Claims
- 1. A compound of the formula: ##STR28## wherein R.sup.1 is H, OH, loweralkyl, cycloloweralkyl, loweralkynyl, loweralkenyl, substituted or unsubstituted phenyl(wherein the substituents are 1 or 2 of halo, loweralkyl, loweralkoxy, or hydroxy), --(CH.sub.2).sub.m NR.sup.4 R.sup.5, CX.sub.3.sup.10, or --(CH.sub.2).sub.n COOR.sup.6 ;
- R.sup.2 is H, loweralkyl, substituted or unsubstituted phenyl (wherein the substitutents are 1 or 2 of halo, loweralkyl, loweralkoxy, loweralkylthio, carboxyl, carboxyloweralkyl, nitro, --CF.sub.3, ##STR29## or hydroxy), or --(CH.sub.2).sub.m COOR.sup.6 ; R.sup.3 is --(CH.sub.2).sub.n R.sup.7, ##STR30## R.sup.4 and R.sup.5 are independently H, loweralkyl, or cycloloweralkyl or are connected to form a hetero ring ##STR31## wherein n is 2-6; R.sup.6 is H, loweralkyl, cycloloweralkyl, substituted or unsubstituted phenyl (wherein the substituents are 1 or 2 of halo, loweralkyl, loweralkoxy, nitro, or CF.sub.3), or substituted or unsubstituted phenylloweralkyl (wherein the substituents are 1 or 2 of halo, loweralkyl, loweralkoxy, nitro, or CF.sub.3);
- R.sup.7 and R.sub.a.sup.7 are independently .alpha.- or .beta.-naphthyl, substituted or unsubstituted phenyl (wherein the substituents are 1 to 2 of halo, --NO.sub.2, --OH, --NR.sup.4 R.sup.5, cyano, phenyl, trifluoromethyl, acetylamino, acetyloxy, loweralkylthio, SCF.sub.3, --C.tbd.CH, CH.sub.2 SCF.sub.3, OCHF.sub.2, SH, S-phenyl, PO.sub.3 H, or loweralkoxy), ##STR32## (with the proviso that q is not 0 or 1 in --(CH.sub.2).sub.n NH(CH.sub.2).sub.q R.sup.7 and that q is not 0 in ##STR33## when R.sup.7 or R.sub.a.sup.7 is ##STR34## R.sup.8 is H, loweralkyl, cycloloweralkyl, --(CH.sub.2).sub.m CONH.sub.2, --(CH.sub.2).sub.m COOR.sup.6, --(CH.sub.2).sub.n -cycloloweralkyl, --(CH.sub.2).sub.m NR.sub.4 R.sub.5, ##STR35## R.sup.9 and R.sup.10 are independently H, --OH, or --CH.sub.3 ; R.sup.11 and R.sup.12 are independently loweralkyl or cycloloweralkyl;
- R.sup.13 is H, loweralkyl, acyl, O, or cycloloweralkyl;
- R.sup.14 is loweralkyl or phenylloweralkyl;
- R.sup.18 is H, loweralkyl, or acyl;
- m is 1-4;
- n is 0-4;
- p is 0 when its adjacent is unsaturated or when R.sup.3 is =CHR.sup.7, and it is 1 when its adjacent is saturated, except that when R.sup.13 is O, p=1 and is unsaturated;
- q is 0-4;
- r is 1 or 2;
- X.sup.1 is H, --NO.sub.2, CF.sub.3 CN, OH, loweralkyl, halo, loweralkylthio, loweralkoxy, --(CH.sub.2).sub.n COOR.sup.6, --NR.sup.4 R.sup.5, or ##STR36## X.sup.2 and X.sup.3 are independently H, --OH, --NO.sub.2, halo, loweralkylthio, loweralkyl, loweralkoxy or ##STR37## X.sup.4 is S, O, CH.sub.2, or NR.sup.8 ; X.sup.5 is H, CF.sub.3, CN, --COOR.sup.6, NO.sub.2, or halo;
- X.sup.6 is O or HH;
- X.sup.8 is H or loweralkyl;
- X.sup.9 and X.sub.a.sup.9 are independently NR.sup.18, O
- X.sup.10 is F, Cl, Br;
- is a saturated or unsaturated bond, such that both bonds in the seven-membered ring of Formula I may be saturated (single bonds), but both may not be unsaturated (double bonds),
- and the pharmaceutically acceptable salts thereof.
