Patent ID: 6153628
Filing Date: 2000-11-28
Classification: A61P,C07D

Abstract:
A compound of the formula ##STR21## or pharmaceutically acceptable salts thereof, wherein: R.sup.1 is selected from: ##STR22## G is selected from O or S; R.sup.2 and R.sup.3 are independently selected from: H, C.sub.1 -C.sub.4 alkoxy, NR.sup.11 R.sup.12, .dbd.NR.sup.12, halogen, NO.sub.2, CN, CF.sub.3, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, C.sub.6 -C.sub.10 aryl, C.sub.7 -C.sub.11 arylalkyl, C.sub.2 -C.sub.7 alkylcarbonyl, or C.sub.7 -C.sub.11 arylcarbonyl;U is selected from:--(CH.sub.2).sub.n --,--(CH.sub.2).sub.n N(R.sup.12)(CH.sub.2).sub.m --, or--(CH.sub.2).sub.n NHNH(CH.sub.2).sub.m --;V is selected from:--(CH.sub.2).sub.n --,--(C.sub.1 -C.sub.6 alkylene)--Q--, substituted with 0-3 groups independently selected from R.sup.13,--(C.sub.2 -C.sub.7 alkenylene)--Q--, substituted with 0-3 groups independently selected from R.sup.13,--(C.sub.2 -C.sub.7 alkynylene)--Q--, substituted with 0-3 groups independently selected from R.sup.13, or--(phenyl)--Q--, wherein said phenyl is substituted with 0-2 groups independently selected from R.sup.13 ;Q is selected from:--(CH.sub.2).sub.n --,--(CH.sub.2).sub.n O(CH.sub.2).sub.m --, or--(CH.sub.2).sub.n N(R.sup.12)(CH.sub.2).sub.m --;W is selected from:--(CH.sub.2).sub.q C(.dbd.O)N(R.sup.10)--, --SCH.sub.2 C(.dbd.O)N(R.sup.10)--, or--C(.dbd.O)--N(R.sup.10)--(CH.sub.2).sub.q --;X is selected from:--(CH.sub.2).sub.q --CH(R.sup.8)--CH(R.sup.9) --(CH.sub.2).sub.q --CH(CH.sub.2 R.sup.9) or --CH.sub.2 --;R.sup.5 is selected from: H, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.7 -C.sub.14 bicycloalkyl, hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 alkylsulfonyl, nitro, C.sub.1 -C.sub.6 alkylcarbonyl, C.sub.6 -C.sub.10 aryl, --N(R.sup.11)R.sup.12 ; halo, CF.sub.3, CN, C.sub.1 -C.sub.6 alkoxycarbonyl, carboxy, piperidinyl, morpholinyl or pyridinyl;R.sup.6 is selected from:H, C.sub.1 -C.sub.4 alkyl, hydroxy, C.sub.1 -C.sub.4 alkoxy, nitro, C.sub.1 -C.sub.6 alkylcarbonyl, --N(R.sup.11)R.sup.12, cyano, halo, --S(O)mR.sup.10, CO.sub.2 R.sup.10, OR.sup.10,C.sub.6 to C.sub.10 aryl optionally substituted with 1-3 groups selected from halogen, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkyl, CF.sub.3, S(O).sub.m Me, or --NMe.sub.2 ;methylenedioxy when R.sup.6 is a substituent on aryl, or a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, isoxazolinyl, isoxazolyl, or morpholinyl;R.sup.8 is selected from:H,C.sub.1 -C.sub.10 alkyl, substituted with 0-3 R.sup.6,C.sub.2 -C.sub.10 alkenyl, substituted with 0-3 R.sup.6,C.sub.2 -C.sub.10 alkynyl, substituted with 0-3 R.sup.6,C.sub.3 -C.sub.8 cycloalkyl, substituted with 0-3 R.sup.6,C.sub.5 -C.sub.6 cycloalkenyl, substituted with 0-3 R.sup.6,aryl, substituted with 0-3 R.sup.6,a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, isoxazolinyl, isoxazolyl or morpholinyl;R.sup.9 is selected from: H, hydroxy, C.sub.1 -C.sub.10 alkoxy, N(R.sup.10)R.sup.11, or --N(R.sup.16)R.sup.17 ;R.sup.10 is selected from H or C.sub.1 -C.sub.10 alkyl substituted with 0-2 R.sup.5 ;R.sup.11 is selected from hydrogen, hydroxy, C.sub.1 to C.sub.8 alkyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 to C.sub.11 cycloalkyl, C.sub.4 to C.sub.11 cycloalkylmethyl, C.sub.1 -C.sub.6 alkoxy, benzyloxy, C.sub.6 to C.sub.10 aryl, heteroaryl, heteroarylalkyl, C.sub.7 to C.sub.11 arylalkyl, adamantylmethyl, or C.sub.1 -C.sub.10 alkyl substituted with 0-2 R.sup.5 ;alternatively, R.sup.10 and R.sup.11 when both are substituents on the same nitrogen atom (as in --NR.sup.10 R.sup.11) can be taken together with the nitrogen atom to which they are attached to form a heterocycle selected from: 3-azabicyclononyl, 