Title:
NOVEL MEDOXOMIL AND HEMIACETAL ESTERS OF PEMETREXED, PRODUCTION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION CONTAINING ESTER PRODRUG
Document Type and Number:
WIPO Patent Application WO/2018/096853
Kind Code:
A1
Abstract:
Provided are medoxomil and hemiacetal esters that are intended for oral administration of pemetrexed, the development of a method for producing medoxomil and hemiacetal esters that is essential for verifying the efficacy of the medoxomil and hemiacetal esters as prodrugs, and pharmaceutical compositions containing prodrugs of medoxomil and hemiacetal esters of pemetrexed. The present invention provides (i) pemetrexed medoxomil and hemiacetal ester compounds, (ii) pharmaceutical compositions containing pemetrexed medoxomil and hemiacetal ester prodrugs that are capable of reproducing ingredients by intestinal absorption, and (iii) production methods wherein, with L-glutamic acid serving as a starting ingredient, the carboxyl group thereof is subjected to medoxomil and hemiacetal esterification, and thereafter coupling with pemetrexed acid of the main skeleton proceeds to produce pemetrexed medoxomil and hemiacetal ester prodrugs.
Inventors:
MATSUYAMA KENJI (JP)
OTORI TORU (JP)
MAEGAWA TOMOHIRO (JP)
KIMACHI TETSUTARO (JP)
SATO MAKOTO (JP)
OTORI TORU (JP)
MAEGAWA TOMOHIRO (JP)
KIMACHI TETSUTARO (JP)
SATO MAKOTO (JP)
Application Number:
PCT/JP2017/037966
Publication Date:
May 31, 2018
Filing Date:
October 20, 2017
Export Citation:
Assignee:
UNIV KINKI (JP)
EDUCATIONAL CORP MUKOGAWA GAKUIN (JP)
NIPRO CORP (JP)
EDUCATIONAL CORP MUKOGAWA GAKUIN (JP)
NIPRO CORP (JP)
International Classes:
C07D487/04; A61K31/519; A61P29/00; A61P35/00
Foreign References:
| JPS63227588A | 1988-09-21 | |||
| JP2016525564A | 2016-08-25 | |||
| JP2016501887A | 2016-01-21 |
Other References:
BARNNETT, C. J. ET AL.: "A PRACTICAL SYNTHESIS OF MULTITARGETED ANTIFOLATE LY231514", ORGANIC PROCESS RESEARCH & DEVELOPMENT, vol. 3, 1999, pages 184 - 188, XP000982091
TEICHER, B. A. ET AL.: "Treatment Regimens Including the Multitargeted AntifolateLY231514 in Human Tumor Xenografts", CLINICAL CANCER RESEARCH, vol. 6, 2000, pages 1016 - 1023, XP055507502
TEICHER, B. A. ET AL.: "Treatment Regimens Including the Multitargeted AntifolateLY231514 in Human Tumor Xenografts", CLINICAL CANCER RESEARCH, vol. 6, 2000, pages 1016 - 1023, XP055507502
Attorney, Agent or Firm:
SHINKYU PARTNERS P.C. (JP)
Download PDF: