Journey Toward New Drugs

It is also interesting to note that the methyl group is an optimum substituent on N in both the chroman and benzofuran series of compounds. Replacement of N— Me by N—H (Table 19.1, entry 12c) or N— Et (Table 19.1, entry 12b) leads to a reduction of plasma glucose-lowering activities. 

To obtain further insight into the structure-activity relationship, we examined several indole derivatives (29e to 29k). The effect of various substituents on the indole ring was examined. The presence of an electron-withdrawing group such as COOH or COOMe (29e and 29f) or electron-donating group such as methyl (29i, and 29j) has a 

Percent reduction of plasma triglyceride (mean S.E. n = 4) after 6 days of treatment N.D. not done. 

Additionally, we envisaged incorporating a N— Me group of rosiglitzone in the side chain of the linker with the help of a carbon atom or other heteroatom, as shown in 

Finally, we selected the maleate and hydrochloride salts of 36a, the maleate salt of saturated TZD (37a), and the sodium salt of 37b for dose-response studies in db/db mice and compared them with rosiglitazone maleate. The animals were treated with different doses 

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JOURNEY TOWARD NEW DRUGS 103 TABLE 19.4 Euglycemic and Hypolipidemic Activities of Unsaturated TZDs... 

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