- Stereoselective synthesis and biological evaluations of novel 3′-deoxy-4′-azaribonucleosides as inhibitors of hepatitis C virus RNA replication
-
3′-Deoxy-4′-azaribonucleosides (15a-d) were synthesized starting from the commercially available (4R)-trans-4-hydroxy-L-proline 7. From biological evaluations, 15b and 15d emerged as potent inhibitors of HCV replication on a replicon assay. These findings demonstrate that synthesized pyrrolidine nucleosides represent a new template for antiviral or other biological studies and could be considered for novel combination therapy against HCV infection using nucleoside inhibitors and non-nucleoside inhibitors of HCV NS5B.
- Chiacchio, Ugo,Borrello, Luisa,Crispino, Lia,Rescifina, Antonio,Merino, Pedro,Macchi, Beatrice,Balestrieri, Emanuela,Mastino, Antonio,Piperno, Anna,Romeo, Giovanni
-
-
Read Online
- Regioselective oxidation of N-alkylpyrrolidines to pyrrolidin-5-ones by RuCl3/NaIO4
-
RuCl3/NaIO4 under EtOAc/H2O biphasic conditions, selectively oxidizes the Nα-endo-methylene group of pyrrolidine derivatives, without affecting the exo-methylene group adjacent to the N-heteroatom.
- Sharma, Nagendra K.,Ganesh, Krishna N.
-
-
Read Online
- Tricyclic-Carbocyclic RORγt Inverse Agonists - Discovery of BMS-986313
-
SAR efforts directed at identifying RORγt inverse agonists structurally different from our clinical compound 1 (BMS-986251) led to tricyclic-carbocyclic analogues represented by 3-7 and culminated in the identification of 3d (BMS-986313), with structural differences distinct from 1. The X-ray co-crystal structure of 3d with the ligand binding domain of RORγt revealed several key interactions, which are different from 1. The in vitro and in vivo PK profiles of 3d are described. In addition, we demonstrate robust efficacy of 3d in two preclinical models of psoriasis - the IMQ-induced skin lesion model and the IL-23-induced acanthosis model. The efficacy seen with 3d in these models is comparable to the results observed with 1.
- Yang, Michael G.,Beaudoin-Bertrand, Myra,Xiao, Zili,Marcoux, David,Weigelt, Carolyn A.,Yip, Shiuhang,Wu, Dauh-Rurng,Ruzanov, Max,Sack, John S.,Wang, Jinhong,Yarde, Melissa,Li, Sha,Shuster, David J.,Xie, Jenny H.,Sherry, Tara,Obermeier, Mary T.,Fura, Aberra,Stefanski, Kevin,Cornelius, Georgia,Khandelwal, Purnima,Karmakar, Ananta,Basha, Mushkin,Babu, Venkatesh,Gupta, Arun Kumar,Mathur, Arvind,Salter-Cid, Luisa,Denton, Rex,Zhao, Qihong,Dhar, T. G. Murali
-
p. 2714 - 2724
(2021/03/09)
-
- TRICYCLIC SULFONES AS ROR GAMMA MODULATORS
-
There are described RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.
- -
-
-
- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
-
Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.
- -
-
-
- THERAPEUTICALLY ACTIVE COMPOUNDS AND USE THEREOF
-
Provided are therapeutically active compounds and the use in manufacture of medicaments for treating a cancer characterized by the presence of a mutant allele of IDH1.
- -
-
-
- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
-
Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.
- -
-
-
- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
-
Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.
- -
-
-
- Synthesis of 3-guaninyl- and 3-adeninyl-5-hydroxymethyl-2-pyrrolidinone nucleosides
-
l- And d-glutamic acids, as well as trans-4-hydroxy-l-proline, are converted to the corresponding 3-guaninyl-5-hydroxymethyl-2-pyrrolidinone (4) or 3-adeninyl-5-hydroxymethyl-2-pyrrolidinone (5) nucleoside analog. The protecting group used to block the lactam nitrogen in key intermediates has a significant effect on the diastereoselectivity of the coupling reaction with adenine or guanine.
- Saleh, Abdullah,D'Angelo, John G.,Morton, Martha D.,Quinn, Jesse,Redden, Kendra,Mielguz, Rafal W.,Pavlik, Christopher,Smith, Michael B.
-
p. 5574 - 5583
(2011/10/02)
-
- The asymmetric total synthesis of (-)-securinine
-
The alkaloid (-)-securinine was synthesized in 18 steps and 16% overall yield from trans-4-hydroxy-l-proline. The Royal Society of Chemistry.
- Dhudshia, Bhartesh,Cooper, Benjamin F. T.,MacDonald, Charles L. B.,Thadani, Avinash N.
-
supporting information; experimental part
p. 463 - 465
(2009/05/06)
-
- ANTIVIRAL AZANUCLEOSIDE DERIVATIVES
-
Compounds with azanucleoside structure of formula (I), wherein the groups are as defined below, have antiviral activity, and particularly inhibit RNA-dependent viral polymerases.
- -
-
Page/Page column 6; 15-16
(2010/11/27)
-
- Chiral synthesis of (+)-febrifugine and (-)-isofebrifugine by means of samarium diiodide-promoted carbon-nitrogen bond cleavage reaction
-
(+)-Febrifugine, a potential anti-malarial piperidine alkaloid, was synthesized from (4S)-hydroxyproline methyl ester, stereoselectively, where a samarium diiodide-promoted carbon-nitrogen bond cleavage reaction was involved as a key reaction. A stereocon
- Katoh, Miho,Matsune, Ryuichiro,Honda, Toshio
-
p. 189 - 204
(2007/10/03)
-
- A convenient and high yield method to prepare 4-hydroxypyroglutamic acids
-
RuO2/NaIO4 oxidation of N-Boc-4-silyloxy and 4-acetoxy proline methyl esters under ethyl acetate/water biphase condition gave N-Boc-4-silyloxy and 4-acetoxy pyroglutamic acid derivatives in high yields. Desilylation with TBAF afforded both cis- and trans-N-Boc-methyl-4-hydroxy pyroglutamates.
- Zhang, Xiaojun,Schmitt, Aaron C.,Jiang, Wen
-
p. 5335 - 5338
(2007/10/03)
-