Claims
- 1. A compound having the structural formula ##STR7## wherein L--R.sup.1 is a substituted or unsubstituted triazolyl;
- R.sup.2 is primary or secondary alkyl of two to four carbon atoms, primary alkylamino of one to three carbon atoms, primary alkylmethylamino of two to four carbon atoms, diethylamino or primary alkoxy of one to three carbon atoms; and
- R.sup.3 is from one to three substituents at any or all of the 5-, 6- and 7-positions and is selected from the group consisting of hydrogen, lower-alkyl, cycloalkyl, amino lower-alkyl, lower-alkylamino-lower-alkyl, di-lower-alkylamino-lower-alkyl, hydroxy-lower-alkyl, lower-alkoxy-lower-alkyl, perfluoro-lower-alkyl, perchloro-lower-alkyl, formyl, cyano, carboxy, aminocarbonyl, R-oxycarbonyl, B.dbd.N wherein B.dbd.N is amino, lower-alkylamino, di-lower alkylamino, carboxy-lower-alkylamino, 1-pyrrolidinyl, 1-piperdinyl, 1-azetidinyl, 4-morpholinyl, 1-piperazinyl, 4-lower-alkyl-1-piperazinyl, 4-benzyl-1-piperazinyl or 1-imidazolyl, 1-lower-alkyl-2-pyrrolyl, lower alkylsulfonylamino, perfluoro-lower-alkylsulfonylamino, perchloro-lower alkylsulfonylamino, nitro, hydroxy, lower-alkoxy, cycloalkoxy, B.dbd.N-lower-alkoxy, hydroxy-lower-alkoxy, polyhydroxy-lower-alkoxy, or acetal or ketal thereof, lower-alkoxy-lower-alkoxy, poly-lower-alkoxy lower-alkoxy, hydroxy-poly-lower alkylenoxy, lower-alkoxy-poly-lower-alkylenoxy, B.dbd.N-carbonyloxy, carboxy-lower-alkoxy, R-oxycarbonyl lower-alkoxy, methylenedioxy, di-lower-alkylphosphonyloxy, R-thio, R-sulfinyl, R-sulfonyl, perfluoro-lower-alkylsulfonyl, perchloro-lower alkylsulfonyl, aminosulfonyl, lower-alkylaminosulfonyl, di-lower alkylaminosulfonyl and halo wherein R is lower-alkyl, phenyl, benzyl or naphthyl or phenyl or naphthyl having one or two substituents selected from the group consisting of lower-alkyl, lower-alkoxy and halo;
- or a pharmaceutically acceptable acid addition salt thereof if the compound has a basic functional group or a pharmaceutically acceptable base addition salt thereof if the compound has an acidic functional group.
- 2. A compound according to claim 1 wherein R.sup.2 is primary or secondary alkyl of two to four carbon atoms.
- 3. A compound according to claim 1 wherein R.sup.2 is isopropyl.
- 4. A compound according to claim 3 wherein R.sup.3 is hydroxy, lower-alkoxy, cycloalkoxy, B.dbd.N-lower-alkoxy, hydroxy-lower-alkoxy, polyhydroxy-lower-alkoxy or acetal or ketal thereof, lower-alkoxy-lower-alkoxy, poly-lower-alkoxy-lower-alkoxy, lower-alkoxy-poly-lower-alkoxy, B.dbd.N-carbonyloxy, carboxy-lower-alkoxy, R-oxycarbonyl-lower-alkoxy, or methylenedioxy.
- 5. A compound according to claim 4 wherein R.sup.3 is lower-alkoxy.
- 6. A compound according to claim 5 wherein R.sup.3 is methoxy.
- 7. A compound according to claim 6 wherein R.sup.3 is 6-methoxy.
- 8. A compound according to claim 7 wherein L is N and H--L--R.sup.1 has a pK.sub.a value less than or equal to 6.
