Novel 7H-pyrrolo[2,3-d]pyrimidine derivatives as potent and orally active STAT6 inhibitors

Bioorganic and Medicinal Chemistry

Volumn 17, Issue 19, 2009, Pages 6926-6936

  Nagashima, Shinya ^a   Hondo, Takeshi ^a   Nagata, Hiroshi ^a   Ogiyama, Takashi ^a   Maeda, Jun ^a   Hoshii, Hiroaki ^a   Kontani, Toru ^a   Kuromitsu, Sadao ^a   Ohga, Keiko ^a   Orita, Masaya ^a   Ohno, Kazuki ^a   Moritomo, Ayako ^a   Shiozuka, Koichi ^a   Furutani, Masako ^a   Takeuchi, Makoto ^a   Ohta, Mitsuaki ^a   Tsukamoto, Shin ichi ^a  

^a ASTELLAS PHARMA INC   (Japan)

Author keywords

Allergic disease; Interleukin 4; Signal transducers and activators of transcription 6; Th2 differentiation

Indexed keywords

2 [4 [4 [[7 (3,5 DIFLUOROBENZYL) 7H PYRROLO(2,3 D)PYRIMIDIN 2 YL]AMINO]PHENYL]PIPERAZIN 1 YL]ACETAMIDE; 2 [4 [4 [[7 (3,5 DIFLUOROBENZYL) 7H PYRROLO[2,3 D] PYRIMIDIN 2 YL]AMINO]PHENYL]PIPERAZIN 1 YL]ACETAMIDE; 2 [4 [4 [[7 (3,5 DIFLUOROBENZYL) 7H PYRROLO[2,3 D] PYRIMIDIN 2 YL]AMINO]PHENYL]PIPERAZIN 1 YL]ETHANOL; 2 [4 [4 [[7 (3,5 DIFLUOROBENZYL) 7H PYRROLO[2,3 D]PYRIMIDIN 2 YL]AMINO]PHENYL]PIPERAZIN 1 YL] N METHYLACETAMIDE HYDROCHLORIDE; 4 BENZYLAMINOPYRIMIDINE 5 CARBOXAMIDE; 7 (2 FLUOROBENZYL) N (4 MORPHOLIN 4 YLPHENYL) 7H PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; 7 (3,5 DIFLUOROBENZYL) N (4 MORPHOLIN 4 YLPHENYL) 7H PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; 7 (3,5 DIFLUOROBENZYL) N (4 PIPERAZIN 1 YLPHENYL) 7H PYRROLO[2,3 D]PYRIMIDIN 2 AMINE DIHYDROCHLORIDE; 7 (3,5 DIFLUOROBENZYL) N [4 (4 METHYLPIPERAZIN 1 YL)PHENYL] 7H PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; 7 (4 FLUOROBENZYL) N (4 MORPHOLIN 4 YLPHENYL) 7H PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; 7 BENZYL N (4 MORPHOLIN 4 YLPHENYL) 7H PYRROLO[2,3 D]PYRIMIDIN 2 AMINE; 7H PYRROLO[2,3 D]PYRIMIDINE; ANTIGEN; AS 1810722; CYTOCHROME P450 3A4; N [4 [4 (2 AMINOETHYL)PIPERAZIN 1 YL]PHENYL] 7 [3,5 DIFLUOROBENZYL] 7H PYRROLO[2,3 D]PYRIMIDIN 2 AMINE HYDROCHLORIDE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; ASTHMA; CELL DIFFERENTIATION; CELL INFILTRATION; DRUG POTENCY; ENZYME INHIBITION; EOSINOPHIL; IC 50; IN VITRO STUDY; MOUSE; NONHUMAN; TH1 CELL; TH2 CELL;

ADMINISTRATION, ORAL; ANIMALS; ASTHMA; CYTOCHROME P-450 CYP3A; EOSINOPHILS; HUMANS; IMMUNITY; MICE; PYRIMIDINES; PYRROLES; STAT6 TRANSCRIPTION FACTOR; STRUCTURE-ACTIVITY RELATIONSHIP; TH2 CELLS;

EID: 69949119703     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2009.08.021     Document Type: Article

References (19)

1. Chen W., and Khurana H.G.K. J. Allergy Clin. Immunol. Today 119 (2007) 529
2. Chen W., Daines M.O., and Khurana Hershey G.K. J. Immunol. 172 (2004) 6744
3. Wang Y., Malabarba M.G., Nagy Z.S., and Kirken R. J. Biol. Chem. 279 (2004) 25196
4. Takada K., Tanaka T., Shi N., Matsumoto M., Kawashima S.-I., Nakanishi K., Yoshida N., Kishimoto N., and Akira S. Nature 380 (1996) 627
5. Shimoda K., van Deursen J., Sangster M.Y., Sarawar S.R., Carson R.T., Tripp R.A., Chu C., Quelle F.W., Nosaka T., Vignali D.A.A., Doherty P.C., Grosveld G., Paul W.E., and Ihle J.N. Nature 380 (1996) 630
6. Akimoto T., Numata F., Tamura M., Tanaka Y., Higashida N., Takashi T., Takeda K., and Akira S. J. Exp. Med. 187 (1998) 1537
7. Nagashima S., Nagata H., Iwata M., Yokota M., Moritomo H., Orita M., Kuromitsu S., Koakutsu A., Ohga K., Takeuchi M., Ohta M., and Tsukamoto S. Bioorg. Med. Chem. 16 (2008) 6509
8. Nagashima, S., Nagata, H., Iwata, M., Yokota, M., Moritomo, H., Kuromitsu, S., Ohga, K., Takeuchi, M., Tsukamoto, S., Ohta, M. Abstracts of Papers, 232nd ACS National Meeting, San Francisco, Sept 10-14, 2006 American Chemical Society: Washington, DC, 2006, MEDI-196.
9. Ohga K., Kuromitsu S., Takizawa R., Numazaki M., Ishikawa J., Nagashima S., and Shimizu Y. Eur. J. Pharmacol. 590 (2008) 409
10. Riley R.J., Grime K., and Weaver R. Exp. Opin. Drug Metab. Toxicol. 3 (2007) 51
11. Budesinsky Z., and Vavarina J. Collect. Czech. Chem. Commun. 372 (1972) 1721
12. Ozeki K., Ichikawa T., Takehara H., Tanimura K., Sato M., and Yaginuma H. Chem. Pharm. Bull. 37 (1989) 1780
13. Choi H.-S., Wang Z., Richmond W., He X., Yang K., Jiang T., Sim T., Karanwesky D., Gu X., Zhou V., Liu Y., Ohmori O., Caldwell J., Gray N., and He Y. Bioorg. Med. Chem. Lett. 16 (2006) 2173
14. Cheung M., Harris P.A., and Lackey K.E. Tetrahedron Lett. 42 (2001) 999
15. Sakamoto T., Kondo Y., Yasuhara Y., and Yanamaka H. Heterocycles 31 (1990) 219
16. 115 Morgan Drive, Sedona, AZ 86351, USA.
17. Nagashima S., Yokota M., Nakai E., Kuromitsu S., Ohga K., Takeuchi M., Tsukamoto S., and Ohta M. Bioorg. Med. Chem. 15 (2007) 1044
18. MOE 200810; Chemical Computing Group: Montreal, Canada.
19. Connolly M.L. J. Appl. Crystallogr. 16 (1983) 548