Activation of 6-bromoquinoline by nitration: Synthesis of morpholinyl and piperazinyl quinolones
Quinoline forms the key skeletal component of a number of important natural products and pharmacologically-Active compounds. Despite a tremendous amount of research pertaining to the derivatization of quinoline, very few general synthetic routes are described in the literature starting from quinoline or tetrahydroquinoline. A simple and convenient method for the polyfunctionalization of quinolines via nitration of bromoquinolines has been developed. This method represents a new synthetic approach to convert brominated nitroquinoline derivatives into useful cyclic amines via nucleophilic-substitution (SNAr) reaction. Formula parented.
?akmak, Osman,?kten, Salih,Alimli, Dilek,Saddiqa, Aisha,Ersanli, Cem C?neyt
p. 362 - 374
(2018/07/05)
A Molecular Hybridization Approach for the Design of Potent, Highly Selective, and Brain-Penetrant N-Myristoyltransferase Inhibitors
Crystallography has guided the hybridization of two series of Trypanosoma brucei N-myristoyltransferase (NMT) inhibitors, leading to a novel highly selective series. The effect of combining the selectivity enhancing elements from two pharmacophores is shown to be additive and has led to compounds that have greater than 1000-fold selectivity for TbNMT vs HsNMT. Further optimization of the hybrid series has identified compounds with significant trypanocidal activity capable of crossing the blood-brain barrier. By using CF-1 mdr1a deficient mice, we were able to demonstrate full cures in vivo in a mouse model of stage 2 African sleeping sickness. This and previous work provides very strong validation for NMT as a drug target for human African trypanosomiasis in both the peripheral and central nervous system stages of disease.
Harrison, Justin R.,Brand, Stephen,Smith, Victoria,Robinson, David A.,Thompson, Stephen,Smith, Alasdair,Davies, Kenneth,Mok, Ngai,Torrie, Leah S.,Collie, Iain,Hallyburton, Irene,Norval, Suzanne,Simeons, Frederick R. C.,Stojanovski, Laste,Frearson, Julie A.,Brenk, Ruth,Wyatt, Paul G.,Gilbert, Ian H.,Read, Kevin D.
supporting information
p. 8374 - 8389
(2018/09/25)
A Mild and General Larock Indolization Protocol for the Preparation of Unnatural Tryptophans
A mild and general protocol for the Pd(0)-catalyzed heteroannulation of o-bromoanilines and alkynes is described. Application of a Pd(0)/P(tBu)3 catalyst system enables the efficient coupling of o-bromoanilines at 60 °C, mitigating deleterious side reactions and enabling access to a broad range of useful unnatural tryptophans. The utility of this new protocol is demonstrated in the highly convergent total synthesis of the bisindole natural product (-)-aspergilazine A.
Chuang, Kangway V.,Kieffer, Madeleine E.,Reisman, Sarah E.
supporting information
p. 4750 - 4753
(2016/09/28)
BICYCLIC TRIAZOLES AS PROTEIN KINASE MODULATORS
The present disclosure provides bicyclic triazole protein kinase modulators and methods of using these compounds to treat diseases mediated by kinase activity.
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Page/Page column 78
(2008/12/05)
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