- A new synthetic approach for pyrazolo[1,5-a]pyrazine-4(5H)-one derivatives and their antiproliferative effects on lung adenocarcinoma cell line
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Abstract: Starting from the 3,5-dimethyl pyrazole ring and acetophenone derivatives, five different N-propargylated C-3 substituted pyrazoles were obtained. These derivatives were reacted with different amine derivatives using Cs2CO3 in methanol and 11 different pyrazolo [1,5-a] pyrazine-4(5H)-one derivatives were obtained, which are not found in the literature. The cytotoxic effects of these derivatives in the A549 cell line were investigated. The 160?μM concentration of two derivatives was found to increase cell death rate to 50%, and two derivatives increased cell death rate by up to 40%. The structure–activity relationship (SAR) study revealed an amide group with a long alkyl chain and benzene ring with a p-CF3 group could be important for efficiency. With theoretical ADMET studies of pyrazolopyrazine derivatives, pharmacokinetic phases were predicted to be suitable. Graphic abstract: [Figure not available: see fulltext.].
- Uygun, Meltem Tan,Amudi, Karina,Tura?l?, ?rem Do?an,Menges, Nurettin
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- COMPOUNDS AS CASEIN KINASE INHIBITORS
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Provided are novel casein kinase inhibitors, or pharmaceutically acceptable salts thereof. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also provided.
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Paragraph 00352-00355; 00450-00453
(2021/10/02)
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- Design, synthesis, and biological evaluation of novel thiazolyl substituted bis-pyrazole oxime derivatives with potent antitumor activities by selectively inducing apoptosis and ros in cancer cells
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Background: A large number of pyrazole derivatives have different biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic and antiepileptic activity. Among them, pyrazole oximes have attracted much attention due to their potential pharmacological activities, particularly anticancer activities. Objective: Our goal is to synthesize novel thiazolyl substituted bis-pyrazole oxime derivatives with potent antitumor activities by selectively inducing apoptosis and Reactive Oxygen Species (ROS) accumulation in cancer cells. Methods: Eighteen bis-pyrazole oximes were synthesized by conjugating thiazolyl substituted pyrazoles with pyrazoxime. The target compounds were characterized by1HNMR,13C NMR, and HRMS, and screened for their antiproliferative activity against four cancer cells in MTT assay. The most potent compound was examined for its inhibitory effect and ROS accumulation in both cancer cells HCT116 and normal intestinal epithelial cells CCD841. Finally, the most potent compound was further evaluated for its apoptotic induction by flow cytometry analysis and immunoblot analysis of apoptosis-related proteins and DNA damage proteins. Results: Most compounds displayed potent antiproliferative activity against four cancer cell lines in vitro, displaying potencies superior to 5-FU. In particular, the most potent compound 13l selectively inhibited proliferation of colorectal cancer HCT116 cells but not normal colon CCD841 cells. Furthermore, compound 13l also selectively promoted intracellular ROS accumulation in HCT116 which was involved in 13l inhibition of cancer cell proliferation and induction of cell apoptosis. Finally, compound 13l also dose-dependently induced cancer cell apoptosis by regulating apoptotic and DNA damage related proteins expressions. Conclusion: Our synthetic bis-pyrazole oxime derivatives possess potent antitumor activities by selectively inducing apoptosis and ROS accumulation in cancer cells, which may hold great promise as therapeutic agents for the treatment of human cancers.
- Xiong, Biao,Chen, Shi,Zhu, Peng,Huang, Meiling,Gao, Weijie,Zhu, Rui,Qian, Jianqiang,Peng, Yanfu,Zhang, Yanan,Dai, Hong,Ling, Yong
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p. 743 - 754
(2019/11/02)
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- The First Example of Azole-Fused Cyclic Anhydride Reacting in the Castagnoli-Cushman Way
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Pyrazole-fused cyclic anhydrides have been employed for the first time as the Castagnoli-Cushman reaction partners to produce hitherto unknown 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5- a ]pyrazine-7-carboxylates in remarkably convenient and speedy fashion. At
- Moreau, Ella,Dar'In, Dmitry,Krasavin, Mikhail
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supporting information
p. 890 - 893
(2018/03/06)
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- 1. 3, 5 - tri-substituted pyrazole compound and its preparation method and application
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The invention discloses 1,3,5-trisubstituted pyrazole compounds, and a preparation method and application thereof. The structure of the compounds is shown as a general formula (I), and in the general formula (I), R1 is hydrogen, halogens, methyl or triflu
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Paragraph 0114; 0115; 0116; 0117
(2017/04/18)
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- Substituted pyrazolo-piperazines as casein kinase 1 δ/ε inhibitors
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The invention provides compounds of Formula (I): and pharmaceutically acceptable salts thereof. The compounds of Formula (I) inhibit protein kinase activity thereby making them useful as anticancer agents.
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Page/Page column 61; 62
(2016/03/19)
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- Synthesis and biological evaluation of 3-(4-fluorophenyl)-1H-pyrazole derivatives as androgen receptor antagonists
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A novel series of 3-(4-fluorophenyl)-1H-pyrazole derivatives were synthesized and evaluated for their antiproliferative activity against two prostate cancer cell lines (LNCaP and PC-3) and androgen receptor target gene prostate-specific antigen (PSA) inhibitory activity in LNCaP cells. Several compounds showed potent antiproliferative activity against LNCaP cells and showed a promising PSA downregulation rate. Among these, compound 10e selectively inhibited LNCaP cell growth with an IC50 value of 18 μmol/l and showed a PSA downregulation rate of 46%, which was better than the lead compound T3.
