Terrence L. Jr. Smalley
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Featured researches published by Terrence L. Jr. Smalley.
Journal of Medicinal Chemistry | 2015
Curt Dale Haffner; J. David Becherer; Eric E. Boros; Rodolfo Cadilla; Tiffany Carpenter; David John Cowan; David N. Deaton; Yu Guo; W. Wallace Harrington; Brad R. Henke; Michael Jeune; Istvan Kaldor; Naphtali Milliken; Kim G. Petrov; Frank Preugschat; Christie Schulte; Barry George Shearer; Todd W. Shearer; Terrence L. Jr. Smalley; Eugene L. Stewart; J. Darren Stuart; John C. Ulrich
A series of thiazoloquin(az)olinones were synthesized and found to have potent inhibitory activity against CD38. Several of these compounds were also shown to have good pharmacokinetic properties and demonstrated the ability to elevate NAD levels in plasma, liver, and muscle tissue. In particular, compound 78c was given to diet induced obese (DIO) C57Bl6 mice, elevating NAD > 5-fold in liver and >1.2-fold in muscle versus control animals at a 2 h time point. The compounds described herein possess the most potent CD38 inhibitory activity of any small molecules described in the literature to date. The inhibitors should allow for a more detailed assessment of how NAD elevation via CD38 inhibition affects physiology in NAD deficient states.
Journal of Medicinal Chemistry | 2015
J.D Becherer; Eric E. Boros; Tiffany Carpenter; David John Cowan; David N. Deaton; Curt Dale Haffner; Michael Jeune; Istvan Kaldor; J.C Poole; Frank Preugschat; T.R Rheault; Christie Schulte; Barry George Shearer; Todd W. Shearer; L.M Shewchuk; Terrence L. Jr. Smalley; Eugene L. Stewart; J.D Stuart; John C. Ulrich
Starting from the micromolar 8-quinoline carboxamide high-throughput screening hit 1a, a systematic exploration of the structure-activity relationships (SAR) of the 4-, 6-, and 8-substituents of the quinoline ring resulted in the identification of approximately 10-100-fold more potent human CD38 inhibitors. Several of these molecules also exhibited pharmacokinetic parameters suitable for in vivo animal studies, including low clearances and decent oral bioavailability. Two of these CD38 inhibitors, 1ah and 1ai, were shown to elevate NAD tissue levels in liver and muscle in a diet-induced obese (DIO) C57BL/6 mouse model. These inhibitor tool compounds will enable further biological studies of the CD38 enzyme as well as the investigation of the therapeutic implications of NAD enhancement in disease models of abnormally low NAD.
Synthetic Communications | 2004
Terrence L. Jr. Smalley
Abstract A synthesis of TAK‐779 that relies on construction of a key carboxylic acid intermediate by a ring expansion with TMSCHN2 is described.
Bioorganic & Medicinal Chemistry Letters | 2015
Terrence L. Jr. Smalley; Sharon D. Boggs; Justin A. Caravella; Lihong Chen; Katrina L. Creech; David N. Deaton; Istvan Kaldor; Derek J. Parks
The farnesoid X receptor (FXR) may play a crucial role in a number of metabolic diseases and, as such, could potentially serve as a target for the development of therapeutics as a treatment for those diseases. Previous work has described GW4064 as an FXR agonist with an interesting activity profile. This manuscript will describe the synthesis of novel analogs of GW4064 and the activity profile of those analogs.
Bioorganic & Medicinal Chemistry Letters | 2006
Dulce Maria Garrido; David F. Corbett; Kate A. Dwornik; Aaron S. Goetz; Thomas R. Littleton; Steve C. McKeown; Wendy Yoon Mills; Terrence L. Jr. Smalley; Celia P. Briscoe; Andrew J. Peat
Archive | 1994
Robert Carl Andrews; Judd Berman; Peter J. Brown; David N. Deaton; David H. Drewry; Michael A. Foley; Deanna T. Garrison; Brian Edward Marron; Stewart Alywyn Noble; Terrence L. Jr. Smalley
Bioorganic & Medicinal Chemistry Letters | 2004
Andrew J. Peat; Joyce A. Boucheron; Scott Howard Dickerson; Dulce Maria Garrido; Wendy Yoon Mills; Jennifer Poole Peckham; Frank Preugschat; Terrence L. Jr. Smalley; Stephanie L Schweiker; Jayme Lyn Roark Wilson; Tony Y. Wang; Hui-Qiang Q. Zhou; Stephen A. Thomson
Bioorganic & Medicinal Chemistry Letters | 2006
Terrence L. Jr. Smalley; Andrew J. Peat; Joyce A. Boucheron; Scott Howard Dickerson; Dulce Maria Garrido; Frank Preugschat; Stephanie L Schweiker; Stephen A. Thomson; Tony Y. Wang
Bioorganic & Medicinal Chemistry Letters | 2007
Terrence L. Jr. Smalley; Stanley D. Chamberlain; Wendy Yoon Mills; David L. Musso; Sab Randhawa; John A. Ray; Vicente Samano; Lloyd Frick
Journal of Heterocyclic Chemistry | 2005
Terrence L. Jr. Smalley; Wendy Yoon Mills