Title:
FEBRIFUGINE AND ISOFEBRIFUGINE AND PROCESSES FOR THE PREPARATION OF BOTH
Document Type and Number:
WIPO Patent Application WO/2000/052005
Kind Code:
A1
Abstract:
Febrifugine represented by formula (A) and isofebrifugine represented by formula (B), having an extremely potent activity on $i(Plasmodium falciparum); and total synthesis routes permitting efficient mass production of both.
Inventors:
KOBAYASHI SHU (JP)
WATAYA YUSUKE (JP)
KIM HYE-SOOK (JP)
WATAYA YUSUKE (JP)
KIM HYE-SOOK (JP)
Application Number:
PCT/JP2000/001192
Publication Date:
September 08, 2000
Filing Date:
March 01, 2000
Export Citation:
Assignee:
JAPAN SCIENCE & TECH CORP (JP)
KOBAYASHI SHU (JP)
WATAYA YUSUKE (JP)
KIM HYE SOOK (JP)
KOBAYASHI SHU (JP)
WATAYA YUSUKE (JP)
KIM HYE SOOK (JP)
International Classes:
A61K31/00; A61K31/505; A61K31/517; A61K31/519; A61K31/529; A61P33/00; A61P33/06; B01J31/12; B01J31/18; C07B61/00; C07D401/06; C07D491/04; C07D491/048; (IPC1-7): C07D401/06; C07D491/048; A61K31/517; A61P33/06
Other References:
UESATO S. ET. AL.: "Conformational analysis of febrifugines and halofuginones in organic slovents.", CHEM. PHARM. BULL., vol. 46, no. 1, 1998, pages 1 - 5, XP002928294
BARRINGER D. F. ET. AL.: "The stereochemistry of febrigine. II. Evidence for the trans. configuration in the piperidine ring.", J. ORG. CHEM., vol. 38, no. 10, 1973, pages 1937 - 1940, XP002928295
BURGESS L. E. ET. AL.: "The preparation of alpha-sustituted beta-hydroxy piperidines and pyrrolidines: The total synthesis of febrifugine.", TETRAHEDRON LETT., vol. 37, no. 19, 1996, pages 3255 - 3258, XP002928296
MURATA K. ET. AL.: "Enhancement of NO production in activated macrophages in vivo by an antimalarial crude drug, dichroafebrifuga.", J. NAT. PROD., vol. 61, no. 6, 1998, pages 729 - 733, XP002928297
KOBAYASHI S. ET. AL.: "Catalytic asymmetric synthesis of febrifugine and isofebrifugine.", TETRAHEDRON LETT., vol. 40, no. 11, 1999, pages 2175 - 2178, XP002928298
KOBAYASHI S. ET. AL.: "Catalytic asymmetric synthesis of antimalarial alkaloids febrifugine and Isofebrifugine and their biological activity.", J. ORG. CHEM., vol. 64, no. 18, 1999, pages 6833 - 6841, XP002928299
TAKEUCHI Y. ET. AL.: "Total synthesis of dl-febrifugine and dl-isofebrifugine.", CHEM. PHARM. BULL., vol. 47, no. 6, 1999, pages 905 - 906, XP002928709
TAKEUCHI Y. ET. AL.: "Synthesis of D/L-febrifugine and D/L-isofebrifugine.", SYNTHESIS, vol. 10, 1999, pages 1814 - 1818, XP002928710
TAKAYA Y. ET. AL.: "New type of febrifugine analogues, bearing a quinolizidine moeity, show potent antimalarial activity against plasmodium malaria parasite.", J. MED. CHEM., vol. 42, no. 16, 1999, pages 3163 - 3166, XP002928711
See also references of EP 1076057A4
BARRINGER D. F. ET. AL.: "The stereochemistry of febrigine. II. Evidence for the trans. configuration in the piperidine ring.", J. ORG. CHEM., vol. 38, no. 10, 1973, pages 1937 - 1940, XP002928295
BURGESS L. E. ET. AL.: "The preparation of alpha-sustituted beta-hydroxy piperidines and pyrrolidines: The total synthesis of febrifugine.", TETRAHEDRON LETT., vol. 37, no. 19, 1996, pages 3255 - 3258, XP002928296
MURATA K. ET. AL.: "Enhancement of NO production in activated macrophages in vivo by an antimalarial crude drug, dichroafebrifuga.", J. NAT. PROD., vol. 61, no. 6, 1998, pages 729 - 733, XP002928297
KOBAYASHI S. ET. AL.: "Catalytic asymmetric synthesis of febrifugine and isofebrifugine.", TETRAHEDRON LETT., vol. 40, no. 11, 1999, pages 2175 - 2178, XP002928298
KOBAYASHI S. ET. AL.: "Catalytic asymmetric synthesis of antimalarial alkaloids febrifugine and Isofebrifugine and their biological activity.", J. ORG. CHEM., vol. 64, no. 18, 1999, pages 6833 - 6841, XP002928299
TAKEUCHI Y. ET. AL.: "Total synthesis of dl-febrifugine and dl-isofebrifugine.", CHEM. PHARM. BULL., vol. 47, no. 6, 1999, pages 905 - 906, XP002928709
TAKEUCHI Y. ET. AL.: "Synthesis of D/L-febrifugine and D/L-isofebrifugine.", SYNTHESIS, vol. 10, 1999, pages 1814 - 1818, XP002928710
TAKAYA Y. ET. AL.: "New type of febrifugine analogues, bearing a quinolizidine moeity, show potent antimalarial activity against plasmodium malaria parasite.", J. MED. CHEM., vol. 42, no. 16, 1999, pages 3163 - 3166, XP002928711
See also references of EP 1076057A4
Attorney, Agent or Firm:
Nishizawa, Toshio (Udagawa-cho Shibuya-ku Tokyo, Udagawa-cho Shibuya-ku Tokyo, JP)
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