123963-64-4

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 123963-68-8 S-<4-(9-fluorenylmethoxy)-4-oxobutyl>-L-cysteine 
• 24324-17-2 9-Fluorenylmethanol 
• 123963-67-7 4-bromobutyric acid 9-fluorenylmethyl ester 

Relevant academic research and scientific papers

Synthesis and Biological Activity of Atrial Natriuretic Factor Analogues: Effect of Modifications to the Disulfide Bridge

A series of natriuretic factor (ANF) analogues with modifications to the disulfide bridge and lacking the exocyclic N-terminal sequence was synthesized.The native cystine residue was substituted by isofunctional deamino carba, β,β-dimethyl carba and dehydro dicarba spanners that bridge residues 106 and 120.The compounds were prepared by segment condensation coupling using the base-labile (9-fluorenylmethyl)carboxyl protecting group.Biological evaluation revealed that the exocyclic N-terminal segment of ANF is not necessary for expression of high biological activity.The compounds retained high affinity for ANF receptors in bovine adrenal zona glomerulosa cells and were found to be potent antihypertensive and diuretic agents, indicating that the native disulfide bridge can be mimicked by isosteric spanning residues.It was noted that the reported analogues, unlike the endogenous hormone, show marked reduced inhibitory activity on PGE1-stimulated aldosterone secretion from adrenal zona glomerulosa cells.This lack of inhibition may be a contributing element to the low saluresis in spite of the high level of diuresis observed with some analogues.

ANE derivatives with novel bridging

Disclosed herein are derivatives of atrial natriuretic peptides wherein the exocyclic N-terminal peptide segment is deleted and the two cysteinyl residues (at positions 105 and 121) of the natural sequence are replaced with a trivalent unit, --NHCH(CO--)--Q--X--Y--CH2 CH2 CO-- wherein Q is methylene, ethylene or CR'R" wherein R' and R" each independently is lower alkyl, X is oxy or thio, and Y is methylene or des-Y. The derivatives may be optionally substituted at various positions including positions 106, 107 and 124. The derivatives possess ANF-like activity and are indicated for treating hypertension and for treating pathological conditions resulting from an imbalance of body fluids and electrolytes.