Structure-Based Design of Potent, Selective, and Orally Bioavailable VPS34 Kinase Inhibitors
VPS34 is a class III phosphoinositide 3-kinase involved in endosomal trafficking and autophagosome formation. Inhibitors of VPS34 were believed to have value as anticancer agents, but genetic and pharmacological data suggest that sustained inhibition of V
Chan, Grace Ka Yan,Chen, Huifen,Chen, Yong,Dimitrova, Yoana N.,Hu, Dennis X.,Huang, Haochu,Lee, Joanna Y.,Lim, Junghyun,McNamara, Erin,Moffat, John G.,Murthy, Aditya,Pang, Jodie,Patel, Snahel,Prangley, Madeleine S.,Salphati, Laurent,Schutt, Leah K.,Siu, Michael,Sneeringer, Christopher J.,Staben, Steven T.,Wallweber, Heidi Ackerly,Wang, Shumei,Wang, Yunli,Wu, Kai C.,Zhao, Wensheng
supporting information
(2021/12/02)
Substituted pyrazolo-piperazines as casein kinase 1 δ/ε inhibitors
The invention provides compounds of Formula (I): and pharmaceutically acceptable salts thereof. The compounds of Formula (I) inhibit protein kinase activity thereby making them useful as anticancer agents.
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(2016/03/19)
GLYCOSAMINOGLYCAN DERIVATIVE AND METHOD FOR PRODUCING SAME
The present invention provides a glycosaminoglycan derivative in which a group derived from glycosaminoglycan and a group derived from a physiologically active substance having at least one of a carboxy group and a hydroxy group are coupled by covalent bond with a spacer therebetween, in which the spacer is selected in accordance with the decomposition rate of the covalent bond to the group derived from the physiologically active substance.
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Paragraph 0472-0476
(2016/06/28)
Long-range diastereoselectivity in an Ugi reaction: Stereocontrolled and diversity-oriented synthesis of tetrahydrobenzoxazepines
Salicylaldehydes and protected 1,2-amino alcohols have been convergently converted into a series of 2,3-dihydrobenzo[f][1,4]oxazepines, which undergo an Ugi-Joullie multicomponent reaction with unusual long-range diastereoselectivity. This protocol allows
The invention provides a method of producing an oxy-Michael adduct comprising allowing a Michael acceptor to react with an alkoxide of an alcohol of formula R0H having a chiral centre at the hydroxy carbon, in the presence of a multidentate ligand. The
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Page 14-15
(2010/02/08)
Highly diastereoselective oxy-Michael additions of enantiopure δ-lactol anions to nitroalkenes: Asymmetric synthesis of 1,2-amino alcohols
The "naked" alkoxide 1 of (S)-6-methyl-δ-lactol acts as an excellent chiral hydroxide equivalent in highly diastereoselective oxy-Michael additions to nitroalkenes (see scheme). The excellent stereoinduction arises from what becomes a superb protecting gr
Adderley, Nicola J.,Buchanan, David J.,Dixon, Darren J.,Laine, Dramane I.
p. 4241 - 4244
(2007/10/03)
Diastereo- and enantioselective synthesis of vicinal amino alcohols by oxa Michael addition of N-formylnorephedrine to nitro alkenes
The first intermolecular asymmetric oxa Michael additions with removable chirality information within the hydroxide source are reported. As enantiopure oxygen nucleophile functioning as chiral hydroxide equivalent N-formylnorephedrine (7) was used and conjugate additions to aliphatic (E)-nitro alkenes 2a-j were carned out in good yields (35-87%) and excellent diastereomeric excesses (de = 94-≥98%). After reduction of the nitro group and protection of the amino function (11a-h, 73-87%, both steps), the cleavage of the auxiliary occurred without epimerisation (69-99%) using Na/NH3. The Boc-protected 2-amino alcohols 12a-h could be obtained in good overall yields (30-58 %, four steps) and excellent diastereomeric and enantiomeric excesses (de, ee = 94-≥98%). Transition states explaining the overall stereochemical outcome are presented based on the absolute configuration determined by X-ray structure analysis on 8b.
Enders, Dieter,Haertwig, Andreas,Raabe, Gerhard,Runsink, Jan
p. 1771 - 1792
(2007/10/03)
Enantioselektive Synthese von vicinalen Aminoalkoholen durch Oxa-Michael-Addition