1,2,3,4-tetrahydro-1-quinolinyl, 1,2,3,4-tetrahydro-2-isoquinolinyl, 1-piperidinyl, 1-morpholinyl, 1-pyrrolidinyl, thiamorpholinyl, thiazolidinyl or 1-piperazinyl; said heterocycle being optionally substituted with 1-3 groups selected from: C.sub.1 -C.sub.6 alkyl, C.sub.6 -C.sub.10 aryl, heteroaryl, C.sub.7 -C.sub.11 arylalkyl, C.sub.1 -C.sub.6 alkylcarbonyl, C.sub.3 -C.sub.7 cycloalkylcarbonyl, C.sub.1 -C.sub.6 alkoxycarbonyl, C.sub.7 -C.sub.11 arylalkoxycarbonyl, C.sub.1 -C.sub.6 alkylsulfonyl or C.sub.6 -C.sub.10 arylsulfonyl;R.sup.12 is selected from:H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.6 alkylcarbonyl, C.sub.1 -C.sub.6 alkylsulfonyl, aryl(C.sub.1 -C.sub.4 alkyl)sulfonyl, arylsulfonyl, aryl, heteroarylcarbonyl, or heteroarylalkylcarbonyl, wherein said aryl groups are substituted with 0-3 substituents selected from the group consisting of: C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, CF.sub.3, and NO.sub.2 ;R.sup.13 is selected from H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl, C.sub.1 -C.sub.10 alkoxy, aryl, heteroaryl or C.sub.1 -C.sub.10 alkoxycarbonyl, CO.sub.2 R.sup.10 or --C(.dbd.O)N(R.sup.10)R.sup.11 ;R.sup.16 is selected from:--C(.dbd.O)--O--R.sup.18a,--C(.dbd.O)--R.sup.18b,--SO.sub.2 --R.sup.18a,--SO.sub.2 --N(18.sup.b).sub.2 ;R.sup.17 is selected from H or C.sub.1 -C.sub.4 alkyl;R.sup.18a is selected from:C.sub.1 -C.sub.8 alkyl substituted with 0-2 R.sup.19,C.sub.2 -C.sub.8 alkenyl substituted with 0-2 R.sup.19,C.sub.2 -C.sub.8 alkynyl substituted with 0-2 R.sup.19,C.sub.3 -C.sub.8 cycloalkyl substituted with 0-2 R.sup.19,aryl substituted with 0-4 R.sup.19,aryl(C.sub.1 -C.sub.6 alkyl)- substituted with 0-4 R.sup.19, a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, benzofuranyl, indolyl, indolinyl, quinolinyl, isoquinolinyl, isoxazolinyl, isoxazolyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyrimidinyl, 3H-indolyl, carbazolyl, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-4 R.sup.19 ;C.sub.1 -C.sub.6 alkyl substituted with a heterocyclic ring system selected from pyridinyl, furanyl, thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolinyl, isoxazolyl, benzofuranyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, tetrahydrofuranyl, pyranyl, pyridinyl, 3H-indolyl, indolyl, carbazole, pyrrolidinyl, piperidinyl, indolinyl, or morpholinyl, said heterocyclic ring being substituted with 0-4 R.sup.19 ;R.sup.18b is selected from R.sup.18a or H;R.sup.19 is selected from: H, halogen, CF.sub.3, CN, NO.sub.2, NR.sup.11 R.sup.12, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)--, C.sub.1 -C.sub.6 alkoxy, or C.sub.1 -C.sub.4 alkoxycarbonyl;R.sup.20 is selected from:hydroxy;C.sub.1 to C.sub.10 alkoxy;methylcarbonyloxymethoxy-,ethylcarbonyloxymethoxy-,t-butylcarbonyloxymethoxy-,cyclohexylcarbonyloxymethoxy-,1-(methylcarbonyloxy)ethoxy-,1-(ethylcarbonyloxy)ethoxy-,1-(t-butylcarbonyloxy)ethoxy-,1-(cyclohexylcarbonyloxy)ethoxy-,i-propyloxycarbonyloxymethoxy-,t-butyloxycarbonyloxymethoxy-,1-(i-propyloxycarbonyloxy)ethoxy-,1-(cyclohexyloxycarbonyloxy)ethoxy-,1-(t-butyloxycarbonyloxy)ethoxy-,dimethylaminoethoxy-,diethylaminoethoxy-,(5-methyl-1,3-dioxacyclopenten-2-on-4-yl)methoxy-,(5-(t-butyl)-1,3-dioxacyclopenten-2-on-4-yl)methoxy-,(1,3-dioxa-5-phenyl-cyclopenten-2-on-4-yl)methoxy-,1-(2-(2-methoxypropyl)carbonyloxy)ethoxy-,R.sup.21 is selected from C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11, cycloalkyl, C.sub.4 -C.sub.11 cycloalkylmethyl, C.sub.6 -C.sub.10 aryl, C.sub.7 -C.sub.11 arylalkyl, or C.sub.1 -C.sub.10 alkyl substituted with 0-2 R.sup.5 ;m is 0-2;n is 0-2;p is 0-2;q is 0-1; andr is 0-2;with the proviso that when V is -(phenyl)--Q--, then either: U is not a direct bond or Q is not a direct bond.