1.Bicyclic lactam inhibitors of angiotensin converting enzyme.
Watthey JW, Gavin T, Desai M. J Med Chem. 1984 Jun;27(6):816-8.
Syntheses of the potent angiotensin converting enzyme inhibitor 1-(carboxymethyl)-3-(mercaptomethyl)-2,3,4,5-tetrahydro-1H-1- benzazep in -2-one (4a) and the corresponding eight-membered ring analogue (4b) are described. The influence of ring size on the inhibitory potencies of these substances is discussed.
2.In vitro evaluation of the clastogenicity of fumagillin.
Stevanovic J1, Stanimirovic Z, Radakovic M, Stojic V. Environ Mol Mutagen. 2008 Oct;49(8):594-601. doi: 10.1002/em.20409.
Fumagillin, an antibiotic compound produced by Aspergillus fumigatus, is effective against microsporidia and various Amoeba species, but is also toxic when administered systemically to mammals. Furthermore, a recent in vivo study by Stanimirovic Z et al. 2007: (Mutat Res 628:1-10) indicated genotoxic effects of fumagillin. The aim of the present study was to investigate and explain the clastogenic effects of fumagillin (in the form of fumagillin dicyclohexylamine salt) on human peripheral blood lymphocytes in vitro by sister-chromatid exchanges (SCE), chromosome aberrations (CA), and micronucleus (MN) tests. The mitotic index (MI), proliferation index (PI), and nuclear division index (NDI) were calculated to evaluate the cytotoxic potential of fumagillin. Five concentrations of fumagillin (0.34, 0.68, 1.02, 3.07, and 9.20 microg/ml) were applied to lymphocyte cultures. All the tested concentrations of fumagillin increased the frequency of SCE per cell significantly (P < 0.
3.Diastereoselective arylithium addition to an alpha-trifluoromethyl imine. Practical synthesis of a potent cathepsin K inhibitor.
Roy A1, Gosselin F, O'Shea PD, Chen CY. J Org Chem. 2006 May 26;71(11):4320-3.
A practical, chromatography-free synthesis of potent cathepsin K inhibitor 1 is described. The addition of 4-bromophenyllithium to an alpha-trifluoromethylimine derived from commercially available (S)-leucinol was accomplished in a highly diastereoselective manner (97.6% de, 91% yield). Subsequent Suzuki cross-coupling afforded biaryl 7. Oxidation of the alcohol and sulfide functionalities led to the formation of carboxylic acid 8. Crystallization of 7 and acid 8 as its dicyclohexylamine salt gave excellent impurity rejection. The final amide coupling with commercially available aminoacetonitrile hydrochloride afforded 1 in excellent purity (99.6A% by HPLC, 100% de, <3 ppm Pd, W, Cr).
4.Efficacy of fumagillin against Thelohanellus kitauei infection of Israel carp, Cyprinus carpio nudus.
Rhee JK1, Kim HC, Park BK. Korean J Parasitol. 1993 Mar;31(1):57-65.
The potential of fumagillin dicyclohexylamine salt to treat and prevent intestinal giant-cystic disease in Israel carp, Cyprinus carpio nudus, was monitored in field experimental studies. In experiment 1 (therapeutic), most fish were already naturally infected with more advanced stage of Thelohanellus kitauei. Fumagillin was administered to fish (mean body weight of 830 g) for a period of one month at a dose of 10.62 mg in the first group and 5.3 mg in the second group per fish per day. In experiment 2 (prophylactic), most fish also were already naturally infected with an early developmental stage of the protozoa and fish (average body weight of 484 g) were administered fumagillin for 45 days at a dose of 3.95 mg per fish per day. In both experiments, the cumulative mortalities of fish and the extrusion rates of the polar filaments of the spores were significantly decreased in a dose-independent fashion. In experiment 2 no dead fish were observed.
![(S)-2-[(t-Butoxycarbonyl)amino]-5-phenylpentanoic acid dicyclohexylammonium salt](https://resource.bocsci.com/structure/113756-89-1.gif)
