排序方式: 共有32条查询结果,搜索用时 31 毫秒
1.
Swati P. Mercer Anthony J. Roecker Susan Garson Duane R. Reiss C. Meacham Harrell Kathy L. Murphy Joseph G. Bruno Rodney A. Bednar Wei Lemaire Donghui Cui Tamara D. Cabalu Cuyue Tang Thomayant Prueksaritanont George D. Hartman Steven D. Young Christopher J. Winrow John J. Renger Paul J. Coleman 《Bioorganic & medicinal chemistry letters》2013,23(24):6620-6624
The orexin (or hypocretin) system has been identified as a novel target for the treatment of insomnia due to the wealth of biological and genetic data discovered over the past decade. Recently, clinical proof-of-concept was achieved for the treatment of primary insomnia using dual (OX1R/OX2R) orexin receptor antagonists. However, elucidation of the pharmacology associated with selective orexin-2 receptor antagonists (2-SORAs) has been hampered by the lack of orally bioavailable, highly selective small molecule probes. Herein, the discovery and optimization of a novel series of 2,5-diarylnicotinamides as potent and orally bioavailable orexin-2 receptor selective antagonists is described. A compound from this series demonstrated potent sleep promotion when dosed orally to EEG telemetrized rats. 相似文献
2.
Brashear KM Hunt CA Kucer BT Duggan ME Hartman GD Rodan GA Rodan SB Leu CT Prueksaritanont T Fernandez-Metzler C Barrish A Homnick CF Hutchinson JH Coleman PJ 《Bioorganic & medicinal chemistry letters》2002,12(23):3483-3486
A series of novel, highly potent alpha(v)beta(3) receptor antagonists with favorable pharmacokinetic profiles has been identified. In this series of antagonists, 2-aryl beta-amino acids function as potent aspartic acid replacements. 相似文献
3.
Coleman PJ Askew BC Hutchinson JH Whitman DB Perkins JJ Hartman GD Rodan GA Leu CT Prueksaritanont T Fernandez-Metzler C Merkle KM Lynch R Lynch JJ Rodan SB Duggan ME 《Bioorganic & medicinal chemistry letters》2002,12(17):2463-2465
Potent non-peptidic alpha(v)beta(3) antagonists have been prepared where deletion of an amide bond from an earlier series of linear RGD-mimetics provides a novel series of chain-shortened alpha(v)beta(3) antagonists with significantly improved oral pharmacokinetics. These chain-shortened alpha(v)beta(3) antagonists represent structurally novel integrin inhibitors. 相似文献
4.
Breslin MJ Duggan ME Halczenko W Fernandez-Metzler C Hunt CA Leu CT Merkle KM Naylor-Olsen AM Prueksaritanont T Stump G Wallace A Rodan SB Hutchinson JH 《Bioorganic & medicinal chemistry letters》2003,13(10):1809-1812
Two novel series of small-molecule RGD mimetics containing either a substituted pyridone or pyrazinone central constraint were prepared. Modification of the beta-alanine 3-substituent produced compounds that are potent and selective alpha(v)beta(3) antagonists and exhibit a range of physicochemical properties. 相似文献
5.
Kuduk SD DiPardo RM Chang RK Di Marco CN Murphy KL Ransom RW Reiss DR Tang C Prueksaritanont T Pettibone DJ Bock MG 《Bioorganic & medicinal chemistry letters》2007,17(13):3608-3612
SAR study of the biphenyl region of cyclopropanecarboxamide derived bradykinin B(1) antagonists was examined. Incorporation of a pyridine in place of the proximal phenyl ring and chlorination of the distal phenyl ring proved to be well tolerated and provided compounds with improved pharmacokinetic profiles, CNS penetration, and enhanced receptor occupancy. 相似文献
6.
Reger TS Yang ZQ Schlegel KA Shu Y Mattern C Cube R Rittle KE McGaughey GB Hartman GD Tang C Ballard J Kuo Y Prueksaritanont T Nuss CE Doran SM Fox SV Garson SL Li Y Kraus RL Uebele VN Renger JJ Barrow JC 《Bioorganic & medicinal chemistry letters》2011,21(6):1692-1696
A novel series of amide T-type calcium channel antagonists were prepared and evaluated using in vitro and in vivo assays. Optimization of the screening hit 3 led to identification of the potent and selective T-type antagonist 37 that displayed in vivo efficacy in rodent models of epilepsy and sleep. 相似文献
7.
Kuduk SD Chang RK Ng C Murphy KL Ransom RW Tang C Prueksaritanont T Freidinger RM Pettibone DJ Bock MG 《Bioorganic & medicinal chemistry letters》2005,15(17):3925-3929
SAR study of the biphenyl region of 2,3-diaminopyridine bradykinin B1 antagonists was investigated with non-aromatic carbo- and heterocyclic rings. A piperidine ring was found to be a good replacement for the proximal phenyl ring while replacement of the distal phenyl was optimal with a cyclohexyl group leading to a dramatic improvement in affinity for the B1 receptor. 相似文献
8.
Feng DM Wai JM Kuduk SD Ng C Murphy KL Ransom RW Reiss D Chang RS Harrell CM MacNeil T Tang C Prueksaritanont T Freidinger RM Pettibone DJ Bock MG 《Bioorganic & medicinal chemistry letters》2005,15(9):2385-2388
A novel class of 2,3-diaminopyridine bradykinin B1 receptor antagonists is disclosed. Structure-activity relationship studies (SARs) that led to compounds with significantly improved potency and pharmacokinetic properties relative to the lead compound are described. 相似文献
9.
Kuduk SD Chang RK Dipardo RM Di Marco CN Murphy KL Ransom RW Reiss DR Tang C Prueksaritanont T Pettibone DJ Bock MG 《Bioorganic & medicinal chemistry letters》2008,18(18):5107-5110
A series of carbo- and heterocyclic alpha-hydroxy amide-derived bradykinin B1 antagonists was prepared and evaluated. A 4,4-difluorocyclohexyl alpha-hydroxy amide was incorporated along with a 2-methyl tetrazole in lieu of an oxadiazole to afford a suitable compound with good pharmacokinetic properties, CNS penetration, and clearance by multiple metabolic pathways. 相似文献
10.
Paul J Coleman Karen M Brashear Cecilia A Hunt William F Hoffman John H Hutchinson Michael J Breslin Carol A McVean Ben C Askew George D Hartman Sevgi B Rodan Gideon A Rodan Chih Tai Leu Thomayant Prueksaritanont Carmen Fernandez-Metzler Bennett Ma Laura A Libby Kara M Merkle Gary L Stump Audrey A Wallace Joseph J Lynch Robert Lynch Mark E Duggan 《Bioorganic & medicinal chemistry letters》2002,12(1):31-34
Potent non-peptidic alpha(v)beta(3) antagonists have been prepared incorporating various beta-amino acids as aspartic acid mimetics. Modification of the beta-alanine 3-substituents alters the potency and physicochemical properties of these receptor antagonists and in some cases provides orally bioavailable alpha(v)beta(3) inhibitors. 相似文献