The basal SAR of a novel insulin receptor activator

Bioorganic and Medicinal Chemistry Letters

Volumn 10, Issue 11, 2000, Pages 1189-1192

  Wood Jr , Harold B ^a   Black, Regina ^a   Salituro, Gino ^a   Szalkowski, Deborah ^a   Li, Zhihua ^a   Zhang, Yan ^a   Moller, David E ^a   Zhang, Bei ^a   Jones, A Brian ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG ANALOG; INDOLE; INSULIN RECEPTOR; INSULIN RECEPTOR ACTIVATOR; QUINONE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL MODIFICATION; DRUG ACTIVITY; STRUCTURE ACTIVITY RELATION;

RECEPTOR, INSULIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0342699721     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(00)00206-7     Document Type: Article

References (13)

1. Hulin B., McCarthy P.A., Gibbs E.M. Curr. Pharmaceut. Des. 2:1996;85.
2. Stevenson, R. W.; Gibbs, E. M.; Kreutter, D. K.; McPherson, R. K.; Clark, C. A.; Hulin, B.; Goldstein, S. W.; Parker, J. C.; Swick, A. G.; Treadway, J. L.; Hargrove, D. M.; Schulman, G. I. In Diabetes Annual; Marshall, S.; Home, P.; Rizza, R., Eds.; Elsevier Science: Amsterdam, 1995; Vol. 9, p 175.
3. Williams G. Lancet. 343:1994;95.
4. Hulin B. Prog. Med. Chem. 31:1994;1.
5. Zhang B., Salituro G., Szalkowski D., Li Z., Zhang Y., Royo I., Vilella D., Diez M.T., Pelaez F., Ruby C., Kendall R.L., Mao X., Griffin P., Calaycay J., Zierath J.R., Heck J.V., Smith R.G., Moller D.E. Science. 284:1999;974.
6. 4(9 g). An organic extract of the broth was purified by gel filtration and two subsequent cycles of reverse phase HPLC. 1 crystallized as dark purple needles from ethyl acetate/hexane when stored at 4 °C.
7. Osman A.-M. J. Am. Chem. Soc. 79:1957;966.
8. 32P]ATP and poly(Glu:tyr) (4:1) as substrate. The activities of test compounds were expressed as percentage of the maximal activity achieved with 100 nM insulin.
9. Luo Y.-L., Chou T.-C., Cheng C.C. J. Heterocycl. Chem. 33:1996;113.
10. The tertiary alcohol in compound 11 is the result of addition of trifluoroacetic acid to the trisubstituted olefin during concentration of the fractions after HPLC purification. The hydroxy group has a negligible effect upon biological activity. See compound 16, Table 3 for comparison.
11. Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.; Hartung, J.; Jeong, J.-S.; Kwong, H.-L.; Morikawa, K.; Wang, Z.-M.; Xu, D.; Zhang, X.-L. J. Org. Chem. 1992, 57, 2768. The enantioselectivity of the dihydroxylation to yield diol 17 was not determined.
12. All compounds gave satisfactory analytical data.
13. Liu K., Wood H.B., Jones A.B. Tetrahedron Lett. 40:1999;5119.