cas 276863-95-7, 3-(4-chlorobutanoyl)-1H-indole-5-carbonitrile

Articles about 276863-95-7Total 18 be found

Article title
Article abstract
Author
Journal number and time
Download

Design, synthesis and evaluation of vilazodone-tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment
Depression, a severe mental disease, is greatly difficult to treat and easy to induce other neuropsychiatric symptoms, the most frequent one is cognitive impairment. In this study, a series of novel vilazodone-tacrine hybrids were designed, synthesized and evaluated as multitarget agents against depression with cognitive impairment. Most compounds exhibited good multitarget activities and appropriate blood-brain barrier permeability. Specifically, compounds 1d and 2a exhibited excellent 5-HT1A agonist activities (1d, EC50 = 0.36 ± 0.08 nM; 2a, EC50 = 0.58 ± 0.14 nM) and 5-HT reuptake inhibitory activities (1d, IC50 = 20.42 ± 6.60 nM; 2a, IC50 = 22.10 ± 5.80 nM). In addition, they showed moderate ChE inhibitory activities (1d, AChE IC50 = 1.72 ± 0.217 μM, BuChE IC50 = 0.34 ± 0.03 μM; 2a, AChE IC50 = 2.36 ± 0.34 μM, BuChE IC50 = 0.10 ± 0.01 μM). Good multitarget activities with goodt blood-brain barrier permeability of 1d and 2a make them good lead compounds for the further study of depression with cognitive impairment.
Liu, Wenwen,Wang, Huan,Li, Xiaokang,Xu, Yixiang,Zhang, Jian,Wang, Wei,Gong, Qi,Qiu, Xiaoxia,Zhu, Jin,Mao, Fei,Zhang, Haiyan,Li, Jian
supporting information
p. 3117 - 3125
(2018/05/16)

Substituted indole compound and method and use thereof
The invention provides a new indole compound, pharmaceutically acceptable salts and medicinal preparations thereof, and a use of the new indole compound in selective inhibition of 5-hydroxytryptamine reuptake and /or excitation of a 5-HT1A receptor. The invention also relates to medicinal compositions comprising the compounds, and a method for treating the central nervous system dysfunction of mammals, especially humans by using the medicinal compositions.
-
Paragraph 0371; 0373; 0374

(2018/11/03)

Substituted indole compounds, as well as using method and application thereof
The invention relates to substituted indole compounds, a using method and application of the substituted indole compounds, as well as a medicine composition including the compounds and application thereof. The compounds or medicine composition can be used for inhibiting reuptake of 5-hydroxytryptamine. The invention further relates to a method for preparing the compounds and the medicine composition, as well as application of the compounds and medicine composition in treatment of central nervous system dysfunction.
-
Paragraph 0144; 0194; 0195; 0196

(2017/08/02)

Intermediate the vera assists the alkone 5-cyano -3 (4-chlorobutyl)-indole new synthetic process
The invention discloses a new synthetic process of a vilazodone intermediate 5-cyano-3(4-chlorobutyl)-indole. The synthetic process comprises the steps of enabling 5-amino-formyl-indole and 4-chlorobutyryl chloride undergo a 3-bit acylation reaction and a dehydration reaction of an amido bond in the presence of a catalyst to produce 5-bit cyan, then performing a decarbonylation reaction in the presence of a reducing agent to generate a product, and finally refining by the product by use of methanol to obtain high-purity high-content 5-cyano-3(4-chlorobutyl)-indole. The process is concise, simple to operate and applicable to large-scale industrial production.
-
Paragraph 0020; 0021

(2017/02/09)

Preparation method of substituted indoles compounds
The invention belongs to the field of medical technology, and discloses a preparation method of 3-substituted indoles compounds. The preparation method includes using a compound represented by formula (2) as an initial raw material, performing a Friedel-Crafts reaction with 4-chlorobutyryl chloride in the presence of anhydrous titanium tetrachloride catalyst to obtain a compound represented by formula (3), and performing a reaction with paratoluensulfonyl chloride in the presence of an organic solvent and an acid-binding agent to obtain the target compound. The preparation method overcomes the defects of the synthetic method in the prior art, and is suitable for the industrial production. The product has high content, and the purity of the product reaches over 99%.
-
Paragraph 0015; 0016

(2016/10/07)

