Optically active antifungal azoles. VII. Synthesis and antifungal activity of stereoisomers of 2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1- methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-[4-(2,2,3,3- tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone (TAK-187)

Chemical and Pharmaceutical Bulletin

Volumn 45, Issue 2, 1997, Pages 321-326

  Tasaka, Akihiro ^a   Kitazaki, Tomoyuki ^a   Tsuchimori, Noboru ^a   Matsushita, Yoshihiro ^a   Hayashi, Ryogo ^a   Okonogi, Kenji ^a   Itoh, Katsumi ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

1,2,4 triazolone; antifungal activity; optically active antifungal azole; stereocontrolled synthesis; stereoisomer; TAK 187

Indexed keywords

2 [2 (2,4 DIFLUOROPHENYL) 2 HYDROXY 1 METHYL 3 (1H 1,2,4 TRIAZOL 1 YL)PROPYL] 4 [4 (2,2,3,3 TETRAFLUOROPROPOXY)PHENYL] 1,2,4 TRIAZOL 3(2H) ONE; 2 [2 (2,4 DIFLUOROPHENYL) 2 HYDROXY 1 METHYL 3 (1H 1,2,4 TRIAZOL 1 YL)PROPYL] 4 [4 (2,2,3,3 TETRAFLUOROPROPOXY)PHENYL] 3(2H,4H) 1,2,4 TRIAZOLONE; ANTIFUNGAL AGENT; PYRROLE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIFUNGAL ACTIVITY; ARTICLE; CANDIDA ALBICANS; DRUG ACTIVITY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; NONHUMAN; STEREOCHEMISTRY;

EID: 0030942455     PISSN: 00092363     EISSN: None     Source Type: Journal    
DOI: 10.1248/cpb.45.321     Document Type: Article

References (11)

1. Part VI: Kitazaki T., Tamura N., Tasaka A., Matsushita Y., Hayashi R., Okonogi K., Itoh K., Chem. Pharm. Bull., 44, 314-327 (1996).
2. a) Tasaka A., Tamura N., Matsushita Y., Teranishi K., Hayashi R., Okonogi K., Itoh K., Chem. Pharm. Bull., 41, 1035-1042 (1993);
3. b) Tasaka A., Tsuchimori N., Kitazaki T., Hiroe K., Hayashi R., Okonogi K., Itoh K., ibid., 43, 441-449 (1995);
4. c) Tasaka A., Tamura N., Matsushita Y., Hayashi R., Okonogi K., Itoh K., ibid., 41, 1043-1048 (1993).
5. RPMI 1640 was purchased from Gibco BRL.
6. 2 was developed in our laboratories. This susceptibility test gave MIC values nearly equal to those determined by the broth dilution method proposed by the National Committee for Clinical Laboratory Standards (NCCLS protocol, NCCLS Document M27-P, Vol. 12, No. 25). Details of the experimental procedure will be described in a separate paper; Yoshida T., Jono K., Okonogi K., Antimicrob. Agents Chemother., submitted.
7. Okonogi K., Hayashi R., Obita J., Tsuchimori N., Tasaka A., Kitazaki T., Itoh K., Antimicrob. Agents Chemother., in preparation.
8. An alternative method for the synthesis of the (1S,2′R)- and (1R,2′R)- oxiranylethanols has already been reported: a) Konosu T., Miyaoka T., Tajima Y., Oida S., Chem. Pharm. Bull., 39, 2241-2246 (1991); b) Sankyo Co., European Patent 0332387A1 (1989) [Chem. Abstr., 113, 231379y (1990)]; c) Sankyo Co., Japan. Patent, laid open to the public, 3-128338 (1991) [Chem. Abstr., 115, 231852p (1991)].
9. An alternative method for the synthesis of the (1S,2′R)- and (1R,2′R)- oxiranylethanols has already been reported: a) Konosu T., Miyaoka T., Tajima Y., Oida S., Chem. Pharm. Bull., 39, 2241-2246 (1991); b) Sankyo Co., European Patent 0332387A1 (1989) [Chem. Abstr., 113, 231379y (1990)]; c) Sankyo Co., Japan. Patent, laid open to the public, 3-128338 (1991) [Chem. Abstr., 115, 231852p (1991)].
10. An alternative method for the synthesis of the (1S,2′R)- and (1R,2′R)- oxiranylethanols has already been reported: a) Konosu T., Miyaoka T., Tajima Y., Oida S., Chem. Pharm. Bull., 39, 2241-2246 (1991); b) Sankyo Co., European Patent 0332387A1 (1989) [Chem. Abstr., 113, 231379y (1990)]; c) Sankyo Co., Japan. Patent, laid open to the public, 3-128338 (1991) [Chem. Abstr., 115, 231852p (1991)].
11. Considerable decomposition was observed during attempted isolation of the inflate. Therefore, the concentrated eluate containing the triflate was used directly in the subsequent nucleophilic displacement reaction.