191731-37-0Relevant articles and documents
Multikilogram Synthesis of a Potent Dual Bcl-2/Bcl-xL Antagonist. 2. Manufacture of the 1,3-Diamine Moiety and Improvement of the Final Coupling Reaction
Hardouin, Christophe,Baillard, Sandrine,Barière, Fran?ois,Craquelin, Anthony,Grandjean, Mathieu,Janvier, Solenn,Le Roux, Stéphane,Penloup, Christine,Russo, Olivier
, p. 670 - 685 (2019/12/24)
This paper describes the synthesis of kilogram quantities of the sulfonamide moiety 3 involved in a coupling reaction with acid moiety 2 to provide batches of drug candidate 1 for preclinical studies and first-in-human clinical trials. A first approach relying on a chiral separation furnished the desired enantiomer of 1,3-diamine 20, precursor of sulfonamide 3. An enantiomeric synthesis of 20 using the Ellman's chiral auxiliary coupled with an aza-Reformatsky reaction to control the stereochemistry is also discussed. Coupling conditions of the final step involving EDCI to provide 1 under a cGMP process are detailed. An alternative approach using N-(1-methanesulfonyl)benzotriazole is also presented.
MACROCYCLIC COMPOUNDS USEFUL AS INHIBITORS OF KINASES AND HSP90
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Page/Page column 90, (2010/11/30)
Disclosed are macrocyclic compounds of formulae I-V,which are analogs of the pochonin resorcylic acid lactones, and processes for the preparation of the compounds. The compounds disclosed are useful as inhibitors of kinases and Heat Shock Protein 90 (HSP 90). Also disclosed are pharmaceutical compositions comprising an effective kinase-inhibiting amount or an effective HSP90-inhibiting amount of the compounds and methods for the treatment of disorders that are mediated by kinases and HSP90.
Modular asymmetric synthesis of pochonin C
Barluenga, Sofia,Lopez, Pilar,Moulin, Emilie,Winssinger, Nicolas
, p. 3467 - 3470 (2007/10/03)
Back to its origins: Pochonin C was synthesized in 11 steps from the four fragments shown in the scheme. This asymmetric synthesis and the conversion of pochonin C into radicicol defines the configuration at the center bearing the chlorine atom as S. lpc
