Patent ID: 6306891
Filing Date: 2001-10-23
Classification: A61K

Abstract:
A compound of structural formula (I): ##STR222##and tautomers and pharmaceutically acceptable salts thereof, wherein:A is a five-membered heteroaromatic ring containing 1 or 2 nitrogen atoms and substituted on carbon or nitrogen by R.sup.1, R.sup.2 and R.sup.8 ; the heteroaromatic ring may optionally be fused with a phenyl ring to form a fused ring system, provided that when A is a fused ring system, the nitrogen-containing heteroaromatic ring is substituted by the dioxobutyric acid/ester moiety;R.sub.1 is selected from:(1) --H,(2) --C.sub.1-5 alkyl,(3) --CF.sub.3,(4) -halo,(5) --NO.sub.2,(6) --N(R.sup.4)(R.sup.5),(7) --R.sup.6,(8) --C.sub.2-5 alkenyl-R.sup.3,(9) --C.sub.2-5 alkynyl-R.sup.3,(10) --O--R.sup.6,(11) --O--C.sub.1-6 alkyl, and(12) --C(O)CH.sub.2 C(O)C(O)OR.sup.7 ;R.sup.2 is selected from:(1) --H,(2) --R.sup.3,(3) --C.sub.1-6 alkyl,(4) --C.sub.1-6 alkyl substituted with R.sup.3,(5) --O--R.sup.6,(6) --O--C.sub.1-6 alkyl-OR.sup.6,(7) --S(O)n-R.sup.6,(8) --C.sub.1-6 alkyl (OR.sup.6)(R.sup.4),(9) --C.sub.1-6 alkyl-N(R.sup.4)(R.sup.6),(10) --C.sub.1-6 alkyl S(O)n-R.sup.6,(11) --C.sub.1-6 alkyl C(O)--R.sup.6,(12) --C.sub.1-6 alkyl C(S)--R.sup.6,(13) --C.sub.1-6 alkyl NR.sup.4 C(O)--R.sup.6, and(14) --C.sub.1-6 alkyl-C(O)N(R.sup.4)(R.sup.5);each R.sup.3 is independently selected from:(1) a 5 or 6 membered aromatic or heteroaromatic ring, containing 0, 1, 2, 3, or 4 heteroatoms selected from oxygen, nitrogen and sulfur, unsubstituted or substituted on a nitrogen or carbon atom by 1 to 5 substituents selected from:(a) halogen,(b) C.sub.1-6 alkyl,(c) C.sub.1-6 alkyloxy-,(d) phenyl,(e) --CF.sub.3,(f) --OCF.sub.3,(g) --CN,(h) hydroxy,(i) phenyloxy, and(j) substituted phenyloxy with 1, 2, or 3 substituents selected from:(i) halogen,(ii) C.sub.1-6 alkyl,(iii) --CF.sub.3, and(iv) hydroxy;(2) a 3 to 6 membered saturated ring containing 0 or 1 heteroatoms selected from oxygen, nitrogen or sulfur, unsubstituted or substituted with 1 to 5 substituents selected from:(a) halogen,(b) C.sub.1-6 alkyl,(c) C.sub.1-6 alkyloxy-,(d) --CF.sub.3,(e) --OCF.sub.3,(f) --CN,(g) .dbd.O, and(h) hydroxy;(3) unsubstituted or substituted hexahydrothieno[3,4-d]imidazolyl with one or two substituents selected from:(a) oxo,(b) halogen,(c) C.sub.1-6 alkyl,(d) C.sub.1-6 alkyloxy-,(e) --CF.sub.3,(f) --OCF.sub.3,(g) --CN, and(h) hydroxy;(4) a 5 or 6 membered aromatic or heteroaromatic ring, containing 0, 1, or 2 heteroatoms selected from oxygen, nitrogen and sulfur, fused with a phenyl ring; wherein the ring system is unsubstituted or substituted on a nitrogen or carbon atom by 1 to 3 substituents selected from:(a) -halogen,(b) --C.sub.1-6 alkyl,(c) --C.sub.1-6 alkyloxy-,(d) --CF.sub.3,(e) --OCF.sub.3,(f) --CN, and(g) -hydroxy;(5) a 3 to 6 membered saturated ring containing 0 or 1 heteroatoms selected from oxygen, nitrogen or sulfur, fused with a phenyl ring, unsubstituted or substituted with 1 or 2 substituents selected from:(a) halogen,(b) C.sub.1-6 alkyl,(c) C.sub.1-6 alkyloxy-,(d) --CF.sub.3,(e) --OCF.sub.3,(f) --CN,(g) .dbd.O, and(h) hydroxy; and(6) a 5 to 6 membered ring containing 0, 1 or 2 heteroatoms selected from oxygen, nitrogen or sulfur, containing 2 or 3 double bonds, unsubstituted or substituted with 1 or 2 substituents selected from:(a) halogen,(b) C.sub.1-6 alkyl,(c) C.sub.1-6 alkyloxy-,(d) --CF.sub.3,(e) --OCF.sub.3,(f) --CN,(g) .dbd.O, and(h) hydroxy;each R.sup.4 is independently selected from:(1) --H,(2) --C.sub.1-3 alkyl,(3) --CF.sub.3,(4) --R.sup.3,(5) --C.sub.2-3 alkenyl,(6) --C.sub.1-3 alkyl-R.sup.3,(7) --C.sub.2-3 alkenyl-R.sup.3,(8) --S(O).sub.n --R.sup.3, and(9) --C(O)--R.sup.3 ;each R.sup.5 is independently selected from:(1) --H,(2) --C.sub.1-3 alkyl,(3) --CF.sub.3,(4) --R.sup.3,(5) --C.sub.2-3 alkenyl,(6) --C.sub.1-3 alkyl-R.sup.3,(7) --C.sub.2-3 alkenyl-R.sup.3,(8) --S(O).sub.n --R.sup.3, and(9) --C(O)--R.sup.3 ;each R.sup.6 is independently selected from:(1) --C.sub.1-3 alkyl-R.sup.3, and(2) --R.sup.3 ;R.sup.7 is selected from:(1) --H, and(2) C.sub.1-6 alkyl;R.sup.8 is selected from:(1) --H,(2) C.sub.1-6 alkyl-oxy, and(3) C.sub.1-6 alkyl; andeach n is independently selected from 0, 1 and 2; andfurther provided that when R.sup.7 is C.sub.1-6 alkyl, then R.sup.2 is not --H or --C.sub.1-6 alkyl.