共查询到20条相似文献,搜索用时 15 毫秒
1.
Songliang Wu Yu Sun Yi Hu Hongmei Zhang Lijuan Hou Xing Liu Yufeng Li Haiying He Zhi Luo Yuan Chen Yuhe Wang Weihua Shi Liang Shen Changqing Cao Wei Liang Qing Xu Qiang Lv Jiong Lan Shuhui Chen 《Bioorganic & medicinal chemistry letters》2017,27(6):1458-1462
A series of octahydropyrrolo[3,4-c]pyrroles were synthesized and evaluated by orexin 1 and 2 receptor (OX1 & 2 R) antagonists assays. Compound 14l with potent OXR antagonist activity and suitable pharmacokinetic behavior was chosen to be investigated in an EEG study, which demonstrated effects of sleep promotion comparable to Suvorexant. Furthermore, the di-fluro substituted analogs exhibited reduced hERG inhibition while maintaining moderate potency. 相似文献
2.
Kathleen H. Mortell Michael R. Schrimpf William H. Bunnelle David J. Anderson Jens Halvard Gronlien Kirsten Thorin Hagene Murali Gopalakrishnan 《Bioorganic & medicinal chemistry letters》2010,20(1):104-107
A series of α7 neuronal nicotinic acetylcholine receptor ligands were designed based on a structural combination of a potent, but non-selective ligand, epibatidine, with a selective lead structure, 2. Three series of compounds in which aryl moieties were attached via a linker to different positions on the core structure were studied. A potent and functionally efficacious analog, (3aR,6aS)-2-(6-phenylpyridazin-3-yl)-5-(pyridin-3-ylmethyl)octahydropyrrolo[3,4-c]pyrrole (3a), was identified. 相似文献
3.
《Bioorganic & medicinal chemistry letters》2014,24(8):1993-1997
Efforts investigating spatially comparative alternates of the ethylene-bridged piperazine in BMS-791325 that would offer a maintained or improved virologic and pharmacokinetic profile have been multifaceted. One foray involved the utilization of various octahydropyrrolo[3,4-c]pyrrole propellanes. Many of the propellane analogs described in this work exhibited better than targeted potency (less than 20 nM). Additionally, improved exposure in rats was achieved through the employment of two newly invented and now readily accessible carbon bridged propellanes as compared to their heteroatom bridged analogs. 相似文献
4.
Aleksandra Redzicka Łukasz Szczukowski Andrzej Kochel Benita Wiatrak Katarzyna Gębczak Żaneta Czyżnikowska 《Bioorganic & medicinal chemistry》2019,27(17):3918-3928
In the present paper we describe the biological activity of newly designed and synthesized series of pyrrolo[3,4-c]pyrrole Mannich bases (7a-n). The Mannich bases were obtained in good yields by one-pot, three-component condensation of pyrrolo[3,4–c]pyrrole scaffold (6a-c) with secondary amines and an excess of formaldehyde solution in C2H5OH. The chemical structures of the compounds were characterized by 1H NMR, 13C NMR, FT-IR, and elemental analysis. Moreover, single crystal X-ray diffraction has been recorded for compound 7l. All synthesized derivatives were investigated for their potencies to inhibit COX-1 and COX-2 enzymes by colorimetric inhibitor screening assay. In order to analyse the intermolecular interactions between the ligands and cyclooxygenase, experimental data were supported with the results of molecular docking simulations. According to the results, all of the tested compounds inhibited the activity of COX-1 and COX-2. 相似文献
5.
《Bioorganic & medicinal chemistry letters》2020,30(21):127474
A novel series of 5H-chromeno[3,4-c]pyridine, 6H-isochromeno[3,4-c]pyridine and 6H-isochromeno[4,3-d]pyrimidine derivatives as dual ROCK1 and ROCK2 inhibitors is described. Optimization led to compounds with sub-nanomolar inhibitory affinity for both kinases and excellent kinome selectivity. Compound 19 exhibited ROCK1 and ROCK2 IC50 of 0.67 nM and 0.18 nM respectively. 相似文献
6.
