97801-78-0Relevant articles and documents
DRUG DERIVATIVES
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Paragraph 0384, (2013/09/12)
The present invention relates to derivatives of known active pharmaceutical compounds. These derivatives are differentiated from the parent active compound by virtue of being redox derivatives of the active compound. This means that one or more of the functional groups in the active compound has been converted to another group in one or more reactions which may be considered to represent a change of oxidation state. We refer to these compounds generally as redox derivatives. The derivatives of the invention may be related to the original parent active pharmaceutical compound by only a single step transformation, or may be related via several synthetic steps including one or more changes of oxidation state. In certain cases, the functional group obtained after two or more transformations may be in the same oxidation state as the parent active compound (and we include these compounds in our definition of redox derivatives). In other cases, the oxidation state of the derivative of the invention may be regarded as being different from that of the parent compound. In many cases, the compounds of the invention have inherent therapeutic activity on their own account. In some cases, this activity relative to the same target or targets of the parent compound is as good as or better than the activity which the parent compound has against the target or targets.
PROCESS FOR THE RECYCLE OF A WASTE PRODUCT OF DILTIAZEM SYNTHESIS
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, (2008/06/13)
A process which allows the re-use of compounds of formula in diltiazem synthesis through a process of conversion to a mixture of enantiomers III-(2R,3R) and III-(2S,3S) is described.
Asymmetric reduction of a 1,5-benzothiazepine derivative with sodium borohydride-(S)-α-amino acids: An efficient synthesis of a key intermediate of diltiazem
Yamada, Shin-Ichi,Mori, Yoshikazu,Morimatsu, Katsuji,Ishizu, Yoshinori,Ozaki, Yasuhiko,Yoshioka, Ryuzo,Nakatani, Tadashi,Seko, Hiroyasu
, p. 8586 - 8590 (2007/10/03)
A key intermediate of diltiazem synthesis, (2S,3S)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4 (5H)-one [(2S,3S)-1], has been efficiently synthesized by an asymmetric reduction of the prochiral ketone, 2-(4-methoxyphenyl)-1,5-benzothiazepine-3,4(2H,5H)-dione (3), with NaBH4 and chiral α-amino acids. As the chiral sources, β-branched-chain amino acids, such as (S)-valine, (S)-isoleucine, and (S)-tert-leucine, were found to be effective. In particular, using (S)-tert-leucine as a ligand resulted in the formation of (2S,3S)-1 with excellent enantioselectivity. (95% ee for cis-isomers). The addition of AcOH to the reaction permitted further improvement of both conversion and stereoselectivity. As a result, optically pure (2S,3S)-1 could be isolated in 86% yield. This asymmetric reduction proceeded via dynamic kinetic resolution and made it possible to control the two adjacent asymmetric carbons through keto-enol tautomerism.
