88013-15-4Relevant academic research and scientific papers
Identification of the minimum PAR4 inhibitor pharmacophore and optimization of a series of 2-methoxy-6-arylimidazo[2,1-b][1,3,4]thiadiazoles
Temple, Kayla J.,Duvernay, Matthew T.,Maeng, Jae G.,Blobaum, Anna L.,Stauffer, Shaun R.,Hamm, Heidi E.,Lindsley, Craig W.
, p. 5481 - 5486 (2016/11/09)
This letter describes the further deconstruction of the known PAR4 inhibitor chemotypes (MWs 490–525 and with high plasma protein binding) to identify a minimum PAR4 pharmacophore devoid of metabolic liabilities and improved properties. This exercise identified a greatly simplified 2-methoxy-6-arylimidazo[2,1-b][1,3,4]thiadiazole scaffold that afforded nanomolar inhibition of both activating peptide and γ-thrombin mediated PAR4 stimulation, while reducing both molecular weight and the number of hydrogen bond donors/acceptors by ～50%. This minimum PAR4 pharmacophore, with competitive inhibition, versus non-competitive of the larger chemotypes, allows an ideal starting point to incorporate desired functional groups to engender optimal DMPK properties towards a preclinical candidate.
Synthesis of 2,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazoles through cyclization and Suzuki-Miyaura cross-coupling reactions
Copin, Chloe,Henry, Nicolas,Buron, Frederic,Routier, Sylvain
supporting information; experimental part, p. 3079 - 3083 (2012/07/01)
Highly substituted imidazo[2,1-b][1,3,4]thiadiazole derivatives were synthesized through successive cyclization and Suzuki-Miyaura cross-coupling reactions. The palladium-catalyzed coupling reaction was optimized and a wide range of boronic acids was used to evaluate the scope and limitations of the methodology. The final compounds were obtained in fair to very good yields and high compatibility with various chemical functions or (hetero)cycles was observed. Copyright
Preparation of 5-bromo-6-phenylimidazo[2,1-b][1,3,4]thiadiazol-2-ylamines
Safarov, Saifidin,Rahmon, Rahmonov,Kukaniev, Muhamacho Amadovich,Schollmeyer, Dieter,Karpuk, Elena,Meier, Herbert
, p. 299 - 302 (2008/09/19)
(Chemical Equation Presented) The reaction of primary or secondary amines with 2,5-dibromo-6-phenylimidazo[2,1-b][1,3,4]-thiadiazole (5) leads to a chemoselective replacement of the 2-Br substituent. The process represents a convenient route to the corresponding 2-ylamines 7a-d. Hydrazine reacts in an analogous fashion (5 → 7e). The structure determinations are based on an X-ray crystal structure analysis and on one- and two-dimensional NMR measurements.
