70205-70-8Relevant articles and documents
Identification and preliminary characterization of a potent, safe, and orally efficacious inhibitor of acyl-CoA:Diacylglycerol acyltransferase 1
Yeh, Vince S. C.,Beno, David W. A.,Brodjian, Sevan,Brune, Michael E.,Cullen, Steven C.,Dayton, Brian D.,Dhaon, Madhup K.,Falls, Hugh D.,Gao, Ju,Grihalde, Nelson,Hajduk, Philip,Hansen, T. Matthew,Judd, Andrew S.,King, Andrew J.,Klix, Russel C.,Larson, Kelly J.,Lau, Yau Y.,Marsh, Kennan C.,Mittelstadt, Scott W.,Plata, Dan,Rozema, Michael J.,Segreti, Jason A.,Stoner, Eric J.,Voorbach, Martin J.,Wang, Xiaojun,Xin, Xili,Zhao, Gang,Collins, Christine A.,Cox, Bryan F.,Reilly, Regina M.,Kym, Philip R.,Souers, Andrew J.
supporting information; experimental part, p. 1751 - 1757 (2012/05/04)
A high-throughput screen against human DGAT-1 led to the identification of a core structure that was subsequently optimized to afford the potent, selective, and orally bioavailable compound 14. Oral administration at doses ≥0.03 mg/kg significantly reduced postprandial triglycerides in mice following an oral lipid challenge. Further assessment in both acute and chronic safety pharmacology and toxicology studies demonstrated a clean profile up to high plasma levels, thus culminating in the nomination of 14 as clinical candidate ABT-046.
Synthesis and initial SAR studies of 3,6-disubstituted pyrazolo[1,5-a]pyrimidines: A new class of KDR kinase inhibitors
Fraley, Mark E.,Hoffman, William F.,Rubino, Robert S.,Hungate, Randall W.,Tebben, Andrew J.,Rutledge, Ruth Z.,McFall, Rosemary C.,Huckle, William R.,Kendall, Richard L.,Coll, Kathleen E.,Thomas, Kenneth A.
, p. 2767 - 2770 (2007/10/03)
We have synthesized and evaluated the activity of 3,6-disubstituted pyrazolo[1,5-a]pyrimidines as a new class of KDR kinase inhibitors. Starting with screening lead 1, potency against isolated KDR was fully optimized with 3-thienyl and 4-methoxyphenyl substituents at the 6- and 3-positions (3g, KDR IC50=19 nM), respectively. The synthesis and SAR of these compounds are described.
Orthoamides, XXXIII.-Contributions to the Chemistry of Bis(dialkylamino)acetonitriles
Kantlehner, Willi,Baur, Richard,Bredereck, Hellmut
, p. 358 - 371 (2007/10/02)
Bis(dialkylamino)acetonitriles 2a-d react with acetyl chloride and antimony pentachloride to give N,N,N',N'-tetraalkylformamidinium hexachloroantimonates 5a-d.Reaction of p-nitrophenol with 2a,b affords N,N,N',N'-tetraalkylformamidinium salts 8a,b, while reaction of aromatic aldehydes 11 with compounds 2 gives aryl(dialkylamino)acetonitriles 12.Phenyl isothiocyanate reacts with the nitriles 2a-c to give 1:1 adducts for which the structure of N,N,N',N'-tetraalkylformamidinium cyano-N-(phenyl)thioformamidates 19 is proposed.N,N,N',N'-Tetraalkylformamidinium p-toluenesulfonates 30a,b have been prepared from nitriles 2a,b and methyl p-toluoenesulfonate (28).Alkylation of 2c with 28 at higher temperatures affords 1,1-dimethylpiperidinium p-toluoenesulfonate (34) and a small amount (1-piperidinyl)malonodinitrile (33).The nitrile 2a reacts with CH acidic compounds such as ethyl cyanoacetate, malonodinitrile and benzyl cyanide to form the enamines 38.
