Hydroxamic Acids as Potent Inhibitors of Endothelin-Converting Enzyme from Human Bronchiolar Smooth Muscle was written by Bihovsky, Ron;Levinson, Barry L.;Loewi, Rivka C.;Erhardt, Paul W.;Polokoff, Mark A.. And the article was included in Journal of Medicinal Chemistry in 1995.COA of Formula: C11H20O4 This article mentions the following:
Hydroxamic acids HONHCOCHRCO-X-R1 (I; R = H. CHMe2, CH2CHMe2; X = β-Ala, Asn, Trp, Gly; R1 = OH. NH2), derived from malonyl amino acids, and HONHCHCH2CH(CHMe2)CO-X-R1 (X = Asn, β-Ala, Trp, R1 = OH, NH2), derived from succinyl amino acids, were synthesized as inhibitors of human bronchiolar smooth muscle endothelin-converting enzyme (HBSM ECE). Several unexpected side reactions were discovered, particularly in the synthesis of hydroxamates derived from succinates. In vitro evaluation against human bronchiolar ECE revealed that in all cases hydroxamates derived from malonate were more potent than hydroxamates derived from succinate. P1‘ side chains R = CHMe2, CH2CHMe2 were suitable; omission of the P1‘ side chain (R = H) seriously diminished potency. In the P2‘ position, several amino acids gave potent malonate-derived hydroxamate inhibitors (IC50 = 0.2-6.8 nM), and I (R = CHMe2, X = β-Ala, R1 = OH) (II) provided an extremely potent inhibitor (IC50 = 0.01 nM). C-terminus carboxylates are much more potent ECE inhibitors than the corresponding amides. Most of the hydroxamates were also potent inhibitors of thermolysin and neutral endopeptidase (NEP); however, the P2‘ β-Ala derivative II uniquely inhibited HBSM ECE much more potently than NEP. In the experiment, the researchers used many compounds, for example, Diethyl isobutylmalonate (cas: 10203-58-4COA of Formula: C11H20O4).
Diethyl isobutylmalonate (cas: 10203-58-4) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits. Because of their lack of hydrogen-bond-donating ability, esters do not self-associate. Consequently, esters are more volatile than carboxylic acids of similar molecular weight.COA of Formula: C11H20O4
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics