US 5,698,584 AGranted

3,4-diaryl-2-hydroxy-2,5-dihydrofurans as prodrugs to COX-2 inhibitors

AssigneeMerck Frosst Canada, Inc.

InventorsCameron Black, Serge Leger, Petpiboon Prasit, Zhaoyin Wang, Pierre Hamel, Yongxin Han, Gregory Hughes

Life of this patent

Estimating the term…

Abstract

The invention encompasses the novel compound of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases. ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.

Claims18

Dependent claims

A compound of Formula I ##STR65## or a pharmaceutically acceptable salt thereof wherein:

R.sup.1 is selected from the group consisting of
(a) S(O).sub.2 CH.sub.3,
(b) S(O).sub.2 NHR.sup.8,
(c) S(O).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,
(g) P(O)(CH.sub.3).sub.2, and
(h) C(S)NH.sub.2 ;
R.sup.2 is selected from the group consisting of
(a) NR.sup.10 R.sup.11,
(b) SR.sup.11,
(c) OR.sup.11,
(d) R.sup.11,
(e) C1-10alkenyl,
(f) C1-10alkynyl,
(g) unsubstituted, mono-, di-, tri- or tetra-substituted C.sub.3 -C.sub.10 cycloalkenyl wherein the substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-6 alkoxy,
(3) C.sub.1-6 alkylthio,
(4) CN,
(5) CF.sub.3,
(6) C.sub.1-10 alkyl,
(7) N.sub.3,
(8) --CO.sub.2 H,
(9) --CO.sub.2 --C.sub.1-10 alkyl,
(10) --C(R.sup.12)(R.sup.13)--OH,
(11) --C(R.sup.12)(R.sup.13)--O--C.sub.1-4 alkyl,
(12) --C.sub.1-10 alkyl-CO.sub.2 --R.sup.12 ;
(13) benzyloxy,
(14) --O--(C.sub.1-10 alkyl)-CO.sub.2 R.sup.12, and
(15) --O--(C.sub.1-10 alkyl)-NR.sup.12 R.sup.13 ;
(h) a mono-, di-, tri- or tetra-substituted heterocycloalkyl group of 5, 6 or 7 members or a benzoheterocycle wherein said heterocycloalkyl or benzoheterocycle contains 1 or 2 heteroatoms selected from O, S, or N and optionally contains a carbonyl group or a sulfonyl group, and wherein said substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-10 alkyl,
(3) C.sub.1-10 alkoxy,
(4) C.sub.1-10 alkylthio,
(5) CN,
(6) CF.sub.3,
(7) N.sub.3,
(8) --C(R.sup.12)(R.sup.13)--OH, and
(9) --C(R.sup.12)(R.sup.13)--O--C.sub.1-10 alkyl;
(i) styryl or mono or di-substituted styryl wherein the substituent are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-6 alkoxy,
(3) C.sub.1-6 alkylthio,
(4) CN,
(5) CF.sub.3,
(6) C.sub.1-10 alkyl,
(7) N.sub.3,
(8) --CO.sub.2 H,
(9) --CO.sub.2 --C.sub.1-10 alkyl,
(10) --C(R.sup.12)(R.sup.13)--OH,
(11) --C(R.sup.12)(R.sup.13)--O--C.sub.1-4 alkyl,
(12) --C.sub.1-10 alkyl-CO.sub.2 --R.sup.12 ;
(13) benzyloxy,
(14) --O--(C.sub.1-10 alkyl)-CO.sub.2 R.sup.12, and
(15) --O--(C.sub.1-10 alkyl)-NR.sup.12 R.sup.13 ;
(j) phenylacetylene or mono- or di-substituted phenylacetylene wherein the substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-6 alkoxy,
(3) C.sub.1-6 alkylthio,
(4) CN,
(5) CF.sub.3,
(6) C.sub.1-10 alkyl,
(7) N.sub.3,
(8) --CO.sub.2 H,
(9) --CO.sub.2 --C.sub.1-10 alkyl,
(10) --C(R.sup.12)(R.sup.13)--OH,
(11) --C(R.sup.12)(R.sup.13)--O--C.sub.1-4 alkyl,
(12) --C.sub.1-10 alkyl-CO.sub.2 --R.sup.12,
(13) benzyloxy,
(14) --O--(C.sub.1-10 alkyl)-CO.sub.2 R.sup.12,
(15) --O--(C.sub.1-10 alkyl)-NR.sup.12 R.sup.13,
(k) C.sub.1-10 fluoroalkenyl, and
