68527-67-3Relevant articles and documents
Metal-Binding Pharmacophore Library Yields the Discovery of a Glyoxalase 1 Inhibitor
Perez, Christian,Barkley-Levenson, Amanda M.,Dick, Benjamin L.,Glatt, Peter F.,Martinez, Yadira,Siegel, Dionicio,Momper, Jeremiah D.,Palmer, Abraham A.,Cohen, Seth M.
supporting information, p. 1609 - 1625 (2019/02/14)
Anxiety and depression are common, highly comorbid psychiatric diseases that account for a large proportion of worldwide medical disability. Glyoxalase 1 (GLO1) has been identified as a possible target for the treatment of anxiety and depression. GLO1 is a Zn2+-dependent enzyme that isomerizes a hemithioacetal, formed from glutathione and methylglyoxal, to a lactic acid thioester. To develop active inhibitors of GLO1, fragment-based drug discovery was used to identify fragments that could serve as core scaffolds for lead development. After screening a focused library of metal-binding pharmacophores, 8-(methylsulfonylamino)quinoline (8-MSQ) was identified as a hit. Through computational modeling and synthetic elaboration, a potent GLO1 inhibitor was developed with a novel sulfonamide core pharmacophore. A lead compound was demonstrated to penetrate the blood-brain barrier, elevate levels of methylglyoxal in the brain, and reduce depression-like behavior in mice. These findings provide the basis for GLO1 inhibitors to treat depression and related psychiatric illnesses.
Visible Light-Promoted Photocatalytic C-5 Carboxylation of 8-Aminoquinoline Amides and Sulfonamides via a Single Electron Transfer Pathway
Sen, Chiranjit,Sahoo, Tapan,Singh, Harshvardhan,Suresh, Eringathodi,Ghosh, Subhash Chandra
, p. 9869 - 9896 (2019/08/20)
An efficient photocatalytic method was developed for the remote C5-H bond carboxylation of 8-aminoquinoline amide and sulfonamide derivatives. This methodology uses in situ generated ?CBr3 radical as a carboxylation agent with alcohol and is further extended to a variety of arenes and heteroarenes to synthesize the desired carboxylated product in moderate-to-good yields. The reaction proceeding through a single electron transfer pathway was established by a control experiment, and a butylated hydroxytoluene-trapped aryl radical cation intermediate in high-resolution mass spectrometry was identified.
Influence of Functionalized Substituents on the Electron-Transfer Abilities of Copper Guanidinoquinoline Complexes
Stanek, Julia,Konrad, Marc,Mannsperger, Johannes,Hoffmann, Alexander,Herres-Pawlis, Sonja
, p. 4997 - 5006 (2018/12/11)
The influence of functionalized ligands on the electron-transfer abilities of copper guanidinoquinoline complexes as entatic state models has been examined. An electron donating group (OCH3) or electron withdrawing group (Br) was introduced in 6-position of the quinoline unit of the ligands TMGqu and DMEGqu. The electron self-exchange rates k11 of the copper complexes with these ligands were determined using the Marcus cross relation. The k11 values of the functionalized complexes are smaller or equal to the values of their unsubstituted forms. These results were complemented by the examination of the reorganization energies of the electron-transfer via Eyring theory and DFT calculations. The higher reorganization energies of the [Cu(DMEG6Xqu)2]+/2+ (X = H, Br, OCH3) systems correspond with their decelerated electron-transfer velocities. Additionally, the calculated molecular electrostatic potentials show the influence of the functional groups on the electron-transfer. With the addition of the substituent a further charge distribution over the CH3O-/Br-group leads to a larger reorganization required during the oxidation reaction. The impact of the functionalization of the ligand on the electron-transfer of the [Cu(GUA6Xqu)2]+/2+ cations reveals a closer insight in the electronic structure of the complexes and its influence on their electron-transfer abilities.
Synthesis and in vitro evaluation of novel 8-aminoquinoline-pyrazolopyrimidine hybrids as potent antimalarial agents
Kannan, Murugan,Raichurkar, Anandkumar V.,Khan, Fazlur Rahman Nawaz,Iyer, Pravin S.
supporting information, p. 1100 - 1103 (2015/02/19)
In the search of novel chemotherapeutic agents for emerging drug resistant parasites, the hybridization approaches have successfully emerged as an efficient tool in malarial chemotherapy. Herein, a rational design and synthesis of novel 8-aminoquinoline and pyrazolopyrimidine hybrids and their antimalarial activity against wild type Plasmodium falciparum (Pf-NF54) and resistant strain (Pf-K1) is reported. The medicinal chemistry approach to expand the scope of this series resulted in an identification of potent compounds with nanomolar potency (best IC50 5-10 nM). Systematic structure activity relationship (SAR) studies revealed that pyrazolopyrimidine and 8-aminoquinoline ring are essential for achieving good P. falciparum potency. The docking study revealed that the compound 6 can retain some of the critical interactions within pfDHODH drug target.
ARYLPIPERAZINYL-CYCLOHEXYL INDOLE DERIVATIVES FOR THE TREATMENT OF DEPRESSION
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Page 45-46, (2010/02/07)
Compounds are provided which are useful for the treatment of serotonin-affected neurological disorders which comprise (I) wherein: Ra, R1, R2 and R3 are each, independently, hydrogen, or a substituent selected from halogen, CF3, alkyl, alkoxy, MeSO2, amino or aminocarbonyl (each optionally substituted by one or two groups selected from alkyl and benzyl) carboxy, or alkoxycarbonyl; or two adjacent of Ra and R1-4 together can form a 5-7 membered carbocyclic or heterocyclic ring which is optionally substituted by a substituent defined above; R4 is hydrogen, halogen, or alkyl; R5 is hydrogen, alkyl, arylalkyl, or aryl; R6 is hydrogen, halogen, CF3, CN, carbamide, alkoxy or benzyloxy; X1, X2 and X3 are each carbon or one of X1, X2 or X3 may be nitrogen; Y is CH or nitrogen; and Z is carbon or nitrogen; or pharmaceutically acceptable salts thereof.
Preparation and Fungitoxicity of 3,6-Dichloro- and 3,6-Dibromo-8-Quinolinols
Gershon, H.,Clarke, D. D.,Gershon, M.
, p. 723 - 730 (2007/10/02)
3,6-Dichloro- and 3,6-dibromo-8-quinolinols were prepared by direct halogenation of 8-nitroquinoline by N-halosuccinimide in acetic acid or by halogenation of the corresponding 6-halo-8-nitroquinoline prepared via a Skraup reaction.The nitro group was reduced to amino and the amine was hydrolyzed to the phenol in 70percent sulfuric acid at 220 deg C.The fungitoxicity of 3,6-dichloro- and 3,6-dibromo-8-quinolinols, as well as intermediates in their preparation, against Aspergillus niger, Aspergillus oryzae, Myrothecium verrucaria, Trichoderma viride, and Mucor cirinelloides was determined. 3,6-dichloro-8-quinolinol is the most fungitoxic analogue of this class of compounds observed to date. - Keywords. 3,6-dichloro-8-nitroquinoline; 3,6-dibromo-8-nitroquinoline; 8-amino-3,6-dichloroquinoline; 8-amino-3,6-dibromoquinoline; 3,6-dichloro-8-quinolinol; 3,6-dibromo-8-quinolinol; 1H NMR spectra.
