AuthorGharat, Laxmikant Atmaram.
Committee ChairMartin, Arnold R.
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PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractThe major focus of our research has been the design, synthesis and pharmacological evaluation of serotonin or 5-hydroxytryptamine (5-HT; 1) analogs. These include the conformationally restricted, rigid and semirigid analogs and those with a variety of different substituents, both electron donating and electron withdrawing, on the critically important indole 5-position. Two most interesting analogs in the tryptamine series are 5- carboxamidotryptamine (5-CT; 3a), a potent agonist at 5-HT₁ receptor and N,N-dipropyl- 5-carboxamido tryptamine (5-DPCT; 3b), a potent and selective agonist at the 5-HT₁ₐ receptor. We have found that this potency also extends to the semirigid analogs, 5- carboxamido-3-tetrahydropyridyl indoles (2a, 2b) (Agarwal et aI., 1993; Dahlgren et aI., 1995). In my research we decided to replace the 5-carboxyamido group by a group called the ɑ-fluoroethenyl or the ɑ-fluorovinyl group which was first proposed as an amide bond isostere in peptides (Allmendinger et aI., 1990). We synthesized 5-(ɑ-fluorovinyl)- 3-tetrahydropyridyl indoles (I, II) and 5-(a-fluorovinyl) tryptamines (III, IV) which could be potential bioisosteres of 2a, 2b, 3a and 3b. The a-fluorovinyl group was introduced on the indole 5-position using an "atypical" Heck reaction to prepare 5-(afluorovinyl) indole (5), the starting material for all the target compounds. We also performed some experiments to confirm the mechanism of the base-catalyzed direct condensation ofN-methyl-3- and -4-piperidones with indoles, a method employed for the synthesis of 3-tetrahydropyridylindoles I and II.
Degree ProgramPharmaceutical Sciences