Cyclase inhibitor

Gille A, Seifert R (2003) 2 (3 )-O-(A-methylanthraniloyl)-substituted GTP analogs a novel class of potent competitive adenylyl cyclase inhibitors. J Biol Chem 278 12672-12679... 

Marks, G. A. Birabil, C. G. (2000). Infusion of adenylyl cyclase inhibitor SQ22.536 into the medial pontine reticular formation of rats enhances rapid eye movement sleep. Neuroscience 98, 31115. 

Manetsch, R., Zheng, L, Reymond, M.T., Woggon, W.D. and Reymond, J.L (2004) A catalytic antibody against a tocopherol cyclase inhibitor. Chemistry, 10,2487-2506. 

PKG and cyclic nucleotide phosphodiesterases (PDEs) (reviewed by Baxter37). A rapid release of natriuretic peptides and induction of their de novo synthesis occurs in myocardial ischemia. Natriuretic peptides may have a cardioprotective role. BNP-32 administration in perfused rat hearts prior to left main coronary artery occlusion and until 30 min of reperfusion resulted in limitation of infarct size in a concentration dependent manner. Furthermore, this effect was abolished by 5-hydroxydecanoate (presumed to be a selective blocker of mitochondrial KATp channels), L-NAME, an inhibitor of NOS and ODQ, a specific soluble guanyl cyclase inhibitor.38 Similarly, human recombinant ANP limited infarct size and reperfusion arrhythmias in a canine model of coronary occlusion and reperfusion.39... 

Benzimidazole-based glutaminyl cyclase inhibitors Benzimidazolyl-1,2,3 -triazoles Benzimidazolyl-1,3,4 -thiadiazoles... 

Benzo[d]isothiazoles 220 and 221 (Scheme 56) were synthesised as oxi-dosqualene cyclase inhibitors. By reaction of fluorobenzophenones 216 with potassium benzylthiolate followed by S-chlorination, cleavage of the benzyl group with SO2CI2 and reaction with NH3, compound 217 was formed. Methoxy deprotection and alkylation with 1,6-dibromohexane gave intermediate 218, which was converted to 220 with Af-allylmethylamine. Intermediate 218 was oxidised to the S,S-dioxide 219 and then functionalised at C-6 affording 221. Similarly, benzo[d]isothiazole 223 was prepared from benzophenone 222 [68]. 

Scheme 56 Synthesis of 3-aryl substituted benzisothiazoles as oxidosqualene cyclase inhibitors...

Shenoy, S. D., Spencer, T. A., Mercer-Haines, N. A., Abdolalipour, M., Wurster, W. L., Runge-Morris, M., and Kocarek, T. A. (2004) Induction of CYP3A by 2,3-oxidosqualenedanosterol cyclase inhibitors is mediated by an endogenous squalene metabolite in primary cultured rat hepatocytes. Mol. Pharmacol. 65, 1302-1312. 

Our results failed to support the findings of Ko et al. in that endothelium-removal, methylene blue and lH-[l,2,4]oxadiazolo- [4,3-a]quinoxalin-l-one (ODQ, a soluble guanylate cyclase inhibitor) all right-shifted the phthalide 20 dose-response curve against U-46619-induced vasoconstriction [352], These right-shifts may be explained either by... 

Feelisch, M., Kotsonis, P., Siebe, J., Clement, B., Sehmidt, H. H. (1999) The soluble guanylyl cyclase inhibitor lH-[l,2,4]oxadiazolo[4,3,-a] quinoxalin-l-one is a nonselective heme protein inhibitor of nitrie oxide synthase and other eytoehrome P-450 enzymes involved in nitric oxide donor bioaetivation. Mol. Pharmacol. 56 243-253. 

The guanylate cyclase inhibitor LY83583 inhibited human alveolar macrophage spreading and staining for cGMP-dependent protein kinase at the cell periphery (Pryzwansky et al. 1995). 

Dihydrotanshinone relaxed isolated rat coronary arteries stimulated with 5-hydroxytryptamine (5-HT). The effect was blocked by the guanylate cyclase inhibitor ODQ, indicating a mechanism involving inhibition of calcium influx in smooth muscle cells of the vasculature [59],... 

Xia, Z. T. Combination products of a guanylate cyclase inhibitor and a local anesthetic for pain relief PCT Int. Appl. WO 2000030630, 2000 Chem. Abstr. 2000, 133, 12755. 

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