(l) mono- or di-substituted bicyclic heteroaryl of 8, 9 or 10 members, containing 2, 3, 4 or 5 heteroatoms, wherein at least one heteroatom resides on each ring of said bicyclic heteroaryl, said heteroatoms independently selected from O, S and N and said substituents are independently 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.1-6 alkylthio,
(6) CN,
(7) C.sub.1-6 fluoroalkyl, including 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;
R.sup.3 is hydrogen, C.sub.1-10 alkyl, CH.sub.2 OR.sup.8, CN, CH.sub.2 CN, or C.sub.1-6 fluoroalkyl, F, CONR.sup.8.sub.2, unsubstituted or mono- or di-substituted phenyl, unsubstituted or mono or di-substituted benzyl, unsubstituted or mono- or di-substituted heteroaryl, unsubstituted or mono or di-substituted heteroarylmethyl, wherein the substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-10 alkyl,
(3) C.sub.1-10 alkoxy,
(4) C.sub.1-10 alkylthio,
(5) CN,
(6) CF.sub.3,
(7) N.sub.3,
(8) --C(R.sup.12)(R.sup.13)--OH, and
(9) --C(R.sup.12)(R.sup.13)--O--C.sub.1-10 alkyl;
R.sup.4 is
(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.8,
(g) --SH,
(h) --SCOR.sup.8,
(i) --OCO.sub.2 R.sup.9,
(j) --SCO.sub.2 R.sup.9,
(k) OCONR.sup.8.sub.2,
(l) SCONR.sup.8.sub.2 ;
(m) C.sub.3-10 cycloalkoxy, and
(n) C.sub.3-10 cycloalkylthio,
or R.sup.3 and R.sup.4 together with the carbon to which they are attached form a monocyclic ring of 3, 4, 5, 6, or 7 members which ring optionally contains one or two heteroatoms selected from O, S or N;
R.sup.5 is selected from the group consisting of
(a) OR.sup.17,
(b) SR.sup.18,
(c) NR.sup.17 R.sup.18,
(d) NHS(O).sub.2 R.sup.18,
(e) S(O)R.sup.18,
(f) S(O).sub.2 R.sup.18,
(g) S(O).sub.2 NR.sup.17.sub.2,
(h) OP(O)(OR.sup.16).sub.2 ;
each R.sup.8 is independently selected from the group consisting of
(a) hydrogen and
(b) R.sup.9 ;
each R.sup.9 is independently selected from the group consisting of
(a) C.sub.1-10 alkyl,
(b) --C.sub.1-10 alkyl-CO.sub.2 H
(c) C.sub.1-10 alkyl-NH.sub.2
(d) phenyl or mono-, di- or tri-substituted phenyl wherein the substituents are independently selected from halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alklyCO.sub.2 H, C.sub.1-10 alkylNH.sub.2, CN, CO.sub.2 H and CF.sub.3,
(e) benzyl or mono-, di- or tri-substituted benzyl wherein the substituents are independently selected from halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alkylCO.sub.2 H, C.sub.1-10 alkylNH.sub.2, CN, CO.sub.2 H and CF.sub.3,
(f) C.sub.3-10 cycloalkyl,
(g) C.sub.1-10 alkanoyl, and
(h) benzoyl or mono-, di-, or trisubstituted benzoyl wherein the substituents are independently selected from halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alkylCO.sub.2 H, --C.sub.1-10 alkylNH.sub.2, CN, CO.sub.2 H and CF.sub.3,
each R.sup.10 is independently selected from the group consisting of
(a) hydrogen and
(b) R.sup.11 ;
R.sup.11 is selected from the group consisting of
(a) C.sub.1-10 alkyl,
(b) C.sub.3-10 cycloalkyl,
(c) unsubstituted, mono-, di- or tri-substituted phenyl or naphthyl wherein the substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-10 alkoxy,
(3) C.sub.1-10 alkylthio,
(4) CN,
(5) CF.sub.3,
(6) C.sub.1-10 alkyl,
