3364-37-2

Upstream product

• 15591-70-5 methyl 4-(1H-indol-3-yl)butanoate 
• 34067-76-0 6-hydroxyhexanal 
• 100-63-0 phenylhydrazine 
• 5299-60-5 6-hydroxy-hexanoic acid ethyl ester 
• 27983-42-2 5-carboethoxypentanal 
• 502-44-3 hexahydro-2H-oxepin-2-one 
• 1022576-81-3 ethyl 4-[4-(1H-indol-3-yl)butanoyl]piperazine-1-carboxylate 
• 31529-29-0 4-(2-carboxy-indol-3-yl)-butyric acid 
• 63183-76-6 4-(2-ethoxycarbonyl-indol-3-yl)-butyric acid ethyl ester 
• 120-72-9 indole 
• 835-45-0 4-(1H-indol-3-yl)-4-oxobutanoic acid 
• 133-32-4 4-indol-3-yl-butyric acid 
• 49850-32-0 ethyl 4-(1H-indol-3-yl) butanoate 
• 1655-07-8 ethyl 2-oxocyclohexane carboxylate 

Downstream Products

• 21903-93-5 4-(1H-indol-3-yl)butyl 4-methylbenzenesulfonate 
• 147372-95-0 4-<1-(4-fluorophenyl)-1H-indol-3-yl>-1-butanol 
• 163631-03-6 4-(1-benzyl-1H-indol-3-yl)-1-butanol 
• 65610-87-9 1,2-bis(1H-indol-3-yl)ethane-1,2-dione 
• 1374326-95-0 Methyl 4-formyl-1-(3-(hydroxymethyl)benzyl)-5-iodo-1H-pyrrole-2-carboxylate 
• 1004546-72-8 4-(2-(4-butyl-4-(dimethylamino)cyclohexyl)-1H-indol-3-yl)butyl acetate 

Relevant academic research and scientific papers

Novel bisubstrate analog inhibitors of serotonin N-acetyltransferase: The importance of being neutral

Linker modified novel bisubstrate analog inhibitors 4-7 for serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) have been designed and synthesized. Examination of these inhibitors with AANAT in vitro suggested that: (i) linker hydrogen bonding makes only modest contributions to the affinity of bisubstrate analog inhibitors studied; (ii) greater than or equal to four methylene groups between the indole and the coenzyme A (CoASH) moieties are required for a bisubstrate analog inhibitor to achieve strong AANAT inhibition; (iii) the AANAT active site appears not to accommodate positively charged linkers as well as neutral ones; and (iv) substrate amine pKa depression may constitute one strategy for AANAT substrate recognition and catalysis. The results reported here have enhanced our understanding of AANAT substrate recognition/catalysis, and are important for novel inhibitor design. Since AANAT belongs to the GCN5-related N-acetyltransferase (GNAT) superfamily, our experimental strategies should find applications for other acetyltransferases.

Multisubstrate adducts as potential inhibitors of S-adenosylmethionine dependent methylases: inhibition of indole N-methyltransferase by (5'-deoxyadenosyl)[3-(3-indolyl)prop-1-yl]methylsulfonium and (5'-deoxyadenosyl)[4-(3-indolyl)but-1-yl]methylsulfonium salts.

Multisubstrate adducts of the indole N-methyltransferase reaction have been designed in which a structural moiety representing the nucleophilic methyl acceptor is attached through the sulfur atom to the 5-(methylthio)adenosine and/or methionine moieties of the methyl donor, S-adenosyl-L-methionine. Indole derivatives attached through a 4-(3-indolyl)butyl sulfide or a 3-(3-indolyl)propyl sulfide linkage to 5'-thioadenosine or homocysteine have been synthesized, together with their corresponding methylsulfonium salts. These compounds have been assayed for their ability to inhibit rabbit lung indole N-methyltransferase. The adenosylsulfonium salts (5'-deoxyadenosyl)[4-(3-indolyl)but-1-yl]methylsulfonium perchlorate and (5'-deoxyadenosyl)[3-(3-indolyl)prop-1-yl]-methylsulfonium perchlorate were found to be inhibitors of this enzyme with Ki's of 12 and 44 microM, respectively. Neither of these compounds was effective in inhibiting the methylation of 3,4-dihydroxybenzoic acid, catalyzed by purified porcine catechol O-methyltransferase.

Electrochemical Synthesis of Bisindolylmethanes from Indoles and Ethers

An electrochemical bisindolylation of ethers was developed. Carried out under ambient conditions and in the absence of any chemical oxidants, this reaction exhibits a broad substrate scope and good functional group compatibility.

Practical and Scalable Manufacturing Process for a Novel Dual-Acting Serotonergic Antidepressant Vilazodone

Vilazodone combines the effects of a selective serotonin reuptake inhibitor with the 5-HT1A receptor partial agonist activity. Here, we report the development of a viable and scalable process for manufacturing vilazodone that features a convergent synthetic approach, with low cost and high purity. The key indole synthesis was improved to first make up the hydrazone intermediate and then modify a pendant hydroxy group to realize a much increased overall yield. This process was successfully used to prepare >2 kg of vilazodone hydrochloride with a total yield of 56.2% and purity of 99.93%.

ALKYLATED TETRAHYDROISOQUINOLINES FOR BINDING TO CENTRAL NERVOUS SYSTEM RECEPTORS

Derivatives of 1,2,3,4-tetrahydroisoquinoline (THIQ) having the general formula A-(CH2)n—B are provided, wherein A is THIQ or a substituted derivative thereof and B is an aryl, cycloalkylaryl, or cycloalkyl group, wherein A and B are linked to each other by an alkyl or substituted alkyl chain. The compounds are useful as selective ligands (agonists or antagonists) of central nervous system receptors, and in particular of the seratonin receptors. The compounds or their salts can be formulated into pharmaceutical in need thereof by any route of administration suitable for a desired treatment protocol and especially for the treatment of psychiatric disorders.

Development of CNS multi-receptor ligands: Modification of known D2pharmacophores

Several known D2pharmacophores have been explored as templates for identifying ligands with multiple binding affinities at dopamine and serotonin receptors considered as clinically relevant receptors in the treatment of neuropsychiatric disease

Design and synthesis of dual 5-HT1Aand 5-HT7receptor ligands

5-HT1Aand 5-HT7receptors have been at the center of discussions recently due in part to their major role in the etiology of major central nervous system diseases such as depression, sleep disorders, and schizophrenia. As part of our search to identify dual targeting ligands for these receptors, we have carried out a systematic modification of a selective 5HT7receptor ligand culminating in the identification of several dual 5-HT1Aand 5-HT7receptor ligands. Compound 16, a butyrophenone derivative of tetrahydroisoquinoline (THIQ), was identified as the most potent agent with low nanomolar binding affinities to both receptors. Interestingly, compound 16 also displayed moderate affinity to other clinically relevant dopamine receptors. Thus, it is anticipated that compound 16 may serve as a lead for further exploitation in our quest to identify new ligands with the potential to treat diseases of CNS origin.

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.

CuCl2/TBHP-mediated direct chlorooxidation of indoles

CuCl2/TBHP-mediated direct chlorooxidation of indole derivatives under simple aerobic conditions was reported, leading to facile preparations of a range of 3,3-disubstituted 3-chlorooxindoles in good yields and selectivities.

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.