23611-75-8Relevant articles and documents
THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
-
Paragraph 1151, (2015/02/18)
Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.
Novel lead generation of an anti-tuberculosis agent active against non-replicating mycobacteria: Exploring hybridization of pyrazinamide with multiple fragments
Markad, Shankar D.,Kaur, Parvinder,Kishore Reddy,Chinnapattu, Murugan,Raichurkar, Anandkumar,Nandishaiah, Radha,Panda, Manoranjan,Iyer, Pravin S.
, p. 2986 - 2992 (2015/03/14)
The key to shortening tuberculosis (TB) drug regimen lies in eliminating the reservoir of non-replicating persistent (NRP) Mycobacterium tuberculosis (Mtb). Pyrazinamide (PZA) is the only known drug used as part of a combination therapy that is believed to kill NRP Mtb and achieve sterilization. PZA is active only under low pH screening conditions. Screening and identification of NRP-active anti-TB compounds are severely limited because compounds are usually inactive under regular assay conditions. In an effort to design novel NRP-active anti-TB compounds, we used pyrazinamide as a core and hybridized it with the fragments derived from marketed drugs. One of these designs, compound 8, was a hybrid with fluoroquinolone. This compound exhibited >10 fold improvement in NRP activity under low pH condition as compared to pyrazinamide and a modest activity (0.8 log10 kill) under nutritionally starved NRP condition. Furthermore, compound 8 was active against fluoroquinolone-resistant strains and did not show any activity in a DNA supercoiling assay (gyrase inhibition), suggesting that its mechanism of action is not that of the parent fluoroquinolone. These results provide a novel avenue in the exploration of new chemotypes that are active against non-replicating Mtb.
Structure-activity studies of diazabicyclo[3.3.0]octane-substituted pyrazines and pyridines as Potent α4β2 nicotinic acetylcholine receptor ligands
Scanio, Marc J. C.,Shi, Lei,Bunnelle, William H.,Anderson, David J.,Helfrich, Rosalind J.,Malysz, John,Thorin-Hagene, Kirsten K.,Van Handel, Ceclia E.,Marsh, Kennan C.,Lee, Chih-Hung,Gopalakrishnan, Murali
experimental part, p. 7678 - 7692 (2012/01/06)
A series of diazabicyclo[3.3.0]octane substituted pyridines and pyrazines was synthesized and characterized at the α4β2 neuronal nicotinic acetylcholine receptor (nAChR). The compounds were designed to mimic the profile of ABT-089, high affinity binding ligand for the α4β2 nAChR, with limited agonist activity. Carboxamide derivatives of 3-(diazabicyclo[3.3.0] octane)-substituted pyridines or 2-(diazabicyclo[3.3.0]octane)-substituted pyrazines were found to have the desired binding and activity profile. The structure-activity relationship of these compounds is presented.