5-substituted-3-(1,2,3,6-tetrahydropyridin-4-yl)-and 3-(piperidin-4-yl)-1h-indoles: 5-HT.sub.1F agonists
AssigneeEli Lilly and Company
InventorsJames Edmund Audia, Bruce Anthony Dressman, James Joseph Droste, James Erwin Fritz, Stephen Warren Kaldor, Daniel James Koch, Joseph Herman Krushinski, Jr., Jeffrey Scott Nissen, Vincent Patrick Rocco, John Mehnert Schaus, Dennis Charles Thompson
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Abstract
This invention provides novel 5-HT.sub.1F agonists of Formula I ##STR1## where A--B, R,R.sup.1 and X are as defined in the specification, which are useful for the treatment of migraine and associated disorders.
Claims12
A compound of Formula I:
- ##STR13## in which A--B is --CH--CH.sub.2 -- or --C.dbd.CH--;
- R is H or C.sub.1 -C.sub.6 alkyl;
- R.sup.1 is H or C.sub.1 -C.sub.4 alkyl;
- X is --S--R.sup.2, or --C(O)R.sup.3 ;
- where
- R.sup.2 is phenyl(C.sub.1 -C.sub.4 alkylene), or phenyl(C.sub.1 -C.sub.4 alkylene) substituted in the phenyl ring;
- R.sup.3 is naphthyl, N-methyl-N-methoxyamino, heteroaryl, substituted heteroaryl, heteroaryl(C.sub.1 -C.sub.4 alkyl), or substituted heteroaryl(C.sub.1 -C.sub.4 alkyl);
- and pharmaceutically acceptable acid addition salts and solvates thereof.
A pharmaceutical formulation which comprises, in association with a pharmaceutically acceptable carrier, diluent or excipient, a compound of formula:
- ##STR14## in which A--B is --CH--CH.sub.2 -- or --C.dbd.CH--;
- R is H or C.sub.1 -C.sub.6 alkyl;
- R.sup.1 is H or C.sub.1 -C.sub.4 alkyl;
- X is --S--R.sup.2, or --C(O)R.sup.3 ;
- where
- R.sup.2 is phenyl(C.sub.1 -C.sub.4 alkylene), or phenyl(C.sub.1 -C.sub.4 alkylene) substituted in the phenyl ring;
- R.sup.3 is naphthyl, N-methyl-N-methoxyamino, heteroaryl, substituted heteroaryl, heteroaryl(C.sub.1 -C.sub.4 alkyl), or substituted heteroaryl(C.sub.1 -C.sub.4 alkyl);
- or pharmaceutically acceptable acid addition salts and solvates thereof.
A method for the activation of 5-HT.sub.1F receptors in mammals, comprising administering to a mammal in need of such activation an effective amount of a compound of formula:
- ##STR15## in which A--B is --CH--CH.sub.2 -- or --C.dbd.CH--:
- R is H or C.sub.1 -C.sub.6 alkyl;
- R.sup.1 is H or C.sub.1 -C.sub.4 alkyl;
- X is --S--R.sup.2, or --C(O)R.sup.3 ;
- R.sup.2 is phenyl, substituted phenyl, phenyl(C.sub.1 -C.sub.4 alkylene), phenyl(C.sub.1 -C.sub.4 alkylene) substituted in the phenyl ring, or pyridinyl;
- R.sup.3 is C.sub.1 -C.sub.6 alkyl, phenyl(C.sub.1 -C.sub.4 alkylene), phenyl(C.sub.1 -C.sub.4 alkylene) substituted in the Phenyl ring, naphthyl, N-methyl-N-methoxyamino, heteroaryl, substituted heteroaryl, heteroaryl(C.sub.1 -C.sub.4 alkyl), or substituted heteroaryl(C.sub.1 -C.sub.4 alkyl);
- or pharmaceutically acceptable salts and solvates thereof.
A method for the inhibition of neuronal protein extravasation, comprising administering to a mammal in need thereof an effective amount of a compound of formula:
- ##STR16## in which A--B is --CH--CH.sub.2 -- or --C.dbd.CH--;
- R is H or C.sub.1 -C.sub.6 alkyl;
- R.sup.1 is H or C.sub.1 -C.sub.4 alkyl;
- X is --S--R.sup.2, or --C(O)R.sup.3 ;
- R.sup.2 is phenyl, substituted phenyl, phenyl(C.sub.1 -C.sub.4 alkylene), phenyl(C.sub.1 -C.sub.4 alkylene) substituted in the phenyl ring, or pyridinyl;
- R.sup.3 is C.sub.1 -C.sub.6 alkyl, phenyl(C.sub.1 -C.sub.4 alkylene), phenyl(C.sub.1 -C.sub.4 alkylene) substituted in the phenyl ring, naphthyl, N-methyl-N-methoxyamino, heteroaryl, substituted heteroaryl, heteroaryl(C.sub.1 -C.sub.4 alkyl), or substituted heteroaryl(C.sub.1 -C.sub.4 alkyl);
- or pharmaceutically acceptable salts and solvates thereof.
Dependencies are inferred from the claim text.