- RADIOACTIVE HALOGEN LABELED COMPOUNDS OR SALTS THEREOF, AND PHARMACEUTICALS CONTAINING THE SAME
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PROBLEM TO BE SOLVED: To provide: radioactive halogen labeled compounds which have high selectivity for aldosterone synthase (CYP11B2) over steroid 11β-hydroxylase (CYP11B1) and high accumulation selectivity in the adrenal gland compared to the surroundin
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Paragraph 0064
(2016/12/22)
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- RADIOACTIVE HALOGEN LABELED COMPOUNDS OR SALTS THEREOF, AND PHARMACEUTICALS CONTAINING THE SAME
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PROBLEM TO BE SOLVED: To provide radioactive halogen labeled compounds which have high selectivity for CYP11B2 over CYP11B1 and accumulation selectivity in the adrenal gland compared to the surrounding organs. SOLUTION: The present invention provides radi
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Paragraph 0053; 0054
(2018/12/12)
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- Triazole ligands reveal distinct molecular features that induce histaine H4 receptor affinity and subtly govern H4/H3 subtype selectivity
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The histamine H3 (H3R) and H4 (H 4R) receptors attract considerable interest from the medicinal chemistry community. Given their relatively high homology yet widely differing therapeutic promises, ligand selectivity for the two receptors is crucial. We interrogated H4R/H3R selectivities using ligands with a [1,2,3]triazole core. Cu(I)-assisted "click chemistry" was used to assemble diverse [1,2,3]triazole compounds (6a-w and 7a-f), many containing a peripheral imidazole group. The imidazole ring posed some problems in the click chemistry putatively due to Cu(II) coordination, but Boc protection of the imidazole and removal of oxygen from the reaction mixture provided effective strategies. Pharmacological studies revealed two monosubstituted imidazoles (6h,p) with 4R affinities and >10-fold H 4R/H3R selectivity. Both compounds possess a cycloalkylmethyl group and appear to target a lipophilic pocket in H 4R with high steric precision. The use of the [1,2,3]triazole scaffold is further demonstrated by the notion that simple changes in spacer length or peripheral groups can reverse the selectivity toward H3R. Computational evidence is provided to account for two key selectivity switches and to pinpoint a lipophilic pocket as an important handle for H4R over H3R selectivity.
- Wijtmans, Maikel,De Graaf, Chris,De Kloe, Gerdien,Istyastono, Enade P.,Smit, Judith,Lim, Herman,Boonnak, Ratchanok,Nijmeijer, Saskia,Smits, Rogier A.,Jongejan, Aldo,Zuiderveld, Obbe,De Esch, Iwan J. P.,Leurs, Rob
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p. 1693 - 1703
(2011/05/05)
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- INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
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The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras
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- Novel 1,2,4-oxadiazoles as potent and selective histamine H3 receptor antagonists
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Replacement of the isothiourea moiety of known histamine H3 antagonists by certain 5-membered heteroaromatic systems can give compounds with an improved activity profile. One of these, 3-[(4-chlorophenyl)methyl]-5-[2-(1H-imidazol-4-yl)ethyl] 1,2,4-oxadiazole (GR175737) is a potent, selective, orally active and centally penetrating H3 antagonist.
- Clitherow,Beswick,Irving,Scopes,Barnes,Clapham,Brown,Evans,Hayes
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p. 833 - 838
(2007/10/03)
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- A novel series of (phenoxyalkyl)imidazoles as potent H3-receptor histamine antagonists
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[[(4-Nitrophenyl)X]alkyl]imidazole isosteres (where X = NH, S, CH2S, O) of previously described [[(5-nitropyrid-2-yl)X]ethyl]imidazoles (where X = NH, S) have been synthesized and evaluated for H3-receptor histamine antagonism in vitro (K(i) for [3H]histamine release from rat cerebral cortex synaptosomes) and in vivo (ED50 per os in mice on brain tele- methylhistamine levels). Encouraging results led to the synthesis and testing of a novel series of substituted (phenoxyethyl)- and (phenoxypropyl)imidazoles. From the latter, 4-[3-(4-cyanophenoxy)propyl]-1H- imidazole (10a, UCL 1390; K(i) = 12 nM, ED50 = 0.54 mg/kg) and 4-[3-[4- (trifluoromethyl)-phenoxy]propyl]-1H-imidazole (10c, UCL 1409; K(i) = 14 nM, ED50 = 0.60 mg/kg) have been selected as potential candidates for drug development. For 16 [(aryloxy)ethyl]imidazoles the relationship between in vitro and in vivo potency is described by the equation log ED50 = 0.47 log K(i) + 0.20 (r = 0.78).
- Ganellin, C. Robin,Fkyerat, Abdellatif,Bang-Andersen, Benny,Athmani, Salah,Tertiuk, Wasyl,Garbarg, Monique,Ligneau, Xavier,Schwartz, Jean-Charles
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p. 3806 - 3813
(2007/10/03)
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- Bifunctional Chelating Agents. Part 2. Synthesis of 1-(2-Carboxyethyl)ethylenediaminetetra-acetic Acid by Ring Cleavage of a Substituted Imidazole
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The synthesis of 1-(2-carboxyethyl)ethylenediaminetetra-acetic acid, a new bifunctional analogue of ethylenediaminetetra-acetic acid (EDTA) is described.This is carried out via ring-opening benzoylation of ethyl imidazol-4-ylpropanoate, hydrogenation and hydrolysis to 4,5-diaminovaleric acid (DL-γ-ornithine) dihydrochloride, and subsequent alkylation.
- Altman, Janina,Shoef, Nurit,Wilchek, Meir,Warshawsky, Abraham
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