138679-49-9Relevant academic research and scientific papers
Synthesis and antimuscarinic properties of some N-substituted 5- (aminomethyl)-3,3-diphenyl-2(3H)-furanones
Kaiser,Spagnuolo,Adams Jr.,Audia,Dupont,Hatoum,Lowe,Prosser,Sturm,Noronha-Blob
, p. 4415 - 4424 (2007/10/02)
In a study aimed toward developing new, selective antimuscarinic drugs with potential utility in the treatment of urinary incontinence associated with bladder muscle instability, a series of N-substituted 5-(aminomethyl)- 3,3-diphenyl-2(3H)-furanones, conformationally-constrained lactone relatives of benactyzine, was prepared. The compounds were examined in several paradigms that measure muscarinic (M1, M2, and M3) receptor antagonist activity. Selected members of the series that displayed potency and/or selectivity in these tests were studied for their effects on urinary bladder contraction, mydriasis, and salivation in guinea pigs. These studies revealed that incorporation of the amino functionality into an imidazole or pyrazole ring resulted in some novel, potent, and selective antimuscarinic agents. Appropriate alkyl substitution of position 2 of the imidazole strikingly affected muscarinic, particularly M3, receptor activity and may reflect a complementary site of interaction. Some of the compounds selectively reduced bladder pressure in a cystometrogram (CMG) model without producing concomitant mydriatic and salivary effects. The separate and distinct action of several compounds of this series in these in vivo protocols suggests the possibility of subtypes of muscarinic receptors that may correspond to previously characterized molecular cloned subpopulations. In this article, structure-activity relationships for the series of substituted lactones are discussed. These studies led to the identification of (R)-[(2-isopropyl-1H- imidazol-1-yl)methyl]-4,5-dihydro-3,3-diphenyl-2(3H)-furanone (23) as a clinical candidate for treating urinary bladder dysfunction.
DIHYDRO-3,3-DIPHENYL-5-(1H-PYRAZOL-1-YLMETHYL-2(3H)-FURANONE AND DIHYDRO-5-((SUBSTITUTED-1H-PYRAZOL-1-YL)METHYL)-3,3-DIPHENYL-2(3H)-FURANONE DERIVATIVES
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, (2008/06/13)
Dihydrofuranone compounds having anticholinergic activity are described. The compounds have the formula: STR1 wherein: R 1 is hydrogen or lower alkyl,R 2 is hydrogen or lower alkyl,R 3 is hydrogen or lower alkyl, and Ph is phenyl.Also described are the lower alkyl quaternary and acid addition salts of the compounds. Pharmaceutical compositions effective as anticholinergics and methods utilizing such compounds are disclosed.
