Claims
- 1. A method for producing an agonist effect at the 5HT.sub.1A or 5HT.sub.1D receptor comprising administering a compound of the formula: ##STR44## in which Y is represented by hydrogen or C.sub.1-3 alkyl; R is represented by a substituent selected from the group consisting of hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen, --CF.sub.3, --OCF.sub.3, and --OH; R.sub.1 is represented by hydrogen, cycloalkyl, C.sub.1-6 alkyl, phenyl optionally substituted, phenylalkyl, or phenylamidoalkyl; X is represented by hydrogen, --(CH.sub.2).sub.n X.sub.1, CH.dbd.CHX.sub.1 or CHX.sub.2 -(CH.sub.2).sub.q --CH.sub.3 ; n is an integer from 0-2; q is either the integer 0 or 1; X.sub.1 is represented by --OH--, --OR.sub.2, --NR.sub.2 R.sub.3, --CO.sub.2 R.sub.2, --CONR.sub.2 R.sub.3, --CN, or --COR.sub.2 ; R.sub.2 and R.sub.3 are each independently represented by hydrogen, C.sub.1-4 alkyl, phenyl optionally substituted, phenylalkyl, or R.sub.2 and R.sub.3 together form a (CH.sub.2).sub.m cycloalkyl, where m=2-6; X.sub.2 is --OR.sub.4 or --NR.sub.4 R.sub.5 in which R.sub.4 and R.sub.5 are each independently hydrogen or C.sub.1-4 alkyl; and the pharmaceutically acceptable addition salts thereof; with the proviso that when n is O or X is --CH.dbd.CHX.sub.1, then X.sub.1 is not OH, OR.sub.2, or NR.sub.2 R.sub.3 ; to a patient in need thereof.
- 2. A method for the treatment of angina comprising administering a compound of the formula: ##STR45## in which Y is represented by hydrogen or C.sub.1-3 alkyl; R is represented by a substituent selected from the group consisting of hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen, --CF.sub.3, --OCF.sub.3, and --OH; R.sub.1 is represented by hydrogen, cycloalkyl, C.sub.1-6 alkyl, phenyl optionally substituted, phenylalkyl, or phenylamidoalkyl; X is represented by hydrogen, --(CH.sub.2).sub.n X.sub.1, CH.dbd.CHX.sub.1 or CHX.sub.2 -(CH.sub.2).sub.q -CH.sub.3 ; n is an integer from 0-2; q is either the integer 0 or 1; X.sub.1 is represented by --OH--, --OR.sub.2, --NR.sub.2 R.sub.3, --CO.sub.2 R.sub.2, --CONR.sub.2 R.sub.3, --CN, or --COR.sub.2 ; R.sub.2 and R.sub.3 are each independently represented by hydrogen, C.sub.1-4 alkyl, phenyl optionally substituted, phenylalkyl, or R.sub.2 and R.sub.3 together form a (CH.sub.2).sub.m cycloalkyl, where m=2-6; X.sub.2 is --OR.sub.4 or --NR.sub.4 R.sub.5 in which R.sub.4 and R.sub.5 are each independently hydrogen or C.sub.1-4 alkyl; and the pharmaceutically acceptable addition salts thereof; with the proviso that when n is O or X is --CH.dbd.CHX.sub.1, then X.sub.1 is not OH, OR.sub.2, or NR.sub.2 R.sub.3 ; to a patient in need thereof.
Parent Case Info
This is a Continuation-in-part of U.S. Ser. No. 08/079,692 filed Jun. 16, 1993 now abandoned; which was a continuation of U.S. Ser. No 07/947,007, filed Sep. 17, 1992, now abandoned.
The present invention is directed to a new class of serotonin 5HT.sub.1A and 5HT.sub.1D receptor agents, both agonists and antagonists, their use in the treatment of anxiety, depression, migraine, stroke, angina and hypertension as well as pharmaceutical and diagnostic compositions containing them.
