Claims
- 1. A compound of Formula (I) ##STR7## wherein: R.sub.1 is independently --(CR4R5)nC(O)O(CR4R5)mR6, --(CR4R5)nC(O)NR4(CR4R5)mR6, --(CR4R5)nO(CR4R5)mR6, or --(CR4R5)rR6 wherein the alkyl moieties are unsubstituted or substituted with one or more halogens;
- m is 0 to 2;
- n is 1 to 4;
- r is 0 to 6;
- R.sub.4 and R.sub.5 are independently hydrogen or a C.sub.1-2 alkyl;
- R.sub.6 is independently hydrogen, methyl, hydroxyl, aryl, halo substituted aryl, aryloxyC.sub.1-3 alkyl, halo substituted aryloxyC.sub.1-3 alkyl, indanyl, indenyl, C.sub.7-11 polycycloalkyl, tetrahydrofuranyl, furanyl, tetrahydropyranyl, pyranyl, tetrahydrothienyl, thienyl, tetrahydrothiopyranyl, thiopyranyl, C.sub.3-6 cycloalkyl, or a C.sub.4-6 cycloalkyl containing one or two unsaturated bonds, wherein the cycloalkyl or heterocyclic moiety may be unsubstituted or substituted by 1 to 3 methyl groups, one ethyl group or an hydroxyl group;
- provided that:
- a) when R.sub.6 is hydroxyl, then m is 2; or
- b) when R.sub.6 is hydroxyl, then r is 2 to 6; or
- c) when R.sub.6 is 2-tetrahydropyranyl, 2-tetrahydrothiopyranyl, 2-tetrahydrofuranyl, or 2-tetrahydrothienyl, then m is 1 or 2; or
- d) when R.sub.6 is 2-tetrahydropyranyl, 2-tetrahydrothiopyranyl, 2-tetrahydrofuranyl, or 2-tetrahydrothienyl, then r is 1 to 6;
- e) when n is 1 and m is 0, then R.sub.6 is other than H in --(CR.sub.4 R.sub.5).sub.n O(CR.sub.4 R.sub.5).sub.m R.sub.6 ;
- X is independently YR.sub.2, fluorine, NR.sub.4 R.sub.5, or formyl amine;
- Y is independently O or S(O).sub.m' ;
- m' is 0, 1, or 2;
- X.sub.2 is O or NR.sub.8 ;
- X.sub.3 is independently hydrogen or X;
- R.sub.2 is independently --CH.sub.3 or --CH.sub.2 CH.sub.3 unsubstituted or substituted by 1 or more halogen
- s is 0 to 4;
- W is alkyl of 2 to 6 carbons, alkenyl of 2 to 6 carbons or alkynyl of 2 to 6 carbons;
- Z is independently S(O).sub.m' R.sub.9, OS(O).sub.2 R.sub.9, OR.sub.9, OC(O)NR.sub.7 R.sub.7, OC(O)(O).sub.q R.sub.7, O(CR.sub.4 R.sub.5).sub.n OR.sub.9, or NR.sub.9 R.sub.9 ;
- q is 0 or 1;
- R.sub.7 is independently hydrogen or R.sub.9 ;
- R.sub.8 is independently hydrogen or C.sub.1-4 alkyl unsubstituted or substituted by one to three fluorines, or when R.sub.8 and R.sub.10 are as --NR.sub.8 R.sub.10 they may together with the nitrogen form a a 5 to 7 membered ring comprised only of carbon atoms or carbon atoms and at least one heteroatom selected from O, N, or S;
- R.sub.9 is independently C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.3-7 cycloalkyl, C.sub.4-6 cycloalkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, each of which may be unsubstituted or substituted by one or more fluorine atoms, or two R.sub.9 terms appearing as NR.sub.9 R.sub.9 may together with the nitrogen form a 5 to 7 membered ring comprised only of carbon atoms or carbon atoms and at least one heteroatom selected from O, N, or S;
- R.sub.10 is independently OR.sub.8 or R.sub.8 ;
- provided that:
- f) when q is 1 in OC(O)(O).sub.q R.sub.7, then R.sub.7 is not hydrogen;
- or the pharmaceutically acceptable salts thereof.
