550346-46-8Relevant articles and documents
Polyheterocyclic substituted pyrimidines or pyridylamine derivatives Composition and medical application thereof
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Paragraph 0318-0320, (2021/09/26)
The invention discloses a polycyclic substituted pyrimidine or pyridine amine derivative, and the structure is shown in a formula (I). The invention further discloses a pharmaceutically acceptable salt of the derivative, a solvate, a stereoisomer, a prodrug, a pharmaceutical composition and and an application thereof in medicine. The compounds of the present invention have significant adenosine A. 2A Receptor and/or adenosine A2B The receptor antagonism activity is very practical.
MACROCYCLIC FUSED PYRRAZOLES AS MCL-1 INHIBITORS
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Paragraph 0905, (2020/08/13)
Provided are compounds represented by Formula IA: (IA), and the pharmaceutically acceptable salts and solvates thereof, wherein R, R 1a, R 1b, L 1, L 2, L 3, X, A, B and C are as defined as set forth
MACROCYCLIC INDOLES AS MCL-1 INHIBITORS
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Paragraph 1320-1321, (2020/06/10)
Disclosed is compound of formula I and the pharmaceutically acceptable salts and solvates thereof, wherein R, R1a, R1b, R1h, L1, L2, L3, ?, ?, ? are as defined as set forth in the specification. Disclosed is compound of formula I for use to treat a condition or disorder responsive to Mcl-1 inhibition such as cancer.
Big ring indole used as MCL-1 inhibitor
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Paragraph 1759; 1762-1764, (2020/03/12)
The invention provides a compound represented by a formula (I) and a pharmaceutical salt and solvate thereof. In the formula (I), the definitions of R, R1a, R1b, R1h, L1, L2, and L3 are shown in the description. The invention also provides a compound represented by the formula (I), and the compound can be used to treat disease or disorder related with MCL-1 inhibition, such as cancers.
ETHANEDIAMINE-HETEROCYCLE DERIVATIVES AS INHIBITORS OF PROTEIN ARGININE METHYLTRANSFERASES
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Paragraph 0750, (2019/09/15)
The present invention relates to ethanediamine-heterocycle compounds that are able to act as inhibitors of PRMTs (protein arginine methyltransferases) for treating cancer and other diseases mediated by PRMTs.
Synthesis and aqueous chemistry of α-acetoxy-N-nitrosomorpholine: Reactive intermediates and products
Zink, Charles N.,Kim, Hyun-Joong,Fishbein, James C.
, p. 202 - 209 (2007/10/03)
α-Acetoxy-N-nitrosomorpholine (7) has been synthesized starting by the anodic oxidation of N-acetylmorpholine in methanol. The 55% yield of N-nitrosomorpholinic acid, after cyanide-for-methoxy group exchange and hydrolysis, is an improvement of ～10-fold over our original 10-step method, and this is readily converted to 7. A study of the kinetics of decomposition of 7 in aqueous media at 25 °C and 1 M ionic strength was conducted over the pH range from 1 to 12. The reaction exhibited good first-order kinetics at all values of pH, and a plot of the log of k0, the buffer-independent rate constant for decomposition, against pH indicated that a pH-independent reaction dominates in the neutral pH region whereas acid- and base-catalyzed reactions dominate in the low and high pH regions, respectively. Reaction at neutral pH in the presence of increasing concentrations of acetate ion results in a decrease in the value of kobsd, to an apparent limiting value consistent with a common-ion inhibition by the capture, and competing base-catalyzed hydration of, an N-nitrosiminium ion intermediate The 100-fold smaller reactivity of 7 at neutral pH compared with its carbon analogue, α-acetoxy-N-nitrosopiperidine, is also consistent with the electronic effects expected for such a reaction. The dinitrophenylhydrazones derived from pH-independent and acid-catalyzed reactions are identical in kind and quantity, within experimental error, to those observed in the decay of α-hydroxy-N-nitrosomorpholine. Decay of 7 in the presence of benzimidazole buffer results in the formation of 2-(2-(1H-benzo[d]imidazol-1-yl)ethoxy) acetaldehyde (12) and 2-(1H-benzo[d]imidazol-1-yl)ethanol (13). Independent synthesis and study of 12 indicates that it is stable at 80 °C in 0.1 M DCl, but it slowly decomposes to 13 in neutral and basic media in a reaction that is stimulated by primary and secondary amines, but not by tertiary amines and carbonate buffer. The benzimidazole trapping studies and those of the stability of 12 indicate the possibility that metabolic activation of N-nitrosomorpholine by hydroxylation α to the nitroso nitrogen can result in the deposition of a metastable ethoxyacetaldehyde adduct on the heteroatoms of DNA.
Structure-activity relationship of 6-methylidene penems bearing 6,5 bicyclic heterocycles as broad-spectrum β-lactamase inhibitors: Evidence for 1,4-thiazepine intermediates with C7 R stereochemistry by computational methods
Venkatesan, Aranapakam M.,Agarwal, Atul,Abe, Takao,Ushirogochi, Hideki,Yamamura, Itsuka,Ado, Mihira,Tsuyoshi, Takasaki,Dos Santos, Osvaldo,Gu, Yansong,Sum, Fuk-Wah,Li, Zhong,Francisco, Gerry,Lin, Yang-I.,Petersen, Peter J.,Yang, Youjun,Kumagai, Toshio,Weiss, William J.,Shlaes, David M.,Knox, James R.,Mansour, Tarek S.
, p. 4623 - 4637 (2007/10/03)
The design and synthesis of a series of 6-methylidene penems containing [6,5]-fused bicycles (thiophene, imidazole, or pyrazle-fused system) as novel class A, B, and C β-lactamase inhibitors is described. These penems proved to be potent inhibitors of the TEM-1 (class A) and AmpC (class C) β-lactamases and less so against the class B metallo-β-lactamase CcrA. Their in vitro and in vivo activities in combination with piperacillin are discussed. On the basis of the crystallographic structures of a serine-bound reaction intermediate of 2 with SHV-1 (class A) and GC1 (class C) enzymes, compounds 14a-1 were designed and synthesized. Penems are proposed to form a seven-membered 1,4 thiazepine ring in both class A and C β-lactamases. The interaction energy calculation for the enzyme-bound intermediates favor the formation of the C7 R enantiomer over the S enantiomer of the 1,4-thiazepine in both β-lactamases, which is consistent with those obtained from the crystal structure of 2 with SHV-1 and GC1.
Bicyclic 6-alkylidene-penems as class-D beta-lactamases inhibitors
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Page/Page column 41, (2010/11/25)
This invention relates to certain bicyclic 6-alkylidene penems which act as a inhibitor of class-D enzymes. β-Lactamases hydrolyze β-lactam antibiotics, and as such serve as the primary cause of bacterial resistance. The compounds of the present invention when combined with β-lactam antibiotics will provide an effective treatment against life threatening bacterial infections. In accordance with the present invention there are provided compounds of general formula I or a pharmaceutically acceptable salt or in vivo hydrolyzable ester R5 thereof: wherein: One of A and B denotes hydrogen and the other an optionally substituted fused bicyclic heteroaryl group; and X═O or S.
Process for preparing 6-alkylidene penem derivatives
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, (2008/06/13)
The present invention provides a process of making compounds of formula I, which are useful for the treatment of bacterial infection or disease.
BICYCLIC 6-ALKYLIDENE-PENEMS AS ?-LACTAMASES INHIBITORS
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Page/Page column 134-135, (2008/06/13)
The present invention provides a compound of Formula (I), pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof.
