Synthesis of new class of indole compounds as non-imidazole histamine H-3 antagonists

ORGN 803

Yi-Yin Ku, yiyin.ku@abbott.com1, Yu-Ming Pu1, Tim Grieme, timothy.grieme@abbott.com1, Timothy A. Esbenshade2, and Marlon Cowart2. (1) D-R450, Process Chemistry, Abbott Laboratories, 1401 Sheridan Rd, North Chicago, IL 60064, (2) Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R4MN, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064
An efficient process for the synthesis of indole core involving a convergent strategy has been developed. The key steps proceed through a Pd-catalyzed Sonogashira coupling reaction followed by a ring closure affected by a strong base in NMP (1-methyl-2-pyrrolidinone). A variety of indole compounds derived from the indole core were found to be potent H-3 antagonists for both human and rat.

 

Total Synthesis, Materials, Molecular Recognition, Process R&D, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006