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US 5,635,510 AGranted
Substituted pyrrolidin-3-yl-alkyl-piperidines
AssigneeMerrell Pharmaceuticals Inc.
InventorsTimothy P. Burkholder, Elizabeth M. Kudlacz, George D. Maynard
Life of this patent
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Abstract
The present invention relates to substituted pyrrolidinyl-3-yl-alkyl-piperidines, their stereoisomers, and pharmaceutically acceptable salts thereof and processes for preparation of the same. The compounds of the present invention are useful in their pharmacological activities such as tachykinin antagonism, especially substance P and neurokinin A antagonism, and the like. Compounds having the property of tachykinin antagonism are indicated for conditions associated with neurogenic inflammation and other diseases described herein.
Claims57
A compound of the formula ##STR51## wherein G.sub.1 is --CH.sub.2 -- or --C(O)--;
- G.sub.2 is --CH.sub.2 -- or --C(O)--;
- m is 2 or 3;
- n is 0 or 1;
- Ar.sub.1 is a radical chosen from the group:
- ##STR52## wherein j R.sub.1 is from 1 to 3 substituents each independently chosen from the group consisting of hydrogen, halogen, hydroxy, CF.sub.3, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;
- R.sub.2 is from 1 to 2 substituents each independently chosen from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;
- Ar.sub.2 is a radical chosen from the group ##STR53## wherein R.sub.3 is from 1 to 3 substituents each independently chosen from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkoxy, hydroxy, --O--C(O)O--CH.sub.2 -CH.sub.3, --OC(O)CM.sub.3, --CF.sub.2 H, --(CH.sub.2).sub.q NR.sub.6 R.sub.7, and --(CH.sub.2).sub.q NR.sub.8 R.sub.9 wherein q is 2 or 3, R.sub.6 is C.sub.1 -C.sub.6 alkyl, R.sub.7 is C.sub.1 -C.sub.6 alkyl, R.sub.8 and R.sub.9 taken together with the bonded nitrogen form a morpholine ring, piperidine ring, 4-methylpiperazine ring, or pyrrolidine ring;
- R.sub.4 is from 1 to 2 substituents each independently chosen from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;
- Y.sub.1 is --C(O)NHR.sub.5, --C(O)NR.sub.6 R.sub.7, or --C(O)NR.sub.8 R.sub.9
- wherein
- R.sub.5 is chosen from the group consisting of hydrogen, 3-hydroxy-2-butyryl-C.sub.1 -C.sub.6 alkyl ester, 2-glutaryl-C.sub.1 -C.sub.6 alkyl ester, --(CH.sub.2).sub.q NR.sub.6 R.sub.7, and --(CH.sub.2).sub.q NR.sub.8 R.sub.9 ;
- q is 2 or 3;
- R.sub.6 is C.sub.1 -C.sub.6 alkyl;
- R.sub.7 is C.sub.1 -C.sub.6 alkyl;
- R.sub.8 and R.sub.9 taken together with the bonded nitrogen form a morpholine ring, piperidine ring, 4-methylpiperazine ring, or pyrrolidine ring;
- Y.sub.2 is a radical chosen from the group ##STR54## wherein R.sub.10 is from 1 to 3 substituents each independently chosen from the group consisting of hydrogen, halogen, CF.sub.3, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;
- R.sub.11 is from 1 to 2 substituents each independently chosen from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;
- or stereoisomers, or an N-oxide, or a pharmaceutically acceptable salt thereof.
15 more elements
A compound of the formula ##STR55## wherein G.sub.1 is --CH.sub.2 -- or --C(O)--;
- G.sub.2 is --CH.sub.2 -- or --C(O)--;
- m is 2 or 3;
- n is 0 or 1;
- Ar.sub.1 is a radical chosen from the group:
- ##STR56## wherein R.sub.1 is from 1 to 3 substituents each independently chosen from the group consisting of hydrogen, halogen, hydroxy, CF.sub.3, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;
- R.sub.2 is from 1 to 2 substituents each independently chosen from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;
- Ar.sub.2 as a radical chosen from the group ##STR57## wherein R.sub.3 is from 1 to 3 substituents each independently chosen from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkoxy, hydroxy, --O--C(O)O--CH.sub.2 --CR.sub.3, --OC(O)CH.sub.3, --CF.sub.2 H, --(C.sub.2).sub.q NR.sub.6 R.sub.7, and --(CH.sub.2).sub.q NR.sub.8 R.sub.9 wherein q is 2 or 3, R.sub.6 is C.sub.1 -C.sub.6 alkyl, R.sub.7 is C.sub.1 -C.sub.6 alkyl, R.sub.8 and R.sub.9 taken together with the bonded nitrogen form a morpholine ring, piperidine ring, 4-methylpiperazine ring, or pyrrolidine ring;
- R.sub.4 is from 1 to 2 substituents each independently chosen from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;
- Y.sub.1 and Y.sub.2 together with their attached carbon form a spirocyclic ring chosen from the group ##STR58## wherein R.sub.12 is from 1 to 3 substituents each independently chosen from the group consisting of hydrogen, halogen, CF.sub.3, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;
- R.sub.13 is hydrogen, C.sub.1 -C.sub.6 alkyl, or benzyl;
- or stereoisomers, or an N-oxide, or a pharmaceutically acceptable salt thereof.
8 more elements
Dependencies are inferred from the claim text.