3364-37-2Relevant articles and documents
Novel bisubstrate analog inhibitors of serotonin N-acetyltransferase: The importance of being neutral
Zheng, Weiping,Cole, Philip A.
, p. 398 - 411 (2003)
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.
Electrochemical Synthesis of Bisindolylmethanes from Indoles and Ethers
Du, Ke-Si,Huang, Jing-Mei
, p. 2911 - 2915 (2018)
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.
ALKYLATED TETRAHYDROISOQUINOLINES FOR BINDING TO CENTRAL NERVOUS SYSTEM RECEPTORS
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Paragraph 0012; 0145, (2018/07/31)
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.
Design and synthesis of dual 5-HT1Aand 5-HT7receptor ligands
Ofori, Edward,Zhu, Xue Y.,Etukala, Jagan R.,Peprah, Kwakye,Jordan, Kamanski R.,Adkins, Adia A.,Bricker, Barbara A.,Kang, Hye J.,Huang, Xi-Ping,Roth, Bryan L.,Ablordeppey, Seth Y.
, p. 3464 - 3471 (2016/07/21)
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.