In accordance with the present invention a new class of serotonin 5HT.sub.1A and 5HT.sub.1D receptor agents have been discovered which can be described by the following formula: ##STR2## in which Y is represented by hydrogen or C.sub.1-3 alkyl; R is represented by a substituent selected from the group consisting of hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen, --CF.sub.3, --OCF.sub.3, and --OH; R.sub.1 is represented by hydrogen, cycloalkyl, C.sub.1-6 alkyl, phenyl optionally substituted, phenylalkyl, or phenylamidoalkyl; X is represented by hydrogen, --(CH.sub.2).sub.n X.sub.1, --CH=CHX.sub.1 or --CHX.sub.2 --(CH.sub.2).sub.q --CH.sub.3 ; n is an integer from 0-2; q is either the integer 0 or 1; X.sub.1 is represented by --OH, --OR.sub.2, --NR.sub.2 R.sub.3, --CO.sub.2 R.sub.2, --CONR.sub.2 R.sub.3, --CN, CH.sub.2 OH or --COR.sub.2 ; R.sub.2 and R.sub.3 are each independently represented by hydrogen, C.sub.1-4 alkyl, phenyl optionally substituted, phenylalkyl, or R.sub.2 and R.sub.3 together form a (CH.sub.2).sub.m cycloalkyl, where m=2-6; X.sub.2 is --OR.sub.4 or --NR.sub.4 R.sub.5 in which R.sub.4 and R.sub.5 are each independently hydrogen or C.sub.1-4 alkyl; and the pharmaceutically acceptable addition salts thereof; with the proviso that when n is O or X is --CH=CHX.sub.1, then X.sub.1 is not OH, OR.sub.2, or NR.sub.2 R.sub.3.
These benzothiophene derivatives mimic or block the effects of serotonin at the 5HT.sub.1A and .sub.1D receptors. They are useful in the treatment of anxiety, depression, migraine, stroke, angina and hypertension.
As used in this application:
The expression "pharmaceutically acceptable acid addition salts" is intended to apply to any non-toxic organic or inorganic acid addition salt of the base compounds represented by Formula I or any of its intermediates. Illustrative inorganic acids which form suitable salts include hydrochloric, hydrobromic, sulphuric, and phosphoric acid and acid metal salts such as sodium monohydrogen orthophosphate, and potassium hydrogen sulfate. Illustrative organic acids which form suitable salts include the mono-, di-, and tricarboxylic acids. Illustrative of such acids are, for example, acetic, glycolic, lactic, pyruvic, malonic, succinic, glutaric, fumaric, malic, tartaric, citric, ascorbic, maleic, hydroxymaleic, benzoic, hydroxy-benzoic, phenylacetic, cinnamic, salicyclic, 2-phenoxy-benzoic, p-toluenesulfonic acid, and sulfonic acids such as methanesulfonic acid and 2-hydroxyethane sulfonic acid. Such salts can exist in either a hydrated or substantially anhydrous form. In general, the acid addition salts of these compounds are soluble in water and various hydrophilic organic solvents, and which in comparison to their free base forms, generally demonstrate higher melting points.
The expression "pharmaceutically acceptable basic addition salts" is intended to apply to any non-toxic organic or inorganic basic addition salts of the compounds represented by Formula I or any of its intermediates. Illustrative bases which form suitable salts include alkali metal or alkaline-earth metal hydroxides such as sodium, potassium, calcium, magnesium, or barium hydroxides; ammonia, and aliphatic, alicyclic, or aromatic organic amines such as methylamine, dimethylamine, trimethylamine, and picoline. Either the mono- or di-basic salts can be formed with those compounds.
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Continuations (1)
|
Number |
Date |
Country |
| Parent |
947007 |
Sep 1992 |
|
Continuation in Parts (1)
|
Number |
Date |
Country |
| Parent |
79692 |
Jun 1993 |
|
Patent Grant
5436246
