Results 11 to 20 of about 212,806 (232)

Design, Synthesis, Pharmacology, and In Silico Studies of (1S,2S,3S)-2-((S)-Amino(carboxy)methyl)-3-(carboxymethyl)cyclopropane-1-carboxylic Acid (LBG30300): A Picomolar Potency Subtype-Selective mGlu₂ Receptor Agonist

Journal of Medicinal Chemistry
Metabotropic glutamate (Glu) receptors (mGlu receptors) play a key role in modulating excitatory neurotransmission in the central nervous system (CNS).
Na Liu, Floriane Eshak, Fanny Malhaire, Isabelle Brabet, Laurent Prézeau, Emma Renard, Jean‐Philippe Pin, Francine Acher, Markus Staudt, Lennart Bunch   +9 more
semanticscholar   +7 more sources

Discovery of oxazole-based PDE4 inhibitors with picomolar potency

Bioorganic & Medicinal Chemistry Letters, 2012
Optimization of oxazole-based PDE4 inhibitors has led to the discovery of a series of quinolyl oxazoles, with 4-benzylcarboxamide and 5-α-aminoethyl groups which exhibit picomolar potency against PDE4. Selectivity profiles and in vivo biological activity are also reported.
Rongze Kuang, Ho‐Jane Shue, Li Xiao, David J. Blythin, Neng‐Yang Shih, Xiaohong Chen, Danlin Gu, John H. Schwerdt, Ling Lin, Pauline C. Ting, Jianhua Cao, Robert Aslanian, John J. Piwinski, Daniel Prelusky, Ping Wu, Ji Zhang, Xiang Zhang, Chander Celly, Motasim Billah, Peng Wang   +19 more
semanticscholar   +5 more sources

Discovery of CC Chemokine Receptor-3 (CCR3) Antagonists with Picomolar Potency

Journal of Medicinal Chemistry, 2005
Starting with our previously described(20) class of CC chemokine receptor-3 (CCR3) antagonist, we improved the potency by replacing the phenyl linker of 1 with a cyclohexyl linker and by replacing the 4-benzylpiperidine with a 3-benzylpiperidine. The resulting compound, 32, is a potent and selective antagonist of CCR3.
George V. De Lucca, Ui Tae Kim, Brian J. Vargo, John V. Duncia, Joseph B. Santella, Daniel S. Gardner, Changsheng Zheng, Ann Y. Liauw, Zhang Wang, George Emmett, Dean A. Wacker, Patricia K. Welch, Maryanne Covington, Nicole Stowell, Eric Wadman, Anuk Das, Paul Davies, Swamy Yeleswaram, Danielle Graden, Kimberly A. Solomon, Robert Newton, George L. Trainor, Carl P. Decicco, Soo S. Ko   +23 more
semanticscholar   +4 more sources

HIV protease inhibitors with picomolar potency against PI-Resistant HIV-1 by extension of the P3 substituent

Bioorganic & Medicinal Chemistry Letters, 2003
A biaryl pyridylfuran P(3) substituent on the hydroxyethylene isostere scaffold affords HIV protease inhibitors (PI's) with picomolar (IC(50)) potency against the protease enzymes from PI-resistant HIV-1 strains. Inclusion of a gem-dimethyl substituent afforded compound 3 with 100% oral bioavailability (dogs) and more than double the t(1/2) of ...
Joseph Duffy, Thomas A. Rano, Nancy J. Kevin, Kevin T. Chapman, William A. Schleif, David B. Olsen, Mark W. Stahlhut, Carrie A. Rutkowski, Lawrence C. Kuo, Lixia Jin, Jiunn H. Lin, Emilio A. Emini, James R. Tata   +12 more
semanticscholar   +4 more sources

Preclinical assessment of capsid assembly modulators (CAMs) of varying potency revealed a novel class of picomolar-acting CAMs inducing neither significant HBcAg cytoplasmic retention nor adverse interactions with HBcAg-specific adaptive immunity

