Patent ID: 6114328
Filing Date: 2000-09-05
Classification: A61P,C07D

Abstract:
A compound of Formula I: ##STR380## or pharmaceutically acceptable salt form thereof wherein: b is a carbon-carbon single or double bond;R.sup.1 is selected from R.sup.2 (R.sup.3)N(CH.sub.2).sub.q Z--, R.sup.2 (R.sup.3)N(R.sup.2 N.dbd.)CN(R.sup.2)(CH.sub.2).sub.q Z--, piperazinyl--(CH.sub.2).sub.q Z-- or ##STR381## Z is selected from O, S, S(.dbd.O), or S(.dbd.O).sub.2 ; R.sup.2 and R.sup.3 are independently selected from: H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 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, C.sub.6 -C.sub.10 arylcarbonyl, C.sub.2 -C.sub.10 alkoxycarbonyl, C.sub.4 -C.sub.11 cycloalkoxycarbonyl, C.sub.7 -C.sub.11 bicycloalkoxycarbonyl, C.sub.6 -C.sub.10 aryloxycarbonyl, aryl(C.sub.1 -C.sub.10 alkoxy)carbonyl, C.sub.1 -C.sub.6 alkylcarbonyloxy(C.sub.1 -C.sub.4 alkoxy)carbonyl, C.sub.6 -C.sub.10 arylcarbonyloxy(C.sub.1 -C.sub.4 alkoxy)carbonyl, C.sub.4 -C.sub.11 cycloalkylcarbonyloxy(C.sub.1 -C.sub.4 alkoxy)carbonyl;U is selected from:a single bond,--(C.sub.1 -C.sub.7 alkyl)--,--(C.sub.2 -C.sub.7 alkenyl)--,--(C.sub.2 -C.sub.7 alkynyl)--,--(aryl)--substituted with 0-3 R.sup.6a, or--(pyridyl)--substituted with 0-3 R.sup.6a ;V is selected from:a single bond;--(C.sub.1 -C.sub.7 alkyl)--, substituted with 0-3 groups independently selected from R.sup.6 or R.sup.7 ;--(C.sub.2 -C.sub.7 alkenyl)--, substituted with 0-3 groups independently selected from R.sup.6 or R.sup.7 ;--(C.sub.2 -C.sub.7 alkynyl)--, substituted with 0-2 groups independently selected from R.sup.6 or R.sup.7 ;-(aryl)-, substituted with 0-2 groups independently selected from R.sup.6 or R.sup.7 ;-(pyridyl)-, substituted with 0-2 groups independently selected from R.sup.6 or R.sup.7 ; or-(pyridazinyl)-, substituted with 0-2 groups independently selected from R.sup.6 or R.sup.7 ;W is selected from:a single bond,--(C.sub.1 -C.sub.7 alkyl)-,--(C.sub.2 -C.sub.7 alkenyl)-,--(C.sub.2 -C.sub.7 alkynyl)-, or--(C(R.sup.5).sub.2).sub.n C(.dbd.O) N(R.sup.5a)--;X is selected from:a single bond;--(C.sub.1 -C.sub.7 alkyl)-, substituted with 0-3 groups independently selected from R.sup.4, R.sup.8 or R.sup.14 ;--(C.sub.2 -C.sub.7 alkenyl)-, substituted with 0-3 groups independently selected from R.sup.4, R.sup.8 or R.sup.14 ;--(C.sub.2 -C.sub.7 alkynyl)-, substituted with 0-2 groups independently selected from R.sup.4, R.sup.8 or R.sup.14 ; or ##STR382## Y is selected from hydroxy, C.sub.1 to C.sub.10 alkyloxy, C.sub.3 to C.sub.11 cycloalkyloxy, C.sub.6 to C.sub.10 aryloxy, C.sub.7 to C.sub.11 aralkyloxy, C.sub.3 to C.sub.10 alkylcarbonyloxyalkyloxy, C.sub.3 to C.sub.10 alkoxycarbonyloxyalkyloxy, C.sub.2 to C.sub.10 alkoxycarbonylalkyloxy, C.sub.5 to C.sub.10 cycloalkylcarbonyloxyalkyloxy, C.sub.5 to C.sub.10 cycloalkoxycarbonyloxyalkyloxy, C.sub.5 to C.sub.10 cycloalkoxycarbonylalkyloxy, C.sub.7 to C.sub.11 aryloxycarbonylalkyloxy, C.sub.8 to C.sub.12 aryloxycarbonyloxyalkyloxy, C.sub.8 to C.sub.12 arylcarbonyloxyalkyloxy, C.sub.5 to C.sub.10 alkoxyalkylcarbonyloxyalkyloxy, C.sub.5 to C.sub.10 (5-alkyl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, C.sub.10 to C.sub.14 (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy; or (R.sup.2)(R.sup.3)N--(C.sub.1 -C.sub.10 alkoxy)-;R.sup.4 and R.sup.4b are independently selected from H, C.sub.1 -C.sub.10 alkyl, hydroxy, C.sub.1 -C.sub.10 alkoxy, nitro, C.sub.1 -C.sub.10 alkylcarbonyl, or --N(R.sup.12)R.sup.13 ;R.sup.5 is selected from H, 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.4b ;R.sup.5a is selected from hydrogen, hydroxy, C.sub.1 to C.sub.8 alkyl, C.sub.2 to 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.4b ;alternately, R.sup.5 and R.sup.5 a can be taken together to be 3-azabicyclononyl, 1-piperidinyl, 1-morpholinyl or 1-piperazinyl, each being optionally substituted with 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.5b 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.4b ;R.sup.6 is selected from H, C.sub.1 -C.sub.10 alkyl, hydroxy, C.sub.1 -C.sub.10 alkoxy, nitro, C.sub.1 -C.sub.10 alkylcarbonyl, --N(R.sup.12)R.sup.13, cyano, halo, CF.sub.3, CHO, CO.sub.2 R.sup.5, C(.dbd.O)R.sup.5a, CONR.sup.5 R.sup.5a, OC(.dbd.O)R.sup.5a, OC(.dbd.O)OR.sup.5b, OR.sup.5a, OC(.dbd.O)NR.sup.5 R.sup.5a, OCH.sub.2 CO.sub.2 R.sup.5, CO.sub.2 CH.sub.2 CO.sub.2 R.sup.5, NO.sub.2, NR.sup.5a C(.dbd.O)R.sup.5a, NR.sup.5a C(.dbd.O)OR.sup.5b, NR.sup.5a C(.dbd.O) NR.sup.5 R.sup.5a, NR.sup.5a SO.sub.2 NR.sup.5 R.sup.5a, NR.sup.5a SO.sub.2 R.sup.5, S(O).sub.p R.sup.5a, SO.sub.2 NR.sup.5 R.sup.5a, C.sub.2 to C.sub.6 alkenyl, C.sub.3 to C.sub.11 cycloalkyl, C.sub.4 to C.sub.11 cycloalkylmethyl;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 ;C.sub.7 to C.sub.11 arylalkyl, said aryl being 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; ora 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R.sup.7 ;R.sup.6a is selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, CF.sub.3, NO.sub.2, or NR.sup.12 R.sup.13 ;R.sup.7 is selected from H, C.sub.1 -C.sub.10 alkyl, hydroxy, C.sub.1 -C.sub.10 alkoxy, nitro, C.sub.1 -C.sub.10 alkylcarbonyl, --N(R.sup.12)R.sup.13, cyano, halo, CF.sub.3, CHO, CO.sub.2 R.sup.5, C(.dbd.O)R.sup.5a, CONR.sup.5 R.sup.5a, OC(.dbd.O)R.sup.5a, OC(.dbd.O)OR.sup.5b, OR.sup.5a, OC(.dbd.O)NR.sup.5 R.sup.5a, OCH.sub.2 CO.sub.2 R.sup.5, CO.sub.2 CH.sub.2 CO.sub.2 R.sup.5, NO.sub.2, NR.sup.5a C(.dbd.O)R.sup.5a, NR.sup.5a C(.dbd.O)OR.sup.5b, NR.sup.5a C(.dbd.O)NR.sup.5 R.sup.5a, NR.sup.5a SO.sub.2 NR.sup.5 R.sup.5a, NR.sup.5a SO.sub.2 R.sup.5, S(O).sub.p R.sup.5a, SO.sub.2 NR.sup.5 R.sup.5a, C.sub.2 to C.sub.6 alkenyl, C.sub.3 to C.sub.11 cycloalkyl, C.sub.4 to C.sub.11 cycloalkylmethyl, C.sub.6 to C.sub.10 aryl, or C.sub.7 to C.sub.11 arylalkyl;R.sup.8 is selected from:H;R.sup.6 ;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 0-2 R.sup.6 ;aryl, substituted with 0-2 R.sup.6 ;- 10membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R.sup.6 ;R.sup.12 and R.sup.13 are independently H, C.sub.1 -C.sub.10 alkyl, C.sub.1 -C.sub.10 alkoxycarbonyl, C.sub.1 -C.sub.10 alkylcarbonyl, C.sub.1 -C.sub.10 alkylsulfonyl, aryl(C.sub.1 -C.sub.10 alkyl)sulfonyl, arylsulfonyl, aryl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, C.sub.7 -C.sub.11 arylalkyl, C.sub.2 -C.sub.7 alkylcarbonyl, C.sub.7 -C.sub.11 arylcarbonyl, C.sub.2 -C.sub.10 alkoxycarbonyl, C.sub.4 -C.sub.11 cycloalkoxycarbonyl, C.sub.7 -C.sub.11 bicycloalkoxycarbonyl, C.sub.7 -C.sub.11 aryloxycarbonyl, heteroarylcarbonyl, heteroarylsulfonyl, heteroarylalkylcarbonyl or aryl(C.sub.1 -C.sub.10 alkoxy)carbonyl;R.sup.14 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.5 or --C(.dbd.O)N(R.sup.5)R.sup.5a ;R.sup.15 is selected from:H;R.sup.6 ;C.sub.1 -C.sub.10 alkyl, substituted with 0-8 R.sup.6 ;C.sub.2 -C.sub.10 alkenyl, substituted with 0-6 R.sup.6 ;C.sub.1 -C.sub.10 alkoxy, substituted with 0-6 R.sup.6 ;aryl, substituted with 0-5 R.sup.6 ;- 6membered heterocyclic ring containing 1-2 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-5 R.sup.6 ;C.sub.1 -C.sub.10 alkoxycarbonyl substituted with 0-8 R.sup.6 ;CO.sub.2 R.sup.5 ; or--C(.dbd.O)N(R.sup.5)R.sup.5a ;provided that when b is a double bond, only one of R.sup.14 or R.sup.15 is present;n is 0-4;q is 2-7;r is 0-3;provided that n, q, and r are chosen such that the number of atoms connecting R.sup.1 and Y is in the range of 8-18.