CAS: 6740-86-9; (1-Bromocyclopentyl)(2-Chlorophenyl)Methanone

上下游产品

邻氯苯基环戊基酮 (2-Chlorophenyl)(Cyclopentyl)Methanone 6740-85-8

📜邻氯苯腈置于n-溴代丁二酰亚胺(Nbs),碘,对甲苯磺酸,Magnesium体系中,用 乙醚,二氯甲烷 作为反应溶剂,化学反应 23.0H,反应生成 1-溴环戊基-2-氯苯基甲酮
参考文献:Thecyp2B6*6Allele Significantly Alters Then-Demethylation Of Ketamine Enantiomers In Vitro
标题:Thecyp2B6*6Allele Significantly Alters Then-Demethylation Of Ketamine Enantiomers In Vitro
摘要:氯胺酮主要通过肝脏 Cyp2B6 和 Cyp3A4 介导的 N-去甲基化作用代谢为诺可他明.然而,每种酶的相对贡献仍然存在争议.cyp2B6*6 等位基因与酶的表达和活性降低有关,这可能会导致氯胺酮代谢的个体间差异.我们使用 Cyp2B6*6 等位基因基因分型的人肝微粒体(hlms),昆虫细胞表达的重组 Cyp2B6 和 Cyp3A4 酶以及 Cos-1 细胞表达的重组 Cyp2B6.1 和 Cyp2B6.6 蛋白变体研究了氯胺酮对映体的 N-去甲基化.在 Hlms 中还测定了 Cyp 选择性抑制剂对诺可他明形成的影响.双酶 Michaelis-Menten 模型最符合 Hlm 动力学数据.高亲和力酶和低亲和力酶的迈克尔斯-门顿常数(k M)分别与表达的 Cyp2B6 和 Cyp3A4 相似.在具有 Cyp2B6*1/\*1 基因型的 Hlms 中,高亲和力酶对两种氯胺酮对映体的内在清除率分别比 Cyp2B6*1/\*6 基因型和 Cyp2B6*6/\*6 基因型高至少 2 倍和 6 倍.cyp2B6.1 的最大 V 值和 K M 值分别约为 Cyp2B6.6 的 160% 和 70%.在临床相关浓度下,N,N'n'-三乙烯硫代磷酰胺(thiotepa)(cyp2B6 抑制剂,25 μ M)和 Cyp2B6 单克隆抗体可抑制氯胺酮 N-去甲基化,但曲安奈德霉素(cyp3A4 抑制剂,25 μ M)或 Cyp3A4 单克隆抗体不能抑制氯胺酮 N-去甲基化.具有 Cyp2B6*6 等位基因的 Hlms 的抑制程度明显降低(基因剂量 P < 0.05).这些结果表明,Cyp2B6 在体外氯胺酮 N-去甲基化过程中起着重要作用,Cyp2B6*6 等位基因对酶与氯胺酮的结合和催化活性有重大影响.
DOI:10.1124/dmd.113.051631

专利信息

专利号:US-11718578-B2
优先权日:2017-12-29
标 题:Ketamine flow synthesis
发明人：TOUPY THOMAS; GERARDY ROMARIC; MONBALIU JEAN-CHRISTOPHE; COLLIN DIEGO; KASSIN VICTOR-EMMANUEL
权利人:UNIV LIEGE
摘要:The invention provides a method for synthesizing a compound of formulawherein each R independently represents an optionally substituted aryl, heteroaryl, alkyl, perfluoroalkyl, cycloalkyl, alkoxy, aryloxy, acyl, carboxyl, hydroxyl, halogen, amino, nitro, cyano, sulfo or sulfhydryl group, in ortho, meta or para position to the cycloalkylamine moiety; R1 and R2 each independently represents a hydrogen atom, a lower alkyl group or a cycloalkyl group; R3 represents a hydrogen group, substituted aryl, heteroaryl, alkyl, perfluoroalkyl, cycloalkyl, alkoxy, aryloxy group; Y represents an oxygen atom, a sulfur atom, a NH group, a NR4 group or a CH2 group;R4 represents a hydrogen atom or an alkyl, aryl or a heteroaryl group; and n and m each independently represents an integer from 1 to 5; or a pharmaceutically acceptable salt thereof; or a precursor thereof; wherein the method comprises one or more of the following steps: (a) reacting a compound of formula (II)wherein R, R3, Y, n and m are as defined above in relation to the compound of formula (I) with an oxygenating agent, a first additive and a second additive in a solvent in a fluidic network or in a batch process under thermal and/or photochemical conditions to form a compound of formula (III):wherein R, R3, Y, n and m are as defined above in relation to the compound of formula (I), (b) reacting a compound of formula (III) with a nitrogen containing nucleophile in the presence of a third additive and/or a solvent in the fluidic network or in a batch process under thermal conditions to form a compound of formula (IV):wherein R, R1, R2, R3, Y, n and m are as defined above in relation to the compound of formula (I); and/or(c) reacting a compound of formula (IV) in a fluidic network or in a batch process, optionally in the presence of a fourth additive, under thermal conditions to form a compound of formula (I); wherein one or more of steps (a), (b) and/or (c) is carried out in a fluidic network that comprises micro- and/or meso-channels having an internal dimension of from 100 μm to 2000 μm.

专利号:US-11186539-B2
优先权日:2018-06-04
标题:Process for synthesis and purification of (2R,6R)-hydroxynorketamine
发明人：THOMAS CRAIG J; MORRIS PATRICK JOSEPH; CASTLEDINE RICHARD ANDREW; BOURNE SAMUEL LAWRENCE
权利人:US HEALTH
摘要:A process for the preparation of (2R,6R)-hydroxynorketamine is provided. The process requires no chromatography purification and affords the (2R,6R)-hydroxynorketamine in eight steps with a 26% overall yield and greater than 97% purity.

专利号:WO-2019236557-A1
优先权日:2018-06-04
标 题:Process for synthesis and purification of (2r,6r)-hydroxynorketamine

专利号:JP-2021527038-A
优先权日:2018-06-04
标 题 :Process for the synthesis and purification of (2R, 6R) -hydroxynorketamine

专利号:US-2021246099-A1
优先权日:2018-06-04
标 题 :Process for synthesis and purification of (2r,6r)-hydroxynorketamine

专利号:CN-112424157-A
优先权日:2018-06-04
标题 :Method for the synthesis and purification of (2R,6R)-hydroxynorketamine