共查询到10条相似文献,搜索用时 148 毫秒
1.
Mark D. Andrews Martin P. Green Charlotte M.N. Allerton David V. Batchelor Julian Blagg Alan D. Brown David W. Gordon Gordon McMurray Daniel J. Millns Carly L. Nichols Lesa Watson 《Bioorganic & medicinal chemistry letters》2009,19(18):5346-5350
This Letter reports the design and synthesis of several novel series of piperazinyl pyrimidinones as 5-HT2C agonists. Several of the compounds presented exhibit good in vitro potency and selectivity over the closely related 5-HT2A and 5-HT2B receptors. Compound 11 was active in in vivo models of stress urinary incontinence. 相似文献
2.
Silvia Franchini Adolfo Prandi Claudia Sorbi Annalisa Tait Annamaria Baraldi Piero Angeli Michela Buccioni Antonio Cilia Elena Poggesi Paola Fossa Livio Brasili 《Bioorganic & medicinal chemistry letters》2010,20(6):2017-2020
Starting from compounds previously identified as α1-adrenoceptor antagonists that were also found to bind to the 5-HT1A receptor, in an attempt to separate the two activities, a new series of 5-HT1A receptor agonists was identified and shown to have high potency and/or high selectivity. Of these, compound 13, which combines high selectivity (5-HT1A/α1 = 151) and good agonist potency (pD2 = 7.82; Emax = 76), was found to be the most interesting. 相似文献
3.
Suk Youn Kang Eun-Jung Park Woo-Kyu Park Hyun Jung Kim Daeyoung Jeong Myung Eun Jung Kwang-Seop Song Suk Ho Lee Hee Jeong Seo Min Ju Kim MinWoo Lee Ho-Kyun Han Eun-Jung Son Ae Nim Pae Jeongmin Kim Jinhwa Lee 《Bioorganic & medicinal chemistry letters》2010,20(5):1705-1711
Arylpiperzine-containing pyrrole 3-carboxamide derivatives were synthesized and evaluated as novel antidepressant compounds. The various analogues were efficiently prepared and bio-assayed for binding to 5-HT2A, 5-HT2C receptor, and 5-HT transporter. Based on their in vitro and in vivo activities as well as selectivity over other neurotransmitter receptors and PK profiles, 33 and 34 were identified as lead compounds. Consequently, this pyrrole series of compounds appears to be promising enough to warrant further investigation. 相似文献
4.
《Bioorganic & medicinal chemistry》2020,28(15):115578
Aporphine alkaloids containing a C10 nitrogen motif were synthesized and evaluated for affinity at 5-HT1AR, 5-HT2AR, 5-HT6R and 5-HT7AR. Three series of racemic aporphines were investigated: 1,2,10-trisubstituted, C10 N-monosubstituted and compounds containing a C10 benzofused aminothiazole moiety. The 1,2,10-trisubstituted series of compounds as a group displayed modest selectivity for 5-HT7AR and also had moderate 5-HT7AR affinity. Compounds from the C10 N-monosubstituted series generally lacked affinity for 5-HT2AR and 5-HT6R and showed strong affinity for 5-HT1A or 5-HT7AR. Compounds in this series that contained an N6-methyl group were up to 27-fold selective for 5-HT7AR over 5-HT1AR, whereas compounds with an N6-propyl substituent showed a reversal in this selectivity. The C10 benzofused aminothiazole analogues showed a similar binding profile as the C10 N-monosubstituted series i.e. strong affinity for 5-HT1AR or 5-HT7AR, with selectivity between the two receptors being similarly influenced by N6-methyl or N6-propyl substituents. Compounds 29 and 34a exhibit high 5-HT7AR affinity, excellent selectivity versus dopamine receptors and function as antagonists in 5-HT7AR cAMP-based assays. Compounds 29 and 34a have been identified as new lead molecules for further tool and pharmaceutical optimization. 相似文献
5.
