97968-80-4Relevant academic research and scientific papers
Metal-Free-Visible Light C-H Alkylation of Heteroaromatics via Hypervalent Iodine-Promoted Decarboxylation
Genovino, Julien,Lian, Yajing,Zhang, Yuan,Hope, Taylor O.,Juneau, Antoine,Gagné, Yohann,Ingle, Gajendra,Frenette, Mathieu
supporting information, p. 3229 - 3232 (2018/06/11)
A metal-free photoredox C-H alkylation of heteroaromatics from readily available carboxylic acids using an organic photocatalyst and hypervalent iodine reagents under blue LED light is reported. The developed methodology tolerates a broad range of functional groups and can be applied to the late-stage functionalization of drugs and drug-like molecules. The reaction mechanism was investigated with control experiments and photophysical experiments as well as DFT calculations.
Photochemical Homologation for the Preparation of Aliphatic Aldehydes in Flow
Chen, Yiding,Leonardi, Marco,Dingwall, Paul,Labes, Ricardo,Pasau, Patrick,Blakemore, David C.,Ley, Steven V.
, p. 15558 - 15568 (2019/01/04)
Cheap and readily available aqueous formaldehyde was used as a formylating reagent in a homologation reaction with nonstabilized diazo compounds, enabled by UV photolysis of bench-stable oxadiazolines in a flow photoreactor. Various aliphatic aldehydes were synthesized along with the corresponding derivatized alcohols and benzimidazoles. No transition-metal catalyst or additive was required to affect the reaction, which proceeded at room temperature in 80 min.
Catalyst free approach to benzimidazoles using air as the oxidant at room temperature
Zhang, Chun,Zhang, Liangren,Jiao, Ning
supporting information, p. 3273 - 3276 (2013/01/16)
A green and practical method to construct benzimidazoles, which are ubiquitous structural units in a number of biologically active compounds, has been developed. The catalyst and additive free conditions, using air as oxidant and the mild conditions make
Discovery of dual inducible/neuronal nitric oxide synthase (iNOS/nNOS) inhibitor development candidate 4-((2-cyclobutyl-1 H-imidazo[4,5- b ]pyrazin-1-yl)methyl)-7,8-difluoroquinolin-2(1 H)-one (KD7332) Part 2: Identification of a novel, potent, and selective series of benzimidazole- quinolinone iNOS/nNOS dimerization inhibitors that are orally active in pain models
Payne, Joseph E.,Bonnefous, Céline,Symons, Kent T.,Nguyen, Phan M.,Sablad, Marciano,Rozenkrants, Natasha,Zhang, Yan,Wang, Li,Yazdani, Nahid,Shiau, Andrew K.,Noble, Stewart A.,Rix, Peter,Rao, Tadimeti S.,Hassig, Christian A.,Smith, Nicholas D.
supporting information; experimental part, p. 7739 - 7755 (2011/02/22)
Three isoforms of nitric oxide synthase (NOS), dimeric enzymes that catalyze the formation of nitric oxide (NO) from arginine, have been identified. Inappropriate or excessive NO produced by iNOS and/or nNOS is associated with inflammatory and neuropathic pain. Previously, we described the identification of a series of amide-quinolinone iNOS dimerization inhibitors that although potent, suffered from high clearance and limited exposure in vivo. By conformationally restricting the amide of this progenitor series, we describe the identification of a novel series of benzimidazole-quinolinone dual iNOS/nNOS inhibitors with low clearance and sustained exposure in vivo. Compounds were triaged utilizing an LPS challenge assay coupled with mouse and rhesus pharmacokinetics and led to the identification of 4,7-imidazopyrazine 42 as the lead compound. 42 (KD7332) (J. Med. Chem. 2009, 52, 3047 -3062) was confirmed as an iNOS dimerization inhibitor and was efficacious in the mouse formalin model of nociception and Chung model of neuropathic pain, without showing tolerance after repeat dosing. Further 42 did not affect motor coordination up to doses of 1000 mg/kg, demonstrating a wide therapeutic margin.
