2-Pyridyl P1′-Substituted Symmetry-Based Human Immunodeficiency Virus Protease Inhibitors (A-792611 and A-790742) with Potential for Convenient Dosing and Reduced Side Effects was written by De Goey, David A.;Grampovnik, David J.;Flentge, Charles A.;Flosi, William J.;Chen, Hui-ju;Yeung, Clinton M.;Randolph, John T.;Klein, Larry L.;Dekhtyar, Tatyana;Colletti, Lynn;Marsh, Kennan C.;Stoll, Vincent;Mamo, Mulugeta;Morfitt, David C.;Nguyen, Bach;Schmidt, James M.;Swanson, Sue J.;Mo, Hongmei;Kati, Warren M.;Molla, Akhteruzzaman;Kempf, Dale J.. And the article was included in Journal of Medicinal Chemistry in 2009.COA of Formula: C9H8N2O This article mentions the following:
A series of symmetry-based HIV protease inhibitors I (R1 = 2-FC6H4, 3-MeC6H4, 2-H2NC6H4, 6-methyl-2-pyridyl, 4-quinazolyl, 2-methyl-4-thiazolyl, 1-methyl-2-benzimidazolyl, etc.; R2 = OH, R3 = H; R2 = H, R3 = OH) was designed and synthesized. Modification of the core regiochem. and stereochem. significantly affected the potency, metabolic stability, and oral bioavailability of the inhibitors, as did the variation of a pendant arylmethyl P3 group. Optimization led to the selection of two compounds, (R)-I [R1 = 6-(2-hydroxypropan-2-yl)-2-pyridyl; R2 = OH; R3 = H] (A-790742) and (S)-I (R1 = Ph; R2 = OH; R3 = H) (A-792611), for advancement to preclin. studies. Both compounds displayed low nanomolar potency against wild type HIV in the presence of human serum, low rates of metabolism in human liver microsomes, and high oral bioavailability in animal models. The compounds were examined in a preclin. model for the hyperbilirubinemia observed with some HIV PIs, and both exhibited less bilirubin elevation than comparator compounds X-ray crystallog. analyses of the new cores were used to examine differences in their binding modes. The antiviral activity of the compounds against protease inhibitor resistant strains of HIV was also determined In the experiment, the researchers used many compounds, for example, 1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde (cas: 3012-80-4COA of Formula: C9H8N2O).
1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde (cas: 3012-80-4) belongs to imidazole derivatives. Imidazole is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam.COA of Formula: C9H8N2O
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem