Optimization of a Series of RIPK2 PROTACs was written by Miah, Afjal H.;Smith, Ian E. D.;Rackham, Mark;Mares, Alina;Thawani, Aditya R.;Nagilla, Rakesh;Haile, Pamela A.;Votta, Bartholomew J.;Gordon, Laurie J.;Watt, Gillian;Denyer, Jane;Fisher, Don T.;Dace, Phoebe;Giffen, Paul;Goncalves, Andrea;Churcher, Ian;Scott-Stevens, Paul;Harling, John D.. And the article was included in Journal of Medicinal Chemistry in 2021.Computed Properties of C13H18N2O2 This article mentions the following:
Receptor-interacting serine/threonine protein kinase 2 (RIPK2) is an important kinase of the innate immune system. Herein, we describe the optimization of a series of RIPK2 PROTACs which recruit members of the inhibitor of apoptosis (IAP) family of E3 ligases. Our PROTAC optimization strategy focused on reducing the lipophilicity of the early lead which resulted in the identification of analogs with improved solubility and increased human and rat microsomal stability. We identified a range of IAP binders that were successfully incorporated into potent RIPK2 PROTACs with attractive pharmacokinetic profiles. Compound 20 possessed the best overall profile with good solubility, potent degradation of RIPK2, and associated inhibition of TNFα release. A proof-of-concept study utilizing a slow release matrix demonstrated the feasibility of a long-acting parenteral formulation with >1 mo duration. This represents an attractive alternative dosing paradigm to oral delivery, especially for chronic diseases where compliance can be challenging. In the experiment, the researchers used many compounds, for example, (R)-1-Cbz-3-methylpiperazine (cas: 623586-00-5Computed Properties of C13H18N2O2).
(R)-1-Cbz-3-methylpiperazine (cas: 623586-00-5) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Computed Properties of C13H18N2O2
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics