Claims
- 1. A method for treating osteoporosis in an animal comprising administering to said animal a therapeutically-effective amount of a compound having the structure: ##STR86## or a pharmaceutically-acceptable salt thereof, wherein: R.sup.1 is: hydrogen, halogen or --CF.sub.3 ;
- R.sup.2 is: hydrogen, halogen, --OH or --OCH.sub.3 ;
- Z is: oxygen, sulfur, ##STR87## X is: --CH.dbd.CH--, --CF.sub.2 --, --CHF--, --(CH.sub.2).sub.n -- or --(CH.sub.2).sub.p --CH.dbd.CH--;
- Y is: ##STR88## sulfur, ##STR89## or oxygen; q is: 0 or 1;
- r is: 0 or 1, provided that r is not 0 when:
- (1) X is --CH.dbd.CH--, --(CH.sub.2).sub.n -- or --(CH.sub.2).sub.p --CH.dbd.CH--, q is 1 and Ar is imidazolyl or phenyl,
- (2) X is --(CH.sub.2).sub.n --, q is 1 and Ar is phenyl or alkyl-substituted phenyl, or
- (3) q is 0, m is 1, 2, 3, 4, 5 or 6, and Ar is imidazolyl, phenyl or alkyl-substituted phenyl;
- m is: an integer of from 0 to 6, provided that m is not 0 when X is --(CH.sub.2).sub.n --,
- q is 1, Y is oxygen, sulfur, ##STR90## r is 1, and Ar is phenyl or alkyl-substituted phenyl; n is: an integer of from 1 to 6;
- p is: an integer of from 1 to 6;
- R.sup.3 is: hydrogen or t-butyloxycarbonyl; and
- Ar is: aryl, alkyl-substituted aryl or aryl-substituted aryl.
- 2. The method of claim 1 wherein the compound is selected from the group consisting of:
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(2-pyridinyl)propyl]-hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(2-pyridinyl)propyl]hydrazide, monohydrochloride;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-4-(2-thienyl)butyl]-hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-3-hydroxy-1-oxo-3-(2-pyridinyl)propyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-3-hydroxy-1-oxo-3-(2-pyridinyl)propyl]hydrazide, monohydrochloride;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[(2-furanylmethyl)thio]-1-oxopropyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(2-thienylmethyl)-amino]propylhydrazide, monohydrochloride;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[(2-thienylmethoxy)acetyl]-hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[(2-furanylmethyl)amino]-1-oxopropyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-3-hydroxyl-1-oxo-3-(2thienyl)propyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]-hydrazide, monohydrochloride;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[2-(pyridylmethyl)thio]-1-oxopropyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[(2-furanylmethyl)sulfinyl]-1-oxopropyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[(2-furanylmethyl)sulfonyl]-1-oxopropyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-3R-hydroxy-1-oxo-3-(2-pyridinyl)propyl]hydrazide, monohydrochloride;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-3S-hydroxy-1-oxo-3-(2-pyridinyl)propyl]hydrazide, acetate, monohydrochloride; and
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-1-oxo-3-(2-pyridinyl)propyl]hydrazide.
- 3. A method for treating ischemia in an animal comprising administering to said animal a therapeutically-effective amount of a compound having the structure: ##STR91## or a pharmaceutically-acceptable salt thereof, wherein: R.sup.1 is: hydrogen, halogen or --CF.sub.3 ;
- R.sup.2 is: hydrogen, halogen, --OH or --OCH.sub.3 ;
- Z is: oxygen, sulfur, ##STR92## X is: --CH.dbd.CH--, --CF.sub.2 --, --CHF--, --(CH.sub.2).sub.n -- or --(CH.sub.2).sub.p --CH.dbd.CH--;
- Y is: ##STR93## sulfur, ##STR94## or oxygen; q is: 0 or 1;
- r is: 0 or 1, provided that r is not 0 when:
- (1) X is --CH.dbd.CH--, --(CH.sub.2).sub.n -- or --(CH.sub.2).sub.p --CH.dbd.CH--, q is 1 and Ar is imidazolyl or phenyl,
- (2) X is --(CH.sub.2).sub.n --, q is 1 and Ar is phenyl or alkyl-substituted phenyl, or
- (3) q is 0, m is 1, 2, 3, 4, 5 or 6, and Ar is imidazolyl, phenyl or alkyl-substituted phenyl;
- m is: an integer of from 0 to 6, provided that m is not 0 when X is --(CH.sub.2).sub.n --,
- q is 1, Y is oxygen, sulfur, ##STR95## r is 1, and Ar is phenyl or alkyl-substituted phenyl; n is: an integer of from 1 to 6;
- p is: an integer of from 1 to 6;
- R.sup.3 is: hydrogen or t-butyloxycarbonyl; and
- Ar is: aryl, alkyl-substituted aryl or aryl-substituted aryl.
- 4. The method of claim 3 wherein the compound is selected from the group consisting of:
- 8-chlorodibenz [b,f][1,4]oxazepine-10(11H) -carboxylic acid, 2-[1-oxo-3-(2-pyridinyl)propyl]-hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(2-pyridinyl)propyl]hydrazide, monohydrochloride;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-4-(2-thienyl)butyl]-hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-3-hydroxy-1-oxo-3-(2-pyridinyl)propyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-3-hydroxy-1-oxo-3-(2-pyridinyl)propyl]hydrazide, monohydrochloride;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[(2-furanylmethyl)thio]-1-oxopropyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(2-thienylmethyl)-amino]propylhydrazide, monohydrochloride;
- 8-chlorodibenz[b,f][1,4]oxazepine-10 (11H) -carboxylic acid, 2-[(2-thienylmethoxy)acetyl]-hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[(2-furanylmethyl)amino]-1-oxopropyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-3-hydroxyl-1-oxo-3-(2-thienyl)propyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]-hydrazide, monohydrochloride;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[2-(pyridylmethyl)thio]-1-oxopropyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[(2-furanylmethyl)sulfinyl]-1-oxopropyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[(2-furanylmethyl)sulfonyl]-1-oxopropyl]hydrazide;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-3R-hydroxy-1-oxo-3-(2-pyridinyl)propyl]hydrazide, monohydrochloride;
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-3S-hydroxy-1-oxo-3-(2-pyridinyl)propyl]hydrazide, acetate, monohydrochloride; and
- 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[2,2-difluoro-1-oxo-3-(2-pyridinyl)propyl]hydrazide.
Parent Case Info
This application is a divisional application under 37 CFR .sctn.1.60 of application Ser. No. 08/295,302, filed on Aug. 24, 1994, now U.S. Pat. No. 5,464,830, which is a continuation application under 37 CFU .sctn.1.60 of application Ser. No. 08/108,551, filed on Aug. 24, 1993, now U.S. Pat. No. 5,378,840, which is a continuation-in-part application of Ser. No. 07/695,654, filed on May 3, 1991, now abandoned.
US Referenced Citations (16)
Foreign Referenced Citations (1)
Number |
Date |
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0012385 |
Jun 1980 |
EPX |
Divisions (1)
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Number |
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295302 |
Aug 1994 |
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Continuations (1)
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108551 |
Aug 1993 |
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Continuation in Parts (1)
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695654 |
May 1991 |
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