- Guo, Guangzhu,Liu, Jianzhen,Wang, Guanjie,Zhang, Daoguang,Lu, Jinjie,Zhao, Guisen
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p. 278 - 285
(2016/03/30)
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- Synthesis of (Z)-(arylamino)-pyrazolyl/isoxazolyl-2-propenones as tubulin targeting anticancer agents and apoptotic inducers
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A new class of pyrazole and isoxazole conjugates were synthesized and evaluated for their cytotoxic activity against various human cancer cell lines. These compounds have shown significant cytotoxicity with lower IC50 values. FACS results revealed that A549 cells treated with these compounds arrested cells at the G2/M phase of the cell cycle apart from activating cyclin B1 protein levels. Particularly, compounds 9a and 9b demonstrated a remarkable inhibitory effect on tubulin polymerization and showed a pronounced inhibitory effect on tubulin polymerization with IC50 values of 1.28 μM and 0.28 μM respectively, whereas nocodazole, a positive control, has shown lower antitubulin activity with an IC50 value of 2.64 μM. Furthermore, these compounds induced apoptosis by loss of mitochondrial membrane potential, propidium iodide (PI) staining and the activation of caspase-3. Results of a fluorescence based competitive colchicine binding assay suggest that these conjugates bind successfully at the colchicine binding site of tubulin. These investigations reveal that such conjugates containing pyrazole with a trimethoxy phenyl ring and indole moieties have potential for the development of newer chemotherapeutic agents. This journal is
- Kamal, Ahmed,Reddy, Vangala Santhosh,Shaik, Anver Basha,Kumar, G. Bharath,Vishnuvardhan,Polepalli, Sowjanya,Jain, Nishant
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p. 3416 - 3431
(2015/03/18)
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- IMIDAZO-PYRIDAZNE DERIVATIVES AS CASEIN KINASE 1 DELTA/EPSILON INHIBITORS
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The invention provides compounds of Formula (I) and pharmaceutically-acceptable salts thereof. The compounds of Formula (I) inhibit protein kinase activity thereby making them useful as anticancer agents.
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Page/Page column 40; 41
(2016/04/26)
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- COMPOUNDS CAPABLE OF INHIBITING VOLTAGE GATED CALCIUM ION CHANNEL, AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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Disclosed herein are an N-(pyrazolylmethyl)arylsulfonamide derivative useful as a calcium ion channel blocker, a pharmaceutically acceptable salt thereof, and the medicinal use thereof as a therapeutic agent using its calcium ion channel blocking effect.
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Paragraph 0237; 0238
(2015/12/12)
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- On water synthesis of N-unsubstituted pyrazoles: Semicarbazide hydrochloride as an alternative to hydrazine for preparation of pyrazole-3-carboxylate derivatives and 3,5-disubstituted pyrazoles
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A green, simple and highly efficient method for the synthesis of pyrazole-3-carboxylates and 3,5-disubstituted pyrazoles by cyclization of 4-aryl(hetaryl, alkyl)-2,4-diketoesters and 1,3-diketones with semicarbazide hydrochloride under on water conditions has been developed. This method also does not require toxic hydrazine and product purification, eliminating the use of toxic liquid chemicals.
- Markovi, Violeta,Joksovi, Milan D.
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supporting information
p. 842 - 847
(2015/03/04)
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- Cascade regioselective synthesis of pyrazoles from nitroallylic acetates and N-tosyl hydrazine
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A simple, practical, and regioselective synthetic protocol for the formation of pyrazoles was developed. Unlike all other previously reported reactions of nitroallylic acetates, this process was initiated by a S N2 reaction at the electrophilic γ site. A plausible mechanism for the cascade SN2-Michael synthesis is proposed.
- Shao, Nana,Chen, Tong,Zhang, Taotao,Zhu, Huajian,Zheng, Qunxiong,Zou, Hongbin
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p. 795 - 799
(2014/01/23)
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- NOVEL COMPOUNDS FOR THE TREATMENT OF DISEASES ASSOCIATED WITH AMYLOID OR AMYLOID-LIKE PROTEINS
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The present invention relates to novel compounds that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.
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Page/Page column 69-70
(2008/12/05)
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- Synthesis of pyrazole-3-carboxylates and pyrazole-1,5-dicarboxylates by one-pot cyclization of hydrazone dianions with diethyl oxalate
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The one-pot cyclization of hydrazone dianions with diethyl oxalate allows a convenient synthesis of pyrazole-3-carboxylates and pyrazole-1,5-dicarboxylates.
- Dang, Tung T.,Dang, Tuan T.,Fischer, Christine,G?rls, Helmar,Langer, Peter
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p. 2207 - 2215
(2008/09/18)
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- One-pot synthesis of pyrazole-5-carboxylates by cyclization of hydrazone 1,4-dianions with diethyl oxalate
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The cyclization of hydrazone dianions with diethyl oxalate afforded pyrazole-5-carboxylates.
- Dang, Tuan Thanh,Dang, Tung Thanh,Langer, Peter
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p. 3591 - 3593
(2008/02/02)
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- ALKOXYPHENYLPROPANOIC ACID DERIVATIVES
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The present invention aims at provision of a novel compound having a GPR40 receptor function modulating action, which is useful as an insulin secretagogue, an agent for the prophylaxis or treatment of diabetes and the like. The compound represented by the formula: wherein each symbol is as defined in the description, a salt thereof, and a prodrug thereof of the present invention unexpectedly have a superior GPR40 receptor agonistic activity and superior properties as pharmaceutical products such as stability and the like, and can be safe and useful pharmaceutical agents as agents for the prophylaxis or treatment of GPR40 receptor-related pathology or diseases in mammals.
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Page/Page column 51
(2008/06/13)
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