- 6-Fluorophenylbenzohydrazides inhibit Mycobacterium tuberculosis growth through alteration of tryptophan biosynthesis
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A major constraint in reducing tuberculosis epidemic is the emergence of strains resistant to one or more of clinically approved antibiotics, which emphasizes the need of novel drugs with novel targets. Genetic knockout strains of Mycobacterium tuberculosis (Mtb) have established that tryptophan (Trp) biosynthesis is essential for the bacterium to survive in vivo and cause disease in animal models. An anthranilate-like compound, 6-FABA, was previously shown to synergize with the host immune response to Mtb infection in vivo. Herein, we present a class of anthranilate-like compounds endowed with good antimycobacterial activity and low cytotoxicity. We show how replacing the carboxylic moiety with a hydrazide led to a significant improvement in both activity and cytotoxicity relative to the parent compound 6-FABA. Several new benzohydrazides (compounds 20–31, 33, 34, 36, 38 and 39) showed good activities against Mtb (0.625 ≤ MIC≤6.25 μM) and demonstrated no detectable cytotoxicity against Vero cell assay (CC50 ≥ 1360 μM). The target preliminary studies confirmed the hypothesis that this new class of compounds inhibits Trp biosynthesis. Taken together, these findings indicate that fluorophenylbenzohydrazides represent good candidates to be assessed for drug discovery.
- Arora, Kriti,Biava, Mariangela,Boshoff, Helena I.,Consalvi, Sara,De Logu, Alessandro,Ioerger, Thomas R.,Poce, Giovanna,Rubin, Eric J.,Venditti, Giulia,Zhu, Junhao
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- 1,2,4-OXADIAZOLE SUBSTITUTED PIPERIDINE AND PIPERAZINE DERIVATIVES AS SMO ANTAGONISTS
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The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts, stereoisomers or tautomers thereof which are inhibitors of the Sonic Hedgehog pathway, in particular Smo antagonists. Thus the compounds of this invention are useful for the treatment of diseases associated with abnormal hedgehog pathway activation, including cancer, for example basal cell carcinoma, medulloblastoma, prostate, pancreatic, breast, colon, bone and small cell lung cancers, and cancers of the upper GI tract.
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Page/Page column 62
(2010/04/03)
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- A highly selective tandem cross-coupling of gem-dihaloolefins for a modular, efficient synthesis of highly functionalized indoles
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(Chemical Equation Presented) A highly efficient method of indole synthesis using gem-dihalovinylaniline substrates and an organoboron reagent was developed via a Pd-catalyzed tandem intramolecular amination and an intermolecular Suzuki coupling. Aryl, alkenyl, and alkyl boron reagents are all successfully employed, making for a versatile modular approach. The reaction tolerates a variety of substitution patterns on the aniline leading to indoles with group at C2-C7. The orthogonal approach of the sequential copper- and palladium-mediated synthesis of 1,2-diarylindoles exploited the wide availability of diverse organoboron reagents.
- Fang, Yuan-Qing,Lautens, Mark
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p. 538 - 549
(2008/09/17)
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- Heterocyclyl-substituted dihydroquinazolines and their use as antiviral agents
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The invention relates to heterocyclyl-substituted dihydroquinazolines of formula (I), to processes for their preparation, to medicaments containing them, and to methods for the treatment and/or prophylaxis of diseases, in particular, for use as anti-viral agents, in particular, against cytomegaloviruses.
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- Substituted Dihydroquinazolines II
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The invention relates to substituted dihydroquinazolines and to a method for the production thereof, the use thereof for treating and/or preventing diseases and for producing drugs for treating and/or preventing diseases, in particular for the use of the inventive dihydroquinazolines in the form of antiviral agents, in particular against cytomegaloviruses.
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- SUBSTITUTED DIHYDROQUINAZOLINES II
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The invention relates to substituted dihydroquinazolines and to a method for the production thereof, the use thereof for treating and/or preventing diseases and for producing drugs for treating and/or preventing diseases, in particular for the use of the inventive dihydroquinazolines in the form of antiviral agents, in particular against cytomegaloviruses.
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Page/Page column 23
(2008/06/13)
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- SUBSTITUTED DIHYDROCHINAZOLINES HAVING ANTIVIRAL PROPERTIES
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The invention relates to substituted dihydrochinazolines of formula (I), methods for the production thereof, and the use thereof for producing medicaments used for treating and/or preventing diseases, particularly as antiviral agents, especially against cytomegaloviruses.
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Page/Page column 26
(2008/06/13)
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- HETEROCYCLYL-SUBSTITUTED DIHYDROQUINAZOLINES AND USE THEREOF AS AN ANTIVIRAL AGENT
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The invention relates to heterocyclyl-substituted dihydroquinazolines of formula (I), methods for the production and use thereof for the production of medicaments for the treatment and/or prophylaxis of diseases, in particular, for use as anti-viral agents, in particular, against cytomegaloviruses.
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Page/Page column 27-28
(2010/02/09)
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- Benzothiadiazinyl-indole derivatives and their use as serotonin receptor ligands
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Compounds having the formula: in which n is 1 or 2, m is 1 or 2, p is 1 to 6, q is 0 or 1 to 3, R1and R2are each hydrogen or C1-4alkyl, R3, R4and R5are each hydrogen, C1-4alkyl, optionally substituted phenyl or optionally substituted phenyl-C1-4alkyl, or R3and R4together form an alkylene link of formula -(CH2)3- or -(CH2)4-, or R4and R5together with the carbon atom to which they are attached form a C3-6cycloalkyl group, R6is C1-4alkyl, C1-4alkoxy, carboxy, hydroxy, cyano, halo, trifluoromethyl, nitro or amino, the dotted line represents an optional double bond, and the fluorine atom is attached at the 6 or 7-position; and salts and esters thereof, are binding to the 5-HT serotonin receptor and are useful in the treatment of CNS disorders.
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- 1H-2,1,3-benzothiadiazine-2,2-dioxide compounds or derivatives thereof
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A pharmaceutical compound having the formula: STR1 in which n is 1 or 2, m is 1 or 2, p is 1 to 6, q is 0 or 1 to 3, R1 and R2 are each hydrogen or C1-4 alkyl, R3, R4 and R5 are each hydrogen, C1-4 alkyl, optionally substituted phenyl or optionally substituted phenyl-C1-4 alkyl, or R3 and R4 together form an alkylene link of formula --(CH2)3 -- or --(CH2)4 --, or R4 and R5 together with the carbon atom to which they are attached form a C3-6 cycloalkyl group, R6 is C1-4 alkyl, C1-4 alkoxy, carboxy, hydroxy, cyano, halo, trifluoromethyl, nitro or amino, the dotted line represents an optional double bond, and the fluorine atom is attached at the 6 or 7-position; and salts and esters thereof.
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