- 2. A compound of claim 1 wherein:
- R.sup.1 is H, loweralkyl, unsubstituted phenyl --(CH.sub.2).sub.n COOR.sup.6, or --(CH.sub.2).sub.m NR.sup.4 R.sup.5 ;
- R.sup.2 is substituted or unsubstituted phenyl (wherein the substituents are 1 or 2 of halo, loweralkyl, loweralkoxy, carboxyl, carboxyloweralkyl, nitro, --CF.sub.3, or hydroxy), or --(CH.sub.2).sub.m COOR.sup.6 ;
- R.sup.3 is ##STR38## R.sup.4 and R.sup.5 are independently H or loweralkyl; R.sup.6 is H or loweralkyl;
- R.sup.7 is .alpha.- or .beta.-naphthyl. ##STR39## substituted or unsubstituted phenyl (wherein the substituents are 1 to 2 of halo, --NO.sub.2, --OH, --NR.sup.4 R.sup.5, loweralkyl, CF.sub.3, loweralkoxy loweralkylthio, CN, --C.tbd.CH, SCF.sub.3, ##STR40## OCHF.sub.2, or SPh), ##STR41## R.sup.8 is H, loweralkyl, or ##STR42## R.sup.9 and R.sup.10 are independently H, --OH, or --CH.sub.3 ; R.sup.11 and R.sup.12 are independently loweralkyl;
- R.sup.13 is H, O, loweralkyl, or acyl;
- R.sup.14 is loweralkyl;
- m is 1-4;
- n is 0-4;
- p is 0 when its adjacent is unsaturated and 1 when its adjacent is saturated, except that when R.sup.13 is O, p=1 and is unsaturated.
- q is 0-4;
- r is 1 or 2;
- X.sup.1 is H, --NO.sub.2, CF.sub.3, CN, OH, loweralkyl, halo, loweralkylthio, loweralkoxy, --(CH.sub.2).sub.n COOR.sup.6, or --NR.sup.4 R.sup.5 ;
- X.sup.2 and X.sup.3 are independently H, --OH, --NO.sub.2, halo, loweralkylthio, loweralkyl, or loweralkoxy;
- X.sup.4 is S, O, or NR.sup.8 ;
- X.sup.6 is O or NH;
- is a saturated or unsaturated bond
- and the pharmaceutically acceptable salts thereof.
- 3. A compound of claim 2 wherein:
- R.sup.1 is H, methyl, ethyl, unsubstituted phenyl, carboxyl, carboxymethyl, or --CH.sub.2 N(CH.sub.3).sub.2 ;
- R.sup.2 is substituted or unsubstituted phenyl (wherein the substitutents are 1 or 2 of halo or carboxyl), or --(CH.sub.2).sub.1-2 COOR.sup.6 ;
- R.sup.3 is ##STR43## R.sup.6 is H or loweralkyl; R.sup.7 is .alpha.- or .beta.-naphthyl, ##STR44## substituted phenyl (wherein the substituents are 1 or 2 of halo, loweralkyl, or CF.sub.3), or ##STR45## R.sup.8 is H, methyl, or ethyl; R.sup.9 and R.sup.10 are independently H, --OH, or --CH.sub.3 ;
- R.sup.13 is H, methyl or formyl;
- R.sup.14 is t-butyl;
- n is 0-4;
- p is 0 when its adjacent is unsaturated and 1 when its adjacent is saturated;
- q is 0-4;
- r is 1 or 2;
- X.sup.1 is H, --NO.sub.2, CF.sub.3, CN, OH, or halo;
- X.sup.2 and X.sup.3 are independently H, --OH, --NO.sub.2, or halo;
- is a saturated or unsaturated bond
- and the pharmaceutically acceptable salts thereof.
