83623-88-5Relevant academic research and scientific papers
PYRROLIDINE ANALOGUE FOR PREVENTING NEUROGENIC PAIN AND METHOD FOR PRODUCTION THEREOF
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Page/Page column 42-43, (2009/06/27)
[Problems] To provide a pyrrolidine analogue having an inhibitory activity on the induction of allodynia, a method for producing the pyrrolidine analogue, and an agent for preventing a neurogenic pain. [Means for Solving the Problems] A pyrrolidine analog
PROLINE DERIVATIVES HAVING AFFINITY FOR THE CALCIUM CHANNEL ALPHA-2-DELTA SUBUNIT
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Page/Page column 62, (2010/02/06)
The compounds of formula (I) or a pharmaceutically acceptable salt, solvate or pro-drug thereof, are proline derivatives useful in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, fibromyalgia, arthritis, neuropathalogical disorders, sleep disorders, visceral pain disorders and gastrointestinal disorders. Processes for the preparation of the final products and intermediates useful in the process are included. Pharmaceutical compositions containing one or more of the compounds are also included. Wherein either X is O, S, NH or CH2 and Y is CH2 or a direct bond, or Y is O, S or NH and X is CH2; and R is a 3-12 membered cycloalkyl, 4-12 membered heterocycloalkyl, heteroaryl or aryl, where any ring may be optionally substituted with one or more substituents independently selected from halogen, hydroxy, cyano, nitro, amino, hydroxycarbonyl, Cl-C6 alkyl, Cl-C6 alkenyl, CI-C6 alkynyl, Cl-C6 alkoxy, hydroxyC,-C6 alkyl, Cl-C6 alkoxyC,-C6 alkyl, perfluoro Cl-C6 alkyl, perfluoroC,-C6 alkoxy, Cl-C6 alkylamino, di- C1-C6 alkylamino, aminoC1-C6 alkyl, Cl-C6 alkylaminoC,-C6 alkyl, di-Cl-C6 alkylaminoC,-C6 alkyl, CI-C6acyl, C1-C6acyloxy, Cl-C6acyloxyC,-C6 alkyl, Cl-C6 acylamino, Cl-C6 alkylthio, C1-C6 alkylthiocarbonyl, C1-C6 alkylthioxo, C1-C6 alkoxycarbonyl, Cl-C6 alkylsulfonyl, C1-C6 alkylsulfonylamino, aminosulfonyl, Cl-C6 alkylaminosulfonyl, di-Cl-C6 alkylaminosulfonyl, 3-8 membered cycloalkyl, 4-8 membered heterocycloalkyl, phenyl and monocyclic heteroaryl; or a pharmaceutically acceptable salt, solvate or pro-drug thereof.
Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines
Krapcho,Turk,Cushman,Powell,DeForrest,Spitzmiller,Karanewsky,Duggan,Rovnvak,Schwartz,Natarajan,Godfrey,Ryono,Neubeck,Atwa,Petrillo Jr.
, p. 1148 - 1160 (2007/10/02)
Analogues of captopril, enalaprilat, and the phosphinic acid [[hydroxy(4-phenylbutyl)phosphinyl]acetyl)-L-proline incorporating 4-substituted proline derivatives have been synthesized and evaluated as inhibitors of angiotensin-converting enzyme (ACE) in vitro and in vivo. The 4-substituted prolines, incorporating alkyl, aryl, alkoxy, aryloxy, alkylthio, and arylthio substituents were prepared from derivatives of 4-hydroxy- and 4-ketoproline. In general, analogues of all three classes of inhibitors with hydrophobic substituents on proline were more potent in vitro than the corresponding unsubstituted proline compounds. 4-Substituted analogues of captopril showed greater potency and duration of action than the parent compound as inhibitors of the angiotensin I induced pressor response in normotensive rats. The S-benzoyl derivative of cis-4-(phenylthio)captopril, zofenopril, was found to be one of the most potent compounds of this class and is now being evaluated clinically as an antihypertensive agent. In the phosphinic acid series, the 4-ethylenethioketal and trans-4-cyclohexyl derivatives were found to be the most potent compounds in vitro and in vivo. A prodrug of the latter compound, fosinopril, is also being evaluated in clinical trials.