- 9. A compound of claim 1 wherein the triazolyl is substituted with one or two of the following: butylsulfonyl; methoxycarbonyl; phenylsulfonyl; phenyl, ethoxycarbonyl; carboxy; trimethylsilyl; isopropyl; aminocarbonyl; dicarboxy; dimethylaminosulfonyl; t-butyl; cyano; 1-piperdinylcarbonyl; or trifluoromethyl.
- 10. A compound of claim 1 wherein L--R.sup.1 is 1,2,3-triazo-1-yl or 1,2,3-triazo-2-yl having substituted thereon, 4,5-di(t-butylsulfonyl); 4,5, di(methoxycarbonyl); 4-phenylsulfonyl; 4-methoxycarbonyl; 5-methoxycarbonyl; 4-phenyl-5-ethoxycarbonyl; 4-ethoxycarbonyl-5-phenyl; 4-carboxy; 4-trimethylsilyl-5-phenylsulfonyl; 5-phenylsulfonyl; 4-isopropyl-5-phenylsulfonyl; 4,5-di(aminocarbonyl); 4,5-dicarboxy; 4-trimethylsilyl-5-dimethylaminosulfonyl; 4-(t-butyl)-5-dimethylaminosulfonyl; 4-dimethylaminosulfonyl-5-(t-butyl); 4-trimethylsilyl; 4,5-dicyano; 4,5-di(1-piperdinylcarbonyl); or 4,5-di(trifluoromethyl).
- 11. A compound of claim 1 wherein L--R1 is 4,5-di(t-butylsulfonyl)-1,2,3-triazo-1-yl; 4,5,di(methoxycarbonyl)-1,2,3-triazo-1-yl; 4-phenylsulfonyl-1,2,3-triazo-1-yl; 4-methoxycarbonyl-1,2,3-triazo-1-yl; 5-methoxycarbonyl-1,2,3-triazo-1-yl; 4-phenyl-5-ethoxycarbonyl-1,2,3-triazo-1-yl; 4-ethoxycarbonyl-5-phenyl-1,2,3-triazo-1-yl; 4-carboxy-1,2,3-triazo-1-yl; 4-trimethylsilyl-5-phenylsulfonyl-1,2,3-triazo-1-yl; 5-phenylsulfonyl-1,2,3-triazo-1-yl; 4-isopropyl-5-phenylsulfonyl-1,2,3-triazo-1-yl; 4,5-di(aminocarbonyl)-1,2,3-triazo-1-yl; 4,5dicarboxy-1,2,3-triazo-1-yl; 4-trimethylsilyl-5-dimethylaminosulfonyl-1,2,3-triazo-1-yl; 4-(t-butyl)-5-dimethylaminosulfonyl-1,2,3-triazo-1-yl; 4-dimethylaminosulfonyl-5-(t-butyl)-1,2,3-triazo-1-yl; 4-trimethylsilyl-1,2,3-triazo-1-yl; 4,5-dicyano-1,2,3-triazo-1-yl; 4,5-di(1-piperdinylcarbonyl)-1,2,3-triazo-1-yl; 4,5-di(trifluoromethyl)-1,2,3-triazo-1-yl; 4,5-di(1-piperdinylcarbonyl)-1,2,3-triazo-2-yl; or 4,5-dicyano-1,2,3-triazo-2-yl.
- 12. A compound of claim 1 wherein the triazolyl is 1,2,3-triazo-1-yl.
- 13. The compound of 2-[4,5-di(t-butylsulfonyl)-1,2,3-triazol-1-yl]methyl-4-isopropyl-6-methoxysaccharin or a pharmaceutically acceptable salt thereof.
