33893-37-7Relevant articles and documents
Synthesis of 3,5-disubstituted [1,2,4]-oxadiazoles
Bora, Rajesh O.,Farooqui, Mazahar
experimental part, p. 569 - 573 (2009/07/18)
Substituted amidoximes have been synthesized, and converted to corresponding oxadiazoles as a novel heterocyclic compounds under mild conditions in good to excellent yield.
Analysis of structure-activity relationships with the N-(3-acyloxy-2- benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea template for vanilloid receptor 1 antagonism
Lee, Jeewoo,Kim, Su Yeon,Lee, Jiyoun,Kang, Myungsim,Kil, Min-Jung,Choi, Hyun-Kyung,Jin, Mi-Kyung,Wang, Yun,Toth, Attila,Pearce, Larry V.,Lundberg, Daniel J.,Tran, Richard,Blumberg, Peter M.
, p. 3411 - 3420 (2007/10/03)
In a continuing effort to elucidate the structure-activity relationships of the lead antagonist N-[2-(3,4-dimethylbenzyl)-3-pivaloyloxypropyl]-N ′-[4-(methylsulfonylamino)benzyl]thiourea (1), the distances between the proposed four pharmacophores in 1 have been varied by insertion or deletion of one carbon to optimize their fit to the receptor. In addition, the acyloxy group of the C region was replaced with amide and N-hydroxy amide to identify the pharmacophoric importance of the ester group in the C2 region. The results indicated that the pharmacophoric arrangement of 1 was optimal for receptor binding affinity and antagonism, and the ester of the C2 region was significant for receptor binding. Among the derivatives, compound 19 showed distinct behavior with a 2-fold improvement in antagonism but a 13-fold reduction in binding affinity compared to 1. The partial separation of pharmacophoric requirements of these two assays has been noted before and compound 19 is thus selective for the calcium entry-linked receptor population. The conformational analysis of 1 generated three distinct conformers having different types of hydrophobic interactions, which will be utilized for exploring the active conformation of the VR1 ligand.
Synthesis and Serotonergic Activity of 5-(Oxadiazolyl)tryptamines: Potent Agonists for 5-HT1D Receptors
Street, Leslie J.,Baker, Raymond,Castro, Jose L.,Chambers, Mark S.,Guiblin, Alexander R.,et al.
, p. 1529 - 1538 (2007/10/02)
The synthesis and 5-HT1D receptor activity of a novel series of 5-(oxadiazolyl)tryptamines is described.Modifications of the oxadiazole 3-substituent, length of the linking chain (n), and the amine substituents are explored and reveal a large binding pocket in the 5-HT1D receptor domain.Oxadiazole substituents such as benzyl are accommodated without loss of agonist potency or efficacy.The incorporation of polar functionality on a phenyl or benzyl spacer group results in a 10-fold increase in affinity and functional potency.Optimal 5-HT1D activity is observed when the heterocycle is conjugated with the indole and the benzyl sulfonamides 20t and 20u represent some of the most potent 5-HT1D agonist known.Replacement of O for S in the heterocycle leads to a further increase in potency.Deletion of oxadiazole N-2 does not reduce activity, suggesting the requirements for only one H-bond acceptor in this location.The selectivity of these compounds for 5-HT1D receptors over other serotonergic receptors is discussed.Sulfonamide 20t shows 1000-fold selectivity for 5-HT1D over 5-HT2, 5-HT1C, and 5-HT3 receptors and 10-fold selectivity with respect to 5-HT1A receptors.The functional activity of this series of compounds is studied and demonstrates high 5-HT1D receptor potency and efficacy comparable to that of 5-HT.
