Claims
- 1. A compound of Formula I: ##STR69## wherein R.sup.1 is --NR.sup.16 R.sup.17,;
- R.sup.2 is H, loweralkyl, substituted or unsubstituted phenyl (wherein the substituents are 1 or 2 of halo, loweralkyl, loweralkoxy, loweralkylthio, carboxyl, carboxyloweralkyl, nitro, --CF.sub.3, or hydroxy), 2-, 3-, 4-pyridyl, ##STR70## R.sup.3 is ##STR71## R.sup.4 and R.sup.5 are independently R.sup.6 or in combination with the N of the NR.sup.4 R.sup.5 group form an unsubstituted or mono or disubstituted, saturated or unsaturated, 4-7 membered heterocyclic ring, or benzofused 4-7 membered heterocyclic ring or said heterocyclic ring or said benzofused heterocyclic ring which further comprises a second heteroatom selected from O and NCH.sub.3 and the substituent(s) is/are independently selected from C.sub.1-4 alkyl;
- R.sup.6 is H, loweralkyl, cycloloweralkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted phenylloweralkyl (wherein the substituents are 1 or 2 of halo, loweralkyl, loweralkoxy, nitro, or CF.sub.3);
- R.sup.7 is a .alpha.- or .beta.-naphthyl, substituted or unsubstituted phenyl (wherein the substituents are 1 to 2 of halo, --NO.sub.2, --OH, --X.sup.11 --NR.sup.4 R.sup.5, loweralkyl, loweralkoxy, CF.sub.3, loweralkylthio, cyano, phenyl, acetylamino, acetoxy, SCF.sub.3, C.tbd.CH, CH.sub.2 SCF.sub.3, OCHF.sub.2, SH or thio-phenyl) 2-, 3-, 4-pyridyl, ##STR72## (with the proviso that q is not 0 in ##STR73## R.sup.8 is H, loweralkyl, cycloloweralkyl, --X.sup.12 CONH.sub.2, --X.sup.12 COOR.sup.6, --X.sup.11 --cycloloweralkyl, ##STR74## R.sup.11 and R.sup.12 are independently loweralkyl or cycloloweralkyl; R.sup.13 is O;
- R.sup.14 is loweralkyl or phenylloweralkyl;
- R.sup.16 and R.sup.17 are, when separate, independently H, loweralkyl, lower alkenyl,
- --X.sup.11 cycloloweralkyl,
- --X.sup.12 --NR.sup.4 R.sup.5,X.sup.12 CONR.sup.4 R.sup.5, --X.sup.12 C.tbd.N, ##STR75## --X.sup.12 COOR.sup.6, or --CN; or, when joined, form with N, a heterocycle ##STR76## wherein n' is 2-6; R.sup.18 is H or loweralkyl;
- p is 0 or 1;
- 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, --X.sup.11 COOR.sup.6 or --X.sup.11 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, 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.sup.9 are independently NR.sup.18, O;
- X.sup.11 is absent or C.sub.1-4 linear or branched alkylene;
- X.sup.12 is C.sub.1-4 linear or branched alkylene.
- and the pharmaceutically acceptable salts thereof.
- 2. A compound of claim 1 wherein:
- R.sup.1 is --NR.sup.16 R.sup.17 ;
- 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), 2-, 3-, 4-pyridyl --X.sup.12 COOR.sup.6 or or ##STR77## R.sup.3 is ##STR78## 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, ##STR79## substituted or unsubstituted phenyl (wherein the substituents are 1 to 2 of halo, --NO.sub.2, --OH, --X.sup.11 NR.sup.4 R.sup.5, loweralkyl, CF.sub.3, loweralkoxy, loweralkylthio, CN, C.tbd.CH, SCF.sub.3, OCHF.sub.2, or thiophenyl), ##STR80## R.sup.8 is H, loweralkyl or ##STR81## R.sup.11 and R.sup.12 are independently loweralkyl; R.sup.14 is loweralkyl;
- R.sup.16 and R.sup.17 are independently H, loweralkyl,
- --X.sup.11 cycloloweralkyl, --X.sup.12 NR.sup.4 R.sup.5,
- --X.sup.12 CONR.sup.4 R.sup.5, --X.sup.12 CN, ##STR82## or --CN; 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, --X.sup.11 COOR.sup.6, or --X.sup.11 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;
- and the pharmaceutically acceptable salts thereof.
