17432-00-7Relevant academic research and scientific papers
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.
Pd(II)-catalyzed ortho - Or meta-C-H olefination of phenol derivatives
Dai, Hui-Xiong,Li, Gang,Zhang, Xing-Guo,Stepan, Antonia F.,Yu, Jin-Quan
supporting information, p. 7567 - 7571 (2013/06/27)
A combination of weakly coordinating auxiliaries and ligand acceleration allows for the development of both ortho- and meta-selective C-H olefination of phenol derivatives. These reactions demonstrate the feasibility of directing C-H functionalizations when functional groups are distal to target C-H bonds. The meta-C-H functionalization of electron-rich phenol derivatives is unprecedented and orthogonal to previous electrophilic substitution of phenols in terms of regioselectivity. These methods are also applied to functionalize α-phenoxyacetic acids, a fibrate class of drug scaffolds.