- 14. A pharmaceutical composition for the treatment of generative disease which comprises a proteolytic inhibiting concentration of a compound in a pharmaceutical carrier, wherein the compound has the structure: ##STR8## wherein L--R.sup.1 is a substituted or unsubstituted triazolyl;
- R.sup.2 is primary or secondary alkyl of two to four carbon atoms, primary alkylamino of one to three carbon atoms, primary alkylmethylamino of two to four carbon atoms, diethylamino or primary alkoxy of one to three carbon atoms; and
- R.sup.3 is from one to three substituents at any or all of the 5-, 6- and 7-positions and is selected from the group consisting of hydrogen, lower-alkyl, cycloalkyl, amino lower-alkyl, lower-alkylamino-lower-alkyl, di-lower-alkylamino-lower-alkyl, hydroxy-lower-alkyl, lower-alkoxy-lower-alkyl, perfluoro-lower-alkyl, perchloro-lower-alkyl, formyl, cyano, carboxy, aminocarbonyl, R-oxycarbonyl, B.dbd.N wherein B.dbd.N is amino, lower-alkylamino, di-lower alkylamino, carboxy-lower-alkylamino, 1-pyrrolidinyl, 1-piperidinyl, 1-azetidinyl, 4-morpholinyl, 1-piperazinyl, 4-lower-alkyl-1-piperazinyl, 4-benzyl-1-piperazinyl or 1-imidazolyl, 1-lower-alkyl-2-pyrrolyl, lower alkylsulfonylamino, perfluoro-lower-alkylsulfonylamino, perchloro-lower alkylsulfonylamino, nitro, hydroxy, lower-alkoxy, cycloalkoxy, B.dbd.N-lower-alkoxy, hydroxy-lower-alkoxy, polyhydroxy-lower-alkoxy, or acetal or ketal thereof, lower-alkoxy-lower-alkoxy, poly-lower-alkoxy lower-alkoxy, hydroxy-poly-lower alkylenoxy, lower-alkoxy-poly-lower-alkylenoxy, B.dbd.N-carbonyloxy, carboxy-lower-alkoxy, R-oxycarbonyl lower-alkoxy, methylenedioxy, di-lower-alkylphosphonyloxy, R-thio, R-sulfinyl, R-sulfonyl, perfluoro-lower-alkylsulfonyl, perchloro-lower alkylsulfonyl, aminosulfonyl, lower-alkylaminosulfonyl, di-lower alkylaminosulfonyl and halo wherein R is lower-alkyl, phenyl, benzyl or naphthyl or phenyl or naphthyl having one or two substituents selected from the group consisting of lower-alkyl, lower-alkoxy and halo;
- or a pharmaceutically acceptable acid addition salt thereof if the compound has a basic functional group or a pharmaceutically acceptable base addition salt thereof if the compound has an acidic functional group.
- 15. A compound of claim 14 wherein the triazolyl is substituted with one or two of the following: butylsulfonyl; methoxycarbonyl; phenylsulfonyl phenyl; ethoxycarbonyl; carboxy; trimethylsilyl; isopropyl; aminocarbonyl; dicarboxy; dimethylaminosulfonyl; t-butyl; cyano; 1-piperdinylcarbonyl; or trifluoromethyl.
- 16. A compound of claim 14 wherein L--R.sup.1 is 1,2,3-triazo-1-yl or 1,2,3-triazo-2-yl having substituted thereon, 4,5-di(t-butylsulfonyl); 4,5, di(methoxycarbonyl); 4-phenylsulfonyl; 4-methoxycarbonyl; 5-methoxycarbonyl; 4-phenyl-5-ethoxycarbonyl; 4-ethoxycarbonyl-5-phenyl; 4-carboxy; 4-trimethylsilyl-5-phenylsulfonyl; 5-phenylsulfonyl; 4-phenylsulfonyl-5-isopropyl; 4-isopropyl-5-phenylsulfonyl; 4,5-di(aminocarbonyl); 4,5-dicarboxy; 4-trimethylsilyl-5-dimethylaminosulfonyl; 4-(t-butyl)-5-dimethylaminosulfonyl; 4-(t-butyl)-5-dimethylaminosulfonyl; 4-dimethylaminosulfonyl-5-(t-butyl); 4-trimethylsilyl; 4,5-dicyano; 4,5-di(1-piperdinylcarbonyl); or 4,5-di(trifluoromethyl).
