238427-66-2Relevant articles and documents
AGONISTS THAT ENHANCE BINDING OF INTEGRIN-EXPRESSING CELLS TO INTEGRIN RECEPTORS
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Page/Page column 46, (2012/06/01)
A method of enhancing binding of cells to an integrin-binding ligand comprises treating integrin-expressing cells in vitro with an agonist of integrin, wherein the integrin is selected from the group consisting of α4β1, α5β1, α4β7, αvβ3 and αLβ2, and contacting the treated cells with an integrin-binding ligand; integrin agonist compounds having the general formula I; methods of treating integrin-expressing cells with such agonists to enhance binding; and therapeutic methods comprising administering agonist-treated cells or agonist compounds to a mammal.
Synthesis and serotonergic activity of substituted 2,N- benzylcarboxamido-5-(2-ethyl-1-dioxoimidazolidinyl)-N,N-dimethyltryptamine derivatives: Novel antagonists for the vascular 5-HT(1B)-like receptor
Moloney, Gerard P.,Martin, Graeme R.,Mathews, Neil,Milne, Aynsley,Hobbs, Heather,Dodsworth, Susan,Sang, Pang Yih,Knight, Cameron,Williams, Marnie,Maxwell, Miles,Glen, Robert C.
, p. 2504 - 2526 (2007/10/03)
The synthesis and vascular 5-HT(1B)-like receptor activity of a novel series of substituted 2,N-benzylcarboxamido-5-(2-ethyl-1- dioxoimidazolidinyl)-N,N-dimethyltryptamine derivatives are described. Modifications to the 5-ethylene-linked heterocycle and to substituents on the 2-benzylamide side chain have been explored. Several compounds were identified which exhibited affinity at the vascular 5-HT(1B)-like receptor of pK(B) > 7.0, up to 100-fold selectivity over α1-adrenoceptor affinity and 5-HT(2A) receptor affinity, and which exhibited a favorable pharmacokinetic profile. N-Benzyl-3-[2-(dimethylamino)ethyl]-5-[2-(4,4-dimethyl-2,5-dioxo-1- imidazolidinyl)ethyl]-1H-indole-2-carboxamide (23) was identified as a highly potent, silent (as judged by the inability of angiotensin II to unmask 5- HT(1B)-like receptor-mediated agonist activity in the rabbit femoral artery), and competitive vascular 5-HT(1B)-like receptor antagonist with a plasma elimination half-life of ~4 h in dog plasma and with good oral bioavailability. The selectivity of compounds from this series for the vascular 5-HT(1B)-like receptors over other receptor subtypes is discussed as well as a proposed mode of binding to the receptor pharmacophore. It has been proposed that the aromatic ring of the 2,N-benzylcarboxamide group can occupy an aromatic binding site rather than the indole ring. The resulting conformation allows an amine-binding site to be occupied by the ethylamine nitrogen and a hydrogen-bonding site to be occupied by one of the hydantoin carbonyls. The electronic nature of the 2,N-benzylcarboxamide aromatic group as well as the size of substituents on this aromatic group is crucial for producing potent and selective antagonists. The structural requirement on the 3-ethylamine side chain incorporating the protonatable nitrogen is achieved by the bulky 2,N-benzylcarboxamide group and its close proximity to the 3- side chain.
