- Mycobacterium tuberculosis arylamine N-acetyltransferase acetylates and thus inactivates para-aminosalicylic acid
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Mycobacterium tuberculosis arylamine N-acetyltransferase (TBNAT) is able to acetylate para-aminosalicylic acid (PAS) both in vitro and in vivo as determined by high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS) techniques. The antituberculosis activity of the acetylated PAS is significantly reduced. As a result, overexpression of TBNAT in M. tuberculosis results in PAS resistance, as determined by MIC tests and drug exposure experiments. Taken together, our results suggest that TBNAT from M. tuberculosis is able to inactivate PAS by acetylating the compound.
- Wang, Xude,Yang, Shanshan,Gu, Jing,Deng, Jiaoyu
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Read Online
- A tautomeric ligand enables directed C-H hydroxylation with molecular oxygen
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Hydroxylation of aryl carbon-hydrogen bonds with transition metal catalysts has proven challenging when oxygen is used as the oxidant. Here, we report a palladium complex bearing a bidentate pyridine/ pyridone ligand that efficiently catalyzes this reaction at ring positions adjacent to carboxylic acids. Infrared, x-ray, and computational analysis support a possible role of ligand tautomerization from monoanionic (L,X) to neutral (L,L) coordination in the catalytic cycle of aerobic carbon-hydrogen hydroxylation reaction. The conventional site selectivity dictated by heterocycles is overturned by this catalyst, thus allowing late-stage modification of compounds of pharmaceutical interest at previously inaccessible sites.
- Li, Zhen,Wang, Zhen,Chekshin, Nikita,Qian, Shaoqun,Qiao, Jennifer X.,Cheng, Peter T.,Yeung, Kap-Sun,Ewing, William R.,Yu, Jin-Quan
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p. 1452 - 1457
(2021/06/30)
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- Aminobenzoic acid derivative and preparation method and application thereof
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The invention relates to an aminobenzoic acid derivative and a preparation method and application thereof, and belongs to the field of medicinal chemistry, and the structural formula of the aminobenzoic acid derivative is shown in the specification, R is alkyl, substituted phenyl, heteroaromatic ring group or substituted styryl; R is alkyl; R is alkyl, substituted phenyl or benzyl; R is alkyl; R is guanidyl; and R is alkyl. The preparation method is simple and high in yield. Most compounds of the invention have good influenza virus neuraminidase inhibition activity.
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Paragraph 0030-0031
(2020/12/30)
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- Design, synthesis, and pharmacological evaluation of fluorinated azoles as anti-tubercular agents
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Design, synthesis, and biological screening of 2,2-dimethyl-2,3-dihydrobenzofuran tethered 1,3,4-oxadiazole derivatives as anti-tubercular agents were described. The synthesis of the target compounds was conducted by a series of reaction schemes. All the synthesized compounds were characterized by IR, 1H NMR, 13C NMR, and mass spectrometry. The therapeutic potential of the synthesized compounds was confirmed by molecular docking studies. Among the synthesized compounds, 12a, 12c, 12d, 12e, 12g, and 12j were found to be more active against non-replicating than against replicating cultures of Mycobacterium tuberculosis H37Ra ex vivo and in vitro. These compounds exhibit minimum inhibitory concentration (MIC) values in the range of 2.31–23.91 μg/mL. The cytotoxicity study was conducted against the cell lines THP-1, A549 and PANC-1, and the compounds were observed to be non-toxic to host cells. Molecular docking was conducted with InhA (FabI/ENR) and suggested the antimycobacterial potential of the synthesized compounds. The investigation presented here was found to be adventitious for the development of new therapeutic agents against Mycobacterium infection.
