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Dive into the research topics where Terrence L. Jr. Smalley is active.

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Featured researches published by Terrence L. Jr. Smalley.


Journal of Medicinal Chemistry | 2015

Discovery, Synthesis, and Biological Evaluation of Thiazoloquin(az)olin(on)es as Potent CD38 Inhibitors

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

Discovery of 4-Amino-8-quinoline Carboxamides as Novel, Submicromolar Inhibitors of NAD-Hydrolyzing Enzyme CD38.

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

A Ring Expansion Strategy in Antiviral Synthesis: A Novel Approach to TAK‐779

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

Novel heterocyclic scaffolds of GW4064 as farnesoid X receptor agonists.

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

Synthesis and activity of small molecule GPR40 agonists.

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

Quinazoline antagonists of alpha 1c adrenergic receptors

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

Novel pyrazolopyrimidine derivatives as GSK-3 inhibitors

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

Synthesis and evaluation of novel heterocyclic inhibitors of GSK-3

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

Synthesis of novel anilinoquinolines as c-fms inhibitors

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

Regioselective synthesis of 3,3-diethyl-4-(methylene)-1-quinol-2-ones by an intramolecular microwave assisted heck reaction

Terrence L. Jr. Smalley; Wendy Yoon Mills

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