4241-27-4Relevant articles and documents
Synthesis and in–vitro anti–HIV–1 evaluation of novel pyrazolo[4,3–c]pyridin–4–one derivatives
Kumar, Sanjay,Gupta, Shiv,Abadi, Leila Fotooh,Gaikwad, Shraddha,Desai, Dipen,Bhutani, Kamlesh Kumar,Kulkarni, Smita,Singh, Inder Pal
, (2019)
In our continuing efforts to find novel anti–HIV compounds, we have synthesized sixteen novel pyrazolo[4,3–c]pyridin–4–one derivatives. All the synthesized compounds were screened for anti–HIV activity against HIV–1VB59 (R5, subtype C). Compounds 12a–12c and 12e were also tested against HIV–1UG070 (X4, subtype D) in TZM–bl cell line. Compound 12c was found to be the most active against HIV–1VB59 and HIV–1UG070 with IC50 value 3.67 μM and 2.79 μM, and therapeutic indices 185 and 243, respectively. The lead compound 12c inhibited the HIV-192/BR/018 (R5, subtype B) and drug resistant isolates, NIH-119 (X4/R5, subtype B) and NARI-DR (R5, subtype C) effectively. The activity of the lead compound was further confirmed by PBMC assays. The molecular docking data showed that the most active compound 12c binds in the non-nucleoside binding pocket of HIV-1 reverse transcriptase, which was confirmed by the ToA assay. Thus the study indicated that 12c may be considered as a NNRTI and further explored as a lead for anti-HIV drug development.
Design, synthesis and biological activities of pyrrole-3-carboxamide derivatives as EZH2 (enhancer of zeste homologue 2) inhibitors and anticancer agents
Zhou, Qifan,Jia, Lina,Du, Fangyu,Dong, Xiaoyu,Sun, Wanyu,Wang, Lihui,Chen, Guoliang
supporting information, p. 2247 - 2255 (2020/02/20)
Zeste enhancer homolog 2 (EZH2) is highly expressed in various malignant tumors, which could silence tumor suppressor genes via trimethylation of H3K27. Herein was first reported a novel series of pyrrole-3-carboxamide derivatives carrying a pyridone fragment as EZH2 inhibitors. By combining computational modeling, in vitro cellular assays and further rational structure-activity relationship exploration and optimization, compound DM-01 showed powerful inhibition towards EZH2. DM-01 was found to have significant ability to reduce the cellular H3K27me3 level in K562 cells in the Western blot test. Meanwhile, our data showed that knockdown EZH2 in A549 cells resulted in a decrease of cell sensitivity to DM-01 at 50 and 100 μM. DM-01 could also increase the transcription expression of DIRAS3 in a dose-dependent manner, a tumor suppressor in the downstream of EZH2, suggesting it was worth investigating further as a lead compound.
Design, Synthesis and In Vitro Evaluation of Novel Anti-HIV 3-Pyrazol-3- yl-Pyridin-2-One Analogs
Abadi, Leila F.,Bhutani, Late K. K.,Gaikwad, Shraddha,Gupta, Shiv,Kulkarni, Smita,Kumar, Sanjay,Singh, Inder P.
, p. 561 - 570 (2019/07/12)
Background: Natural products have shown potent anti-HIV activity, but some of these also possess toxicity. The pharmacophoric fragments of these natural products have scope of combination with other pharmacophoric fragment and derivatization to reduce toxicity and increase the potency. Combination of natural product fragments from different classes of anti-HIV compounds may lead to a new class of potent anti-HIV agents. Objective: Design, in silico prediction of drug-likeness, ADMET properties and synthesis of pyrazol- pyridones. Evaluation of the anti-HIV-1 activity of synthesized pyrazol-pyridones. Method: Pyrazol-pyridones were designed by combining reported anti-HIV pharmacophoric fragments. Designed molecules were synthesized after in silico prediction of drug-likeness and ADMET properties. Compounds were evaluated for activity against HIV-1VB59 and HIV-1UG070. Result: QED value of designed pyrazol-pyridones was greater than the known drug zidovudine. The designed compounds were predicted to be noncarcinogenic and nonmutagenic in nature. Seventeen novel pyrazol-pyridones were synthesized with good yield. Compound 6q and 6l showed activity with IC50 values 6.14 μM and 15.34 μM against HIV-1VB59 and 16.21 μM and 18.21 μM against HIV-1UG070, respectively. Conclusion: Compound 6q was found to be most potent among the synthesized compounds with a therapeutic index of 54.31against HIV-1VB59. This is the first report of anti-HIV-1 activity of pyrazol-pyridone class of compounds. Although the anti-HIV-1 activity of these compounds is moderate, this study opens up a new class for exploration of chemical space for anti-HIV-1 activity.