- 2. A compound of Formula (II): ##STR8## wherein: R.sub.1 is independently --(CR.sub.4 R.sub.5).sub.n C(O)O(CR.sub.4 R.sub.5).sub.m R.sub.6, --(CR.sub.4 R.sub.5).sub.n C(O)NR.sub.4 (CR.sub.4 R.sub.5).sub.m R.sub.6, --(CR.sub.4 R.sub.5).sub.n O(CR.sub.4 R.sub.5).sub.m R.sub.6, or --(CR.sub.4 R.sub.5).sub.r R.sub.6 wherein the alkyl moieties are unsubstituted or substituted with one or more halogens;
- m is 0 to 2;
- n is 1 to 4;
- r is 0 to 6;
- R.sub.4 and R.sub.5 are independently hydrogen or a C.sub.1-2 alkyl;
- R.sub.6 is independently hydrogen, methyl, hydroxyl, aryl, halo substituted aryl, aryloxyC.sub.1-3 alkyl, halo substituted aryloxyC.sub.1-3 alkyl, indanyl, indenyl, C.sub.7-11 polycycloalkyl, tetrahydrofuranyl, furanyl, tetrahydropyranyl, pyranyl, tetrahydrothienyl, thienyl, tetrahydrothiopyranyl, thiopyranyl, C.sub.3-6 cycloalkyl, or a C.sub.4-6 cycloalkyl containing one or two unsaturated bonds, wherein the cycloalkyl or heterocyclic moiety may be unsubstituted or substituted by 1 to 3 methyl groups, one ethyl group or an hydroxyl group;
- provided that:
- a) when R.sub.6 is hydroxyl, then m is 2; or
- b) when R.sub.6 is hydroxyl, then r is 2 to 6; or
- c) when R.sub.6 is 2-tetrahydropyranyl, 2-tetrahydrothiopyranyl, 2-tetrahydrofuranyl, or 2-tetrahydrothienyl, then m is 1 or 2; or
- d) when R.sub.6 is 2-tetrahydropyranyl, 2-tetrahydrothiopyranyl, 2-tetrahydrofuranyl, or 2-tetrahydrothienyl, then r is 1 to 6;
- e) when n is 1 and m is 0, then R.sub.6 is other than H in --(CR.sub.4 R.sub.5).sub.n O(CR.sub.4 R.sub.5).sub.m R.sub.6 ;
- X is independently YR.sub.2, fluorine, NR.sub.4 R.sub.5, or formyl amine;
- Y is independently O or S(O).sub.m' ;
- m is 0, 1, or 2;
- X.sub.2 is O or NR.sub.8 ;
- X.sub.3 is independently hydrogen or X;
- R.sub.2 is independently --CH.sub.3 or --CH.sub.2 CH.sub.3 unsubstituted or substituted by 1 or more halogens;
- s is 0 to 4;
- W is alkyl of 2 to 6 carbons, alkenyl of 2 to 6 carbons or alkynyl of 2 to 6 carbons;
- Z is independently NHR.sub.14, S(O).sub.m' R.sub.9, OS(O).sub.2 R.sub.9, OR.sub.9, OC(O)NR.sub.7 R.sub.7, OC(O)(O).sub.q R.sub.7, O(CR.sub.4 R.sub.5).sub.n OR.sub.9, or NR.sub.9 R.sub.9 ;
- Z' is independently C(Y')R.sub.14, C(O)OR.sub.14, C(Y')NR.sub.10 R.sub.14, C(NR.sub.10)NR.sub.10 R.sub.14, CN, C(NOR.sub.8)R.sub.14, C(NOR.sub.14)R.sub.8, C(NR.sub.8)NR.sub.10 R.sub.14, C(NR.sub.14)NR.sub.8 R.sub.8 C(NCN)NR.sub.10 R.sub.14, C(NCN)SR.sub.11, (2-, 4- or 5-imidazolyl), (3-, 4- or 5-pyrazolyl), (4- or 5-triazolyl�1,2,3!), (3- or 5-triazolyl�1,2,4!), (5-tetrazolyl), (2-, 4- or 5-oxazolyl), (3-, 4- or 5-isoxazolyl), (3- or 5-oxadiazolyl�1,2,4!), (2-oxadiazolyl�1,3,4!), (2-thiadiazolyl�1,3,4!), (2-, 4-, or 5-thiazolyl), (2-, 4-, or 5-oxazolidinyl), (2-, 4-, or 5-thiazolidinyl), or (2-, 4-, or 5-imidazolidinyl); wherein all of the heterocylic ring systems may be optionally substituted one or more times by R.sub.14 ;
- Y' is O or S;
- q is 0 or 1;
- R.sub.7 is independently hydrogen or R.sub.9 ;
- R.sub.8 is independently hydrogen or C.sub.1-4 alkyl unsubstituted or substituted by one to three fluorines, or when R.sub.8 and R.sub.10 are as --NR.sub.8 R.sub.10 they may together with the nitrogen form a a 5 to 7 membered ring comprised only of carbon atoms or carbon atoms and at least one heteroatom selected from O, N, or S;