(7) N.sub.3,
(8) --CO.sub.2 H,
(9) --CO.sub.2 --C.sub.1-10 alkyl,
(10) --C(R.sup.12)(R.sup.13)--OH,
(11) --C(R.sup.12)(R.sup.13)--O--C.sub.1-4 alkyl,
(12) --C.sub.1-6 alkyl-CO.sub.2 --R.sup.12,
(13) benzyloxy,
(14) --O--(C.sub.1-10 alkyl)-CO.sub.2 R.sup.12, and
(15) --O--(C.sub.1-10 alkyl)-NR.sup.12 R.sup.13,
(d) unsubstituted, 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 said 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, and wherein said substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-10 alkyl,
(3) C.sub.1-10 alkoxy,
(4) C.sub.1-10 alkylthio,
(5) CN,
(6) CF.sub.3,
(7) N.sub.3,
(8) --C(R.sup.12)(R.sup.13)--OH, and
(9) --C(R.sup.12)(R.sup.13)--O--C.sub.1-10 alkyl;
(e) unsubstituted, mono- or di-substituted benzoheterocycle in which the benzoheterocycle is a 5, 6, or 7-membered ring which contains 1 or 2 heteroatoms independently selected from O, S, or N and optionally a carbonyl group or a sulfonyl group, wherein said substituents are selected from the group consisting of
(1) halo,
(2) C.sub.1-10 alkyl,
(3) C.sub.1-10 alkoxy,
(4) C.sub.1-10 alkylthio,
(5) CN,
(6) CF.sub.3,
(7) N.sub.3,
(8) --C(R.sup.12)(R.sup.13)--OH, and
(9) --C(R.sup.12)(R.sup.13)--O--C.sub.1-10 alkyl;
(f) unsubstituted, mono- or di-substituted benzocarbocycle in which the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, wherein said substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-10 alkyl,
(3) C.sub.1-10 alkoxy,
(4) C.sub.1-10 alkylthio,
(5) CN,
(6) CF.sub.3,
(7) N.sub.3,
(8) --C(R.sup.12)(R.sup.13)--OH, and
(9) --C(R.sup.12)(R.sup.13)--O--C.sub.1-10 alkyl;
each R.sup.12 or R.sup.13 is independently selected from the group consisting of
(a) hydrogen, and
(b) C.sub.1-10 alkyl,
or R.sup.12 and R.sup.13 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.16 is independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl and unsubstituted or mono- or disubstituted benzyl, wherein the substituents are selected from halo, CN, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio or C.sub.1-6 fluoroalkyl;
each R.sup.17 is independently selected from the group consisting of
(a) hydrogen and
(b) R.sup.18 ;
and
each R.sup.18 is independently selected from the group consisting of
(a) C.sub.1-10 alkyl,
(b) --C.sub.1-10 alkyl-CO.sub.2 H
(c) C.sub.1-10 alkyl-NH.sub.2
(d) phenyl or mono-, di- or tri-substituted phenyl wherein the substituents are independently selected from halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alklyCO.sub.2 H, C.sub.1-10 alkylNH.sub.2, CN, CO.sub.2 H and CF.sub.3,
(e) benzyl or mono-, di- or tri-substituted benzyl wherein the substituents are independently selected from halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alkylCO.sub.2 H, C.sub.1-10 alkylNH.sub.2, CN, CO.sub.2 H and CF.sub.3,
(f) C.sub.3-10 cycloalkyl,
(g) H-(oxyethyl)n wherein n is 1 to 6,
(h) C.sub.1-10 alkanoyl, and
(i) benzoyl or mono-, di-, or trisubstituted benzoyl wherein the substituents are independently selected from halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alkylCO.sub.2 H, --C.sub.1-10 alkylNH.sub.2, CN, CO.sub.2 H and CF.sub.3.

