Evaluation of 1,1-cyclopropylidene as a thioether isostere in the 4-thio-thienopyrimidine (TTP) series of antimalarials was written by Barrows, Robert D.;Hammill, Jared T.;Tran, Michael C.;Falade, Mofolusho O.;Rice, Amy L.;Davis, Christopher W.;Emge, Thomas J.;Rablen, Paul R.;Guy, R. Kiplin;Knapp, Spencer. And the article was included in Bioorganic & Medicinal Chemistry in 2020.Computed Properties of C8H8N2 This article mentions the following:
The 4-(heteroarylthio)thieno[2,3-d]pyrimidine (TTP) series of antimalarials, represented by I and II, potently inhibit proliferation of the 3D7 strain of P. falciparum (EC50 70-100 nM), but suffer from oxidative metabolism The 1,1-cyclopropylidene isosteres III and IV were designed to obviate this drawback. They were prepared by a short route that featured a combined Peterson methylenation/cyclopropanation transformation of (4-methylthiazol-2-yl)(thieno[2,3-d]pyrimidin-4-yl)methanone. Isosteres III and IV possessed significantly attenuated antimalarial potency. This outcome could be rationalized based on the increased out-of-plane steric demands of the latter two. In support of this hypothesis, the relatively flat (4-methylthiazol-2-yl)(thieno[2,3-d]pyrimidin-4-yl)methanone retained some of the potency of I, even though it appeared to be a comparatively inferior mimic with respect to electronics and bond lengths and angles. Also crystallog. and computationally an apparent increase in the strength of the intramol. sulfur hole interaction of I upon protonation was demonstrated. In the experiment, the researchers used many compounds, for example, 1-Methylbenzimidazole (cas: 1632-83-3Computed Properties of C8H8N2).
1-Methylbenzimidazole (cas: 1632-83-3) 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. Imidazole also acts as a microtubule destabilizing agents and inhibits topoisomerase and Cytochrome P450 Family 26 Subfamily A Member 1 (CYP26A1) enzymes.Computed Properties of C8H8N2
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem