218430-63-8Relevant academic research and scientific papers
Highly enantioselective organocatalytic Biginelli and Biginelli-like condensations: Reversal of the stereochemistry by tuning the 3,3′-disubstituents of phosphoric acids
Li, Nan,Chen, Xiao-Hua,Song, Jin,Luo, Shi-Wei,Fan, Wu,Gong, Liu-Zhu
supporting information; experimental part, p. 15301 - 15310 (2010/01/30)
Organocatalytic enantioselective Biginelli and Biginelli-like reactions by chiral phosphoric acids derived from 3,3′-disubstituted binaphthols have been investigated. The size of 3,3′-substituents of the catalysts is able to control the stereochemistry of
Enantioselective synthesis of SNAP-7941: Chiral dihydropyrimidone inhibitor of MCH1-R
Goss, Jennifer M.,Schaus, Scott E.
supporting information; experimental part, p. 7651 - 7656 (2009/04/11)
(Chemical Equation Presented) An enantioselective synthesis of SNAP-7941, a potent melanin concentrating hormone receptor antagonist, was achieved by using two organocatalytic methods. The first method utilized to synthesize the enantioenriched dihydropyrimidone core was the Cinchona alkaloid-catalyzed Mannich reaction of β-keto esters to acylimines and the second was the chiral phosphoric acid-catalyzed Biginelli reaction. Completion of the synthesis was accomplished via selective urea formation at the N3 position of the dihydropyrimidone with the 3-(4-phenylpiperidin-1-yl)propylamine side chain fragment. The synthesis of SNAP-7921 highlights the utility of asymmetric organocatalytic methods in the construction of an important class of chiral heterocycles.
Efficient synthesis of the optically active dihydropyrimidinone of a potent α1A-selective adrenoceptor antagonist
Sidler, Daniel R.,Barta, Nancy,Li, Wenjie,Hu, Essa,Matty, Louis,Ikemoto, Nori,Campbell, Jeffrey S.,Chartrain, Michel,Gbewonyo, Kozo,Boyd, Russell,Corley, Edward G.,Ball, Richard G.,Larsen, Robert D.,Reider, Paul J.
, p. 646 - 652 (2007/10/03)
The convergent synthesis of a potent α1A-selective adrenoceptor antagonist is described. Salient features of the synthesis include the enzymatic resolution of a racemic dihydropyrimidinone and the use of a palladium coupling reaction in the synthesis of 2,4′-dipyridyl.
Combination therapy for the treatment of benign prostatic hyperplasia
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, (2008/06/13)
This invention relates to combination therapy for the treatment of benign prostatic hyperplasia comprising an alpha-1a antagonist and an endothelin antagonist. More specifically, the use of a selective alpha-1a adrenergic receptor antagonist in combination with a subtype non-selective endothelin antagonist provides relief of lower urinary tract symptoms in patients with symptomatic prostatism or benign prostatic hyperplasia. This combination therapy improves lower urinary tract symptoms including increasing urine flow rate, decreasing residual urine volume and improving overall obstructive and irritative symptoms in patients with benign prostatic hyperplasia or symptomatic prostatism.
Alpha 1a adrenergic receptor antagonists
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, (2008/06/13)
This invention relates to crystalline pharmaceutically acceptable salts of an alpha 1a adrenergic receptor antagonist, Compound A, which are useful in the treatment of benign prostatic hyperplasia. Pharmaceutical compositions employing the crystalline salts, and processes for making and using the crystalline salts and pharmaceutical compositions of Compound A are also disclosed. This invention further relates to a process for obtaining enantiomerically pure intermediate useful for the synthesis of end product alpha 1a adrenergic receptor antagonists. The end product compounds are useful for the treatment of benign prostatic hyperplasia and for relaxing lower urinary tract tissue. The invention also relates to a process for preparing a class of dihydropyrimidinone compounds of which Compound A is a member, wherein the process involves deprotonating a dihydropyrimidinone compound and then coupling the deprotonated derivative with a primary amine.
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.
