Patent ID: 6020343
Filing Date: 2000-02-01
Classification: C07C,C07D

Abstract:
A compound of Formula I ##STR254## or a pharmaceutically acceptable salt thereof wherein:X is selected from the group consisting of:(a) CH.sub.2,(b) CHOH,(c) CO,(d) O,(e) S and(f) N(R.sup.15),with the proviso that when R.sup.3 and R.sup.4 are other than(1) both hydrogen,(2) both C.sub.1-10 alkyl, or(3) joined together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms, thenX is selected from CO, O, S and N(R.sup.15);Y is selected from the group consisting of:(a) C(R.sup.11)(R.sup.12),(b) CO,(c) O and(d) S;R.sup.1 is selected from the group consisting of:(a) SO.sub.2 CH.sub.3,(b) SO.sub.2 NR.sup.16 R.sup.17,(c) SO.sub.2 NHC(O)CF.sub.3,(d) S(O)NH)NH.sub.2,(e) S(O)(NH)NHC(O)CF.sub.3,(f) P(O)(CH.sub.3)NH.sub.2 and(g) P(O)(CH.sub.3).sub.2 ;R.sup.2 is selected from the group consisting of:(a) C.sub.1-10 alkyl,(b) mono-, di-or tri-substituted phenyl and naphthyl wherein the substituents are selected from the group consisting of:(1) hydrogen,(2) halo,(3) C.sub.1-10 alkoxy,(4) C.sub.1-10 alkylthio,(5) CN,(6) C.sub.1-6 fluoroalkyl,(7) C.sub.1-6 alkyl,(8) N.sub.3,(9) --CO.sub.2 H,(10) --CO.sub.2 -C.sub.1-10 alkyl,(11) --C(R.sup.5)(R.sup.6)--OH,(12) --C(R.sup.5)(R.sup.6)--O-C.sub.1-4 alkyl,(13) --C.sub.1-6 alkyl--CO.sub.2 -R.sup.5,(14) benzyloxy,(15) --O--(C.sub.1-6 alkyl)--CO.sub.2 R.sup.5 and(16) --O--(C.sub.1-6 alkyl)--NR.sup.5 R.sup.6 ;(c) mono-, di-or tri-substituted heteroaryl wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one hetero atom which is S, O, or N, and optionally 1, 2, or 3 additional N atoms; or the heteroaryl is a monocyclic ring of 6 atoms, said ring having one hetero atom which is N, and optionally 1, 2, or 3 additional N atoms, wherein the substituents are selected from the group consisting of:(1) hydrogen,(2) halo,(3) C.sub.1-10 alkyl,(4) C.sub.1-10 alkoxy,(5) C.sub.1-10 alkylthio,(6) CN,(7) CF.sub.3,(8) N.sub.3,(9) --C(R.sup.5)(R.sup.6)--OH,(10) --C(R.sup.5)(R.sup.6)--O-C.sub.1-10 alkyl and(11) C.sub.1-6 fluoroalkyl;(d) a mono- or di-substituted benzoheterocycle in which the heterocycle is a 5, 6, or 7-membered ring which may contain 1 or 2 heteroatoms chosen independently from O, S, or N and which may contain a carbonyl group or a sulfonyl group; wherein the substituents are selected from the group consisting of:(1) hydrogen,(2) halo,(3) C.sub.1-10 alkyl,(4) C.sub.1-10 alkoxy,(5) C.sub.1-10 alkylthio,(6) CN,(7) CF.sub.3,(8) N.sub.3,(9) --C(R.sup.5)(R.sup.6)--OH,(10) --C(R.sup.5)(R.sup.6)--O-C.sub.1-10 alkyl and(11) C.sub.1-6 fluoroalkyl;(e) a heterocycloalkyl group of 5, 6 or 7 members which contains 1 or 2 heteroatoms chosen from O, S, or N and optionally contains a carbonyl group or a sulfonyl group;(f) a mono- or di-substituted benzocarbocycle in which the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, wherein the substituents are selected from the group consisting of:(1) hydrogen,(2) halo,(3) C.sub.1-10 alkyl,(4) C.sub.1-10 alkoxy,(5) C.sub.1-10 alkylthio,(6) CN,(7) CF.sub.3,(8) N.sub.3,(9) --C(R.sup.5)(R.sup.6)--OH,(10) --C(R.sup.5)(R.sup.6)--O-C.sub.1-10 alkyl and(11) C.sub.1-6 fluoroalkyl;(g) a mono- or di-substituted bicyclic heteroaryl of 8, 9, or 10 members, containing 2 to 5 heteroatoms chosen independently from O, S or N, and in which each ring contains at least one heteroatom, wherein