Jianyou Shi Guobin Xu Wei Zhu Haoyu Ye Shengyong Yang Youfu Luo Jing Han Jincheng Yang Rui Li Yuquan Wei Lijuan Chen 《Bioorganic & medicinal chemistry letters》2010,20(14):4273-4278
Two series of 3-aminopyrazole compounds including 24 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles and 16 pyrazolo[3,4-b]pyridines were synthesized and evaluated against HCT116, A549, and A2780 tumor cell lines. Among them, three compounds were found to have the ideal anti-proliferative activities in vitro. Docking experiments showed that the novel pyrazolo[3,4-b]pyridines share the similar interaction mode with Aurora-A kinase as PHA739358. 相似文献
7.
Thieno,Furo, and Selenopheno[3,4‐c]pyrrole‐4,6‐dione Copolymers: Air‐Processed Polymer Solar Cells with Power Conversion Efficiency up to 7.1%
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Ahmed Najari Serge Beaupré Nicolas Allard Mariane Ouattara Jean‐Rémi Pouliot Patrick Charest Simon Besner Martin Simoneau Mario Leclerc 《Liver Transplantation》2015,5(23)
Polymers based on thieno[3,4‐c]pyrrole‐4,6‐dione derivatives are interesting and promising candidates for organic bulk heterojunction solar cells. Herein, a series of push–pull conjugated polymers based on thieno[3,4‐c]pyrrole‐4,6‐dione (TPD), furo[3,4‐c]pyrrole‐4,6‐dione (FPD), and selenopheno[3,4‐c]‐pyrrole‐4,6‐dione (SePD) have been synthesized by direct heteroarylation polymerization and fully characterized. The impacts of both the heteroatom (sulfur, oxygen, and selenium) and the side chain (branched or linear) of [3,4‐c]pyrrole‐4,6‐dione unit on the electro‐optical properties have been investigated. Among polymers developed, two new highly processable terthiophene–SePD ( P4 ) and dithienosilole–SePD ( P9 ) copolymers led to air‐processed polymer solar cells with power conversion efficiencies of 5.1% and 7.1% using the following inverted configuration: ITO/ZnO/Polymer:PCBM/MoO3/Ag. These promising results make P4 and P9 good candidates for further upscaling and device optimization. 相似文献
8.
Wang T Liu J Zhong H Chen H Lv Z Zhang Y Zhang M Geng D Niu C Li Y Li K 《Bioorganic & medicinal chemistry letters》2011,21(11):3381-3383
A series of ethyl 3-aryl-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3a-carboxylates were prepared through the metal-catalyzed domino reaction of alkylidene malonates and 1,4-butynediol under a one-pot reaction condition at room temperature. Their in vitro anti-proliferative activities were subsequently evaluated in A549, QGY and HeLa cells. The majority of the compounds showed potent anti-tumor activity against HeLa cells. In particular, compound 3l was the most potent compound with IC50 value of 5.4 μM. For the first time, the X-ray structure of the anti-tumor ethyl 3-aryl-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3a-carboxylates is determined. 相似文献
9.
Lane CA Hay D Mowbray CE Paradowski M Selby MD Swain NA Williams DH 《Bioorganic & medicinal chemistry letters》2012,22(2):1156-1159
This letter describes the discovery and synthesis of a series of octahydropyrrolo[3,4-c]pyrrole based selective histamine hH4 receptor antagonists. The amidine compound 20 was found to be a potent and selective histamine H4 receptor antagonist with moderate clearance and a high volume of distribution. 相似文献
10.
O. V. Goryunova G. M. Zakharchuk O. S. Zhukova L. V. Fetisova N. E. Kuzmina 《Russian Journal of Bioorganic Chemistry》2014,40(1):9-15
N6-derivatives of N12-indolo[2,3-a]pirrolo[3,4-c]carbazole-5,7-dione are synthesized as potential antitumor agents. The pyrrol N6 atom of these compounds is included into the dipeptide residue of the general formula >N6-(CH2) n -CO-Ala/βAla-OMe (n = 2 or 3). These compounds are synthesized by the reaction in DMF at 130°C between 13-methyl-12-(2,3,4-tri-O-acetyl-β-D-ribopyranosyl)indolo[2,3-a]furano[3,4-c]carbazole-5,7-dione and dipeptides containing the free N-terminal amino group. The nitrogen atom of the peptide amino group replaces O6 in the furan ring and is embedded as the N6 imide nitrogen atom of pyrrol. The ability of the compounds obtained to inhibit the growth of the SKOV3 human ovarian carcinoma cells was studied. The only derivative containing the >N6-(CH2)3-CO-L-Ala-OMe radical showed the cytotoxic activity with an inhibitory concentration of IC50 = 8 μM. 相似文献
11.
