Nortropanos substituted urea Derivatives, medicaments containing these Compounds, their use in the treatment of diseases mediated by the inhibition of the Enzyme 11beta hydroxysteroid dehydrogenase and Process for its preparation.

摘要

In particular, these compounds are inhibitors of 11b hydroxydehydrogenase (HSD) 1 and are therefore 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. It also provides a process to get it. ILO Convention No. 1: compounds with formula (1) in which R1 represents arilo or heterosexual, while arilo is defined as phenyl or northwest Africa, heterosexual as pyrethrum, furan, tienilo, pirid Nile, indolillo, benzofurania, benzotiflofennilo, quinurinilo,Isopentylenediol, i.e. pyridol, pyridylene, furan, velvet, pyridylene, in each case, one or two CH groups are replaced by N or indilo, benzofurania, benzotinil, quinolino or isoquinol Nile, in each case, one to three ch groups are replaced by n. Heteromorphic group, one or two groups, n = ch, optionally replaced by - nh-co - and / or - n (tar C1-4) - Co,Although the above alternative heteromorphic and polycyclic arilo groups are partially saturated, they retain an aromatic or heteroaromatic substructure (1) linked to the carbide group in the formulation,In a partially saturated ring, one or two optional ch groups are replaced, regardless of O, s, NH, n (C1-4 tar),1. Carbonate or sulfur, wherein the above groups of arilo, heterosexual, arilo and partially saturated heterosexual can be replaced by one or more substitutes, preferably one to four R2 substitutes, all heterosexual groups are combined with nortrophan structure (1) through carbon atom; Independent of each other,represent hydrogen, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C3-6 cycloalkyl, (het) aryl, C1-4 alkylcarbonyl, C1-4 alkyloxycarbonyl, C1-4 alkylsulfonyl, (het) arylcarbonyl, (het ) arylsulfonyl, where each alkyl, alkenyl and alkynyl group is optionally also mono or polysubstituted with fluorine, and is optionally monosubstituted with hydroxy, C1-4 alkoxy, C1-4 alkylsulfanyl, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, amino, alkylamino C1-4, di- (C1-4 alkyl) amino, C1-4 alkylcarbonylamino, cyano, carboxy, C1-4 alkoxycarbonyl, aminocarbonyl, C1-4 alkylaminocarbonyl, di- (C1-4 alkyl) aminocarbonyl or (het) aryl; R2, independently of each other,represent halogen, nitro, cyano, hydroxy, C3-6 cycloalkyl, C3-6 cycloalkyloxy, tetrahydrofuran-3-yloxy, tetrahydropyran-3-yoxy, tetrahydropyran-4-yloxy, tetrahydrofuranyl-C1-3 alkyloxy, tetrahydropyranyl-C1-3 alkyloxy , (het) aryl, (het) aryloxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkyloxy, C1-6 alkylamino, where in each group a CH2 group is optionally replaced by carbonyl or sulfonyl , and where each group is optionally mono or polyfluorinated, and where each group is optionally further substituted with hydroxy, chloro, C1-3 alkyloxy, amino, C1-3 alkylamino, di- (C1-3 alkyl) -amino, pyrrolidin-1 -yl, 2-oxo-pyrrolidin-1-yl, piperidin-1-yl,2-oxo-piperidin-1-ilo morfolin-4-ilo 3-oxo-morfolin-4-ilo piperazin-1-ilo 2-oxo-piperazin-1-ilo 3-oxo-piperazin-1-ilo 4- (alquil ciano aminocarbonilo alquilaminocarbonilo C1-3 di- (alquil C1-3) -aminocarbonilo pirrolidin-1-ilcarbonilo piperidin-1-ilcarbonilo morfolin-4-ilcarbonilo piperazin-1-ilcarbonilo 4- (alquil C1-3) -piperazin-1 1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-erazin-1-ilo, (HET) arilcarbonibamino, C1-4 hydrocarbon formaldehyde, Aminomethylamine, c1-4-aminotoluene amide, hydrocarbonyl c1-4-aminotoluene amide (HET) arilaminocarbonilamino, di - (c1-3 tar) ammonium carbamate, pirrolidin-1-ilcboniamino, piperidin-1-ilcboniamino, morfolin-4-ilcboniamino, piperazin-1-ilcboniamine, 4 - (c1-3) - pirerazin-1-ilcboniamine, fonilamino-c13,- 1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1) carbon - (HET) arilcarboni lamino, 3) - 1-3) - 1 - (1 (HET) arilsulfonilamino,N- (C1-3 alkyl) - (het) aryl-C1-3 alkylsulfonylamino, carboxy, C1-3 alkyloxycarbonyl, aminocarbonyl, C1-3 alkylaminocarbonyl, di (C1-3 alkyl) -aminocarbonyl, azetidin-1-ylcarbonyl, pyrrolidine -1-ylcarbonyl, piperidin-1-yl-carbonyl, morpho-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4- (C1-3 alkyl) -piperazin-1-yl-carbonyl, (het) arylaminocarbonyl, N- ( C1-3 alkyl) - (het) aryl aminocarbonyl, (het) aryl C1-3 alkylaminocarbonyl, N- (C1-3 alkyl) - (het) aryl C1-3 alkylaminocarbonyl, (het) arylcarbonyl, C1- alkylsulfanyl 3, C1-3 alkylsulfinyl, (het) arylsulfonyl, tritluoromethylsulfanyl, trifluoromethylsulfinyl, aminosulfonyl, C1-3 alkylaminosulfonyl, di- (C1-3 alkyl) -aminosulfonyl,Pirrolidin-1-il-sulfonil, piperidin-1-ilsulfoni, morfolin-4-ilsulfoni, piperazin-1-ilsulfoni, 4 - (c1-3-tar) - piperazin-1-ilsulfoni, all of which can be replaced by one or two independent fluorinated groups, C1-3, alcoxi c1-3, alcoxi c1-3-c1-3-hydrocarbyl c1-3 and hydroxy; V is cy5y6, O NRN; W is absent or cy7y8 o (cy7y8) - (cy9y10);X absent or c118y12 o (c118y12) - (cy139y14);V and W can also be combined into a C3-6 cyclododecyl chemical group, which consists of two carbon atoms adjacent to the aza cycle, one or two CH2 groups can be replaced, whether or not replaced by O, s, NRN, carbonate or sulfuryl, and optionally partially unsaturated and, optionally monkey - or Polychlorinated biphenyls, preferably monomorphic, are modified to be tetrasexual and replaced by selected substitutes, regardless of R3; V and W can also be combined into one (HET) group, using figs with two carbon atoms associated with the aza cycle; R3 represents halogen, C1-4 tar, cyanogen, carboxi, C1-4 tar,aminocarbonyl, C1-3 alkylaminocarbonyl, di- (C1-3 alkyl) -aminocarbonyl, hydroxy, C1-4 alkoxy, amino, C1-3 alkylamino, di- (C1-3 alkyl) -amino, C1-4 alkylcarbonylamino, N- C1-3 alkyl-C1-4 alkylcarbonylamino and (het) aryl, wherein each above-mentioned alkyl group is optionally mono or poly substituted with fluorine, and optionally monosubstituted with hydroxy, C1-4 alkoxy, C1-4 alkylsulfanyl, C1 alkylsulfinyl -4, C1-4 alkylsulfonyl, amino, C1-3 alkylamino, di- (C1-3 alkyl) amino, C1-4 alkylcarbonylamino, cyano, carboxy, C1-4 alkoxycarbonyl, aminocarbonyl, C1-4 alkylaminocarbonyl, di- (C1-4 alkyl) -aminocarbonyl or (het) aryl; Y1 to Y14,which may be identical and / or different, independently of each other, represent hydrogen, halogen, nitro, cyano, hydroxy, C3-6 cycloalkyl, C3-6 cycloalkyloxy, tetrahydrofuran-3-yloxy, tetrahydropyran-3-yloxy, tetrahydropyran-4- yloxy, tetrahydrofuranyl-C1-3 alkyloxy, tetrahydropyranyl-C1-3 alkyloxy, (het) aryl, (het) aryloxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylamino, C1-6 alkylamino , where in each group, a CH2 group is optionally replaced by carbonyl or sulfonyl, and where each group is optionally mono or polyfluorinated, and where each group is optionally further substituted with hydroxy, chloro, C1-3 alkyloxy, amino, C1- alkyl 3-amino,di- (C1-3 alkyl) -amino, pyrrolidin-1-yl, 2-oxo-pyrrolidin-1-yl, piperidin-1-yl, 2-oxo-piperidin-1-yl, morpholin-4-yl, 3 -oxo-morpholin-4-yl, piperazin-1-yl, 2-oxo-piperazin-1-yl, 3-oxo-piperazin-1-yl, 4- (C1-3 alkyl) -piperazin-1-yl, 2-oxo-4- (C1-3 alkyl) -piperazin-1-yl, 3-oxo-4- (C1-3 alkyl) -piperazin-1-yl, carboxy, C1-3 alkyloxycarbonyl, cyano, aminocarbonyl , C1-3 alkylaminocarbonyl, di- (C1-3 alkyl) -aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4- (C1-3 alkyl) - piperazin-1-ylcarbonyl, C1-3 alkylcarbonyl, (het) arylcarbonylamino, C1-3 alkylsulfanyl, C1-3 alkylsulfinyl, C1-3 alkyl sulfonyl,cicloalquilo C3-6 (het) arilo o (het) ariloxi amino di- (alquil C1-3) amino pirrolidin-1-ilo 2-oxo-pirrolidin-1-ilo piperidin-1-ilo 2-oxo-piperidin-1-