161886-22-2Relevant academic research and scientific papers
Pyrazole compound and application thereof
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Paragraph 0230; 0233-0235; 0299; 0301-0303, (2021/03/31)
The invention provides a pyrazole compound and application thereof. The structure of the pyrazole compound is shown in the specification. The pyrazole compound has excellent activity of inhibiting hepatitis B virus, and the pyrazole compound provided by the invention has low cytotoxicity, high safety, good liver selectivity and high bioavailability, and can be used for preventing and/or treating hepatitis B.
Discovery of novel inhibitors of human phosphoglycerate dehydrogenase by activity-directed combinatorial chemical synthesis strategy
Gou, Kun,Luo, Youfu,Luo, Yuan,Sun, Qingxiang,Tan, Yuping,Tao, Lei,Zhao, Yinglan,Zhou, Xia,Zhou, Yue,Zuo, Zeping
, (2021/07/26)
Serine, the source of the one-carbon units essential for de novo purine and deoxythymidine synthesis plays a crucial role in the growth of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) which catalyzes the first, rate-limiting step in de novo serine biosynthesis has become a promising target for the cancer treatment. Here we identified H-G6 as a potential PHGDH inhibitor from the screening of an in-house small molecule library based on the enzymatic assay. We adopted activity-directed combinatorial chemical synthesis strategy to optimize this hit compound. Compound b36 was found to be the noncompetitive and the most promising one with IC50 values of 5.96 ± 0.61 μM against PHGDH. Compound b36 inhibited the proliferation of human breast cancer and ovarian cancer cells, reduced intracellular serine synthesis, damaged DNA synthesis, and induced cell cycle arrest. Collectively, our results suggest that b36 is a novel PHGDH inhibitor, which could be a promising modulator to reprogram the serine synthesis pathway and might be a potential anticancer lead worth further exploration.
Deciphering the robustness of pyrazolo-pyridine carboxylate core structure-based compounds for inhibiting α-synuclein in transgenic C. elegans model of Synucleinopathy
Hoda, Nasimul,Maqbool, Mudasir,Rajvansh, Roshani,Srividya, Kottapalli
, (2020/07/21)
Parkinson's disease (PD), a calamitous neurodegenerative disorder with no cure till date, is closely allied with the misfolding and aggregation of α-Synuclein (α -Syn). Inhibition of α-Syn aggregation is one of the optimistic approaches for the treatment for PD. Here, we carried out hypothesis-driven studies towards synthesising a series of pyrazolo-pyridine carboxylate containing compounds (7a–7m) targeted at reducing deleterious α-Syn aggregation. The target compounds were synthesized through multi-step organic synthesis reactions. From docking studies, compounds 7b, 7g and 7i displayed better interaction with the key residues of α-Syn with values: ?6.8, ?8.9 and ?7.2 Kcal/mol, respectively. In vivo transgenic C. elegans model of Synucleinopathy was used to evaluate the ability of the designed and synthesized compounds to inhibit α-Syn aggregation. These lead compounds 7b, 7g and 7i displayed 1.7, 2.4 and 1.5-fold inhibition of α-Syn with respect to the control. Further, the strategy of employing pyrazolo-pyridine-based compounds worked with success and these scaffolds could be further modified and validated for betterment of endpoints associated with PD.
RENIN INHIBITORS
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Page/Page column 127, (2010/11/17)
The invention relates to compounds having the formula: STR wherein the variables are as defined herein. The invention further relates to methods of making and using these compounds, intermediates which can be used to make the compounds, and pharmaceutical compositions, kits and articles of manufacture which contain the compounds.
Indole-derived arynes and their diels - Alder reactivity with furans
Buszek, Keith R.,Luo, Diheng,Kondrashov, Mikhail,Brown, Neil,VanderVelde, David
, p. 4135 - 4137 (2008/02/13)
Arynes derived from any position of the ubiquitous indole nucleus are unknown. We have now provided the first evidence for the formation and trapping of the 4,5-, 5,6-, and 6,7-indolynes. A series of o-dihalo indoles (CI, Br, F) were synthesized and reacted under metal-halogen exchange conditions to give Diels-Alder cycloadducts in high yield with furan. The use of an excess of fert-butyllithium resulted in the rearrangement of the initially formed cycloadduct; however, employing only a slight excess of n-butyllithium cleanly gave cycloadducts with furan.
An efficient multikilogram synthesis of ABT-963: A selective COX-2 inhibitor
Kerdesky, Francis A. J.,Leanna, M. Robert,Zhang, Ji,Li, Wenke,Lallaman, John E.,Ji, Jianguo,Morton, Howard E.
, p. 512 - 517 (2012/12/22)
An efficient chemical process for the multikilogram synthesis of ABT-963 (3) is described. The potent and selective COX-2 inhibitor was prepared in four steps in 36% overall isolated yield from commercially available 3,4-difluoroaniline (4). The chemistry, which required no chromatography, involved a facile one-pot synthesis of the pyridazinone core, a selective alkoxylation, a high yielding Suzuki coupling, and a very efficient oxidation.
Indole derivatives process for their preparation, pharmaceutical compositions containing them and their medicinal application
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Page/Page column 16, (2010/02/05)
A chemical compound of formula (I) wherein: R1and R2are independently selected from hydrogen and alkyl; R3is alkyl; R4, R6and R7are independently selected from hydrogen, halogen, hydroxy, alkyl, aryl, amino, alkylamino, dialkylamino, alkoxy, aryloxy, alkylthio, alkylsufoxyl, alkylsulfonyl, nitro, carbonitrile, carbo-alkoxy, carbo-aryloxy and carboxyl; R5is selected from hydrogen, halogen, hydroxy, alkyl, aryl, amino, alkylamino, dialkylamino, alkoxy, aryloxy, alkylthio, alkylsulfoxyl, alkylsulfonyl, nitro, carbonitrile, carbo-alkoxy, carbo-aryloxy and carboxyl; A is a 5- or 6-membered partially unsaturated or aromatic heterocyclic ring or a 5- or 6-membered partially unsaturated carbocyclic ring, wherein if A is a 6-membered partially unsaturated carbocyclic ring then at least one of R4to R7is other than hydrogen, and pharmaceutically acceptable salts, addition compounds and prodrugs thereof, and the use thereof in therapy, particularly as an agonist or antagonist of a 5HT receptor, particularly a 5HT2Creceptor, for instance in the treatment of disorders of the central nervous system; damage to the central nervous system; cardiovascular disorders; gastrointestinial disorders; diabetes insipidus, and sleep apnea, and particularly for the treatment of obesity.
Prostaglandin endoperoxide H synthase biosynthesis inhibitors
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, (2008/06/13)
The present invention describes pyridazinone compounds of formula I which are cyclooxygenase (COX) inhibitors, and in particular, are selective inhibitors of cyclooxygenase-2 (COX-2). COX-2 is the inducible isoform associated with inflammation, as opposed to the constitutive isoform, cyclooxygenase-1 (COX-1) which is an important “housekeeping” enzyme in many tissues, including the gastrointestinal (GI) tract and the kidneys. The selectivity of these compounds for COX-2 minimizes the unwanted GI and renal side-effects seen with currently marketed non-steroidal anti-inflammatory drugs (NSAIDs).