Chelliah Bharkavi Sundaravel Vivek Kumar Mohamed Ashraf Ali Hasnah Osman Shanmugam Muthusubramanian Subbu Perumal 《Bioorganic & medicinal chemistry letters》2017,27(14):3071-3075
An efficient one-pot microwave assisted stereoselective synthesis of novel dihydro-2′H-spiro[indene-2,1′-pyrrolo[3,4-c]pyrrole]-tetraone derivatives through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ from ninhydrin and sarcosine with a series of 1-aryl-1H-pyrrole-2,5-diones is described. The synthesised compounds were screened for their antimycobacterial and AChE inhibition activities. Compound 4b (IC50 1.30 µM) has been found to display twelve fold antimycobacterial activity compared to cycloserine and it is thirty seven times more active than pyrimethamine. Compound 4h displays maximum AchE inhibitory activity with IC50 value of 0.78 ± 0.01 µmol/L. 相似文献
12.
Pierfrancesco Biagini Claudio Biancalani Alessia Graziano Nicoletta Cesari Maria Paola Giovannoni Agostino Cilibrizzi Vittorio Dal Piaz Claudia Vergelli Letizia Crocetti Maurizio Delcanale Elisabetta Armani Andrea Rizzi Paola Puccini Paola Maria Gallo Daniele Spinabelli Paola Caruso 《Bioorganic & medicinal chemistry》2010,18(10):3506-3517
A series of pyrazoles and pyrazolo[3,4-d]pyridazinones were synthesized and evaluated for their PDE4 inhibitory activity. All the pyrazoles were found devoid of activity, whereas some of the novel pyrazolo[3,4-d]pyridazinones showed good activity as PDE4 inhibitors. The most potent compounds in this series showed an IC50 in the nanomolar range. The ability to inhibit TNF-α release in human PBMCs was determined for two representative compounds, finding values in the sub-micromolar range. SARs studies demonstrated that the best arranged groups around the heterocyclic core are 2-chloro-, 2-methyl- and 3-nitrophenyl at position 2, an ethyl ester at position 4 and a small alkyl group at position 6. Molecular modeling studies performed on a representative compound allowed to define its binding mode to the PDE4B isoform. 相似文献
13.
New diamino derivatives of pyrano[3,4-c]pyridines were synthesized by the pyridine ring recyclization. The presence of the intramolecular hydrogen bond in 6-[(4-methoxyphenyl)amino]-3,3-dimethyl8-methylamino-3,4-dihydro-1H-pyrano[3,4-c]pyridin-5-carbonitrile was identified by X-ray diffraction. A pharmacological study of the synthesized compounds was carried out in known tests, such as assay for antagonism induced by corazole subcutaneous injection and the open field test. The method of rotating rod was used to evaluate neurotoxicity. The diamino derivatives of pyrano[3,4-c]pyridines were found to possess neutrotropic properties. The synthesized compounds, as well as diazepam, prevent the occurrence of clonic seizures and clonic corazoleinduced convulsions in animals; however, they cause a behavior-depressing sedative effect. 相似文献
14.
《Bioorganic & medicinal chemistry letters》2014,24(9):2053-2056
A novel series of substituted tetrahydropyrrolo[3,4-c]pyrazoles were investigated as blockers of the N-type calcium channel (Cav2.2 channels), a chronic pain target. 相似文献
15.
Michael S. Christodoulou Sandra Liekens Konstantinos M. Kasiotis Serkos A. Haroutounian 《Bioorganic & medicinal chemistry》2010,18(12):4338-4350
The synthesis of a series of novel trisubstituted pyrazole derivatives and their PIFA-mediated conversion to molecules bearing the fused pyrazolo[4,3-c]quinoline ring system is reported. The anti-angiogenic activity of these compounds was evaluated by using in vitro assays for endothelial cell proliferation and migration, and in the chicken chorioallantoic membrane (CAM) assay. Compounds containing the fused pyrazolo[4,3-c]quinoline motifs emerged as potent anti-angiogenic compounds, which also had the ability to inhibit the growth of human breast (MCF-7) and cervical (Hela) carcinoma cells in vitro. 相似文献
16.