- 17. A compound of claim 14 wherein L--R1 is 4,5-di(t-butylsulfonyl)-1,2,3-triazo-1-yl; 4,5, di(methoxycarbonyl)-1,2,3-triazo-1-yl; 4-phenylsulfonyl-1,2,3-triazo-1-yl; 4-methoxycarbonyl-1,2,3-triazo-1-yl; 5-methoxycarbonyl-1,2,3-triazo-1-yl; 4-phenyl-5-ethoxycarbonyl-1,2,3-triazo-1-yl; 4-ethoxycarbonyl-5-phenyl-1,2,3-triazo-1-yl; 4-carboxy-1,2,3-triazo-1-yl; 4-trimethylsilyl-5-phenylsulfonyl-1,2,3-triazo-1-yl; 5-phenylsulfonyl-1,2,3-triazo-1-yl; 4-phenylsulfonyl-5-isopropyl-1,2,3-triazo-1-yl; 4-isopropyl-5-phenylsulfonyl-1,2,3-triazo-1-yl; 4,5-di(aminocarbonyl)-1,2,3-triazo-1-yl; 4,5-dicarboxy-1,2,3-triazo-1-yl; 4-trimethylsilyl-5-dimethylaminosulfonyl-1,2,3-triazo-1-yl; 4-(t-butyl)-5-dimethylaminosulfonyl-1,2,3-triazo-1-yl; 4-dimethylaminosulfonyl-5-(t-butyl)-1,2,3-triazo-1-yl; 4-trimethylsilyl-1,2,3-triazo-1-yl; 4,5-dicyano-1,2,3-triazo-1-yl; 4,5-di(1-piperdinylcarbonyl)-1,2,3-triazo-1-yl; 4,5-di(trifluoromethyl)-1,2,3-triazo-1-yl; 4,5-di(1-piperdinylcarbonyl)-1,2,3-triazo-2-yl; or 4,5-dicyano-1,2,3-triazo-2-yl.
- 18. A compound of claim 14 wherein the triazolyl is 1,2,3-triazo-1-yl.
Parent Case Info
This application is a division of our prior application Ser. No. 08/113,508, filed on Aug. 27, 1993, now U.S. Pat. No. 5,380,737, issued Jan. 10, 1995; which in turn is a continuation of our prior application Ser. No. 07/793,035, filed Nov. 15, 1991, now abandoned; which in turn is a continuation-in-part of our three following prior applications: application Ser. No. 07/514,920, filed Apr. 26, 1990, now abandoned, application Ser. No. 07/608,068, filed Nov. 1, 1990, now abandoned, and application Ser. No. 07/782,016, filed Oct. 24, 1991, now U.S. Pat. No. 5,128,239, issued Jul. 7, 1992. Application Ser. No. 07/514,920 is a continuation-in-part of application Ser. No. 07/347,125 and application Ser. No. 07/347,126, which were both filed May 4, 1989 and are both now abandoned. Application Ser. No. 07/782,016 is a continuation-in-part of application Ser. No. 07/608,068 which is now abandoned.
US Referenced Citations (4)
Foreign Referenced Citations (1)
Number |
Date |
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WO9013549 |
Nov 1990 |
WOX |
Non-Patent Literature Citations (1)
Entry |
Choi et al., J. Heterocyclic Chem. 1989, 26, 1073-1076. |
Divisions (1)
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113508 |
Aug 1993 |
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Continuations (1)
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793035 |
Nov 1991 |
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Continuation in Parts (3)
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514920 |
Apr 1990 |
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347125 |
May 1989 |
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608068 |
Nov 1990 |
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