98051-90-2Relevant academic research and scientific papers
Synthesis and biological properties of amino acid amide ligand-based pyridinioalkanoyl thioesters as anti-HIV agents
Song, Yongsheng,Goel, Atul,Basrur, Venkatesha,Roberts, Paula E.A,Mikovits, Judy A,Inman, John K,Turpin, Jim A,Rice, William G,Appella, Ettore
, p. 1263 - 1273 (2007/10/03)
Hyper-mutable retroviruses such as HIV can become rapidly resistant to drugs used to treat infection. Strategies for coping with drug-resistant strains of virus include combination therapies, using viral protease and reverse transcriptase inhibitors. Another approach is the development of antiviral agents that attack mutationally nonpermissive targets that have functions essential for viral replication. Thus, the highly conserved nucleocapsid protein, NCp7, was chosen as a prime target in our search for novel anti-HIV agents that can overcome the problem of viral drug resistance. Recently, we reported (J. Med. Chem. 1999, 42, 67) a novel chemotype, the pyridinioalkanoyl thioesters (PATEs), based on 2-mercaptobenzamides as the thiol component and having its amide nitrogen substituted with various phenylsulfonyl moieties. These compounds were identified as relatively nontoxic anti-HIV agents in the XTT cytoprotection assay. In this study, we wish to report a separate genre of active PATEs wherein the thiol component consists of an N-2-mercaptobenzoyl-amino acid derivative. Active derivatives (EC50 10 μM) reported herein were confined to amino acid primary amides or methyl amides having side chains no larger than isobutyl. Amino acids terminating in free carboxyl or carboxylic acid ester groups were mostly inactive. Selected compounds were shown to be active on chronically infected CEM/SK-1, TNFα-induced U1, ACH-2 cells and virucidal on cell-free virus, latently infected U1 cells and acutely infected primary peripheral blood mononuclear cells (PBMCs).
A new class of anti-HIV-1 agents targeted toward the nucleocapsid protein NCp7: The 2,2'-dithiobisbenzamides
Domagala, John M.,Bader, John P.,Gogliotti, Rocco D.,Sanchez, Joseph P.,Stier, Michael A.,Song, Yuntao,Vara Prasad,Tummino, Peter J.,Scholten, Jeffrey,Harvey, Patricia,Holler, Tod,Gracheck, Steve,Hupe, Donald,Rice, William G.,Schultz, Robert
, p. 569 - 579 (2007/10/03)
As part of the National Cancer Institute's Drug Screening Program, a new class of antiretrovirals active against the human immunodeficiency virus HIV-1 has been identified, and the HIV-1 nucleocapsid protein NCp7 was proposed as the target of antiviral action. The 2,2'-dithiobis-[4'-(sulfamoyl)benzanilide] (3x) and the 2,2'-dithiobis(5-acetylamino)benzamide (10) represented the prototypic lead structures. A wide variety of 2,2'-dithiobisbenzamides were prepared and tested for anti-HIV-1 activity, cytotoxicity, and their ability to extrude zinc from the zinc fingers for NCp7. The structure-activity relationships demonstrated that the ability to extrude zinc from NCp7 resided in the 2,2'-dithiobisbenzamide core structure. The 3,3' and the 4,4' isomers were inactive. While many analogs based upon the core structure retained the zinc extrusion activity, the best overall anti-HIV-1 activity was only found in a narrow set of derivatives possessing carboxylic acid, carboxamide, or phenylsulfonamide functional groups. These functional groups were more important for reducing cytotoxicity than improving antiviral potency or activity vs NCp7. All of the compounds with antiviral activity also extruded zinc from NCp7. From this study several classes of low μM anti-HIV agents with simple chemical structures were identified as possible chemotherapeutic agents for the treatment of AIDS.
Aminomethylamide derivatives of (3-oxo-1,2-benzisothiazolin-2-yl)acetic acid and 3-(3-oxo-1,2-benzisothiazolin-2-yl)propionic acid
Slawik, Tomasz
, p. 777 - 780 (2007/10/02)
In the search for pharmacological active new derivatives of 1,2-benzisothiazolin-3-one amides of (3-oxo-1,2-benzisothiazolin-2-yl)acetic acid and 3-(3-oxo-1,2-benzisothiazolin-2-yl)propionic acid were obtained.In reaction of these amides with formaldehyde and various secondary amines the title compounds are formed.Morpholinmethylamide of (3-oxo-1,2-benzisothiazolin-2-yl)acetic acid showed activity against Trichomonas vaginalis.In the reaction of ethyl esters of (3-oxo-1,2-benzisothiazolin-2-yl)acetic- and -propionic acids with hydrazine hydrate products of ring-opening of isothiazole-2,2'-dithio-bis and 2,2'-dithio-bisN-(ethoxycarbonylethyl)benzamide are formed.
Synthesis and Antibacterial Activity of 2,2'-Dithiobis(benzamide) Derivatives against Mycobacterium Species
Okachi, Ryo,Niino, Hideki,Kitaura, Kozo,Mineura, Kazuyuki,Nakamizo, Yoshinobu,et al.
, p. 1772 - 1779 (2007/10/02)
A series of compounds, which are analogues of 2,2'-dithiobis(benzamide), were synthesized and tested for in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv including resistant strains against streptomycin, kanamycin, or isonicotinic acid hydrazide.MICs of these compounds against a typical mycobacteria, Mycobacterium kansasii and Mycobacteruim intracellulare were also examined.Structure-activity relationships were found in a series of (acyloxy)alkyl ester derivatives depending upon the length of alkyl carbon chain.The MIC of the most potent compound , 2,2'-dithiobisbenzamide> was superior or at least equivalent to streptomycin, kanamycin, and ethanbutol.All the compounds showed no cross-resistance between the current antitubercular agents.
