Claims
- 1. A 2-benzazepine of the formula: ##STR29## R.sup.1 is H, C.sub.1 -C.sub.4 -alkyl, cyclo-C.sub.3 -C.sub.7 -alkyl, ##STR30## NR.sup.4 R.sup.5, C.sub.1 -C.sub.4 -alkoxy, thio-C.sub.1 -C.sub.4 -alkoxy, OH, or SH;
- R.sup.2 is H; C.sub.1 -C.sub.4 -alkyl; mono- or disubstituted or unsubstituted phenyl, where the substituent(s) is/are independently selected from the group consisting of halo, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylthio, carboxyl, carboxy-C.sub.1 -C.sub.4 -alkyl, nitro, --CF.sub.3, ##STR31## and hydroxy; 2-, 3- or 4-pyridyl; or --(CH.sub.2).sub.m COOR.sup.6 ; R.sup.3 is --(CH.sub.2).sub.n R.sup.7, ##STR32## R.sup.4 and R.sup.5 are independently H, C.sub.1 -C.sub.4 -alkyl, or cyclo-C.sub.3 -C.sub.7 -alkyl or are connected to form a hetero ring of the structure --N(CH.sub.2).sub.k, wherein k is 2 to 6;
- R.sup.6 is H, C.sub.1 -C.sub.4 -alkyl, cyclo-C.sub.3 -C.sub.7 -alkyl, unsubstituted or mono- or disubstituted phenyl, wherein the substituent(s) is/are independently selected from the group consisting of halo, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, nitro, and CF.sub.3, or unsubstituted or mono- or disubstituted phenyl-C.sub.1 -C.sub.4 -alkyl, wherein the substituent(s) is/are selected from the group consisting of halo, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, nitro, and CF.sub.3 ;
- R.sup.7 is .alpha.- or .beta.-naphthyl, unsubstituted or mono- or disubstituted phenyl, wherein the substituent(s) is/are independently selected from the group consisting of halo, --NO.sub.2, --OH, --NR.sup.4 R.sup.5, C.sub.1 -C.sub.4 -alkyl, cyano, phenyl, trifluoromethyl, acetylamino, acetyloxy, C.sub.1 -C.sub.4 -alkylthio, SCF.sub.3, C.tbd.CH, CH.sub.2 SCF.sub.3, OCHF.sub.2, S-phenyl, and C.sub.1 -C.sub.4 -alkoxy, ##STR33## R.sup.8 is H, C.sub.1 -C.sub.4 -alkyl, cyclo-C.sub.3 -C.sub.7 -alkyl, --(CH.sub.2)n-cyclo-C.sub.3 -C.sub.7 -alkyl, O ##STR34## R.sup.9 is OH, OR.sup.11 or ##STR35## R.sup.10 is H, --OH, or --CH.sub.3 ; R.sup.11 and R.sup.12 are independently C.sub.1 -C.sub.4 -alkyl or cyclo-C.sub.3 -C.sub.7 -alkyl;
- R.sup.13 is ##STR36## R.sup.14 is C.sub.1 -C.sub.4 -alkyl or phenyl-C.sub.1 -C.sub.4 -alkyl; R.sup.18 is H, C.sub.1 -C.sub.4 -alkyl, formyl, acetyl, propionyl or butyryl;
- m is 1 to 4;
- n is 0 to 4;
- q is 0 to 4:
- r is 1 or 2;
- X.sup.1 is H, --NO.sub.2, CF.sub.3 CN, OH, C.sub.1 -C.sub.4 -alkyl, halo, C.sub.1 -C.sub.4 -alkylthio, C.sub.1 -C.sub.4 -alkoxy, --(CH.sub.2).sub.n COOR.sup.6, --NR.sup.4 R.sup.5, or ##STR37## X.sup.2 and X.sup.3 are independently H, --OH,--NO.sub.2, halo, C.sub.1 -C.sub.4 -alkylthio, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy or ##STR38## X.sup.4 is S, O, CH.sub.2, or NR.sup.8 ; X.sup.6 is O or HH;
- X.sup.8 is H or C.sub.1 -C.sub.4 -alkyl;
- X.sup.9 and X.sub.a.sup.9 are independently NR.sup.18 or O;
- W is CR.sup.1, N or NH;
- Y is N, S, or O;
- Z is C--H or absent; and
- is a saturated (single) or unsaturated (double) bond;
- or a pharmaceutically-acceptable salt thereof.
- 2. A 2-benzazepine according to claim 1, wherein
- R.sup.1 is H or C.sub.1 -C.sub.4 -alkyl;
- R.sup.2 is unsubstituted of mono- or disubstituted phenyl where the substitutent(s) is/are selected from the group consisting of halo, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, nitro, and --CF.sub.3 ;
- R.sup.3 is --(CH.sub.2).sub.n R.sup.7, ##STR39## R.sup.7 is .alpha.- or .beta.-naphthyl, unsubstituted or mono- or disubstituted phenyl, where the substituent(s) is/are selected from the group consisting of halo, nitro, C.sub.1 -C.sub.4 -alkyl, trifluoromethyl and C.sub.1 -C.sub.4 -alkoxy, ##STR40## R.sup.8 is H, or C.sub.1 -C.sub.4 -alkyl; n is 0 -to- 2;
- q is 0 -to- 2;
- r is 1 or 2;
- X.sup.1 is H, --NO.sub.2, C.sub.1 -C.sub.4 -alkyl, halo, or C.sub.1 -C.sub.4 -alkoxy;
- X.sup.2 and X.sup.3 are independently H, --NO.sub.2, halo, C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkoxy;
- X.sup.4 is S, O, CH.sub.2, or NR.sup.8 ;
- X.sup.8 is is H or C.sub.1 -C.sub.4 -alkyl;
- X.sup.9 and X.sub.a.sup.9 are independently NH or O; and or a pharmaceutically-acceptable salt thereof.