Changwei Chen Peichen Pan Ziyang Deng Dahai Wang Qifan Wu Lei Xu Tingjun Hou Sunliang Cui 《Bioorganic & medicinal chemistry letters》2019,29(7):912-916
A new series of 3,6-diaryl-1H-pyrazolo[3,4-b]pyridine compounds have been discovered as potent anaplastic lymphoma kinase (ALK) inhibitors. The 4-hydroxyphenyl in the 6-position of 1H-pyrazolo[3,4-b]pyridine were crucial and a fluorine atom substitution could give promising inhibitory activity. The IC50 of compound 9v against ALK was up to 1.58?nM and a binding mechanism was proposed. 相似文献
17.
The key intermediate 3-aminopyrazolo[4,3-c]pyridine-4,6-dione (2) is considered as a precursor for some novel pyrazolo[4,3-c]pyridines 4a-c, arylhydrazopyrazolo[4,3-c]pyridines 8a-e, pyrazolo[4,5,1-ij][1,6]naphthyridines 11a-e and pyrido[4′,3′:3,4]pyrazolo[1,5-a]-pyrimidines 15a-d through Knovenegal condensation, coupling reaction and Michael addition. Some of the newly synthesized pyrazolo[4,3-c]pyridine derivatives were investigated for anticancer activity. The results of the cytotoxic activity revealed that compound 6b was the most active compound against the breast and liver carcinoma cell lines which gives IC50 values of 1.937 and 3.695 µg/mL, respectively compared to reference drug (doxorubicin) with IC50 values of 2.527 and 4.749 µg/ml, respectively. Moreover, compound 6c was potent compound against the colon carcinoma cell line which gives the value of IC50 = 2.914 µg/ml compared to doxorubicin with IC50 value of 3.641 µg/ml. Some selected of the novel synthesized compounds were docked inside the active site of ERK2 enzyme and were found display a suitable binding with the active site amino acids according to their bond lengths, angles and conformational energy. 相似文献
18.
Gabriella Guerrini Giovanna Ciciani Simona Daniele Claudia Martini Camilla Costagli Chiara Guarino Silvia Selleri 《Bioorganic & medicinal chemistry》2018,26(9):2475-2487
A comparison between compounds with pyrazolo[1,5-a]pyrimidine structure (series 4–6) and pyrazolo[5,1-c][1,2,4]triazine core (series 9) as ligands at GABAA-receptor subtype, was evaluated. Moreover, for pyrazolotriazine derivatives having binding recognition, the interaction on recombinant rat α(1–3,5) GABAA receptor subtypes, was performed. Among these latter, emerge compounds 9c, 9k, 9l, 9m and 9n as α1-selective and 9h as α2-selective ligands. 相似文献
19.
Kui Wu Jing Ai Qiufeng Liu TianTian Chen Ailing Zhao Xia Peng Yuanxiang Wang Yinchun Ji Qizheng Yao Yechun Xu Meiyu Geng Ao Zhang 《Bioorganic & medicinal chemistry letters》2012,22(20):6368-6372
Two series of new analogues were designed by replacing the quinoline scaffold of our earlier lead 2 (zgwatinib) with quinoxaline and pyrido[2,3-d]pyrimidine frameworks. Moderate c-Met inhibitory activity was observed in the quinoxaline series. Among the pyrido[2,3-d]pyrimidine series, compounds 13a–c possessing an O-linkage were inactive, whilst the N-linked analogues 15a–c retained c-Met inhibitory potency. Highest activity was observed in the 3-nitrobenzyl analog 15b that showed an IC50 value of 6.5 nM. Further structural modifications based on this compound were undergoing. 相似文献
20.
Steven D. Fidanze Dachun Liu Robert A. Mantei Lisa A. Hasvold John K. Pratt George S. Sheppard Le Wang James H. Holms Yujia Dai Ana Aguirre Andrew Bogdan Justin D. Dietrich Jasmina Marjanovic Chang H. Park Charles W. Hutchins Xiaoyu Lin Mai H. Bui Xiaoli Huang Keith F. McDaniel 《Bioorganic & medicinal chemistry letters》2018,28(10):1804-1810
Novel conformationally constrained BET bromodomain inhibitors have been developed. These inhibitors were optimized in two similar, yet distinct chemical series, the 6-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-ones (A) and the 1-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-ones (B). Each series demonstrated excellent activity in binding and cellular assays, and lead compounds from each series demonstrated significant efficacy in in vivo tumor xenograft models. 相似文献