202 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/738,143Filed 25 Oct 1996
Priority: GB 960287713 Feb 1996
Granted: 16 Dec 1997
Term ends: Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07D 307/32
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
C07C 317/22
Having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton: with sulfone or sulfoxide groups bound to…
C07C 323/64
Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio…
C07D 213/34
Sulfur atoms: to which a second hetero atom is attached

Family

No related US applications are recorded in the indexed filing history.

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Abstract

A compound of Formula I ##STR65## or a pharmaceutically acceptable salt thereof wherein:

R.sup.1 is selected from the group consisting of
(a) S(O).sub.2 CH.sub.3,
(b) S(O).sub.2 NHR.sup.8,
(c) S(O).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,
(g) P(O)(CH.sub.3).sub.2, and
(h) C(S)NH.sub.2 ;
R.sup.2 is selected from the group consisting of
(a) NR.sup.10 R.sup.11,
(b) SR.sup.11,
(c) OR.sup.11,
(d) R.sup.11,
(e) C1-10alkenyl,
(f) C1-10alkynyl,
(g) unsubstituted, mono-, di-, tri- or tetra-substituted C.sub.3 -C.sub.10 cycloalkenyl wherein the substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-6 alkoxy,
(3) C.sub.1-6 alkylthio,
(4) CN,
(5) CF.sub.3,
(6) C.sub.1-10 alkyl,
(7) N.sub.3,
(8) --CO.sub.2 H,
(9) --CO.sub.2 --C.sub.1-10 alkyl,
(10) --C(R.sup.12)(R.sup.13)--OH,
(11) --C(R.sup.12)(R.sup.13)--O--C.sub.1-4 alkyl,
(12) --C.sub.1-10 alkyl-CO.sub.2 --R.sup.12 ;
(13) benzyloxy,
(14) --O--(C.sub.1-10 alkyl)-CO.sub.2 R.sup.12, and
(15) --O--(C.sub.1-10 alkyl)-NR.sup.12 R.sup.13 ;
(h) a mono-, di-, tri- or tetra-substituted heterocycloalkyl group of 5, 6 or 7 members or a benzoheterocycle wherein said heterocycloalkyl or benzoheterocycle contains 1 or 2 heteroatoms selected from O, S, or N and optionally contains a carbonyl group or a sulfonyl group, and wherein said substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-10 alkyl,
(3) C.sub.1-10 alkoxy,
(4) C.sub.1-10 alkylthio,
(5) CN,
(6) CF.sub.3,
(7) N.sub.3,
(8) --C(R.sup.12)(R.sup.13)--OH, and
(9) --C(R.sup.12)(R.sup.13)--O--C.sub.1-10 alkyl;
(i) styryl or mono or di-substituted styryl wherein the substituent are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-6 alkoxy,
(3) C.sub.1-6 alkylthio,
(4) CN,
(5) CF.sub.3,
(6) C.sub.1-10 alkyl,
(7) N.sub.3,
(8) --CO.sub.2 H,
(9) --CO.sub.2 --C.sub.1-10 alkyl,
(10) --C(R.sup.12)(R.sup.13)--OH,
(11) --C(R.sup.12)(R.sup.13)--O--C.sub.1-4 alkyl,
(12) --C.sub.1-10 alkyl-CO.sub.2 --R.sup.12 ;
(13) benzyloxy,
(14) --O--(C.sub.1-10 alkyl)-CO.sub.2 R.sup.12, and
(15) --O--(C.sub.1-10 alkyl)-NR.sup.12 R.sup.13 ;
(j) phenylacetylene or mono- or di-substituted phenylacetylene wherein the substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-6 alkoxy,
(3) C.sub.1-6 alkylthio,
(4) CN,
(5) CF.sub.3,
(6) C.sub.1-10 alkyl,
(7) N.sub.3,
(8) --CO.sub.2 H,
(9) --CO.sub.2 --C.sub.1-10 alkyl,
(10) --C(R.sup.12)(R.sup.13)--OH,
(11) --C(R.sup.12)(R.sup.13)--O--C.sub.1-4 alkyl,
(12) --C.sub.1-10 alkyl-CO.sub.2 --R.sup.12,
(13) benzyloxy,
(14) --O--(C.sub.1-10 alkyl)-CO.sub.2 R.sup.12,
(15) --O--(C.sub.1-10 alkyl)-NR.sup.12 R.sup.13,
(k) C.sub.1-10 fluoroalkenyl, and
