4878-14-2Relevant articles and documents
Discovery and optimization of (R)-prolinol-derived agonists of the Growth Hormone Secretagogue receptor (GHSR)
Zhai, Weixu,Flynn, Neil,Longhi, Daniel A.,Tino, Joseph A.,Murphy, Brian J.,Slusarchyk, Dorothy,Gordon, David A.,Pendri, Anna,Shi, Shuhao,Stoffel, Robert,Ma, Baoqing,Sofia, Michael J.,Gerritz, Samuel W.
supporting information; experimental part, p. 5083 - 5086 (2009/07/18)
The discovery and optimization of a novel series of prolinol-derived GHSR agonists is described. This series emerged from a 11,520-member solid-phase library targeting the GPCR protein superfamily, and the rapid optimization of low micromolar hits into single-digit nanomolar leads can be attributed to the solid-phase synthesis of matrix libraries, which revealed multiple non-additive structure-activity relationships. In addition, the separation of potent diastereomers highlighted the influence of the α-methyl stereochemistry of the phenoxyacetamide sidechain on GHSR activity.
Heterocyclic compounds useful as growth hormone secretagogues
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Page/Page column 9-10, (2008/06/13)
The present invention relates to novel heterocyclic compounds, according to Formula I, that stimulate endogenous production and/or release of growth hormone, wherein R1, R2, R3, R4 and X are defined herein. Furt
Presynaptic cholinergic modulators as potent cognition enhancers and analgesic drugs. 2. 2-Phenoxy-, 2-(phenylthio)-, and 2-(phenylamino)alkanoic acid esters
Gualtieri,Bottalico,Calandrella,Dei,Giovannoni,Mealli,Romanelli,Scapecchi,Teodori,Galeotti,Ghelardini,Giotti,Bartolini
, p. 1712 - 1719 (2007/10/02)
Further modifications of the leads ((R)-(+)-hyoscyamine and (p- chlorophenyl)propionic acid α-tropanyl ester), which show analgesic and nootropic activities as a consequence of increased central presynaptic ACh release, are reported. 2-Phenoxy- and 2-(phenylthio)alkanoic acid esters showed the best results. Several members of these classes possess analgesic properties which are comparable to that of morphine and at the same time are able to reverse dicyclomine-induced amnesia. Confirmation was found that the mechanism of action is due to an increase in ACh release at central muscarinic synapses and that both auto- and heteroreceptors controlling ACh release are very likely involved. According to the results obtained with (R)- (+)-hyoscyamine, analgesic activity is stereochemistry dependent, since the R-(+)-enantiomers are always more efficacious than the corresponding S-(-)- ones. On the basis of their potency and acute toxicity, compounds (±)-28 (SM21) and (±)-42 (SM32) were selected for further study.