- Gholap, Somnath,Tambe, Macchindra,Nawale, Laxman,Sarkar, Dhiman,Sangshetti, Jaiprakash,Damale, Manoj
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- Citric acid mosapride intermediate product and application
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The invention belongs to the field of medical chemistry synthesis, and provides a preparation method of citric acid mosapride intermediate product IV 4-[(4-fluorophenyl)methyl]-2-morpholinemethanaminesalt and citric acid mosapride. The 2-(4-fluorobenzoamido)ethanol and 1H-Isoindole-1,3(2H)-dione,2-(2-oxiranylmethyl) are taken as raw materials, and the intermediate product IV 4-[(4-fluorophenyl)methyl]-2-morpholinemethanamine salt is obtained after acid treating is conducted; the intermediate product IV and an intermediate V 2-oxethyl-4-acetamido-5-Chlorobenzoic acid ethyl ester compounds aretaken as raw materials, dichloromethane is taken as a solvent, and EDCI and DMAP are taken as catalysts to prepare mosapride salt; the mosapride salt is reacted with citric acid aqueous solution to prepare citric acid mosapride. The intermediate product has the advantages that products are high in yield, raw materials are easy to obtain, the production cost is low, and the intermediate product issuitable for industrialized production.
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Paragraph 0053; 0054; 0055
(2018/09/08)
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- Discovery of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as potent and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-1
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This letter describes the synthesis and biological evaluation of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as novel mPGES-1 inhibitors, capable of inhibiting an increased PGE2 production in the disease state. Structure-activity optimization afforded many potent mPGES-1 inhibitors having 50 of 14.3 mg/kg in guinea pig.
- Muthukaman, Nagarajan,Tambe, Macchindra,Deshmukh, Sanjay,Pisal, Dnyandeo,Tondlekar, Shital,Shaikh, Mahamadhanif,Sarode, Neelam,Kattige, Vidya G.,Pisat, Monali,Sawant, Pooja,Honnegowda, Srinivasa,Karande, Vikas,Kulkarni, Abhay,Behera, Dayanidhi,Jadhav, Satyawan B.,Sangana, Ramchandra R.,Gudi, Girish S.,Khairatkar-Joshi, Neelima,Gharat, Laxmikant A.
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p. 5131 - 5138
(2017/11/20)
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- Benzoic acid derivatives with trypanocidal activity: Enzymatic analysis and molecular docking studies toward trans-sialidase
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Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (14, 18, and 19) sharing a para-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC50) was 0.15 μM on the NINOA strain, and LC50 0.22 μM on the INC-5 strain. Additionally, compound 18 showed a moderate inhibition (47%) on the trans-sialidase enzyme and a binding model similar to DANA (pattern A).
- Kashif, Muhammad,Moreno-Herrera, Antonio,Villalobos-Rocha, Juan Carlos,Nogueda-Torres, Benjamín,Pérez-Villanueva, Jaime,Rodríguez-Villar, Karen,Medina-Franco, José Luis,De Andrade, Peterson,Carvalho, Ivone,Rivera, Gildardo
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- Detection of Sulfatase Enzyme Activity with a CatalyCEST MRI Contrast Agent
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A chemical exchange saturation transfer (CEST) MRI contrast agent has been developed that detects sulfatase enzyme activity. The agent produces a CEST signal at δ=5.0 ppm before enzyme activity, and a second CEST signal appears at δ=9.0 ppm after the enzyme cleaves a sulfate group from the agent. The comparison of the two signals improved detection of sulfatase activity.
- Sinharay, Sanhita,Fernández-Cuervo, Gabriela,Acfalle, Jasmine P.,Pagel, Mark D.
