amine and obtained intermediate amines are subjected for interaction with acid R 2a COCl chloroanhydride or with isocyanate R 2b N=C=O where R 2a  and R 2b  are indicated above. The end ketone derivatives of pyrazole are synthesized by interaction of derivatives of 3-pyrazole carboxylic acid with compound of the formula R 5 MnX 1  where R 5  is indicated above; X 1  is halogen. Compounds of the formula (I) show affinity to cannabinoid receptors. Invention proposes also pharmaceutical composition showing above indicated activity and containing 0.5-1000 mg compound of the formula (I) as an active component per a dose unit. Invention relates to also intermediate derivatives of 3-pyrazole carboxylic acid of the formula (II) where R′ is hydrogen or (C 1 -C 5 )-alkyl. EFFECT: improved method of synthesis, enhanced effectiveness of compounds synthesized. 19 cl, 192 ex, 20 tbl