For the preparation of the compounds and intermediates thereof the vera assists the alkone and application
The invention belongs to the field of medicinal chemistry and relates to a compound for preparing vilazodone as well as an intermediate and an application thereof. The compound for preparing vilazodone is shown as a formula I, and the intermediate for synthesizing the compound of the formula I is shown as a formula II. The compound of the formula I can be applied to preparation of vilazodone and pharmaceutically acceptable salts thereof. The compound of the formula I serving as a novel intermediate is applied in preparation of the vilazodone, the defects in the conventional literature report are overcome, metal catalysts with high toxicity and organic phosphorus ligands thereof are avoided, the preparation cost is greatly reduced, the operation is simplified, and the compound is stable and controllable in quality and suitable for large-scale industrial preparation.
-
Paragraph 0064-0068

(2017/03/24)

SUBSTITUTED PIPERAZINE COMPOUNDS AND METHODS OF USE AND USE THEREOF
The invention relates to substituted piperazine compounds and methods of use and uses thereof, and further to the pharmaceutical compositions comprising the compounds and uses thereof, wherein the compound has Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. The substituted piperazine compounds and pharmaceutical compositions comprising the compounds disclosed herein can be used for inhibiting 5-hydroxytryptamine reuptake and/or stimulating 5-HT1A receptors. The invention also relates to processes for preparing these compounds and pharmaceutical compositions, and their uses in the treatment of a central nervous system dysfunction.
-
Page/Page column 49

(2016/12/22)

SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE THEREOF
Provided herein are novel heteroaryl compounds, pharmaceutically acceptable salts and pharmaceutical formulations thereof for selectively inhibiting serotonin reuptake and/or acting as 5-HT1A receptor agonists. Also provided herein are pharmaceutical compositions comprising the heteroaryl compounds and methods of using the pharmaceutical compositions in treating central nervous system (CNS) dysfunction in a mammal, especially a human being.
-
Paragraph 00203

(2015/02/25)

SUBSTITUTED PIPERAZINE COMPOUNDS AND METHODS AND USE THEREOF
Provided herein are novel piperazine compounds acting as selective serotonin reuptake inhibitors and/or the 5-HT1A receptor agonists. The invention also relates to the methods of preparing the compound and pharmaceutical composition, and the use of treating central nervous system dysfunction in mammals especially in humans.
-
Paragraph 00232

(2015/11/27)

PROCESS FOR THE PREPARATION OF VILAZODONE HYDROCHLORIDE AND ITS AMORPHOUS FORM
The present invention relates to an improved process for the preparation of vilazodone Hydrochloride and a process for preparation of novel pure amorphous form of vilazodone hydrochloride.
-
Paragraph 0093

(2015/03/31)

CRYSTALLINE FORMS OF VILAZODONE HYDROCHLORIDE AND VILAZODONE FREE BASE
Provided are crystalline and amorphous vilazodone hydrochloride. Further provided are amorphous solid dispersions of vilazodone hydrochloride with pharmaceutically acceptable carries. Also provided is a process for the preparation of form I of vilazodone free base.
-
Paragraph 0505; 0506; 0507

(2015/05/13)

IMPROVED PROCESS FOR PREPARING BENZOFURAN-2-CARBOXAMIDE DERIVATIVES
Provided herein are novel, commercially viable and industrially advantageous processes for the preparation of benzofuran-2-carboxamide derivatives and their intermediates, or a pharmaceutically acceptable salt thereof, in high yield and purity. Provided particularly herein are novel, commercially viable and industrially advantageous processes for the preparation of vilazodone or a pharmaceutically acceptable salt thereof in high yield and purity. Provided also herein is an improved and commercially viable process for the preparation of 3-(4-hydroxybutyl)-1H-indole-5-carbonitrile, in high yield and purity, using novel intermediate compound 3-(4-hydroxybutyryl)-1H-indole-5-carbonitrile.
-
Page/Page column 40; 41

(2014/01/18)

PROCESS FOR PREPARING VILAZODONE HYDROCHLORIDE
The present invention relates, in a first aspect, to a process preparing vilazodone hydrochloride that comprises the reaction of 3-(4-chloro-1-hydroxy-butyl)-1H-indol-5-carbonitrile with 5-piperazin-1-yl-benzofuran-2-carboxylate methyl hydrochloride with the formation of a 1,4-piperazine, with subsequent dehydration, hydrogenation and treatment with ammonia, to obtain vilazodone in free base form that is then converted into the hydrochloride thereof.
-
Paragraph 0075; 0076

(2013/09/12)

