Derivatives of aryl and heteroarilcarbonilo benzomorfanos and related Structures, Pharmaceutical compositions containing such Compounds, obtaining the same, their use in the treatment of diseases mediated by the inhibition of the Enzyme 11beta hydroxysteroid dehydrogenase (HSD) 1 and

摘要

Formula compounds with pharmacological activity (1), especially compounds that inhibit 11b hydroxycholesterol dehydrogenase (HSD 1), are suitable for the treatment and prevention of diseases that may be affected by this enzyme inhibition, such as new and old metabolic diseases, Especially type 2 diabetes, obesity and degreasing. Contains their pharmaceutical ingredients and obtains them. Item 1: those compounds with the formula (1) characteristic of R1 representing arilo or heterosexual, arilo is defined as phenyl or northwest non phenyl, while heterosexual is defined as pyrethroid and furan,thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, quinolinyl, isoquinolinyl, or pyrrolyl, furanyl, thienyl, pyridyl where 1 or 2 CH is replaced by N, or indolyl, benzofuranyl, benzothiotenyl, quinolinyl, or isoquinolinyl, where 1 to 3 CH is replace with N, or 1,2-dihydro-2-oxo-pyridinyl, 1,4-dihydro-4-oxo-pyridinyl, 2,3-dihydro-3-oxo-pyridazinyl, 1,2,3,6-tetrahydro -3,6-dioxo-pyridazinyl, 1,2-dihydro-2-oxo-pyrimidinyl, 3,4-dihydro-4-oxo-pyrimidinyl, 1,2,3,4-tetrahydro-2,4-dioxo-pyrimidinyl 1,2-dihydro-2-oxo-pyrazinyl, 1,2,3,4-tetrahydro-2,3-dioxo-pyrazinyl, indanyl, 1-oxo-indanyl, 2,3-dihydro-indolyl, 2,3 -dihydro-1H-isoindolyl, 2,3-dihydro-2-oxo-indolyl,4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 o-quinine, 1, 2-dihydro-2-oxo-quinine, 1, 4-dihydro-4-oxo-quinolini, 1, 2, 3, Methyldi, 1, 1, 1, 1, 2, 1, 2, 2, 2, 2, 1, 2, 2, 2, 2, 2, 2, 2, 2, 3, 4-tetrahydro-3-oxo-quinoxalini,Nile, one of which can replace one or four or four or four kinds of replaceable foreign matters, one or four of which can replace four or four kinds of substitutes, one or four of which can replace one or four kinds of page: 1 R2 and R3, together with the two bonds connected to them, represent an optional benzo ring, replaced by R7, R8 and R9, an optional Pirlo ring, replaced by R7, R8 and R9, a pirrolo, furo, tieno, piridizino ring,Pyridine or pyridine is selectively substituted by two alternatives selected from R7, R8 and R9, one is substituted by R7, one is substituted by pyridan, pyridan, oxazolo, thiazolo, isoxazolo or isodiazole, or one is substituted by C1-4 or phenyl ring 1, 2, 3-triazolo - 4-ilo, morfolin-4-4-ilo, 3-ox1-1-1-1-1-1-1-1-1-ox1-1-ilo, 2-1-oxo-piperazin-1-ilo,- 1-1-1-1-1-1-1-1-1-1 - (1-1-1-1-1-1-1-1-1-1-1-1-oxo-4 - (c1-3 tar) - piperazin-1-ilo, c1-3 carboniamino tar, 1, 1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-il-carboniamino,C1-3alkyl sulfonylamino, aminosulfonylamino, C1-3alkylamino-sulfonylamino, di- (C1-3alkyl) amino-sulfonylamino, pyrrolidin-1-yl-sulfonylamino, piperidin-1-yl-sulfonylamino, morpholin-4-yl-sulfonylamino , piperazin-1-yl-sulfonylamino, 4- (C1-3alkyl) -piperazin-1-yl-sulfonylamino, (C1-3alkyloxy-carbonylamino) carbonylamino, (het) arylsulfonylamino, (het) aryl-C1-3alkyl -sulfonylamino, N- (C1-3alkyl) -C1-3alkyl-carbonylamino, N- (C1-3alkyl) - (het) arylcarbonylamino, N (C1-3alkyl) - (het) aryl-C1-3alkyl -carbonylamino, N- (C1-3alkyl) -C1-3alkyloxycarbonylamino, N- (aminocarbonyl) -C1-3alkylamino, N- (C1-3alkyl-aminocarbonyl-C1-3alkylamino,N- [di- (C1-3alkyl) aminocarbonyl] -C1-3alkylamino, N- (C1-3alkyl) -C1-3alkyl-sulfonylamino, N- (C1-3alkyl) - (het) arylsulfonylamino, N - (C1-3alkyl) - (het) aryl-C1-3alkyl-sulfonylamino, oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl, 2,5-dioxo-imidazolidin-1- yl, 2-oxo-hexahydropyrimidin-1-yl, where the nitrogen atom at position 3 of the groups mentioned above is optionally substituted with methyl or ethyl, cyano, carboxy, C1-3alkyloxy-carbonyl, aminocarbonyl, C1- alkyl 3-aminocarbonyl, di- (C1-3alkyl) -aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin1-yl-carbonyl, morpholin-4-yl-carbonyl, piperazin-1-yl-carbonyl,4- (C1-3alkyl) -piperazin-1-yl-carbonyl, (het) arylaminocarbonyl, N- (C1-3alkyl) - (het) arylaminocarbonyl, (het) aryl-C1-3alkylaminocarbonyl, N- (alkyl C1-3) - (het) aryl-C1-3alkylaminocarbonyl, C1-3alkyl-carbonyl, (het) aryl-carbonyl, carboxy-C1-3alkyl, C1-3alkyloxy-C1-3alkyl-alkyl, cyano- C1-3alkyl, aminocarbonyl-C1-3alkyl, C1-3alkyl-aminocarbonyl-C1-3alkyl, di- (C1-3alkyl) -aminocarbonyl-C1-3alkyl, pyrrolidin-1-yl-carbonyl-C1-alkyl -3, piperidin-1-yl-carbonyl-C1-3alkyl, morpholin-4-yl-carbonyl-C1-3alkyl, piperazin-1-yl-carbonyl-C1-3alkyl, 4- (C1-3alkyl) -piperazin-1-yl-carbonyl-C1-3alkyl, carboxy-C1-3alkyloxy,1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-2-1-1-1-1 -- 1-carbon-c1-3 tar, 1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-13, 2-oxo-piperidin-1-il-tar c1-3, Mofflin-4-1-tar c1-3,3-oxo-morpholin-4-yl-C1-3-alkyl, piperazin-1-yl-C1-3-alkyl, 2-oxo-piperazin-1-yl-C1-3-alkyl, 3-oxo-piperazin-1-yl -C1-3alkyl, 4- (C1-3alkyl) -piperazin-1-yl-C1-3alkyl, 2-oxo-4- (C1-3alkyl) -piperazin-1-yl-C1-3alkyl, 3-oxo-4- (C1-3alkyl) -piperazin-1-iI-C1-3alkyl, C1-3alkylcarbonylamino-C1-3alkyl, arylcarbonylanyl-C1-3alkyl, hydroxy-C1-3alkyloxy, C1-alkyloxy -3-C1-3 alkyloxy, C1-3 alkylsulfanyl-C1-3 alkyloxy, C1-3 alkylsulfinyl-C1-3 alkyloxy, C1-3 alkylsulfonyl-C1-3 alkyloxy, amino-C1-3 alkyloxy, C1-3 alkylamino- C1-3 alkyloxy, di- (C1-3 alkyl) -amino-C1-3 alkyloxy, pyrrolidin-1-yl-C1-3 alkyloxy, 2-oxo-pyrrolidin-1-yl-C1-3 alkyloxy,piperidin-1-yl-C1-3 alkyloxy, 2-oxo-piperidin-1-yl-C1-3 alkyloxy, morpholin-4-yl-C1-3 alkyloxy, 3-oxo-morpholin-4-yl-C1-alkyloxy 3, piperazin-1-yl-C1-3 alkyloxy, 2-oxo-piperazin-1-iI-C1-3 alkyloxy, 3-oxo-piperazin-1-yl-C1-3 alkyloxy, 4- (C1-3 alkyl ) -piperazin-1-yl-C1-3alkyloxy, 2-oxo-4- (C1-3alkyl) -piperazin-1-yl-C1-3alkyloxy, 3-oxo-4- (C1-3alkyl) - piperazin-1-yl-C1-3 alkyloxy, C1-3 alkylsulfanyl, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, C1-3 alkylsulfonyloxy, (het) arylsulfonyl, (het) arylsulfonyloxy, trifluoromethylsulfanyl, trifluoromethylsulfinyl, trifluoromethylsulfonyl, aminosulphonyl, C1-3-aminosuIfoniIo, di- (C1-3alkyl) -aminosulfonyl,Fluoro-1-1-fluoro-1-yl-1-fluoro-fluoro-1, fluoro-1-1 trifluoromethyl (ethyl) 1-1-1-1-1-1-1-1-1-1-1-1-1, tetrahydrooxyoxyoxy anil-c1-3, tetrahydropyridine tar Xi C1-3donde los restos azetidin-1-ilo pirrolidin-1-ilo y piperidin-1-ilo mencionados anteriormente est n opcionalmente sustituidos con uno o dos grupos seleccionados entre metilo etilo metoximetilo hidroxi o metoxi y donde los restos piperazin-1-ilo y morfolin- benzothiophenyl, quinolinyl, isoquinolinyl where 1 to 3 CH is replaced by N, or 1,2-dihydro-2-oxo-pyridinyl, 1,4-dihydro-4-oxo-pyridinyl, 2,3-dihydro-3-oxo- pyridazinyl, 1,2,3,6-tetrahydro-3,6-dioxo-pyridazinyl, 1,2-dihydro-2-oxo-pyrimidinyl, 3,4-dihydro-4-oxo-pyrimidinyl, 1,2,3, 4-tetrahydro-2,4-dioxo-pyrimidinyl, 1,2-dihydro-2-oxo-pyrazinyl, 1,2,3,4-tetrahydro-2,3-dioxo-pyrazinyl, 2,3-dihydro-2- oxo-indolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydro-2-oxo-1H-benzimidazolyl, 2,