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p. 6491 - 6495
(2016/05/02)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds of Formula IIa: and compositions thereof, and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Paragraph 0235; 0337; 0338
(2014/05/20)
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- Tuning the solubility of hepta(p-benzamide)s via the monomer sequence
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The automated synthesis of hepta(p-benzamide) heterosequences on solid support using a modified peptide synthesizer is reported. The oligomers are synthesized from 4-aminobenzoic acid and 4-amino-2-(hexyloxy)benzoic acid, the latter carrying a solubilizing hexyl side chain. It is known from previous studies that both the unsubstituted hepta(p-benzamide) and the fully hexyloxy-substituted hepta(p-benzamide) are insoluble in all common organic solvents. Heterosequences in which both types of monomers alternate are, however, soluble in polar organic solvents such as DMSO. The heterosequence heptamers behave as strong organogelators when DMSO solutions are left at room temperature for several hours. Transmission electron microscopic (TEM) investigations revealed that the gelation was due to the oligomers forming long entangled fibers via a non-covalent aggregation mechanism. We explain these phenomena by a heterosequence triggered switch of aggregation mechanism. The unsubstituted oligomers strongly aggregate via a directional hydrogen-bond driven mechanism which changes to a less directional π-interaction driven aggregation mechanism for the substituted oligomers. We hereby demonstrate that designed heterosequences in non-natural oligoamides can lead to materials with distinctly different conformations which directly affect the intermolecular interactions and their supramolecular organization.
- Seyler, Helga,Kilbinger, Andreas
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supporting information
p. 753 - 756
(2013/03/13)
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- 4,5-Diamino-3-Halo-2-Hydroxybenzoic Acid Derivatives and Preparations Thereof
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Disclosed are 4,5-diamino-3-halo-2-hydroxybenzoic acid derivatives and manufactures thereof. The 4,5-diamino-3-halo-2-hydroxybenzoic acid derivatives are presented by formula (I): wherein R1 group is H, CH3, or C2H5; R2 group is H, or Br; R3 group is CH3, or C3H7; and R4 group is H, or C(═NH)—NH2. 4,5-diamino-3-halo-2-hydroxybenzoic acid derivatives provided here were non-toxic to MDCK cells, particularly compounds 6a, 6b, 6c, 6e, 6f, 7a, 7b and 8 had better anti-H1N1 activity. In the future, these compounds can be used to focus on viral neuraminidases as targets to develop effective anti-influenza drugs.
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Page/Page column 9
(2012/05/04)
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- PD(II)-CATALYZED HYDROXYLATION OF ARENES WITH O2 OR AIR
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Pd (II) -catalyzed ortho-hydroxylat ion of variously substituted aromatic carboxylic acids under O2 or air is achieved under non-acidic conditions. Extensive labeling studies support a direct oxygenation of aryl C-H bonds with molecular oxygen.
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Page/Page column 14
(2011/04/24)
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- Pd(II)-catalyzed hydroxylation of arenes with 1 atm of O2 or air
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(Chemical Equation Presented) Pd(II)-catalyzed ortho-hydroxylation of variously substituted benzoic acids under 1 atm of O2 or air is achieved under nonacidic conditions. Extensive labeling studies support a direct oxygenation of aryl C-H bonds with molecular oxygen.
- Zhang, Yang-Hui,Yu, Jin-Quan
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supporting information; experimental part
p. 14654 - 14655
(2010/01/06)
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- COMPLEX COMPOUNDS OF BORIC ACID, SALICYLIC ACID OR ITS DERIVATIVES AND SILVER, METHOD OF THEIR PREPARATION, AND A PREPARATION CONTAINING THESE COMPOUNDS FOR KILLING MOULDS, FUNGI AND LIGNIPERDOUS INSECTS
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Object of the invention are complex compounds of boric acid, salicylic acid or its derivatives and silver, having general formula (I), wherein X = H, NH2, NHC(=O)R, wherein the group R is H, or generally C1 to C8 alkyl, and a method of their preparation, consisting in preparing a solution of boric acid (one molar unit) and salicylic acid (two molar units) or its derivative in a polar solvent, the concentration of salicylic acid or its derivative in the solution being in the range of 0.2-50% wt., and the solution is prepared at the temperature in the range of from 0 °C to the boiling point of the polar solvent used; into this solution of boric acid and salicylic acid or its derivative in the polar solvent is added one molar unit of silver nitrate with stirring, the resulting solution is cooled to the temperature of 0-25 °C, and the formed white precipitate of the complex compound is then collected by filtration and dried at the temperature of 25-80 °C. The object of this invention is also a preparation containing these complex compounds for killing moulds, fungi and ligniperdous insects.
