18672-06-5Relevant academic research and scientific papers
Palladium-Catalyzed Methylation of Aryl, Heteroaryl, and Vinyl Boronate Esters
Haydl, Alexander M.,Hartwig, John F.
supporting information, p. 1337 - 1341 (2019/02/26)
A method for the direct methylation of aryl, heteroaryl, and vinyl boronate esters is reported, involving the reaction of iodomethane with aryl-, heteroaryl-, and vinylboronate esters catalyzed by palladium and PtBu2Me. This transformation occurs with a remarkably broad scope and is suitable for late-stage derivatization of biologically active compounds via the boronate esters. The unique capabilities of this method are demonstrated by combining carbon-boron bond-forming reactions with palladium-catalyzed methylation in a tandem transformation.
Design, synthesis of novel, potent, selective, orally bioavailable adenosine A2A receptor antagonists and their biological evaluation
Basu, Sujay,Barawkar, Dinesh A.,Thorat, Sachin,Shejul, Yogesh D.,Patel, Meena,Naykodi, Minakshi,Jain, Vaibhav,Salve, Yogesh,Prasad, Vandna,Chaudhary, Sumit,Ghosh, Indraneel,Bhat, Ganesh,Quraishi, Azfar,Patil, Harish,Ansari, Shariq,Menon, Suraj,Unadkat, Vishal,Thakare, Rhishikesh,Seervi, Madhav S.,Meru, Ashwinkumar V.,De, Siddhartha,Bhamidipati, Ravi K.,Rouduri, Sreekanth R.,Palle, Venkata P.,Chug, Anita,Mookhtiar, Kasim A.
supporting information, p. 681 - 694 (2017/02/05)
Our initial structure-activity relationship studies on 7-methoxy-4-morpholino-benzothiazole derivatives featured by aryloxy-2-methylpropanamide moieties at the 2-position led to identification of compound 25 as a potent and selective A2A adenosine receptor (A2AAdoR) antagonist with reasonable ADME and pharmacokinetic properties. However, poor intrinsic solubility and low to moderate oral bioavailability made this series unsuitable for further development. Further optimization using structure-based drug design approach resulted in discovery of potent and selective adenosine A2A receptor antagonists bearing substituted 1-methylcyclohexyl-carboxamide groups at position 2 of the benzothiazole scaffold and endowed with better solubility and oral bioavailability. Compounds 41 and 49 demonstrated a number of positive attributes with respect to in vitro ADME properties. Both compounds displayed good pharmacokinetic properties with 63% and 61% oral bioavailability, respectively, in rat. Further, compound 49 displayed oral efficacy in 6-OHDA lesioned rat model of Parkinson diseases.
Design, synthesis, and docking studies of novel benzimidazoles for the treatment of metabolic syndrome
Mizuno, Cassia S.,Chittiboyina, Amar G.,Shah, Falgun H.,Patny, Akshay,Kurtz, Theodore W.,Pershadsingh, Harrihar A.,Speth, Robert C.,Karamyan, Vardan T.,Carvalho, Paulo B.,Avery, Mitchell A.
supporting information; experimental part, p. 1076 - 1085 (2010/08/06)
In addition to lowering blood pressure, telmisartan, an angiotensin (AT1) receptor blocker, has recently been shown to exert pleiotropic effects as a partial agonist of nuclear peroxisome proliferator-activated receptor γ (PPARγ). On the basis of these findings and docking pose similarity between telmisartan and rosiglitazone in PPARγ active site, two classes of benzimidazole derivatives were designed and synthesized as dual PPARγ agonist/angiotensin II antagonists for the possible treatment of metabolic syndrome. Compound 4, a bisbenzimidazole derivative showed the best affinity for the AT1 receptor with a Ki=13.4 nM, but it was devoid of PPARγ activity. On the other hand 9, a monobenzimidazole derivative, showed the highest activity in PPARγ transactivation assay (69% activation) with no affinity for the AT1 receptor. Docking studies lead to the designing of a molecule with dual activity, 10, with moderate PPARγ activity (29%) and affinity for the AT1 receptor (Ki=2.5 μM).
