210350-62-2Relevant academic research and scientific papers
Synthesis and antibacterial activity of 3-benzylamide derivatives as FtsZ inhibitors
Hu, Zhongping,Zhang, Shasha,Zhou, Weicheng,Ma, Xiang,Xiang, Guangya
supporting information, p. 1854 - 1858 (2017/04/04)
The emergence and spread of multidrug-resistant strains of the human pathological bacteria are generating a threat to public health worldwide. In the current study, a series of PC190723 derivatives was synthesized and investigated for their antimicrobial activity. The compounds exhibited good activity against several Gram-positive bacteria as determined by comparison of diameters of the zone of inhibition of test compounds and standard antibiotics. Compound 9 with a fluorine substitution on the phenyl ring showed the best antibacterial activity in the series against M. smegmatis with the zone ratio of 0.62, and against S. aureus with the zone ratio of 0.44. The results from this study indicate that based on the unique 3-methoxybenzamide pharmacophore, compound 9 may represent a promising lead candidate against Gram-positive bacteria that are worthy of further investigation
A facile approach to the synthesis of 3-(6-Chloro-thiazolo[5,4-b]pyridin-2- ylmethoxy)-2,6-difluoro-benzamide (PC190723)
Ding, Zi-Chun,Zhou, Weicheng,Ma, Xiang
supporting information; experimental part, p. 1039 - 1042 (2012/06/17)
Practical synthesis of PC 190723, a bacterial cell division protein Ftsz inhibitor, has been achieved in a high overall yield of 45% in six steps from commercially available starting materials. Georg Thieme Verlag Stuttgart · New York.
P38 MAP KINASE INHIBITORS
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Page/Page column 54-55, (2010/07/02)
The present disclosure relates to compounds of formula (I): which are inhibitors of p38 mitogen-activated protein kinase enzymes,particularly the alpha and gamma kinase sub-types thereof, and their use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, such as COPD
The regioexhaustive functionalization of difluorophenols and trifluorophenols through organometallic intermediates
Marzi, Elena,Gorecka, Joanna,Schlosser, Manfred
, p. 1609 - 1618 (2007/10/03)
2,4-Difluorophenol, 2,5-difluorophenol, 2,3-difluorophenol, 3,5-difluorophenol, 3,4-difluorophenol, 2,4,5-trifluorophenol and 2,3,4-trifluorophenol were converted into all 18 possible di- or trifluorinated hydroxybenzoic acids (1a-c, 4a-c, 9a-c, 12a,b, 14a-c, 17a,b, 18a,b), all of them new compounds. The phenolic hydrogen atom was replaced by a methoxymethyl or, less frequently, by a triisopropylsilyl group, which exerted an ortho activating or ortho shielding effect, respectively. Sites flanked by two electronegative substituents (fluorine, alkoxy) were deprotonated with particular ease. They had to be silenced by the reversible attachment of a metalation-blocking trimethylsilyl group or of a metalation-deflecting chlorine atom if the metal was to be introduced elsewhere. In all cases but one, the stage was thus set for an intramolecular competition between metalation at an oxygen-adjacent or a fluorine-adjacent site. It proved indeed possible to secure the desired regioflexibility in either way by relying on an appropriate substrate-reagent matching. This demonstrates once more the potential of the organometallic approach to diversity-oriented synthesis.
Covalent modification of cyclooxygenase-2 (COX-2) by 2-acetoxyphenyl alkyl sulfides, a new class of selective COX-2 inactivators
Kalgutkar, Amit S.,Kozak, Kevin R.,Crews, Brenda C.,Hochgesang Jr., G. Phillip,Marnett, Lawrence J.
, p. 4800 - 4818 (2007/10/03)
All of the selective COX-2 inhibitors described to date inhibit the isoform by binding tightly but noncovalently at the substrate binding site. Recently, we reported the first account of selective covalent modification of COX-2 by a novel inactivator, 2-acetoxyphenyl hept-2-ynyl sulfide (70) (Science 1998, 280, 1268-1270). Compound 70 selectively inactivates COX-2 by acetylating the same serine residue that aspirin acetylates. This paper describes the extensive structure-activity relationship (SAR) studies on the initial lead compound 2-acetoxyphenyl methyl sulfide (36) that led to the discovery of 70. Extension of the S-alkyl chain in 36 with higher alkyl homologues led to significant increases in inhibitory potency. The heptyl chain in 2-acetoxyphenyl heptyl sulfide (46) was optimum for COX-2 inhibitory potency, and introduction of a triple bond in the heptyl chain (compound 70) led to further increments in potency and selectivity. The alkynyl analogues were more potent and selective COX-2 inhibitors than the corresponding alkyl homologues. Sulfides were more potent and selective COX-2 inhibitors than the corresponding sulfoxides or sulfones or other heteroatom-containing compounds. In addition to inhibiting purified COX-2, 36, 46, and 70 also inhibited COX-2 activity in murine macrophages. Analogue 36 which displayed moderate potency and selectivity against purified human COX-2 was a potent inhibitor of COX-2 activity in the mouse macrophages. Tryptic digestion and peptide mapping of COX-2 reacted with [1-14C-acetyl]-36 indicated that selective COX-2 inhibition by 36 also resulted in the acetylation of Ser516. That COX-2 inhibition by aspirin resulted from the acetylation of Ser516 was confirmed by tryptic digestion and peptide mapping of COX-2 labeled with [1- 14C-acetyl]salicyclic acid. The efficacy of the sulfides in inhibiting COX- 2 activity in inflammatory cells, our recent results on the selectivity of 70 in attenuating growth of COX-2-expressing colon cancer cells, and its selectivity for inhibition of COX-2 over COX-1 in vivo indicate that this novel class of covalent modifiers may serve as potential therapeutic agents in inflammatory and proliferative disorders.