Journal of Hepatology, 2020
Romano Di Fabio, Leda Bencheva, Raffaele De Francesco, Lorena Donnici, Vincenzo Summa, Edith Monteagudo, Matteo Iannacone, Luca G. Guidotti   +7 more
semanticscholar   +4 more sources

1,3-Oxazole-based selective picomolar inhibitors of cytosolic human carbonic anhydrase II alleviate ocular hypertension in rabbits: Potency is supported by X-ray crystallography of two leads

Bioorganic & Medicinal Chemistry, 2017
Two lead 1,3-oxazole-based carbonic anhydrase inhibitors (CAIs) earlier identified as selective, picomolar inhibitors of hCA II (a cytosolic target for treatment of glaucoma) have been investigated further. Firstly, they were found to be conveniently synthesized on multigram scale, which enables further development.
Marta Ferraroni, Laura Lucarini, Emanuela Masini, М. К. Корсаков, Andrea Scozzafava, Claudiu T. Supuran, Mikhail Krasavin   +6 more
semanticscholar   +5 more sources

HIV-1 protease inhibitors with picomolar potency against PI-resistant HIV-1 by modification of the P1′ substituent

Bioorganic & Medicinal Chemistry Letters, 2003
Transposition of the pyridyl nitrogen from the P(3) substituent to the P(1)' substituent in HIV-1 protease inhibitors (PI) affords compounds such as 3 with an improved inhibitory profile against multiple P450 isoforms. These compounds also displayed increased potency, with 3 inhibiting viral spread (CIC(95)) at
Joseph Duffy, Brian A. Kirk, Nancy J. Kevin, Kevin T. Chapman, William A. Schleif, David B. Olsen, Mark W. Stahlhut, Carrie A. Rutkowski, Lawrence C. Kuo, Lixia Jin, Jiunn H. Lin, Emilio A. Emini, James R. Tata   +12 more
semanticscholar   +5 more sources

Glycosylated Neurotensin Analogues Exhibit Sub‐picomolar Anticonvulsant Potency in a Pharmacoresistant Model of Epilepsy [PDF]

ChemMedChem, 2009
AbstractThe glycosylation of neuroactive peptides is a promising strategy to treat neurological and psychiatric disorders. Herein we investigated the effects of site‐specific glycosylation of neurotensin (NT). The glycosylated analogues have low‐nanomolar affinities and agonist activities toward NTS1, and suppress seizures with sub‐picomolar potency ...
Hee‐Kyoung Lee, Liuyin Zhang, Misty D. Smith, H. Steve White, Grzegorz Bułaj   +4 more
semanticscholar   +4 more sources

Synthesis and monoamine transporter affinity of new 2β-carbomethoxy-3β-[4-(substituted thiophenyl)]phenyltropanes: discovery of a selective SERT antagonist with picomolar potency

Bioorganic & Medicinal Chemistry Letters, 2004
AbstractFor Abstract see ChemInform Abstract in Full Text.
Gilles Tamagnan, David Alagille, Xing Fu, Nora S. Kula, Ross J. Baldessarini, Robert B. Innis, Ronald M. Baldwin   +6 more
semanticscholar   +4 more sources

6-Position optimization of tricyclic 4-quinolone-based inhibitors of glycogen synthase kinase-3β: Discovery of nitrile derivatives with picomolar potency

Bioorganic & Medicinal Chemistry Letters, 2011
We previously disclosed tricylic, 6-carboxylic acid-bearing 4-quinolones as GSK-3β inhibitors. Herein we discuss the optimization of this series to yield a series of more potent 6-nitrile analogs with insignificant anti-microbial activity. Finally, kinase profiling indicated that members of this class were highly specific GSK-3 inhibitors.
Bei Li, Oana M. Cociorva, Tyzoon Nomanbhoy, Qiang Li, Kai Nakamura, Masahiro Nomura, Kyoko Okada, Kazuhiro Yumoto, Marek Liyanage, Melissa C. Zhang, Arwin Aban, Anna Katrin Szardenings, John W. Kozarich, Yasushi Kohno, Kevin Shreder   +14 more
semanticscholar   +4 more sources