the substituents are selected from the group consisting of:(1) hydrogen,(2) halo,(3) C.sub.1-10 alkyl,(4) C.sub.1-10 alkoxy,(5) C.sub.1-10 alkylthio,(6) CN,(7) CF.sub.3,(8) N.sub.3,(9) --C(R.sup.5)(R.sup.6)--OH,(10) --C(R.sup.5)(R.sup.6)--O-C.sub.1-10 alkyl and(11) C.sub.1-6 fluoroalkyl;R.sup.3 is hydrogen, C.sub.1-10 alkyl, CH.sub.2 OR.sup.7, CN, CH.sub.2 CN, C.sub.1-6 fluoroalkyl, F, CON(R.sup.7).sup.2, mono- or di-substituted phenyl, mono or di-substituted benzyl, mono- or di-substituted heteroaryl, or mono or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of:(1) hydrogen,(2) halo,(3) C.sub.1-6 alkyl,(4) C.sub.1-6 alkoxy,(5) C.sub.1-6 alkylthio,(6) CN,(7) CF.sub.3,(8) N.sub.3,(9) --C(R.sup.5)(R.sup.6)--OH,(10) --C(R.sup.5)(R.sup.6)--O-C.sub.1-4 alkyl and(11) C.sub.1-6 fluoroalkyl;R.sup.4 is selected from the group consisting of:(a) hydrogen,(b) C.sub.1-10 alkyl,(c) C.sub.1-10 alkoxy,(d) C.sub.1-10 alkylthio,(e) --OH,(f) --OCOR.sup.7,(g) --SH,(h) --SCOR.sup.7,(i) --OCO.sub.2 R.sup.8,(j) --SCO.sub.2 R.sup.8,(k) OCON(R.sup.7).sub.2,(l) SCON(R.sup.7).sub.2 and(m) C.sub.1-6 fluoroalkyl;or R.sup.3 and R.sup.4 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms;R.sup.5 and R.sup.6 are each independently selected from the group consisting of:(a) hydrogen and(b) C.sub.1-10 alkyl,or R.sup.5 and R.sup.6 together with the atom to which they are attached form a saturated monocyclic ring of 3,4, 5, 6 or 7 atoms;each R.sup.7 is independently selected from the group consisting of:(a) hydrogen,(b) C.sub.1-6 alkyl,(c) phenyl and monosubstituted phenyl wherein the substituents are selected from halo, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, CN, and CF.sub.3, and(d) benzyl and monosubstituted benzyl wherein the substituents are selected from halo, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, CN, and CF.sub.3, ortwo R.sup.7 groups taken together with the nitrogen to which they are attached form a saturated monocyclic ring of 5, 6 or 7 atoms, optionally containing an additional O, S or NR.sup.5 ;each R.sup.8 is independently selected from the group consisting of:(a) C.sub.1-6 alkyl,(b) phenyl and monosubstituted phenyl wherein the substituents are selected from halo, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, CN, and CF.sub.3, and(c) benzyl and monosubstituted benzyl wherein the substituents are selected from halo, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, CN, or CF.sub.3 ;R.sup.9 and R.sup.10 are independently selected from the group consisting of:(a) hydrogen and(b) C.sub.1-7 alkyl, orR.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a carbonyl or thiocarbonyl group;R.sup.11 and R.sup.12 are independently(a) hydrogen,(b) mono- or di-substituted phenyl or mono- or di-substituted benzyl or mono- or di-substituted heteroaryl or mono- or di-substituted heteroarylmethyl, wherein the substituents are selected from the group consisting of:(1) hydrogen,(2) fluoro, chloro, bromo and iodo,(3) C.sub.1-6 alkyl,(4) C.sub.1-6 alkoxy,(5) C.sub.1-6 alkylthio,(6) CN,(7) CF.sub.3,(8) N.sub.3,(9) --C(R.sup.13)(R.sup.14)--OH,(10) --C(R.sup.13)(R.sup.14)--O-C.sub.1-4 alkyl and(11) C.sub.1-6 fluoroalkyl, or(c) C.sub.1-7 alkyl, CH.sub.2 OR.sup.7, CN, CH.sub.2 CN, C.sub.1-6 fluoroalkyl, CON(R.sup.7).sub.2, F, or OR.sup.7 ; orR.sup.11 and R.sup.12 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms;R.sup.13 