(l) mono- or di-substituted bicyclic heteroaryl of 8, 9 or 10 members, containing 2, 3, 4 or 5 heteroatoms, wherein at least one heteroatom resides on each ring of said bicyclic heteroaryl, said heteroatoms independently selected from O, S and N and said substituents are independently 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.1-6 alkylthio,
(6) CN,
(7) C.sub.1-6 fluoroalkyl, including 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;
R.sup.3 is hydrogen, C.sub.1-10 alkyl, CH.sub.2 OR.sup.8, CN, CH.sub.2 CN, or C.sub.1-6 fluoroalkyl, F, CONR.sup.8.sub.2, unsubstituted or mono- or di-substituted phenyl, unsubstituted or mono or di-substituted benzyl, unsubstituted or mono- or di-substituted heteroaryl, unsubstituted or mono or di-substituted heteroarylmethyl, wherein the substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-10 alkyl,
(3) C.sub.1-10 alkoxy,
(4) C.sub.1-10 alkylthio,
(5) CN,
(6) CF.sub.3,
(7) N.sub.3,
(8) --C(R.sup.12)(R.sup.13)--OH, and
(9) --C(R.sup.12)(R.sup.13)--O--C.sub.1-10 alkyl;
R.sup.4 is
(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.8,
(g) --SH,
(h) --SCOR.sup.8,
(i) --OCO.sub.2 R.sup.9,
(j) --SCO.sub.2 R.sup.9,
(k) OCONR.sup.8.sub.2,
(l) SCONR.sup.8.sub.2 ;
(m) C.sub.3-10 cycloalkoxy, and
(n) C.sub.3-10 cycloalkylthio,
or R.sup.3 and R.sup.4 together with the carbon to which they are attached form a monocyclic ring of 3, 4, 5, 6, or 7 members which ring optionally contains one or two heteroatoms selected from O, S or N;
R.sup.5 is selected from the group consisting of
(a) OR.sup.17,
(b) SR.sup.18,
(c) NR.sup.17 R.sup.18,
(d) NHS(O).sub.2 R.sup.18,
(e) S(O)R.sup.18,
(f) S(O).sub.2 R.sup.18,
(g) S(O).sub.2 NR.sup.17.sub.2,
(h) OP(O)(OR.sup.16).sub.2 ;
each R.sup.8 is independently selected from the group consisting of
(a) hydrogen and
(b) R.sup.9 ;
each R.sup.9 is independently selected from the group consisting of
(a) C.sub.1-10 alkyl,
(b) --C.sub.1-10 alkyl-CO.sub.2 H
(c) C.sub.1-10 alkyl-NH.sub.2
(d) phenyl or mono-, di- or tri-substituted phenyl wherein the substituents are independently selected from halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alklyCO.sub.2 H, C.sub.1-10 alkylNH.sub.2, CN, CO.sub.2 H and CF.sub.3,
(e) benzyl or mono-, di- or tri-substituted benzyl wherein the substituents are independently selected from halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alkylCO.sub.2 H, C.sub.1-10 alkylNH.sub.2, CN, CO.sub.2 H and CF.sub.3,
(f) C.sub.3-10 cycloalkyl,
(g) C.sub.1-10 alkanoyl, and
(h) benzoyl or mono-, di-, or trisubstituted benzoyl wherein the substituents are independently selected from halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alkylCO.sub.2 H, --C.sub.1-10 alkylNH.sub.2, CN, CO.sub.2 H and CF.sub.3,
each R.sup.10 is independently selected from the group consisting of
(a) hydrogen and
(b) R.sup.11 ;
R.sup.11 is selected from the group consisting of
(a) C.sub.1-10 alkyl,
(b) C.sub.3-10 cycloalkyl,
(c) unsubstituted, mono-, di- or tri-substituted phenyl or naphthyl wherein the substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-10 alkoxy,
(3) C.sub.1-10 alkylthio,
(4) CN,
(5) CF.sub.3,
(6) C.sub.1-10 alkyl,
(7) N.sub.3,
(8) --CO.sub.2 H,
(9) --CO.sub.2 --C.sub.1-10 alkyl,
(10) --C(R.sup.12)(R.sup.13)--OH,
(11) --C(R.sup.12)(R.sup.13)--O--C.sub.1-4 alkyl,
(12) --C.sub.1-6 alkyl-CO.sub.2 --R.sup.12,
(13) benzyloxy,
(14) --O--(C.sub.1-10 alkyl)-CO.sub.2 R.sup.12, and
(15) --O--(C.sub.1-10 alkyl)-NR.sup.12 R.sup.13,
(d) unsubstituted, 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 said 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, and wherein said substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-10 alkyl,
(3) C.sub.1-10 alkoxy,
(4) C.sub.1-10 alkylthio,
(5) CN,
(6) CF.sub.3,
(7) N.sub.3,
(8) --C(R.sup.12)(R.sup.13)--OH, and
(9) --C(R.sup.12)(R.sup.13)--O--C.sub.1-10 alkyl;
(e) unsubstituted, mono- or di-substituted benzoheterocycle in which the benzoheterocycle is a 5, 6, or 7-membered ring which contains 1 or 2 heteroatoms independently selected from O, S, or N and optionally a carbonyl group or a sulfonyl group, wherein said substituents are selected from the group consisting of
(1) halo,
(2) C.sub.1-10 alkyl,
(3) C.sub.1-10 alkoxy,
(4) C.sub.1-10 alkylthio,
(5) CN,
(6) CF.sub.3,
(7) N.sub.3,
(8) --C(R.sup.12)(R.sup.13)--OH, and
(9) --C(R.sup.12)(R.sup.13)--O--C.sub.1-10 alkyl;
(f) unsubstituted, mono- or di-substituted benzocarbocycle in which the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, wherein said substituents are independently selected from the group consisting of
(1) halo,
(2) C.sub.1-10 alkyl,
(3) C.sub.1-10 alkoxy,
(4) C.sub.1-10 alkylthio,
(5) CN,
(6) CF.sub.3,
(7) N.sub.3,
(8) --C(R.sup.12)(R.sup.13)--OH, and
(9) --C(R.sup.12)(R.sup.13)--O--C.sub.1-10 alkyl;
each R.sup.12 or R.sup.13 is independently selected from the group consisting of
(a) hydrogen, and
(b) C.sub.1-10 alkyl,
or R.sup.12 and R.sup.13 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.16 is independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl and unsubstituted or mono- or disubstituted benzyl, wherein the substituents are selected from halo, CN, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio or C.sub.1-6 fluoroalkyl;
each R.sup.17 is independently selected from the group consisting of
(a) hydrogen and
(b) R.sup.18 ;
and
each R.sup.18 is independently selected from the group consisting of
(a) C.sub.1-10 alkyl,
(b) --C.sub.1-10 alkyl-CO.sub.2 H
(c) C.sub.1-10 alkyl-NH.sub.2
(d) phenyl or mono-, di- or tri-substituted phenyl wherein the substituents are independently selected from halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alklyCO.sub.2 H, C.sub.1-10 alkylNH.sub.2, CN, CO.sub.2 H and CF.sub.3,
(e) benzyl or mono-, di- or tri-substituted benzyl wherein the substituents are independently selected from halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alkylCO.sub.2 H, C.sub.1-10 alkylNH.sub.2, CN, CO.sub.2 H and CF.sub.3,
(f) C.sub.3-10 cycloalkyl,
(g) H-(oxyethyl)n wherein n is 1 to 6,
(h) C.sub.1-10 alkanoyl, and
(i) benzoyl or mono-, di-, or trisubstituted benzoyl wherein the substituents are independently selected from halo, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alkylCO.sub.2 H, --C.sub.1-10 alkylNH.sub.2, CN, CO.sub.2 H and CF.sub.3.

202 more elements

Facts

Application

08/738,143Filed 25 Oct 1996

Priority

GB 960287713 Feb 1996

Granted

16 Dec 1997

Term ends

Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07D 307/32
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
C07C 317/22
Having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton: with sulfone or sulfoxide groups bound to…
C07C 323/64
Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio…
C07D 213/34
Sulfur atoms: to which a second hetero atom is attached