Process for preparing vilazodone hydrochloride
The present invention relates, in a first aspect, to a process preparing vilazodone hydrochloride that comprises the reaction of 3-(4-chloro-1-hydroxy-butyl)-1H-indol-5-carbonitrile with 5-piperazin-1-yl-benzofuran-2-carboxylate methyl hydrochloride with the formation of a 1,4 -piperazine, with subsequent dehydration, hydrogenation and treatment with ammonia, to obtain vilazodone in free base form that is then converted into the hydrochloride thereof.
-
Paragraph 0055; 0056; 0057

(2013/10/22)

CRYSTALLINE FORMS OF VILAZODONE HYDROCHLORIDE AND VILAZODONE FREE BASE
Provided are crystalline and amorphous vilazodone hydrochloride. Further provided are amorphous solid dispersions of vilazodone hydrochloride with pharmaceutically acceptable carries. Also provided is a process for the preparation of form I of vilazodone free base.
-
Page/Page column 78; 79

(2013/12/03)

Scale-up synthesis of antidepressant drug vilazodone
A scale-up synthesis of antidepressant drug vilazodone was accomplished in five steps. Friedel-Crafts acylation of 1-tosyl-1H-indole-5-carbonitrile with 4-chlorobutyryl chloride, selective deoxygenation in NaBH4/CF 3COOH system coupled with ethyl 5-(piperazin-1-yl)-benzofuran-2- carboxylate hydrochloride, one-step deprotection and esterolysis, and the final ammonolysis led to the target molecule vilazodone in 52.4% overall yield and 99.7% purity. This convenient and economical procedure is remarkably applicable for scale-up production.
Hu, Bin,Song, Qiao,Xu, Yungen
p. 1552 - 1557
(2013/02/25)

Allosteric IGF-1R inhibitors
Targeting allosteric protein sites is a promising approach to interfere selectively with cellular signaling cascades. We have discovered a novel class of allosteric insulin-like growth factor-I receptor (IGF-1R) inhibitors. 3-Cyano-1H-indole-7-carboxylic acid {1-[4-(5-cyano-1H-indol-3-yl)butyl] piperidin-4-yl}amide (10) was found with nanomolar biochemical, micromolar, cellular IGF-1R activity and no relevant interference with cellular insulin receptor signaling up to 30 ?M. The allosteric binding site was characterized by X-ray crystallographic studies, and the structural information was used to explain the unique mode of action of this new class of inhibitors.
Heinrich, Timo,Graedler, Ulrich,Boettcher, Henning,Blaukat, Andree,Shutes, Adam
scheme or table
p. 199 - 203
(2010/12/18)

Synthesis and structure-activity relationship in a class of indolebutylpiperazines as dual 5-HT1A receptor agonists and serotonin reuptake inhibitors
Systematic structural modifications of indolealkylphenylpiperazines led to improved selectivity and affinity within this class of 5-HT1A receptor agonists. Introduction of electron-withdrawing groups in position 5 on the indole raises serotonin transporter affinity, and the cyano group proved to be the best substituent here. 5-Fluoro and 5-cyano substituted indoles show comparable results in in vitro and in vivo tests, and bioisosterism between these substituents was supported by calculation of the molecular electrostatic potentials and dipole moments. Compounds showing promising in vitro data were further examined in ex vivo (p-chloroamphetamine assay) and in vivo (ultrasonic vocalization) tests. Optimization of the arylpiperazine moiety indicated that the 5-benzofuranyl-2-carboxamide was best suited to increase 5-HT transporter and 5-HT1A receptor affinity and to suppress D2 receptor binding. 5-{4-[4-(5-Cyano-3-indolyl)butyl]-1-piperazinyl}benzofuran-2- carboxamide 29 (vilazodone, EMD 68843) was identified as a highly selective 5-HT1A receptor agonist [GTPγS, ED50 = 1.1 nM] with subnanomolar 5-HT1A affinity [IC50 = 0.2 nM] and as a subnanomolar 5-HT reuptake inhibitor [RUI = 0.5 nM] showing a great selectivity to other GPCRs (e.g., D2, IC50 = 666 nM).
Heinrich, Timo,B?ttcher, Henning,Gericke, Rolf,Bartoszyk, Gerd D.,Anzali, Soheila,Seyfried, Christoph A.,Greiner, Hartmut E.,Van Amsterdam, Christoph
p. 4684 - 4692
(2007/10/03)