- 3. A compound of claim 2 wherein:
- R.sup.1 is --NR.sup.16 R.sup.17 ;
- R.sup.2 is substituted or unsubstituted phenyl (wherein the substituents are 1 or 2 of halo or carboxyl) or --(CH.sub.2).sub.1-2 COOR.sup.6 ;
- R.sup.3 is ##STR83## R.sup.6 is H or loweralkyl; R.sup.7 is .alpha.- or .beta.-naphthyl, ##STR84## substituted phenyl (wherein the substituents are 1 or 2 of halo, loweralkyl, loweralkoxy, or CF.sub.3), or ##STR85## R.sup.8 is H, methyl, or ethyl; R.sup.14 is t-butyl;
- R.sup.16 and R.sup.17 are independently H, loweralkyl, --CN, --X.sup.11 cycloloweralkyl, X.sup.12 NR.sup.4 R.sup.5,--X.sup.12 CONR.sup.4 R.sup.5, --X.sup.12 CN;
- 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, loweralkyl or halo;
- and the pharmaceutically acceptable salts thereof.
- 4. A compound of claim 3 wherein:
- R.sup.1 is --NH.sub.2, --NH(CH.sub.2).sub.0-2 CH.sub.3, NHCH.sub.2 COOH, --NHCN, ##STR86## R.sup.2 is phenyl, o-fluorophenyl, o-chlorophenyl, p-fluorophenyl, p-chlorophenyl, 2,6-difluorophenyl, --CH.sub.2 COOEt, --CH.sub.2 COO--t--Bu, o-carboxyphenyl, --CH.sub.2 CH.sub.2 COOEt, or --CH.sub.2 CH.sub.2 COOt--Bu;
- R.sup.3 is --(CH.sub.2).sub.1-2 R.sup.7, ##STR87## and the stereochemistry relates to D-tryptophan when R.sup.3 is linked to the 7-membered ring via a methylene group;
- R.sup.6 is H, methyl or ethyl;
- R.sup.7 is .alpha.- or .beta.-naphthyl, mono- or dihalophenyl, mono- or dimethylphenyl, methoxyphenyl, ##STR88## R.sup.14 is t-butyl; 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 or methyl or ethyl;
- and the pharmaceutically acceptable salts thereof.
- 5. A compound of claim 1 which is
- 2-Phenylamino-3(R)-(3'-indolyl)methyl-5-(2'-fluorophenyl)-2H-1,4-benzodiazepine;
- 2-Amino-3(R)-(3'-indolyl)methyl-5-(2'-fluorophenyl)-2H-1,4-benzodiazepine;
- 2-Methylamino-3(R)-(3'-indolyl)methyl-5-(2'-fluorophenyl)-2H-1,4-benzodiazepine;
- N-[3-(((4-Chlorophenyl)aminocarbonyl)amino)-5-phenyl-3H-1,4-benzodiazepin-2-yl]-glycine;
- N-[3-(((4-Chlorophenyl)aminocarbonyl)amino)-5-phenyl-3H-1,4-benzodiazepin-2-yl]-glycine ethyl ester;
- 2-Ethoxycarbonylmethylamino-3(R)-(3'-indolyl)methyl-5-(2'-fluorophenyl)-2H-1,4-benzodiazepine;
- 2-Cyanoamino-3(R)-(3'-indolyl)methyl-5-(2'-fluorophenyl)-2H-1,4-benzodiazepine;
- 2-n-Propylamino-3(R)-(3'-indolyl)methyl-5-(2'-fluorophenyl)-2H-1,4-benzodiazepine; and
- 2-Carboxymethylamino-3(R)-(3'-indolyl)methyl-5-(2'-fluorophenyl)-2H-1,4-benzodiazepine.