- 4. A compound of claim 3 wherein:
- R.sup.1 is H, methyl, or carboxyl;
- R.sup.2 is phenyl, o-fluorophenyl, p-fluorophenyl, o-chlorophenyl, p-chlorophenyl, o-carboxyphenyl, 2,6-difluorophenyl, --CH.sub.2 COOEt, --CH.sub.2 COO--t--Bu, --CH.sub.2 CH.sub.2 COOEt, or --CH.sub.2 CH.sub.2 COOt--Bu;
- R.sup.3 is ##STR46## and the stereochemistry relates to D-tryptophan; R.sup.6 is H, methyl, or ethyl;
- R.sup.7 is .alpha.- or .beta.-naphthyl, ##STR47## or mono- or dihalophenyl; R.sup.9 and R.sup.10 are independently H or --OH;
- R.sup.13 is H;
- R.sup.14 is t-butyl;
- p is 0 when its adjacent is unsaturated and 1 when its adjacent is saturated;
- r is 1;
- X.sup.1 is H, chloro, fluoro, or nitro;
- X.sup.2 and X.sup.3 are independently H, --OH, fluoro, or chloro;
- is a saturated or unsaturated bond
- and the pharmaceutically acceptable salts thereof.
- 5. A compound of claim 1 which is
- 6-(2-Fluorophenyl)-4-(R)-4-(3'-indolyl)methyl-1-methyl-4 H-s-triazolo[4,3-a]-1,4-benzodiazepine;
- 6-(2-Fluorophenyl)-4(R)-4-(3'-indolyl)methyl-1-phenyl-4H-triazolo[4,3-a]-1,4-benzodiazpine;
- 6-(2-Fluorophenyl)-4(R)-4-(3'-indolyl)methyl-4H-s-triazolo [4,3-a]-1,4-benzodiazepine;
- 6-(2-Fluorophenyl)-4(R)-4-(3'-indolyl)methyl-1-dimethylaminomethyl-4H-s-triazolo[4,3-a]-1,4-benzodiazepine;
- 2,4-Dihydro-3(R)-(3'-indolyl)methyl-6-(2-fluorophenyl)-1H-S-triazolo [4,3-a]-1,4-benzodiazepin-1-one;
- 1-Trichloromethyl-4(R)-(3'-indolyl)methyl-6-(2-fluorophenyl)-4H-S-triazolo[4,3-a]-1,4-benzodiazepine;
- 6-(2-Fluorophenyl)-4-(4-chlorophenyl)carbonylamino-4H-s-triazolo[4,3-a]-1,4-benzodiazepine;
- 6-(2-Fluorophenyl)-4-(indol-2-yl)carbonylamino-4H-s-triazolo[4,3-a]-1,4-benzodiazepine;
- 6-(2-Fluorophenyl)-4-(indol-2-yl)carbonylamino-1-methyl-4H-s-triazolo[4,3-a]-1,4-benzodiazepine; or
- 6-(2-Fluorophenyl)-4-benzyloxycarbonylamino-4H-s-triazolo[4,3-a]-1,4-benzodiazepine.
- 6. A compound of claim 1 having the formula: ##STR48## wherein R.sup.1 is H or CH.sub.3 ; and
- R.sup.3 is --NH--CO--indol--2--yl, --NH--CO--3--chlorophenyl, or --NH--CO--O--CH.sub.2 --phenyl.
- 7. A compound of claim 6 wherein:
- R.sup.3 is ##STR49##
- 8. A pharmaceutical composition useful for treating gastrointestinal disorders, central nervous system disorders, or regulating appetite in mammals, comprising a pharmaceutically effective amount of a compound of Formula I of claim 1 and an acceptable pharmaceutical carrier.
- 9. A pharmaceutical composition of claim 8 useful for treating gastrointestinal disorders, central nervous system disorders, or regulating appetite in mammals, comprising a pharmaceutically effective amount of a compound of Formula I wherein:
- R.sup.1 is H, loweralkyl, unsubstituted phenyl --(CH.sub.2).sub.n COOR.sup.6, or --(CH.sub.2).sub.m NR.sup.4 R.sup.5 ;
- R.sup.2 is substituted or unsubstituted phenyl (wherein the substituents are 1 or 2 of halo, loweralkyl, loweralkoxy, carboxyl, carboxyloweralkyl, nitro, --CF.sub.3, or hydroxy), or --(CH.sub.2).sub.m COOR.sup.6 ;
- R.sup.3 is ##STR50## R.sup.4 and R.sup.5 are independently H or loweralkyl; R.sup.6 is H or loweralkyl;
- R.sup.7 is .alpha.- or .beta.-naphthyl, ##STR51## substituted or unsubstituted phenyl (wherein the substituents are 1 or 2 of halo, --NO.sub.2, --OH, --NR.sup.4 R.sup.5, loweralkyl, loweralkoxy, CF.sub.3, loweralkylamino, CN, C.tbd.CH, SCF.sub.3, ##STR52## OCHF.sub.2, or SPh); ##STR53## R.sup.8 is H, loweralkyl, or ##STR54## R.sup.9 and R.sup.10 are independently H, --OH, or --CH.sub.3 ; R.sup.11 and R.sup.12 are independently loweralkyl;
- R.sup.13 is H, O, loweralkyl, or acyl;
- R.sup.14 is loweralkyl;
- m is 1-4;
- n is 0-4;
- p is 0 when its adjacent is unsaturated and 1 when its adjacent is saturated, except that when R.sup.13 is O, p=1 and is unsaturated;
- q is 0-4;
- r is 1 or 2;
- X.sup.1 is H, --NO.sub.2, CF.sub.3, CN, OH, loweralkyl, halo, loweralkylthio, loweralkoxy, --(CH.sub.2).sub.n COOR.sup.6, or --NR.sup.4 R.sup.5 ;
- X.sup.2 and X.sup.3 are independently H, --OH, --NO.sub.2, halo, loweralkylthio, loweralkyl, or lower-alkoxy;
- X.sup.4 is S, O, or NR.sup.8 ;
- X.sup.6 is O or HH;
- is a saturated or unsaturated bond
- and the pharmaceutically acceptable salts thereof.
