294867-69-9Relevant academic research and scientific papers
Solid phase assisted synthesis of HIV-1 inhibitors. Expedient entry to unsymmetrical substitution of a C2 symmetric template
Oscarsson,Classon,Kvarnstrom,Hallberg,Samuelsson
, p. 829 - 837 (2007/10/03)
A solid phase synthesis has been developed leading up to unsymmetrical HIV-1 protease inhibitors that are not readily available by conventional solution phase chemistry (18a-g). To prepare these compounds the hydroxyl group of (1s,2r)-(-)-cis-1-phthalimido-2-indanol (3) was coupled to a Merrifield resin via a dihydropyrane linker. Cleavage of the phthalimido protecting group and reaction of the liberated amine with the bis-activated symmetrical diacid 15 resulted in the resin bound amide 16. Coupling of 16 with amino acids and amines followed by hydrolysis produced the desired unsymmetrical products 18a-g from which potent HIV-1 protease inhibitors were identified, e.g., 18e (k(i) = 0.1 nM), 18a (k(i) = 0.2 nM) and 18c (k(i) = 2 nM).
