Category: 128947-19-3

Discovery of Potent Cyclophilin Inhibitors Based on the Structural Simplification of Sanglifehrin A was written by Steadman, Victoria A.;Pettit, Simon B.;Poullennec, Karine G.;Lazarides, Linos;Keats, Andrew J.;Dean, David K.;Stanway, Steven J.;Austin, Carol A.;Sanvoisin, Jonathan A.;Watt, Gregory M.;Fliri, Hans G.;Liclican, Albert C.;Jin, Debi;Wong, Melanie H.;Leavitt, Stephanie A.;Lee, Yu-Jen;Tian, Yang;Frey, Christian R.;Appleby, Todd C.;Schmitz, Uli;Jansa, Petr;Mackman, Richard L.;Schultz, Brian E.. And the article was included in Journal of Medicinal Chemistry in 2017.Electric Literature of C13H21NO3S This article mentions the following:

Cyclophilin inhibition has been a target for the treatment of hepatitis C and other diseases, but the generation of potent, drug-like mols. through chem. synthesis has been challenging. In this study, a set of macrocyclic cyclophilin inhibitors was synthesized based on the core structure of the natural product sanglifehrin A. Initial compound optimization identified the valine-m-tyrosine-piperazic acid tripeptide (Val-m-Tyr-Pip) in the sanglifehrin core, stereocenters at C14 and C15, and the hydroxyl group of the m-tyrosine (m-Tyr) residue as key contributors to compound potency. Replacing the C18-C21 diene unit of sanglifehrin with a styryl group led to potent compounds that displayed a novel binding mode in which the styrene moiety engaged in a π-stacking interaction with Arg55 of cyclophilin A (Cyp A), and the m-Tyr residue was displaced into solvent. This observation allowed further simplifications of the scaffold to generate new lead compounds in the search for orally bioavailable cyclophilin inhibitors. In the experiment, the researchers used many compounds, for example, 1-((3aR,6S,7aS)-8,8-Dimethyl-2,2-dioxidohexahydro-1H-3a,6-methanobenzo[c]isothiazol-1-yl)propan-1-one (cas: 128947-19-3Electric Literature of C13H21NO3S).

1-((3aR,6S,7aS)-8,8-Dimethyl-2,2-dioxidohexahydro-1H-3a,6-methanobenzo[c]isothiazol-1-yl)propan-1-one (cas: 128947-19-3) belongs to isothiazole derivatives. Similar to other five-membered heterocycles, isothiazoles react with a wide range of electrophilic and nucleophilic reagents to form diverse products. Various penicillins and cephalosporins having an isothiazole ring system have shown considerable antibacterial efficacy against Gram-positive and Gram-negative bacteria.Electric Literature of C13H21NO3S

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

Total synthesis and determination of the absolute configuration of Rakicidin C was written by Han, Fangzhi;Liu, Guangju;Jin, Chaofan;Wang, Jinghan;Liu, Jianwei;Wang, Liang;Chen, Yue. And the article was included in Organic Letters in 2021.Electric Literature of C13H21NO3S This article mentions the following:

The absolute configuration of rakicidin C was predicted by comparison of optical rotation data and absolute configuration of APD-cyclic depsipeptides and further determined by total synthesis. The absolute configuration of five chiral centers was determined as 2R, 15R, 16R, 17S, and 19S. Our efficient route involves 19 longest linear steps with an overall yield of 1.49%. In the experiment, the researchers used many compounds, for example, 1-((3aR,6S,7aS)-8,8-Dimethyl-2,2-dioxidohexahydro-1H-3a,6-methanobenzo[c]isothiazol-1-yl)propan-1-one (cas: 128947-19-3Electric Literature of C13H21NO3S).

1-((3aR,6S,7aS)-8,8-Dimethyl-2,2-dioxidohexahydro-1H-3a,6-methanobenzo[c]isothiazol-1-yl)propan-1-one (cas: 128947-19-3) belongs to isothiazole derivatives. Isothiazoles and benzisothiazoles are usually liquids or low-melting-point solids; polar substituents increase the melting points because of the possibility of hydrogen bonding and other interactions in the crystalline state. Many compounds with an isothiazole scaffold demonstrated a wide range of biological profiles. Some of these molecules have been efficiently used in the treatment of Alzheimer’s disease.Electric Literature of C13H21NO3S

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com