256951-83-4Relevant articles and documents
Alpha 1A adrenergic receptor antagonists
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Example 5, (2010/01/30)
This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as alpha 1a adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.
Dihydropyridinones and pyrrolinones useful as alpha 1A adrenoceptor antagonists
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, (2008/06/13)
Novel dihydropyridinone and pyrrolinone compounds and pharmaceutically acceptable salts thereof are disclosed. The synthesis of these compounds and their use as alpha1aadrenergic receptor antagonists is also described. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha1areceptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.
In vitro, and in vivo, evaluation of dihydropyrimidinone C-5 amides as potent and selective α(1A) receptor antagonists for the treatment of benign prostatic hyperplasia
Barrow, James C.,Nantermet, Philippe G.,Selnick, Harold G.,Glass, Kristen L.,Rittle, Kenneth E.,Gilbert, Kevin F.,Steele, Thomas G.,Homnick, Carl F.,Freidinger, Roger M.,Ransom, Rick W.,Kling, Paul,Reiss, Duane,Broten, Theodore P.,Schorn, Terry W.,Chang, Raymond S. L.,O'Malley, Stacey S.,Olah, Timothy V.,Ellis, Joan D.,Barrish, Andrea,Kassahun, Kelem,Leppert, Paula,Nagarathnam, Dhanapalan,Forray, Carlos
, p. 2703 - 2718 (2007/10/03)
α1 Adrenergic receptors mediate both vascular and lower urinary tract tone, and α1 receptor antagonists such as terazosin (1b) are used to treat both hypertension and benign prostatic hyperplasia (BPH). Recently, three different subtypes of this receptor have been identified, with the α(1A) receptor being most prevalent in lower urinary tract tissue. This paper explores 4-aryldihydropyrimidinones attached to an aminopropyl-4- arylpiperidine via a C-5 amide as selective α(1A) receptor subtype antagonists. In receptor binding assays, these types of compounds generally display K(i) values for the α(1a) receptor subtype 20%) and half-life (>6 h) in both rats and dogs. Due to its selectivity for the α(1a) over the α(1b) and α(1d) receptors as well as its favorable pharmacokinetic profile, 48 has the potential to relieve the symptoms of BPH without eliciting effects on the cardiovascular system.
Selective alpha1a adrenergic receptor antagonists based on 4-aryl-3,4-dihydropyridine-2-ones.
Nantermet,Barrow,Selnick,Homnick,Freidinger,Chang,O'Malley,Reiss,Broten,Ransom,Pettibone,Olah,Forray
, p. 1625 - 1628 (2007/10/03)
A series of alpha1a receptor antagonists derived from a 4-aryl-3,4-dihydropyridine-2-one heterocycle is disclosed. Potency in the low nanomolar to picomolar range along with high selectivity was obtained. In vivo efficacy in a prostate contraction model in rats was observed with a few derivatives.
