Pharmaceutical compositions containing new or known 3-amino-azetidine derivatives having cannabinoid CB1 receptor antagonist activity, useful e.g. for treating central nervous system, respiratory or gastrointestinal disorders

摘要

Pharmaceutical compositions containing 1-(di(hetero)arylmethyl)-3-(substituted amino)-azetidine derivatives (I) are new. Pharmaceutical compositions contain azetidine derivatives of formula (I), or their optical isomers or mineral or organic acid addition salts, as active agents. R1 = NR4R5, N(R4)COR5 or N(R4)S2R6; R2, R3 = phenyl, naphthyl or indenyl (all optionally substituted (os) by one or more of halo, alkyl, alkoxy, CHO, OH, CF3, OCF3, -CO-alk, CN, COOH, COO-alkyl, CONR7R8, CONHNR9R10, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkyl or -alkyl-NR9R10), benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, pyrimidinyl, furyl, imidazolyl, isochromanyl, isoquinolyl, pyrrolyl, pyridyl, quinolyl, 1,2,3,4-tetrahydroisoquinolyl, thiazolyl or thienyl (all os by one or more of halo, alkyl, alkoxy, OH, CF3, OCF3, CN, COOH, COO-alk, CONR7R8, CONHNR9R10, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkyl or -alkyl-NR9R10); R4 = -C(R11)(R12)-Het, Het, -C(R11)(R12)-Ar, Ar, cycloalkyl or norbornyl; R5 = H, hydroxyalkyl, -alk-COO-alkyl, -alk-CONR7R8, -alk-NR7R8, alkoxy, Ar, Het, CH2Ar, CH2Ar or alkyl (os by one or more halo); R6 = as R5 but not H; R7, R8 = H or alkyl; or NR7R8 = 3-10 membered saturated mono- or bicyclic heterocycle, optionally containing another O, S or N heteroatom and os by one or more alkyl; R9, R10 = H, alkyl, COO-alk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl; or NR9R10 = 3-10 membered saturated mono- or bicyclic heterocycle, optionally containing another O, S or N heteroatom and os by one or more of alkyl, -CO-alk, -COO-alk, -CONH-alk, -CSNH-alk, oxo, hydroxyalkyl, -alk-O-alk or CONH2; R11 = H, hydroxyalkyl, -alk-COO-alkyl, -alk-CONR7R8, -alk-NR7R8, alkoxyalkyl, Ar, Het, CH2Ar, CH2Ar or alkyl (os by one or more halo); R12 = as R11 but not H; or CR11R12 = 3-10 membered saturated mono- or bicyclic ring system, optionally containing an O, S or N heteroatom and os by one or more alkyl; Ar = phenyl, naphthyl or indenyl (all os by one or more of halo, alkyl, alkoxy, -CO-alk, CN, COOH, COO-alk, CONR7R8, CONHNR7R8, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, -alk-NR7R8, NR7R8, alkylthioalkyl, CHO, OH, hydroxyalkyl, Het, -O-alk-NH-cycloalkyl, OCF3, CF3, -NHCO-alk, SO2NH2, NHCOMe, NHCOO-alk, Het or OCH2O (linked to two adjacent C)); Het = 3-10 membered saturated or unsaturated mono- or bicyclic heterocycle, containing one or more O, S or N heteroatom(s) and os by one or more alkyl, alkoxy, halo, alkoxycarbonyl, oxo or OH (N-containing heterocycles optionally being in N-oxide form); alk = alkyl or alkylene; Alkyl or alkylene moieties have 1-6C and cycloalkyl moieties have 3-10C. Independent claims are also included for: (1) (I) (including optical isomers and salts) as new compounds, with the exception of (I; R1 = N(Ph)SO2Me; R2, R3 = Ph); and (2) the preparation of the new compounds (I).