54368-19-3Relevant academic research and scientific papers
Optimization of a Novel Quinazolinone-Based Series of Transient Receptor Potential A1 (TRPA1) Antagonists Demonstrating Potent in Vivo Activity
Schenkel, Laurie B.,Olivieri, Philip R.,Boezio, Alessandro A.,Deak, Holly L.,Emkey, Renee,Graceffa, Russell F.,Gunaydin, Hakan,Guzman-Perez, Angel,Lee, Josie H.,Teffera, Yohannes,Wang, Weiya,Youngblood, Beth D.,Yu, Violeta L.,Zhang, Maosheng,Gavva, Narender R.,Lehto, Sonya G.,Geuns-Meyer, Stephanie
, p. 2794 - 2809 (2016/04/10)
There has been significant interest in developing a transient receptor potential A1 (TRPA1) antagonist for the treatment of pain due to a wealth of data implicating its role in pain pathways. Despite this, identification of a potent small molecule tool possessing pharmacokinetic properties allowing for robust in vivo target coverage has been challenging. Here we describe the optimization of a potent, selective series of quinazolinone-based TRPA1 antagonists. High-throughput screening identified 4, which possessed promising potency and selectivity. A strategy focused on optimizing potency while increasing polarity in order to improve intrinisic clearance culminated with the discovery of purinone 27 (AM-0902), which is a potent, selective antagonist of TRPA1 with pharmacokinetic properties allowing for >30-fold coverage of the rat TRPA1 IC50 in vivo. Compound 27 demonstrated dose-dependent inhibition of AITC-induced flinching in rats, validating its utility as a tool for interrogating the role of TRPA1 in in vivo pain models.
Development of 2-(4-oxoquinazolin-3(4 H)-yl)acetamide derivatives as novel enoyl-acyl carrier protein reductase (InhA) inhibitors for the treatment of tuberculosis
Pedgaonkar, Ganesh S.,Sridevi, Jonnalagadda Padma,Jeankumar, Variam Ullas,Saxena, Shalini,Devi, Parthiban Brindha,Renuka, Janupally,Yogeeswari, Perumal,Sriram, Dharmarajan
, p. 613 - 627 (2015/01/09)
InhA, the enoyl acyl carrier protein reductase of Mycobacterium tuberculosis (MTB) is an attractive target for developing novel anti-tubercular agents. Twenty eight 2-(4-oxoquinazolin-3(4H)-yl)acetamide derivatives were synthesized and evaluated for their in vitro MTB InhA inhibition. Compounds were further evaluated for their in vitro activity against drug sensitive and resistant MTB strains and cytotoxicity against RAW 264.7 cell line. Compounds were docked at the active site of InhA to understand their binding mode and differential scanning fluorimetry was performed to ascertain their protein interaction and stability.
Mukaiyama's reagent promoted C-N bond formation: a new method to synthesize 3-alkylquinazolin-4-ones
Punthasee, Puminun,Vanitcha, Avassaya,Wacharasindhu, Sumrit
supporting information; experimental part, p. 1713 - 1716 (2010/05/03)
A new approach to synthesize 3-alkylquinazolin-4-ones is developed. Treatment of quinazolin-4-ones with Mukaiyama's reagent, a base and a primary amine nucleophile results in the formation of 3-alkylquinazolin-4-ones in moderate to good yields under mild conditions. Using this methodology, a one-step synthesis of the natural alkaloid, echinozolinone, is accomplished.
Synthesis of 2,3-dihydro-4(1H)-quinazolinones
Escalante, Jaime,Flores, Patricia,Priego, Jaime M.
, p. 2019 - 2032 (2007/10/03)
An improved procedure for the synthesis of 2-substituted 2,3-dihydro-4(1H)-quinazolinones through diastereomer separation of the corresponding quinazolinones derivatives is presented. The determination of their absolute configurations was obtained by X-Ra
