Synthesis of spiro[chroman-2,4′-piperidin]-4-one derivatives as acetyl-CoA carboxylase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 3, 2009, Pages 949-953

  Shinde, Pundlik ^a   Srivastava, Sanjay K ^a   Odedara, Rajendra ^a   Tuli, Davinder ^a   Munshi, Siralee ^a   Patel, Jitendra ^a   Zambad, Shitalkumar P ^a   Sonawane, Rajesh ^a   Gupta, Ramesh C ^a   Chauthaiwale, Vijay ^b   Dutt, Chaitanya ^a  

^a Torrent Pharmaceuticals Ltd   (India)

^b DR REDDY'S LABORATORIES LTD   (India)

Author keywords

Acetyl CoA carboxylase inhibitors; Spirochromanones

Indexed keywords

ACETYL COENZYME A CARBOXYLASE INHIBITOR; AMIDE; SPIRO(CHROMAN 2,4' PIPERIDIN) 4 ONE DERIVATIVE; UNCLASSIFIED DRUG; UREA DERIVATIVE;

ARTICLE; C57BL 6 MOUSE; CARBOHYDRATE DIET; DRUG SYNTHESIS; OXIDATION; RESPIRATORY QUOTIENT; STRUCTURE ACTIVITY RELATION;

ACETYL-COA CARBOXYLASE; ADENOSINE TRIPHOSPHATE; ANIMALS; CARBOHYDRATES; CHEMISTRY, PHARMACEUTICAL; CHROMANS; DRUG DESIGN; INHIBITORY CONCENTRATION 50; MICE; MICE, INBRED C57BL; MODELS, CHEMICAL; PIPERIDINES; SPIRO COMPOUNDS; STRUCTURE-ACTIVITY RELATIONSHIP; UREA;

MUS;

EID: 58549089168     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.11.099     Document Type: Article

References (14)

1. Harwood Jr. H.J., Petras S.F., Shelly L.D., Zaccaro L.M., Perry D.A., Makowski M.R., Hargrove D.M., Martin K.A., Tracey W.R., Chapman J.G., Magee W.P., Dalvie D.K., Soliman V.F., Martin W.H., Mularski C.J., and Eisenbeis S.A. J. Biol. Chem. 278 (2003) 37099
2. McGarry J.D., and Brown N.F. Eur. J. Biochem. 244 (1997) 1
3. Abu-Elheiga L., Matzuk M.M., Abo-Hashema K.A., and Wakil S.J. Science 291 (2001) 2613
4. Harwood Jr. H.J. Curr. Opin. Investig. Drugs 5 (2004) 283
5. Takeru, Y.; Hideki J.; Kenji, N.; Koji, Y.; Tomoharu, I.; Mitsuru, O.; Hideaki, I.; Jun S.; Jun, K.; Lihu, Y. WO/2007/011809.
6. Zhang H., Tweel B., Li J., and Tong L. Structure 12 (2004) 1683
7. Yang L., Morriello G., Prendergast K., Cheng K., Jacks T., Chan W.W., Schleim K.D., Smith R.G., and Patchett A.A. Bioorg. Med. Chem. Lett. 8 (1998) 107
8. Clark R.F., Zhang T., Wang X., Wang R., Zhang X., Camp H.S., Beutel B.A., Sham H.L., and Gu Y.G. Bioorg. Med. Chem. Lett. 17 (2007) 1961
9. Beutel, B. A.; Camp, H. S.; Clark, R. F.; Gu, Y.-G.; Hansen, T. M.; Keyes, R. F.; Li, Q.; Liu, G.; Sham, H. L.; Wang, X.; Weitzberg, M.; Xin, Z.; Xu, X.; Zhand, T. US Patent 0,178,400, 2006.
10. 3. The supernatants analyzed by HPLC. The HPLC method used column packed with octadecyl silane, embedded with polar substituents, on silica support as stationary phase and ammonium phosphate buffer and acetonitrile as mobile phase.
11. 3): δ 8.26-8.15 (m, 5H), 7.68-7.65 (m, 3H), 7.55-7.46 (m, 6H), 7.07 (d, 1H, J = 9.2 Hz), 4.62 (d, 1H, J = 13.2 Hz), 3.88 (t, 2H, J = 6.8 Hz), 3.62-3.56 (m, 2H), 3.38-3.32 (m, 1H), 2.79 (s, 2H), 2.63 (t, 2H, J = 8.0 Hz), 2.28-2.15 (m, 3H), 2.09-2.05 (m, 1H) 1.84-1.76 (m, 1H), 1.67-1.66 (m, 1H); ESMS (relative intensity) 558 (M+1) (100%); HPLC purity 98.77%.
12. 2 production. Initial 30-min observation was not been considered in the analysis. This is the time taken by mice to stabilize in the oxymax cages after injection. For determining RQ, the average of initial 8 h reading was calculated and then compared statistically using Student's t test.
13. Tipper J.P., and Witters L.A. Biochim. Biophys. Acta 715 (1982) 162
14. Levert K.L., Waldrop G.L., and Stephens J.M. J. Biol. Chem. 277 (2002) 16347