- R.sub.9 is independently C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.3-7 cycloalkyl, C.sub.4-6 cycloalkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, each of which may be unsubstituted or substituted by one or more fluorine atoms, or two R.sub.9 terms appearing as NR.sub.9 R.sub.9 may together with the nitrogen form a 5 to 7 membered ring comprised only of carbon atoms or carbon atoms and at least one heteroatom selected from O, N, or S;
- R.sub.10 is independently OR.sub.8 or R.sub.8 ;
- R.sub.11 is independently C.sub.1-4 alkyl unsubstituted or substituted by one to three fluorines;
- R.sub.12 is independently R.sub.13, C.sub.3-7 cycloalkyl, (2-, 3- or 4-pyridyl), pyrimidyl, pyrazolyl, (1- or 2-imidazolyl), pyrrolyl, piperazinyl, piperidinyl, morpholinyl, furanyl, (2- or 3-thienyl), quinolinyl, naphthyl, or phenyl;
- R.sub.13 is independently oxazolidinyl, oxazolyl, thiazolyl, pyrazolyl, triazolyl, tetrazolyl, imidazolyl, imidazolidinyl, thiazolidinyl, isoxazolyl, oxadiazolyl, or thiadiazolyl, and each of these heterocyclic rings is connected through a carbon atom and each may be unsubstituted or substituted by one or two C.sub.1-2 alkyl groups;
- R.sub.14 is independently hydrogen or R.sub.15 ; or when R.sub.10 and R.sub.14 are as NR.sub.10 R.sub.14 they may together with the nitrogen form a 5 to 7 membered ring comprised only of carbon atoms or carbon atoms and at least one heteroatom selected from O, N, or S;
- R.sub.15 is independently --(CR.sub.4 R.sub.5).sub.t R.sub.12 or C.sub.1-6 alkyl wherein the R.sub.12 or C.sub.1-6 alkyl group is unsubstituted or substituted by one or more times by methyl or ethyl unsubstituted or substituted by one to three fluorines, --F, --Br, --Cl, --NO.sub.2, --Si(R.sub.4).sub.2, --NR.sub.8 R.sub.10, --C(O)R.sub.8, --C(O)OR.sub.8, --O(CH.sub.2).sub.q R.sub.8, --CN, --C(O)NR.sub.8 R.sub.10, --O(CH.sub.2).sub.q C(O)NR.sub.8 R.sub.10, --O(CH.sub.2).sub.q C(O)R.sub.8, --NR.sub.10 C(O)NR.sub.8 R.sub.10, --NR.sub.10 C(O)R.sub.8, --NR.sub.10 C(O)OR.sub.9, --NR.sub.10 C(O)R.sub.13, --C(NR.sub.10)NR.sub.8 R.sub.10, --C(NCN)NR.sub.8 R.sub.10, --C(NCN)SR.sub.11, --NR.sub.10 C(NCN)SR.sub.11, --NR.sub.10 C(NCN)NR.sub.10 R.sub.8, --NR.sub.10 S(O).sub.2 R.sub.9, --S(O).sub.m' R.sub.11, --NR.sub.10 C(O)C(O)NR.sub.8 R.sub.10, --NR.sub.10 C(O)C(O)R.sub.10, or R.sub.13 ;
- t is 0, 1,or 2;
- provided that:
- f) when q is 1 in OC(O)(O).sub.q R.sub.7, then R.sub.7 is not hydrogen;
- or the pharmaceutically acceptable salts thereof.
- 3. A compound according to claim 1 which is
- 1,4bis-{�4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohex-1-en-1-yl trifluoromethylsulfonato!-4-yl}buta-1,3-diyne, and
- 1,4-bis-{�4-(3-cyclopentyloxy-4-methoxyphenyl)-1-methoxycyclohex-1-en!-4-yl}buta-1,3-diyn.
- 4. A pharmaceutical composition comprising a compound of Formula (I) according to claim 1 and a pharmaceutically acceptable excipient.
- 5. A pharmaceutical composition comprising a compound of Formula (II) according to claim 2 and a pharmaceutically acceptable excipient.
Parent Case Info
This is a continuation of Ser. No. 08/363,179 filed Dec. 23, 1994 abandoned.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US95/13322 |
10/10/1995 |
|
|
6/23/1997 |
6/23/1997 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO96/20162 |
7/4/1997 |
|
|
Non-Patent Literature Citations (1)
Entry |
S. Christensen, "Preparation of cyanocyclohexane compounds as tumor necrosis factor inhibitors", (1995), Chemical Abstracts, vol. 123, Abstract No. 143338. |
Continuations (1)
|
Number |
Date |
Country |
Parent |
363179 |
Dec 1994 |
|