title: Hydrothiolation of benzyl mercaptan to arylacetylene: application to the synthesis of (E) and (Z)-isomers of ON 01910·Na (Rigosertib®), a phase III clinical stage anti-cancer agent.
abstract: A stereoselective and efficient method for free radical addition of benzyl thiol to aryl acetylene in the presence of Et3B-hexane has been developed for the synthesis of (Z) and (E)-styryl benzyl sulfides where base catalyzed hydrothiolations have failed. The scope of this reaction was successfully extended for the synthesis of (E)-ON 01910·Na, a phase III clinical stage anti-cancer agent and its inactive geometrical isomer (Z)-ON 01910·Na. It is interesting to note that all the E-isomers synthesized have shown better cytotoxicity profile on cancer cells compared to the Z-isomers.
authors: Department of Medicinal Chemistry, Onconova Therapeutics Inc., 375 Pheasant Run, Newtown, PA 18940-3423, USA.
authors: Venkat R
authors: VR
authors: Pallela
authors: Muralidhar R
authors: MR
authors: Mallireddigari
authors: Stephen C
authors: SC
authors: Cosenza
authors: Balaiah
authors: B
authors: Akula
authors: D R C Venkata
authors: DR
authors: Subbaiah
authors: E Premkumar
authors: EP
authors: Reddy
authors: M V Ramana
authors: MV
authors: Reddy
mesh_terms: D000480:Alkynes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000480:Alkynes; D000970:Antineoplastic Agents; D013438:Sulfhydryl Compounds; D013450:Sulfones; C507134:ON 01910; D005998:Glycine
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