98045-07-9Relevant academic research and scientific papers
Novel renin inhibitors containing derivatives of N-alkylleucyl-β-hydroxy-γ-amino acids
Winiecka, Iwona,Jaworski, Pawe?,Mazurek, Aleksander Pawe?,Marsza?ek, Dorota,Goldnik, Anna,Sokulski, Daniel
, p. 106 - 115 (2016/02/09)
In search for new drugs lowering arterial blood pressure, which could be applied in anti-hypertensive therapy, research concerning agents blocking of renin-angiotensin-aldosteron system has been conducted. Despite many years of research conducted at many research centers around the world, aliskiren is the only one renin inhibitor, which is used up to now. Four novel potential renin inhibitors, having structure based on the peptide fragment 8-13 of human angiotensinogen, a natural substrate for renin, were designed and synthesized. All these inhibitors contain unnatural moieties that are derivatives of N-methylleucyl-β-hydroxy-γ-amino acids at the P2-P1' position: 4-[N-(N-methylleucyl)-amino]-3-hydroxy-7-(3-nitroguanidino)-heptanoic acid (AHGHA), 4-[N-(N-methylleucyl)-amino]-3-hydroxy-5-phenyl-pentanoic acid (AHPPA) or 4-[N-(N-methylleucyl)-amino]-8-benzyloxycarbonylamino-3-hydroxyoctanoic acid (AAHOA). The previously listed synthetic β-hydroxy-γ-amino acids constitute pseudodipeptidic units that correspond to the P1-P1' position of the inhibitor molecule. An unnatural amino acid, 4-methoxyphenylalanin (Phe(4-OMe)), was introduced at the P3 position of the obtained compounds. Three of these compounds contain isoamylamide of 6-aminohexanoic acid (ε-Ahx-Iaa) at the P2'-P3' position. The proposed modifications of the selected human angiotensinogen fragment are intended to increase bioactivity, bioavailability, and stability of the inhibitor molecule in body fluids and tissues. The inhibitor Boc-Phe(4-OMe)-MeLeu-AHGHA-OEt was obtained in the form of an ethyl ester. The hydrophobicity coefficient, expressed as log P varied between 3.95 and 8.17. In vitro renin inhibitory activity of all obtained compounds was contained within the range 10-6-10-9 M. The compound Boc-Phe(4-OMe)-MeLeu-AHPPA-Ahx-Iaa proved to be the most active (IC50 = 1.05 × 10-9 M). The compounds Boc-Phe(4-OMe)-MeLeu-AHGHA-Ahx-Iaa and Boc-Phe(4-OMe)-MeLeu-AHPPA-Ahx-Iaa are resistant to chymotrypsin.
Synthesis of tetrasubstituted symmetrical pyrazines from β-keto γ-amino esters: A mild strategy for self-dimerization of peptides
Kumar, Mothukuri Ganesh,Thombare, Varsha J.,Bhaisare, Rupal D.,Adak, Anindita,Gopi, Hosahudya N.
, p. 135 - 141 (2015/02/02)
A facile synthesis of highly symmetrical tetrasubstituted pyrazines through simple aerial oxidation of β-keto γ-amino esters is reported. The scope of the reaction was examined by use of various amino acid side-chain functional groups andpeptides. The mil
A Facile Synthesis of Statine and Analogues by Reduction of β-Keto Esters Derived from Boc-Protected Amino Acids. HPLC Analyses of Their Enantiomeric Purity
Maibaum, Juergen,Rich, Daniel H.
, p. 869 - 873 (2007/10/02)
The synthesis of γ-amino-β-keto ester derivatives 3a-e from N-Boc-protected L-amino acids by N,N'-carbonyldiimidazole activation and treatment with the magnesium enolate of hydrogen ethyl malonate is described.Racemization during activation, which depende
