Stability studies of C-4',6' acetal benzylmaltosides synthesized as inhibitors of smooth muscle cell proliferation.
In our investigations to synthesize inhibitors of smooth muscle cell (SMC) proliferation, compound 6a displayed submicromolar activity in in vitro antiproliferative assays and reduced intimal thickening using a rat balloon angioplasty model via i.v. administration. In order to identify analogs that could be administered orally, the chemical instability of the C-4',6' acetal of compound 6a was addressed. Several novel variants with increased acid stability and comparable in vitro activity were prepared.
Mayer
Scott C
SC
Chemical and Screening Sciences Department, Wyeth Research, CN 8000, Princeton, NJ 08543-8000, USA. mayers@wyeth.com
Gallaway
William
W
Kulishoff
John
J
Yin
Maisheng
M
Gadamasetti
Vidya
V
Mitchell
Robert
R
D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D008297:Male; D008320:Maltose / Q000138:chemical synthesis / Q000494:pharmacology*; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D001593:Benzyl Compounds; D008320:Maltose