L
Leonard J. Brand
Researcher at Novartis
Publications - 12
Citations - 319
Leonard J. Brand is an academic researcher from Novartis. The author has contributed to research in topics: Pyruvate dehydrogenase kinase & Alkyl. The author has an hindex of 7, co-authored 12 publications receiving 311 citations.
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Journal ArticleDOI
Secondary Amides of (R)-3,3,3-Trifluoro-2-hydroxy-2-methylpropionic Acid as Inhibitors of Pyruvate Dehydrogenase Kinase
Thomas Daniel Aicher,Robert C. Anderson,Jiaping Gao,Suraj S. Shetty,Gary M. Coppola,James L. Stanton,Douglas C. Knorr,Donald Mark Sperbeck,Leonard J. Brand,Christine C. Vinluan,Emma L. Kaplan,Carol J. Dragland,Tomaselli Hc,A. Islam,R. J. Lozito,Xilin Liu,Wieslawa Maniara,William S. Fillers,Dominick DelGrande,R. E. Walter,William R. Mann +20 more
TL;DR: Methyl substitution of the piperazine at the 2- and 5-positions markedly increased the potency of the lead compound (>1,000-fold) and oral bioavailability of the compounds in this series is good and is optimal when the 4-position of thepiperazine is substituted with an electron-poor benzoyl moiety.
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Anilides of (R)-trifluoro-2-hydroxy-2-methylpropionic acid as inhibitors of pyruvate dehydrogenase kinase.
Gregory Raymond Bebernitz,Thomas Daniel Aicher,James L. Stanton,Jiaping Gao,Suraj S. Shetty,Douglas C. Knorr,Robert J. Strohschein,Jennifer Tan,Leonard J. Brand,Charles Liu,Wei H. Wang,Christine C. Vinluan,Emma L. Kaplan,Carol J. Dragland,Dominick DelGrande,Amin Islam,Robert J. Lozito,Xilin Liu,Wieslawa Maniara,William R. Mann +19 more
TL;DR: Small electron-withdrawing groups on the ortho position of the anilide increased potency 20-40-fold and could be of utility to ameliorate conditions of inappropriate blood lactate elevation.
Journal ArticleDOI
Substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-ones and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones as hypoglycemic agents.
Thomas Daniel Aicher,Bork Balkan,Philip A. Bell,Leonard J. Brand,Cheon Seung Hoon,Rhonda O. Deems,Fell Jay Bradford,William S. Fillers,Fraser James D,Jiaping Gao,Douglas C. Knorr,Gerald G. Kahle,Christina L. Leone,Jeffrey Nadelson,Ronald Simpson,Howard C. Smith +15 more
TL;DR: The synthesis and evaluation of a series of isoxazoles and other monocyclic compounds were evaluated for their ability to enhance glucose utilization in cultured L6 myocytes and SDZ 25a(2S) (SDZ PGU 693) was selected for further pharmacological studies.
Journal ArticleDOI
(R)-3,3,3-Trifluoro-2-hydroxy-2-methylpropionamides are orally active inhibitors of pyruvate dehydrogenase kinase
Thomas Daniel Aicher,Robert C. Anderson,Gregory Raymond Bebernitz,Gary M. Coppola,Charles F. Jewell,Douglas C. Knorr,Chen Liu,Donald Mark Sperbeck,Leonard J. Brand,Robert J. Strohschein,Jianping Gao,Christine C. Vinluan,Suraj S. Shetty,Carol J. Dragland,Emma L. Kaplan,Dominick DelGrande,A. Islam,Xilin Liu,R. J. Lozito,Wieslawa Maniara,R. E. Walter,William R. Mann +21 more
Journal ArticleDOI
Triterpene and diterpene inhibitors of pyruvate dehydrogenase kinase (PDK).
Thomas Daniel Aicher,Robert E. Damon,Judit Koletar,Christine C. Vinluan,Leonard J. Brand,Jiaping Gao,Suraj S. Shetty,Emma L. Kaplan,William R. Mann +8 more
TL;DR: The oxime 12 and dehydroabietyl amine 2 exhibit a blood glucose lowering effect in the diabetic ob/ob mouse after a single oral dose of 100 micromol/kg, however, the mechanism of the blood glucose lowered effect is likely unrelated to PDK inhibition.