166816-11-1Relevant articles and documents
Process development of the synthetic route to sulamserod hydrochloride
Kowalczyk, Bruce A.,Robinson III, James,Gardner, John O.
, p. 116 - 121 (2001)
Sulamserod hydrochloride is a potent S-HT4 receptor antagonist and was a clinical candidate for the treatment of gastrointestinal disorders. Process development of the fairly long synthetic route (12 linear, 14 overall steps) was undertaken. Process improvements were highlighted by aromatic chlorination choices in making dichlorobenzodioxan 2 and acetylaminochloroketone 7, a transfer hydrogenation reducing a nitro group and simultaneous aromatic dechlorination without ketone reduction to give aminoketone 5, and use of the potential mutagenic iodosulfonamide 14 to make quaternary salt 11. The chemistry was scaled-up into pilot plant reactor vessels to produce multikilogram amounts of Sulamserod hydrochloride suitable for drug development.
1-PHENYLALKANONE 5-HT4 RECEPTOR LIGANDS
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, (2008/06/13)
The present invention relates to novel 5-HT 4 receptor ligands which are 1-(5-halo-4-aminophenyl) (C 2-6)alkan-1-one derivatives in which the 5-halo-4-aminophenyl group is substituted at its 2-position with (C 1-4)alkyloxy or phenyl(C 1-4)alkyloxy and optionally substituted at its 3-position with (C 1-4)alkyloxy or substituted at its 2-and 3-positions together with methylenedioxy or ethylenedioxy and the highest numbered carbon of the (C 2-6)alkan-1-one is substituted with di(C 1-4)alkylamino, morpholin-1-yl or pyrrolidin-1-yl or optionally substituted piperidin-1-yl, piperidin-4-yl, azacyclohept-1-yl, azabicyclo[2.2.1]hept-3-yl, azabicylo[2.2.2]oct-3-yl or azabicylo[3.2. 2] non-3-yl; and the pharmaceutically acceptable salts, individual isomers and mixtures of isomers and methods of using and making such derivatives.
