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| 化学名: | アルカフタジン | | 英語化学名: | ALCAFTADINE | | 别名: | ALCAFTADINE;6,11-Dihydro-11-(1-Methyl-4-piperidinylidene)-5H-iMidazo[2,1-b][3]benzazepine-3-carboxaldehyde;R 89674;12-(1-Methylpiperidin-4-ylidene)-4,6,7,12-tetrahydrobenzo[d]pyriMido[1,2-a]azepine-3-carbaldehyde;5H-IMidazo[2,1-b][3]benzazepine-3-carboxaldehyde,6,11-dihydro-11-(1-Methyl-4-piperidinylidene)-;Alcaftadine, >=99%;Alcaftadine (R89674);Lastacaft | | CAS番号: | 147084-10-4 | | 分子式: | C19H21N3O | | 分子量: | 307.39 | | EINECS: | 1308068-626-2 | | カテゴリ情報: | Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals | | Mol File: | 147084-10-4.mol |  |
| 融点 | 167 °C | | 沸点 | 556.2±60.0 °C(Predicted) | | 比重(密度) | 1.24 | | 貯蔵温度 | Inert atmosphere,Store in freezer, under -20°C | | 溶解性 | DMF: 30 mg/ml; DMSO: 30 mg/ml; Ethanol: 30 mg/ml; Ethanol:PBS(pH 7.2) (1:1): 0.5 mg/ml | | 外見 | powder to crystal | | 酸解離定数(Pka) | 8.76±0.20(Predicted) | | 色 | White to Yellow to Orange |
| | アルカフタジン Usage And Synthesis |
| 外観 | 白色～黄色～黄赤色粉末～結晶 | | 効能 | 抗アレルギー薬, 抗炎症薬, H1受容体拮抗薬 | | 説明 | Alcaftadine, a histamine H1/H2 receptor antagonist, was approved in
the United States in 2010 for the prevention of itching and redness associated
with allergic conjunctivitis. Seasonal and perennial allergic conjunctivitis
affects up to 40% of the population worldwide. There are
numerous treatment options, with topical antihistamines being an effective
therapy. Some of the primary symptoms and signs of allergic conjunctivitis
are ocular itching and conjunctival redness. The pharmaceutical
market for conjunctivitis is substantial and steadily increasing. | | Originator | Janssen Research Foundation (United States) | | 使用 | Alcaftadine is a H1 histamine receptor antagonist. Alcaftadine is used to prevent eye irritation and treat the signs and symptoms of allergic conjunctivitis. | | 定義 | ChEBI: An imidazobenzazepine that is 6,11-dihydro-5H-imidazo[2,1-b][3]benzazepine substituted at position 3 by a formyl group and at position 11 by a 1-methylpiperidin-4-ylidene group. An antihistamine used for treatment of allergi
conjunctivitis. | | brand name | LastacaftTM | | 臨床応用 | Alcaftadine, an ophthalmic histamine H1 receptor antagonist,
was approved by the FDA for the prevention of itching associated
with allergic conjunctivitis and was launched under the trade
name Lastacaft in early 2011. Alcaftadine was discovered by
Janssen Pharmaceuticals and marketed by Vistakon Pharmaceuticals,
both subsidiaries of Johnson & Johnson. However, unlike other marketed drugs, the synthesis of alcaftadine was only mentioned
in the patents filed by Janssen’s scientists approximately twenty
years ago. | | 合成 | The synthetic route described in the scheme is based on
the discovery route disclosed in those patents. 1-(2-Phenylethyl)-
1H-imidazole 7 is now commercially available, otherwise
it could be prepared by reacting imidazole (5) with 2-phenylethyl
bromide (6). With pyridine and triethylamine as base, imidazole
7 was reacted with acyl chloride 8 to provide piperidinecarboxylate
9 in 34% yield, followed by acid hydrolysis with 48% HBr
aqueous solution to obtain piperidine dihydrobromide 10 in 98%
yield. The N-methylation of 10 was acheived by Leuckart reaction
with formaldehyde and formic acid to give 4-methylpiperidine 11
in 82% yield. Treatment of 11 with trifluoromethanesulfonic acid
followed by subsequent basification triggered an intramolecular
alkylation¨Cdehydration reaction to generate benzazepine 12. Next,
alcohol 13 was obtained by prolonged exposure (7 days) of 12 to
hydroxymethylation conditions using 40% aqueous formaldehyde.
Oxidation of 13 with manganese (IV) oxide provided alcaftadine
(II). The yields of last three steps from compound 11 to alcaftadine
(II) were not provided in the patent. 
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