- 3. A 2-benzazepine according to claim 1, wherein
- R.sup.1 is H or methyl;
- R.sup.2 is phenyl or o-F-phenyl;
- R.sup.3 is ##STR41## R.sup.7 is ##STR42## X.sup.1 is H; X.sup.2 is H, --NO.sub.2, halo, methyl, or methoxy;
- W is CR.sup.1 ;
- Y is N; and
- Z is CH.
- 4. A 2-benzazepine according to claim 1, wherein
- R.sup.1 is H or methyl;
- R.sup.2 is phenyl or o-F-phenyl;
- R.sup.3 is ##STR43## R.sup.7 is ##STR44## X.sup.1 is H; X.sup.2 is H, --NO.sub.2, halo, methyl, or methoxy;
- W is CR.sup.1 ;
- Y is S; and
- Z is absent.
- 5. A 2-benzazepine according to claim 1, wherein
- R.sup.1 is H or methyl;
- R.sup.2 is phenyl o-F-phenyl;
- R.sup.3 is ##STR45## R.sup.7 is ##STR46## X.sup.1 is H; X.sup.2 is H, --NO.sub.2, halo, methyl, or methoxy;
- W is CR.sup.1 ;
- Y is 0; and
- Z is absent.
- 6. A 2-benzazepine according to claim 1, wherein
- R.sup.2 is phenyl or o-F-phenyl;
- R.sup.3 is ##STR47## R.sup.7 is ##STR48## X.sup.1 is H; X.sup.2 is H, --NO.sub.2, halo, methyl, or methoxy;
- W is NH;
- Y is N; and
- Z is absent.
- 7. A 2-benzazepine according to claim 1 which is:
- 5(S)-5-(2-indolecarbonylamino)-7-phenyl-5H-pyrimido-[5,4-d][2]benzazepine;
- 4(S)-4-(4-chlorophenylcarbonylamino)-2-methyl-6-phenyl-4H-thiazolo-[5,4-d][2]benzazepine;
- 4(S)-4-(2-indolecarbonylamino)-6-phenyl-4H-oxazolo-[5,4-d][2]benzazepine; or
- 4(S)-4-(2-indolecarbonylamino)-6-phenyl-2H,4H-[1,2,3]-triazolo-[5,4-d][2]benzazepine.
- 8. A 2-benzazepine according to claim 1, which is:
- 5(R)-5-(3-methoxyphenylaminocarbonylamino)-7-phenyl-5H-pyrimido[5,4-d][2]benzazepine;
- 4(R)-4-(3-methylphenylaminocarbonylamino)-2-methyl-6-phenyl-4H-[5,4-d][2]benzazepine;
- 4(R)-4-(3-chlorophenylaminocarbonylamino)-6-phenyl-4H-oxazolo-[5,4-d][2]benzazepine; or
- 4(R)-4-(3-methoxyphenylaminocarbonylamino)-6-phenyl-2H, 4H-[1,2,3]triazolo-[5,4-d][2]benzazepine;
- 9. A composition comprising a therapeutically-effective amount for antagonism of the function of cholecystokinins or gastrin in mammals of one or more 2-benzazepines according to claim 1, or pharmaceutically-acceptable salts thereof, and a pharmaceutically-acceptable carrier.
- 10. A composition according to claim 9, further comprising an adjuvant.
- 11. A composition according to claim 9, wherein the therapeutically-effective amount is about 0.05 to 50 mg/kg of body weight.
- 12. A composition according to claim 9, wherein the mammals are humans.
- 13. A method of preventing in mammals or treating mammals for disorders of the gastrointestinal, central nervous or appetite regulatory systems which comprises administering to those mammals a therapeutically-effective amount of one or more 2-benzazepines, or therapeutically-acceptable salts thereof, according to claim 1.
- 14. A method according to claim 13, wherein a pharmaceutically-acceptable carrier or a pharmaceutically-acceptable carrier and an adjuvant are also administered.
- 15. A method according to claim 13, wherein a therapeutically-effective amount is from about 0.1 to about 20 mg/kg of body weight, administered in single or divided doses.
- 16. A method of increasing food intake in animals which comprises administering as a food additive between about 0.05 mg/kg and about 50 mg/kg of body weight of one or more compounds or pharmaceutically-acceptable salts according to claim 1.
Parent Case Info
This is a continuation of application Ser. No. 07/353,224, filed May 15, 1989, which is a continuation of Ser. No. 07/175,641, filed Mar. 28, 1988 both abandoned.
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Name |
Date |
Kind |
4269774 |
Fryev et al. |
May 1981 |
|
4379765 |
Field et al. |
Apr 1983 |
|
4481142 |
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Continuations (2)
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Number |
Date |
Country |
Parent |
353224 |
May 1989 |
|
Parent |
175641 |
Mar 1988 |
|