854739-71-2Relevant articles and documents
Synthesis, antiviral activity, and pharmacokinetic evaluation of P3 pyridylmethyl analogs of oximinoarylsulfonyl HIV-1 protease inhibitors
Randolph, John T.,Huang, Peggy P.,Flosi, William J.,DeGoey, David,Klein, Larry L.,Yeung, Clinton M.,Flentge, Charles,Sun, Mingua,Zhao, Chen,Dekhtyar, Tatyana,Mo, Hongmei,Colletti, Lynn,Kati, Warren,Marsh, Kennan C.,Molla, Akhteruzzaman,Kempf, Dale J.
, p. 4035 - 4046 (2007/10/03)
As a continuation of the recently communicated discovery of oximinoarylsulfonamides as potent inhibitors of HIV-1 aspartyl protease, compounds bearing pyridylmethyl substituents at P3 were designed and synthesized. Potent analogs in this series provided low single-digit nanomolar EC50 values against both wild-type HIV and resistant mutant virus (A17), attenuated some 3- to 12-fold in the presence of 50% human serum. Pharmacokinetic results for compounds in this series showed good to excellent exposure when co-administered orally with an equal amount of ritonavir (5 mg/kg each) in the rat, with average AUC >8 μg h/mL. Similar dosing in dog resulted in significantly lower plasma levels (average AUC i = 2.4 nM).