- 10. A pharmaceutical composition according to claim 8, wherein the mammals are humans.
- 11. A method of treating gastrointestinal disorders, central nervous system disorders, or regulating appetite in mammals which comprises administering to said mammals a pharmaceutically effective amount of a compound of Formula I of claim 1.
- 12. A method of claim 11 of treating gastrointestinal disorders in humans which comprises administering a pharmaceutically effective amount of a compound of Formula I wherein:
- R.sup.1 is H, loweralkyl, unsubstituted phenyl --(CH.sub.2).sub.n COOR.sup.6, or --(CH.sub.2).sub.m NR.sup.4 R.sup.5 ;
- R.sup.2 is substituted or unsubstituted phenyl (wherein the substituents are 1 or 2 of halo, loweralkyl, loweralkoxy, carboxyl, carboxyloweralkoxy, nitro, --CF.sub.3, or hydroxy), or --(CH.sub.2).sub.m COOR.sup.6 ;
- R.sup.3 is ##STR55## R.sup.4 and R.sup.5 are independently H or loweralkyl; R.sup.6 is H or loweralkyl;
- R.sup.7 is .alpha.- or .beta.-naphthyl, ##STR56## substituted or unsubstituted phenyl (wherein the substituents are 1 to 2 of halo, --NO.sub.2, --OH, --NR.sup.4 R.sup.5, loweralkyl, loweralkoxy, CF.sub.3, loweralkylthio, CN, C.tbd.CH, SCF.sub.3, ##STR57## OCHF.sub.2, or SPh); ##STR58## R.sup.8 is H, loweralkyl, or ##STR59## R.sup.9 and R.sup.10 are independently H, --OH, or --CH.sub.3 ; R.sup.11 and R.sup.12 are independently loweralkyl;
- R.sup.13 is H, O, loweralkyl, or acyl;
- R.sup.14 is loweralkyl;
- m is 1-4;
- n is 0-4;
- p is 0 when its adjacent is unsaturated and 1 when its adjacent is saturated, except that when R.sup.13 is O, p-1 and is unsaturated;
- q is 0-4;
- r is 1 or 2;
- X.sup.1 is H, --NO.sub.2, CF.sub.3, CN, OH, loweralkyl, halo, loweralkylthio, loweralkoxy, --(CH.sub.2).sub.n COOR.sup.6, or --NR.sup.4 R.sup.5 ;
- X.sup.2 and X.sup.3 are independently H, --OH, --NO.sub.2, halo, loweralkylthio, loweralkyl, or loweralkoxy;
- X.sup.4 is S, O, or NR.sup.8 ;
- X.sup.6 is O or HH;
- is a saturated or unsaturated bond
- and the pharmaceutically acceptable salts thereof.
CROSS-REFERENCE
This application is a continuation-in-part of U.S. patent application Ser. No. 624,850, filed June 26, 1984, now abandoned.
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Number |
Name |
Date |
Kind |
3880877 |
Sellstedt et al. |
Apr 1975 |
|
4046772 |
Kuwada et al. |
Sep 1977 |
|
4180668 |
Hester |
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|
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
624850 |
Jun 1984 |
|