Patent ID: 6174909
Filing Date: 2001-01-16
Classification: A61P,C07D

Abstract:
A 4-aminotetrahydrobenzisothiazole compound having the general formula Ia or Ib: ##STR12##wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of:A) hydrogen, cycloalkyl, phenyl, or a group ##STR13##where R.sup.7, R.sup.8 and R.sup.9 areindependently selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, phenyl, phenyl-lower alkyl, phenoxy-lower alkyl and heteroaryl selected from 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, imidazolyl, oxazolyl, pyrazolyl, pyrimidinyl, pyrrolyl, thiazolyl, 1,2,4-triazolyl, 2-pyridyl, 3-pyridyl and 4-pyridyl, any phenyl or heteroaryl group present optionally being substituted with one or two substituents selected from halogen, lower alkyl, lower alkoxy, hydroxy, nitro, lower alkylthio, lower alkylsulfonyl, lower alkyl- or di(lower)alkylamino, cyano, trifluoromethyl, trifluoromethylthio, trifluoro-methylsulfonyloxy and phenyl which again may be substituted with halogen, methyl, methoxy or trifluoromethyl; and any alkyl group present being optionally substituted with one to three hydroxy groups which again are optionally esterified with a C.sub.2-18 carboxylic acid;B) a group of general formula Y--(CH.sub.2).sub.r --(CHR.sup.11).sub.s --(CH.sub.2).sub.t -- wherein Y is selected from the following groups (1)-(5): ##STR14##wherein U is CHR.sup.10b, NR.sup.10b, O or S; U.sup.1 is NR.sup.10b, O or S; p is 0 or 1; q is 0 or 1; V is C or N and the dotted line represents a bond when V is C and no bond when V is N;A is O, S, CH.sub.2, (CH.sub.2).sub.2, CH.dbd.CH--CH.sub.2, (CH.sub.2).sub.3, CH.dbd.CH or O--CH.sub.2 ;R.sup.a and R.sup.b each represent one or more substituents selected from hydrogen halogen, lower alkyl, lower alkoxy, hydroxy, nitro, lower alkylthio, lower alkylsulfonyl, lower alkyl- or di(lower alkyl)amino, cyano, trifluoromethyl, trifluoromethylsulfonyloxy and trifluoromethylthio;r and t are independently 0, 1, 2 or 3, s is 0 or 1, provided that when Y is a group (1) wherein U is NR.sup.10b, O or S or a group (4), then r+s+t is at least 2; and when Y is a group (3) or a group (5) where V is N, then r+s+t is at least 1; R.sup.7b, R.sup.8b and R.sup.9b are as defined for R.sup.7, R.sup.8 and R.sup.9 in A) provided that they are not at the same time selected from hydrogen, lower alkyl, lower alkenyl and lower alkynyl;R.sup.10b and R.sup.11 are independently hydrogen, lower alkyl, lower alkenyl or lower alkynyl; andC) a group of the general formula Y.sup.c --(CH.sub.2).sub.n --W--(CH.sub.2).sub.m -- wherein n is 1, 2 or 3, m is 2 or 3; W is O or S; and Y.sup.c is a group (1)-(5) as defined in B) provided that n may not be 1, when Y.sup.c is a group (1) or (4) wherein U or U.sup.1, respectively, is NR.sup.10b, S or O;D) a group of the general formula ##STR15##wherein k is 0, 1, 2 or 3;e is 0, 1, 2 or 3; R.sup.11d is as defined for R.sup.11 in B) above; andY.sup.d is selected from the groups (2) and (5) as defined in B) above and the following groups (6)-(10): ##STR16##wherein p, q, R.sup.a, R.sup.b, and A are as defined in B) and R.sup.7d -R.sup.10d and R.sup.11d are asdefined for R.sup.7b -R.sup.11b and R.sup.11, respectively, under B) or R.sup.1 and R.sup.2 together designate alkylene thereby forming a 4-8 membered nitrogen containing ring; orone of R.sup.1 and R.sup.2 is a group R.sup.2' OCO wherein R.sup.2 is phenyl, or heteroaryl as defined in A) above or phenyl or such heteroaryl substituted with one or more substituents selected from halogen, lower alkyl, lower alkoxy, hydroxy, nitro, lower alkylthio, lower alkylsulfonyl, lower alkyl- or di(lower)alkylamino, cyano, trifluoromethyl, trifluoromethylthio, trifluoromethylsulfonyloxy, phenyl and phenyl substituted with halogen, methyl, methoxy or trifluoromethyl;R.sup.3 -R.sup.6 are independently selected from hydrogen, hydroxy and lower alkyl, any alkyl group optionally being substituted with one or two hydroxy groups;X is sulfur;P is hydrogen or a group ZR whereinZ is CO, CS, SO.sub.2 or CR.sup.t R.sup.u, R.sup.t and R.sup.u being hydrogen, hydroxy or lower alkyl, and if Z is CO or CS, then R is selected from the groups consisting of:i) hydrogen, C.sub.1 -C.sub.18 alkyl, C.sub.2 -C.sub.18 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkenyl or C.sub.4 -C.sub.26 cycloalkenyl-alkenyl, optionally substituted with one or two hydroxy groups, or phenyl optionally substituted with one or more substituents selected from the group consisting of halogen, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.5 acyloxy, and cyano; orii) QRV, wherein Q is O or S and R.sup.v is selected from the substituents defined for R under i) above; andiii) NR.sup.x R.sup.y, wherein R.sup.x and R.sup.y independently are selected from the substituents defined for R under i) above or R.sup.x and R.sup.y are combined to form a four to eight membered heterocyclic ring containing from one to three nitrogen atoms and from zero to three oxygen or sulfur atoms; orif Z is CR.sup.t R.sup.u, R is selected from the groups consisting of:iv) a group QR.sup.v as defined in ii);v) a group NR.sup.x R.sup.y as defined in iii); orvi) a group OC(O)R.sup.z, SC(O)R.sup.z, OC(S)R.sup.z or SC(S)R.sup.z wherein R.sup.z is selected from the substitutents defined for R under i) above;if Z is SO.sup.2, R is selected from group i) defined above;or a pharmaceutically acceptable salt thereof.