CONDENSED AZAHETEROARYL COMPOUNDS HAVING ANTIBACTERIAL ACTIVITY AGAINST TUBERCULOSIS BACTERIA
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Page/Page column 32, (2020/01/08)
Present invention relates to novel compound of general formula (I), their enantiomers, their diastereomers, their pharmaceutically accepted salts, or pro-drugs thereof, which are useful for the treatment of bacterial infection. The compounds of general formula (I) exhibit DprE1 enzyme inhibitory activity.
Zinc (II)-mediated selective O-benzylation of 2-Oxo-1,2-dihydropyridines systems
Zhou, Qifan,Du, Fangyu,Liang, Xinjie,Liu, Wenqiang,Fang, Ting,Chen, Guoliang
, (2018/08/21)
The selective O-benzylation of 2-oxo-1,2-dihydropyridines plays a critical role in organic synthesis of natural products and biological active molecules. Herein we report a novel ternary system of ZnO, ZnCl2 and N,N-diisopropylethylamine (DIEA), that is highly effective for selective O-benzylation of 2-oxo-1,2-dihydropyridines using abundant substituted benzyl halides and related substituted 2-oxo-1,2-dihydropyridines compounds. This process allows access to a variety of O-benzyl products under mild reaction conditions, which are important synthetic intermediates in the protection of functional groups, and represents a new method toward the development for the O-benzylation of 2-oxo-1,2-dihydropyridines.
Preparation method of olprinone and 9-azaindole-5-boric acid
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Paragraph 0023; 0024, (2017/07/15)
The invention relates to a preparation method of olprinone and 9-azaindole-5-boric acid, in particular to a method for preparing olprinone via Suzuki coupling. In the preparation method of olprinone and 9-azaindole-5-boric acid, a converging synthetic route is innovatively designed, has high atom utilization rate as compared with existing three series synthetic processes and is better than existing synthetic routes in overall reaction yield; the preparation method has mild synthetic reaction conditions, is simple to perform and is easy to industrialize; the prepared olprinone may be further olprinone hydrochloride via salifying, and the prepared olprinone hydrochloride has the advantages such as low impurity content, high purity, high yield and good mildness of reaction conditions.
A method for synthesizing milrinone
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Paragraph 0048-0049, (2018/03/13)
The invention discloses a new method for synthesizing milrinone. The method is characterized in that a compound of formula 3 and 4-pyridineboronic acid undergo a Suzuki coupling reaction to synthesize milrinone. The method has the advantages of easily available raw materials, high yield and simple post-treatment.
Pyridine C-region analogs of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists
Ryu, Hyungchul,Seo, Sejin,Lee, Jee-Young,Ha, Tae-Hwan,Lee, Sunho,Jung, Aeran,Ann, Jihyae,Kim, Sung-Eun,Yoon, Suyoung,Hong, Mannkyu,Blumberg, Peter M.,Frank-Foltyn, Robert,Bahrenberg, Gregor,Schiene, Klaus,Stockhausen, Hannelore,Christoph, Thomas,Frormann, Sven,Lee, Jeewoo
, p. 101 - 108 (2015/03/05)
A series of pyridine derivatives in the C-region of N-((6-trifluoromethyl-pyridin-3-yl)methyl) 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. The SAR analysis indicated that 6-difluorochloromethyl pyridine derivatives were the best surrogates of the C-region for previous leads. Among them, compound 31 showed excellent antagonism to capsaicin as well as to multiple hTRPV1 activators. It demonstrated stronganalgesic activity in the formalin test in mice with full efficacy and it blocked capsaicin-induced hypothermia in vivo.
Novel Hepatitis C virus replicon inhibitors: Synthesis and structure-activity relationships of fused pyrimidine derivatives
Chris Krueger,Madigan, Darold L.,Beno, David W.,Betebenner, David A.,Carrick, Robert,Green, Brian E.,He, Wenping,Liu, Dachun,Maring, Clarence J.,McDaniel, Keith F.,Mo, Hongmei,Molla, Akhteruzzaman,Motter, Christopher E.,Pilot-Matias, Tami J.,Tufano, Michael D.,Kempf, Dale J.
scheme or table, p. 2212 - 2215 (2012/04/18)
The synthesis of several pyrido[2,3-d]pyrimidine and pyrimido[4,5-d] pyrimidine analogs is described with one such analog possessing subnanomolar potency in both genotype 1a and 1b cell culture HCV replicon assays.
Synthesis and solid-state structures of alkyl-substituted 3-cyano-2-pyridones
Fischer, Christian B.,Polborn, Kurt,Steininger, Harald,Zipse, Hendrik
, p. 1121 - 1131 (2007/10/03)
A series of 3-cyano-pyridones carrying a variety of alkyl substituents at C-5 and C-6 has been synthesized and their solid-state structures have been studied. Hydrogen bonding interactions between individual pyridone molecules lead either to the formation of symmetric dimers of the R2 2(8) type or to helical chains of the C(4) type. Based on known and calculated structures for the 2-pyridone parent system, the solid-state structures can be divided in two groups representing cases with little external influence on the hydrogen bonding array (group A) and those with a larger external influence (group B).