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Page/Page column 10-11
(2008/12/05)
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- Inotropic activity of heterocyclic analogues of isomazole
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Aryl-substituted benzimidazole, imidazopyridine, imidazopyrazine, imidazopyridazine, oxazolopyridine, purine, pyrollopyridine and thiazolopyridine derivatives have been prepared and evaluated as inotropic agents.Purine 8 and the 1H-imidazo- and pyridazines 9 and 10 proved to be of most interest, having similar in vivo inotropic potencies to sulmazole.The pKa's, protonation sites and lipophilicities for most heterocycles were determined experimentally and some of their electronic properties calculated.For a subset of active heterocycles a correlation was observed between in vitro inotropism and the charge density of the imidazo nitrogen adjacent to the electrostatic potential minimum.Structure-activity relationships are discussed in some detail.
- Barraclough, P.,Beams, R. M.,Black, J. W.,Cambridge, D.,Collard, D.,et al.
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p. 467 - 477
(2007/10/02)
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- Benzoic acid derivatives and use thereof
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A pharmaceutical composition for use in the treatment of psoriasis comprises 4-aminosalicylic acid (4-ASA) or 5-aminosalicylic acid (5-ASA) or a functional derivative thereof, said pharmaceutical composition being in a form suitable for topical administration. Furthermore, 4- or 5-ASA or a functional derivative thereof are used for the manufacture of pharmaceutical compositions for treating psoriasis, atopic dermatitis, allergic dermatitis, contact dermatitis, seborrhoic dermatitis, or acne diseases. The derivatives have the formulae: STR1 where W is COOX, wherein X is H, Li, Na, K, Mg0.5, Ca0.5, Zn0.5, Al0.33, Fe(II)0.5, Fe(III)0.33, NH4, NH3 R1, NH2 R12, NHR13, NR14, or R1, where R1 is substituted or unsubstituted C1-6 -alkyl, aryl-C1-4 -alkyl, or heteroaryl-C1-4 -alkyl; or COX, where X is NR1 R1', where R1' has the same meaning as R1 defined above and R1 and R1' may be identical or different; Y is H or R1 CO, where R1 is defined as above; Z1 and Z2, which may be identical or non-identical are H, R1 or R1 CO, where R1 is defined as above, or Z1 and Z2 represent R2, where R2 is substituted or unsubstituted C1-6 -alkylidene or aryl-C1-6 -alkylidene, or heteroaryl-C1-6 -alkylidene, or Z1, Z2 together with the nitrogen atom to which they are attached may represent a 3 to 7 membered saturated or unsaturated heterocyclic ring, or may represent a group of the formula --N=N--R3 where R3 is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.
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- Aromatic amides of heterocyclic compounds and therapeutic compositions containing same
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The invention relates to aromatic amides N-substituted by heterocyclic groups. More particularly, the invention relates to substituted benzoic acid amides of 1-arylalkylamino or aminoalkyl-N-heterocyclic rings and to pharmaceutical compositions thereof, which have the ability to antagonize the effects of dopamine or dopaminergic agents of endogenous or exogenous origin and which may be used for the treatment of nausea and vomiting resulting from gastrointestinal disorders, congestive heart failure, post operative conditions, etc., other gastrointestinal disorders such as dyspepsia, flatulence, bile regurgitations, hiatus hernia, peptic ulcer, reflux aerophagitis, gastritis, duodenitis, and cholethiasis, and a variety of conditions affecting the central nervous system such as acute and chronic psychoses, maniacal psychosis, schizophrenias, serious disturbances of behavior and non-melancholic depressive state and migraine.
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