219544-69-1Relevant academic research and scientific papers
Synthesis and pharmacological evaluation of (indol-3-yl)alkylamides as potent analgesic agents
Fouchard,Marchand,Le Baut,Emig,Nickel
, p. 814 - 824 (2007/10/03)
A series of (indol-3-yl)alkylamides was synthesized and evaluated for analgesic activity. Two N-(pyridin-4-yl)acetamides, compounds 24 and 25, bearing benzyl or 4-fluorobenzyl moieties in 1-position of indole ring exhibited promising analgesic properties (ED50 = 8.1 and 11 mg/kg p.o., respectively), being as potent as the reference drugs flupirtine (CAS 56995-20-1), ibuprofen (CAS 15687-27-1) and diclofenac (CAS 15307-86-5). The two test compounds were tested for their anti-inflammatory activity by carrageenin-induced edema in rat paw test. 4-Fluorobenzyl derivative 25 whose ID50 was 0.085 ± 0.021 mmol/kg was selected as a lead compound for further pharmacomodulation.
New N-(pyridin-4-yl)-(indol-3-yl)acetamides and propanamides as antiallergic agents
Menciu, Cecilia,Duflos, Muriel,Fouchard, Fabienne,Le Baut, Guillaume,Emig, Peter,Achterrath, Ute,Szelenyi, Istvan,Nickel, Bernd,Schmidt, Jürgen,Kutscher, Bernhard,Günther, Eckhardt
, p. 638 - 648 (2007/10/03)
A series of new N-(pyridin-4-yl)-(indol-3-yl)alkylamides 44-84 has been prepared in the search of novel antiallergic compounds. Synthesis of the desired ethyl (2-methyindol-3-yl)acetates 1-4 was achieved by indolization under Fischer conditions; Japp-Klingemann method followed by 2- decarboxylation afforded the ethyl (indol-3-yl)alkanoates 17-25. Amidification was successfully carried out by condensation of the corresponding acids or their N-aryl(methyl) derivatives with 4-aminopyridine promoted by 2-chloro-1-methylpyridinium iodide. Efforts to improve the antiallergic potency of the title series by variation of the indole substituents (R1, R2, R) and the length of the alkanoic chain (n = 1, 2, 3) led to the selection of N-(pyridin-4-yl)-[1-(4-fluorobenzyl)indol-3- yl]acetamide 45, out of 41 compounds. This amide was 406-fold more potent than astemizole in the ovalbumin-induced histamine release assay, using guinea pig peritoneal mast cells, with an IC50 = 0.016 μM. Its inhibitory activity in IL-4 production test from Th-2 cells was identical to that of the reference histamine antagonist (IC50 = 8.0 μM) and twice higher in IL-5 assay: IC50 = 1.5 and 3.3 μM, respectively. In vivo antiallergic activity evaluation confirmed efficiency of 45 in sensitized guinea pig late phase eosinophilia inhibition, after parenteral and oral administration at 5 and 30 mg/kg, respectively. Its efficiency in inhibition of microvascular permeability was assessed in two rhinitis models; ovalbumin and capsaicin- induced rhinorrhea could be prevented after topical application of submicromolar concentrations of 45 (IC50 = 0.25 and 0.30 μM); and it also exerted significant inhibitory effect in the first test after iv and oral administration, with ID50 = 0.005 and 0.46 mg/kg.
(1-Benzylindole-3-yl)alkanoic acids; novel nonsteroidal inhibitors of steroid 5α-reductase (I)
Sawada, Kozo,Hirai, Hideo,Golden, Patrick,Okada, Satoshi,Sawada, Yuki,Hashimoto, Masashi,Tanaka, Hirokazu
, p. 1683 - 1687 (2007/10/03)
A novel series of indole-3-alkanoic acids with varied N-benzyl substituents were synthesized as nonsteroidal inhibitors of steroid 5α- reductase. The structure-activity relationships in this series were studied and the optimum carboxylic acid side chain w
