Novel tropane derivatives were characterized as muscarinic acetylcholine receptor antagonists (mAChRs). Through optimization of the structure-activity relationship around the tropane scaffold, the quaternary ammonium salt 34 was identified as a very potent M(3) mAChR antagonist. The compound was functionally active and displayed greater than 24 h duration of action in a mouse model of bronchoconstriction.
To compare the safety and efficacy of amprenavir [APV/j Ageneraset; GlaxoSmithKline, [Ware, UK; 600 mg twice a day (bid)] boosted with low-dose ritonavir (RTV, 100 mg bid) with those of other protease inhibitors (PIs) in PI-experienced HIV-infected patients.
Study designParallel-group, randomized, open-label, multicentre study.
MethodsOne hundred and sixty-three patients with HIV predicted to be sensitive to APV, another PI and a nucleoside reverse transcriptase inhibitor (NRTI) were randomly assigned to receive either APV boosted with low-dose RTV (APV/r) or a standard of care (SOC) PI with or without low-dose RTV. The non-inferiority of APV/r to the SOC PIs was assessed by time-weighted average change from baseline (AAUCMB) in plasma viral load (vRNA) at week 16.
ResultsThe antiviral response for APV/r bid was non-inferior to that for the SOC PI group: the vRNA AAUCMB mean treatment difference was 0.043 log 10 HIV-1 RNA copies/mL [95% confidence interval (CI) À 0.250, 0.335]. APV/r bid was generally well tolerated.
ConclusionsResults confirm the antiviral activity, short-term safety and tolerability of APV/r bid in PI-experienced patients.
Fused pyrimidine derivatives R 0515An Improved and Highly Convergent Synthesis of 4-Substituted-pyrido[2,3-d]pyrimidin-7-ones. -Improved syntheses of various title compounds with potential pharmaceutical interest are described. The strategies involve two differentially reactive groups: -SO-Me and -Cl allowing for selective substitution at C-2 (with amines) and C-4 (with arylboronic acids). -(YAN, H.; BOEHM, J. C.; JIN, Q.; KASPAREC, J.; LI, H.; ZHU, C.; WIDDOWSON, K. L.; CALLAHAN, J. F.; WAN*
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.