Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1999-03-01
2000-11-28
Richter, Johann
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
562431, 562442, 562443, 562444, 562452, 562505, 562507, 562426, 560 16, 560 17, 560 38, 560 39, 560121, 560123, 560124, 560125, 514530, 514531, 514538, 514562, 514564, 514567, A01N 3744, C07C32116, C07C32128, C07C22928
Patent
active
061536504
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Compounds of formula ##STR2## wherein R.sub.1 is hydrogen or a lower alkyl radical and n is 4, 5, or 6 are known in U.S. Pat. No. 4,024,175 and its divisional U.S. Pat. No. 4,087,544. The uses disclosed are: protective effect against cramp induced by thiosemicarbazide; protective action against cardiazole cramp; the cerebral diseases, epilepsy, faintness attacks, hypokinesia, and cranial traumas; and improvement in cerebral functions. The compounds are useful in geriatric patients. The patents are hereby incorporated by reference.
SUMMARY OF THE INVENTION
The compounds of the instant invention are novel substituted gamma aminobutyric acids, their derivatives, pharmaceutically acceptable salts, and prodrugs useful in a variety of disorders. The disorders include: epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, inflammatory disease, such as arthritis, and gastrointestinal damage such as gastric ulcers, dyspepsia, gastritis, and peptic ulcer.
The compounds of the invention are those of Formula I ##STR3## or a pharmaceutically acceptable salt thereof wherein: R is hydrogen or lower alkyl; ##STR4## straight or branched alkyl of from 7 to 11 carbon atoms, or --(CH.sub.2).sub.(1-4) --X--(CH.sub.2).sub.(0-4) -phenyl wherein benzyl or phenyl; to 3 substituents each independently selected from alkyl, alkoxy, halogen, hydroxy, carboxy, carboalkoxy, trifluoromethyl, amino, and nitro.
Preferred compounds of the invention are those of Formula I wherein ##STR5##
More preferred are those of Formula I wherein R.sub.1 is hydrogen or methyl and ##STR6##
Other preferred compounds of the invention are those of Formula I wherein
More preferred are compounds of Formula I wherein R.sub.2 is --(CH.sub.2).sub.1 --X--(CH.sub.2).sub.0-4 -phenyl.
Still other preferred compounds of the invention are those of Formula I wherein
The more preferred compounds of the invention are 3-aminomethyl-4-cyclohexyl-butyric acid and 3-aminomethyl-5-phenyl-pentanoic acid ##STR7## 3-Aminomethyl-5-benzylsulfanyl-pentanoic acid; 3-Aminomethyl-5-(4-bromo-benzylsulfanyl)-pentanoic acid;
The invention also is for pharmaceutical compositions of a compound of Formula I and methods of using the compounds of the invention.
DETAILED DESCRIPTION OF THE INVENTION
The compounds of the instant invention and their pharmaceutically acceptable salts are as defined by Formula I.
The term lower alkyl is a straight or branched group of from 1 to 4 carbons.
The term "alkyl" is a straight or branched group of from 1 to 11 carbon atoms including but not limited to methyl, ethyl, propyl, n-propyl, isopropyl, butyl, 2-butyl, tert-butyl, pentyl, hexyl, and n-hexyl, heptyl, octyl, nonyl, decyl, and undecyl except as where otherwise stated.
The cycloalkyl groups are from 3 to 8 carbons and are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.
The benzyl and phenyl groups may be unsubstituted or substituted by from 1 to 3 substituents selected from hydroxy, carboxy, carboalkoxy, halogen, CF.sub.3, nitro, alkyl, and alkoxy. Preferred are halogens.
Since amino acids are amphoteric, pharmacologically compatible salts when R is hydrogen can be salts of appropriate inorganic or organic acids, for example, hydrochloric, sulphuric, phosphoric, acetic, oxalic, lactic, citric, malic, salicylic, malonic, maleic, succinic, methanesulfonic acid, and ascorbic. Starting from corresponding hydroxides or carbonates, salts with alkali metals or alkaline earth metals, for example, sodium, potassium, magnesium, or calcium are formed. Salts with quaternary ammonium ions can also be prepared with, for example, the tetramethyl-ammonium ion. The carboxyl group of the amino acids can be esterified by known means.
Certain of the compounds of the present invention can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms, including hydrated forms, are equivalent to unsolvated forms and
REFERENCES:
patent: 4087544 (1978-05-01), Satzinger et al.
patent: 5219886 (1993-06-01), Smith et al.
Fujii and Yoshifuji, "Lactams. I. Synthesis and acid hydrolysis of 4- and 5-substituted-1-benzyl-2-piperidone derivatives", Tetrahedron, vol. 26, No. 24, 1970, pp. 5953-5958.
Bryans Justin Stephen
Horwell David Christopher
Kneen Clare Octavia
Thorpe Andrew John
Wustrow David Juergen
Anderson Elizabeth M.
Davis Brian J.
Richter Johann
Warner-Lambert & Company
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