Synthesis and SAR of 2-aryl-3-aminomethylquinolines as agonists of the bile acid receptor TGR5

…, S Dhamija, J Anderson, A Fan, L Wang, P Rix…

Index: Herbert, Mark R.; Siegel, Dana L.; Staszewski, Lena; Cayanan, Charmagne; Banerjee, Urmi; Dhamija, Sangeeta; Anderson, Jennifer; Fan, Amy; Wang, Li; Rix, Peter; Shiau, Andrew K.; Rao, Tadimeti S.; Noble, Stewart A.; Heyman, Richard A.; Bischoff, Eric; Guha, Mausumee; Kabakibi, Ayman; Pinkerton, Anthony B. Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 19 p. 5718 - 5721

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Citation Number: 37

Abstract

... Compd, R 1, R 2, hTGR5 EC 50 a (μM), mTGR5 EC 50 a (μM). 15, –OCH 3, –H, 0.065, 3.2. 26, –CH 3, –H, 5.0, >10. 27, –Cl, –H, 6.9, >10. 28, –OEt, –H, 4.5, 9.4. 29, –OCF 3, –H, >10, >10. 30, –CO 2 H, –H, >10, >10. ... Table 3. Selected mouse PK parameters for compounds 15, 26, and 37 a. Compd, Cl p b (mL/min/kg), V d b (L/kg), C max c (μg/mL), AUC c (μg h/mL), t 1/2 c (h), %F. 32, 38, 2.4, 0.37, 0.40, 4.4, 9. 35, 29, 1.4, 0.50, 0.86, 7.7, 10. a Compounds dosed 3 mpk ...