and R.sup.14 are independently selected from the group consisting of:(a) hydrogen and(b) C.sub.1-7 alkyl, orR.sup.13 and R.sup.14 together with the carbon to which they are attached form a carbonyl, --C(.dbd.S)--, or a saturated monocyclic carbon ring of 3, 4, 5, 6, or 7 atoms;R.sup.15 is selected from the group consisting of:(a) hydrogen,(b) C.sub.1-10 alkyl,(c) mono-, di- or tri-substituted phenyl or naphthyl wherein the substituents are selected from the group consisting of:(1) hydrogen,(2) halo,(3) C.sub.1-10 alkoxy,(4) C.sub.1-10 alkylthio,(5) CN,(6) C.sub.1-6 fluoroalkyl,(7) C.sub.1-10 alkyl,(8) N.sub.3,(9) --CO.sub.2 H,(10) --CO.sub.2 -C.sub.1-10 alkyl,(11) --C(R.sup.5)(R.sup.6)--OH,(12) --C(R.sup.5)(R.sup.6)--O-C.sub.1-4 alkyl,(13) --C.sub.1-6 alkyl--CO.sub.2 -R.sup.5,(14) benzyloxy,(15) --O--(C.sub.1-6 alkyl)--CO.sub.2 R.sup.5 and(16) --O--(C.sub.1-6 alkyl)--NR.sup.5 R.sup.6 ;(d) mono-, di- or tri-substituted heteroaryl wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one hetero atom which is S, O, or N, and optionally 1, 2, or 3 additional N atoms; or the heteroaryl is a monocyclic ring of 6 atoms, said ring having one hetero atom which is N, and optionally 1, 2, or 3 additional N atoms, wherein the substituents are selected from the group consisting of:(1) hydrogen,(2) halo,(3) C.sub.1-10 alkyl,(4) C.sub.1-10 alkoxy,(5) C.sub.1-10 alkylthio,(6) CN,(7) CF.sub.3,(8) N.sub.3,(9) --C(R.sup.5)(R.sup.6)--OH,(10) --C(R.sup.5)(R.sup.6)--O-C.sub.1-10 alkyl and(11) C.sub.1-6 fluoroalkyl;(e) a mono- or di-substituted benzoheterocycle in which the heterocycle is a 5, 6, or 7-membered ring which may contain 1 or 2 heteroatoms chosen independently from O, S, or N and which may contain a carbonyl group or a sulfonyl group; wherein the substituents are selected from the group consisting of:(1) hydrogen,(2) halo,(3) C.sub.1-10 alkyl,(4) C.sub.1-10 alkoxy,(5) C.sub.1-10 alkylthio,(6) CN,(7) CF.sub.3,(8) N.sub.3,(9) --C(R.sup.5)(R.sup.6)--OH,(10) --C(R.sup.5)(R.sup.6)--O-C.sub.1-10 alkyl and(11) C.sub.1-6 fluoroalkyl;(f) a heterocycloalkyl group of 5, 6 or 7 members which contains 1 or 2 heteroatoms chosen from O, S, or N and optionally contains a carbonyl group or a sulfonyl group;(g) a mono- or di-substituted benzocarbocycle in which the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, wherein the substituents are selected from the group consisting of:(1) hydrogen,(2) halo,(3) C.sub.1-10 alkyl,(4) C.sub.1-10 alkoxy,(5) C.sub.1-10 alkylthio,(6) CN,(7) CF.sub.3,(8) N.sub.3,(9) --C(R.sup.5)(R.sup.6)--OH,(10) --C(R.sup.5)(R.sup.6)--O-C.sub.1-4 alkyl and(11) C.sub.1-6 fluoroalkyl;R.sup.16 and R.sup.17 are independently selected from the group consisting of:(a) hydrogen,(b) C.sub.1-10 alkyl,(c) C.sub.1-10 alkanoic acid,(d) C.sub.1-10 alkyl amine,(e) phenyl or monosubstituted phenyl wherein the substituents are halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alkanoic acid, C.sub.1-10 alkylamine, CN, CO.sub.2 H and CF.sub.3, and(f) benzyl or monosubstituted benzyl wherein the substituents are halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alkanoic acid, C.sub.1-10 alkylamine, CN, CO.sub.2 H are CF.sub.3, orR16 and R17 together with the nitrogen to which they are attached form a saturated monocyclic ring of 5, 6 or 7 atoms, optionally containing an additional O, S or NR.sup.5.