- 6. 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.
- 7. A pharmaceutical composition of claim 6 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 --NR.sup.16 R.sup.17 ;
- 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), 2-, 3-, 4-pyridyl --X.sup.12 COOR.sup.6 or ##STR89## R.sup.3 is ##STR90## 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, ##STR91## substituted or unsubstituted phenyl (wherein the substituents are 1 to 2 of halo, --NO.sub.2, --OH, --X.sup.11 NR.sup.4 R.sup.5, loweralkyl, CF.sub.3, loweralkoxy, loweralkylthio, CN, C.tbd.CH, SCF.sub.3, OCHF.sub.2, or thiophenyl), ##STR92## R.sup.8 is H, loweralkyl or ##STR93## R.sup.11 and R.sup.12 are independently loweralkyl; R.sup.14 is loweralkyl;
- R.sup.16 and R.sup.17 are independently H, loweralkyl,
- --X.sup.11 cycloloweralkyl, --X.sup.12 NR.sup.4 R.sup.5,
- --X.sup.12 CONR.sup.4 R.sup.5, --X.sup.12 CN, ##STR94## or --CN; 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, --X.sup.11 COOR.sup.6, or --X.sup.11 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;
- and the pharmaceutically acceptable salts thereof.
- 8. 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.
- 9. A method of claim 8 of treating gastrointestinal disorders in humans which comprises administering a pharmaceutically effective amount of a compound of Formula I wherein:
- R.sup.1 is --NR.sup.16 R.sup.17 ;
- 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), 2-, 3-, 4-pyridyl --X.sup.12 COOR.sup.6 or or ##STR95## R.sup.3 is ##STR96## 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, ##STR97## substituted or unsubstituted phenyl (wherein the substituents are 1 to 2 of halo, --NO.sub.2, --OH, --X.sup.11 NR.sup.4 R.sup.5, loweralkyl, CF.sub.3, loweralkoxy, loweralkylthio, CN, C.tbd.CH, SCF.sub.3, OCHF.sub.2, or thiophenyl), ##STR98## R.sup.8 is H, loweralkyl or ##STR99## R.sup.11 and R.sup.12 are independently loweralkyl; R.sup.14 is loweralkyl;
- R.sup.16 and R.sup.17 are independently H, loweralkyl,
- --X.sup.11 cycloloweralkyl, --X.sup.12 NR.sup.4 R.sup.5,
- --X.sup.12 CONR.sup.4 R.sup.5, --X.sup.12 CN, ##STR100## --X.sup.12 COOR.sup.6, or --CN; 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, --X.sup.11 COOR.sup.6, or --X.sup.11 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;
- and the pharmaceutically acceptable salts thereof.
Parent Case Info
The present application is a continuation-in-part of U.S. patent application Ser. No. 741,973, filed July 10, 1985, now abandoned, which in turn is a continuation-in-part of U.S. patent application Ser. No. 624,852, filed June 26, 1984, now abandoned.
US Referenced Citations (5)
Non-Patent Literature Citations (7)
Entry |
J. Heterocyclic Chem., 17, 865 (1980) Gatta et al., pp. 865-868. |
Allgeier et al., Chemical Abstracts, vol. 78 (1973) 29832u. |
Allgeier et al., Chemical Abstracts, vol. 85 (1976) 108681s. |
Watanabe et al., Chemical Abstracts, vol. 97 (1982) 92240g. |
Giacconi et al., Synthesis, (1982) pp. 789-791. |
Natsugari et al., Chem. Pharm. Bull., vol. 27 (1979) pp. 2608-2617. |
Schecker et al., Arch. Pharm., 313 (1980) pp. 926-936. |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
741973 |
Jul 1985 |
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Parent |
624852 |
Jun 1984 |
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