Paul E. Brennan Gavin A. Whitlock Danny K.H. Ho Kelly Conlon Gordon McMurray 《Bioorganic & medicinal chemistry letters》2009,19(17):4999-5003
A range of heterocycle fused azepines were synthesized in order to find a CNS penetrant, selective 5-HT2C agonist for the treatment of incontinence. The pyridazo-azepines such as compound 11 were shown to be potent 5-HT2C agonists and have potential for CNS penetration and good in vitro ADME properties but lacked selectivity against 5-HT2B. Fusing a further heterocycle gave the selective triazolopyrimido-azepines. An example of this series, compound 36, was shown to be potent, selective, metabolically stable in vitro and efficacious in an in vivo model of stress urinary incontinence. 相似文献
6.
David A. Favor James J. Powers Andrew D. White Lawrence W. Fitzgerald Vincent Groppi Kevin A. Serpa 《Bioorganic & medicinal chemistry letters》2010,20(19):5666-5669
A series of 6-alkoxyisoindolin-1-ones with a magic shotgun pharmacological profile are presented as potential antipsychotics. The in vitro pharmacological profile includes D2 partial agonism (30–55%), 5-HT1A partial agonism (60–90%), and 5-HT2A antagonism. Selected compounds in this series displayed good in vivo activity and potency. 相似文献
7.
Charlotte M.N. Allerton Mark D. Andrews Julian Blagg David Ellis Edel Evrard Martin P. Green Kevin K.-C. Liu Gordon McMurray Michael Ralph Vivienne Sanderson Robin Ward Lesa Watson 《Bioorganic & medicinal chemistry letters》2009,19(19):5791-5795
The SAR of a series of pyridazinone derived 5-HT2C agonists has been explored and resulted in identification of a compound with excellent levels of 5-HT2C functional agonism and selectivity over 5-HT2A and 5-HT2B. This compound displayed good in vivo efficacy in pre-clinical models of stress urinary incontinence, despite having physiochemical properties commensurate with impaired CNS penetration. 相似文献
8.
Simon E. Ward Peter Eddershaw Sean T. Flynn Laurie Gordon Peter J. Lovell Susan H. Moore Claire M. Scott Paul W. Smith Kevin M. Thewlis Paul A. Wyman 《Bioorganic & medicinal chemistry letters》2009,19(2):428-432
A series of 5-(piperidinylethyloxy)quinoline 5-HT1 receptor ligands have been studied by elaboration of the series of dual 5-HT1-SSRIs reported previously. These new compounds display a different in vitro pharmacological profile with potent affinity across the 5-HT1A, 5-HT1B and 5-HT1D receptors and selectivity against the serotonin transporter. Furthermore, they have improved pharmacokinetic profiles and CNS penetration. 相似文献
9.
Euna Yoo Juhee Yoon Ae Nim Pae Hyewhon Rhim Woo-Kyu Park Jae Yang Kong Hea-Young Park Choo 《Bioorganic & medicinal chemistry》2010,18(4):1665-1675
A novel series of 5-HT2A ligands that contain a (phenylpiperazinyl-propyl)arylsulfonamides skeleton was synthesized. Thirty-seven N-(cycloalkylmethyl)-4-methoxy-N-(3-(4-arylpiperazin-1-yl)propyl)-arylsulfonamide and N-(4-(4-arylpiperazin-1-yl)butan-2-yl)-arylsulfonamide compounds were obtained. The binding of these compounds to the 5-HT2A, 5-HT2C, and 5-HT7 receptors was evaluated. Most of the compounds showed IC50 values of less than 100 nM and exhibited high selectivity for the 5-HT2A receptor. Among the synthesized compounds, 16a and 16d showed good affinity at 5-HT2A (IC50 = 0.7 nM and 0.5 nM) and good selectivity over 5-HT2C (50–100 times) and 5-HT7 (1500–3000 times). 相似文献
10.
Paul V. Fish Alan D. Brown Edel Evrard Lee R. Roberts 《Bioorganic & medicinal chemistry letters》2009,19(7):1871-1875
New 7-sulfonamido-3-benzazepines 3 are disclosed as 5-HT2C receptor agonists. Appropriate substitution of the amino group (R1R2N–) gave compounds that were potent 5-HT2C agonists with minimal activation of the 5-HT2A and 5-HT2B receptors. Furthermore, representative examples had excellent in vitro ADME properties and good selectivity over ion channel activity. 相似文献