- 3-(dimethylaminomethyl) piperidine-4-alcohol derivative as well as preparation method and pharmaceutical application thereof
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The present invention provides compounds of formula (FWBF) or pharmaceutically acceptable salts thereof, in which the substituents are as defined in the specification, as well as a preparation method and pharmaceutical use thereof.
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Paragraph 0094-0098
(2021/05/08)
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- Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic
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Management of moderate to severe pain by clinically used opioid analgesics is associated with a plethora of side effects. Despite many efforts have been dedicated to reduce undesirable side effects, moderate progress has been made. In this work, starting from Tramadol, a series of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)piperidine-1-carboxamide derivatives were designed and synthesized, and their in vitro and in vivo activities were evaluated. Our campaign afforded selective μ opioid receptor (MOR) ligand 2a (KiMOR: 7.3 ± 0.5 nM; KiDOR: 849.4 ± 96.6 nM; KiKOR: 49.1 ± 6.9 nM) as potent analgesic with ED50 of 3.1 mg/kg in 55 °C hot plate model. Its antinociception effect was blocked by opioid antagonist naloxone. High binding affinity toward MOR of compound 2a was associated with water bridge, salt bridge, hydrogen bond and hydrophobic interaction with MOR. The high selectivity of compound 2a for MOR over δ opioid receptor (DOR) and κ opioid receptor (KOR) was due to steric hindrance of compound 2a with DOR and KOR. 2a, a compound with novel scaffold, could serve as a lead for the development of novel opioid ligands.
- Fu, Wei,Huang, Huoming,Li, Wei,Liu, Jinggen,Wang, Wenli,Wang, Yujun,Xu, Xuejun,Zhu, Chen
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- PRODUCTION METHOD FOR AMIDATE COMPOUND
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A method for producing an amidate compound represented by Formula (3), comprising reacting a urethane compound represented by Formula (1) with a carboxylate compound represented by Formula (2): (in the formulas, A, n, R1, R2, R3, R4, R5, R6, X, and a are as described in the Description).
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Paragraph 0183-0185
(2020/02/13)
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- Amidate compound, catalyst for polyurethane production, and method for producing polyurethane resin
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Provided is an amidate compound represented by the formula (1): wherein A is a substituted or unsubstituted hydrocarbon group, n is an integer of 1 or more, and D is a nitrogen-containing organic group represented by the formula (2): wherein R1, R2, and R3 are the same or different, and are each a hydrocarbon group that may contain a heteroatom; some or all of R1, R2, and R3 may be bonded together to form a ring structure; X is a nitrogen atom, an oxygen atom, or a sulfur atom; and a is 0 or 1, wherein a is 1 when X is a nitrogen atom, and a is 0 when X is an oxygen atom or a sulfur atom.
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Page/Page column 131; 132
(2020/07/09)
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- Highly Regioselective Carbamoylation of Electron-Deficient Nitrogen Heteroarenes with Hydrazinecarboxamides
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The use of hydrazinecarboxamides as a new class of carbamoylating agents has been established through the dehydrazinative Minisci reaction of electron-deficient nitrogen heteroarenes. A wide range of electron-deficient nitrogen heteroarenes, including isoquinoline, quinoline, pyridine, phenanthridine, quinoxaline, and phthalazine, underwent copper/acid-catalyzed oxidative carbamoylation with hydrazinecarboxamide hydrochlorides to afford structurally diverse nitrogen-heteroaryl carboxamides as single regioisomers in moderate to excellent yields. The functional group tolerance was substantially demonstrated in the direct carbamoylation of quinine obviating multistep sequences involving protecting groups and prefunctionalization of the heterocycle.
- He, Zeng-Yang,Huang, Chao-Fan,Tian, Shi-Kai
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supporting information
p. 4850 - 4853
(2017/09/23)
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- Design, synthesis and in vitro trypanocidal and leishmanicidal activities of novel semicarbazone derivatives
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Trypanosomatids are protozoan parasites that cause various diseases in human, such as leishmaniasis, Chagas disease and sleeping sickness. The highly syntenic genomes of the trypanosomatid species lead the assumption that they can encode similar proteins,
- Alves, Marina A.,De Queiroz, Aline C.,Alexandre-Moreira, Magna Suzana,Varela, Javier,Cerecetto, Hugo,González, Mercedes,Doriguetto, Antonio C.,Landre, Iara M.,Barreiro, Eliezer J.,Lima, Lídia M.
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- TRPV1 modulators: Synthesis and in vitro evaluation of 1-heteroaryl piperidinecarboxamide and piperazinylurea derivatives
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Abstract A series of new 1-heteroaryl piperidinecarboxamide and piperazinylurea derivatives was synthesized and evaluated as TRPV1 modulators in a Ca2+ channel assay in HEK-293 cells overexpressing the human recombinant TRPV1 channel. Structura
- Congiu, Cenzo,Onnis, Valentina,Balboni, Gianfranco,Schiano-Moriello, Aniello,Di Marzo, Vincenzo,De Petrocellis, Luciano
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p. 129 - 138
(2015/06/22)
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- Design, synthesis and pharmacological evaluation of 6,7-disubstituted-4- phenoxyquinoline derivatives as potential antitumor agents
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Two series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 2,4-imidazolinedione/pyrazolone scaffold were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against HT-29, H460, A549, MKN-45, and U87MG cancer cell lines in vitro. The pharmacological data indicated that most of the tested compounds showed moderate to significant cytotoxicity and high selectivity against HT-29, H460 and A549 cancer cell lines as compared with foretinib. The SAR analyses indicated that compounds with halogen groups, especially trifluoromethyl groups at 2-position on the phenyl ring (moiety B) were more effective. In this study, a promising compound 17 (c-Met IC50 = 2.20 nM, a multi-target tyrosine kinase inhibitor) showed the most potent antitumor activities with IC50 values of 0.14 μM, 0.18 μM, 0.09 μM, 0.03 μM, and 1.06 μM against HT-29, H460, A549, MKN-45, and U87MG cell lines, respectively.
- Zhou, Shunguang,Ren, Jianguo,Liu, Mingmei,Ren, Lixiang,Liu, Yajing,Gong, Ping
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- Design, synthesis and pharmacological evaluation of 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents
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Two series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 2,4-imidazolinedione/pyrazolone scaffold were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against HT-29, H460, A549, MKN-45, and U87MG cancer cell lines in vitro. The pharmacological data indicated that most of the tested compounds showed moderate to significant cytotoxicity and high selectivity against HT-29, H460 and A549 cancer cell lines as compared with foretinib. The SAR analyses indicated that compounds with halogen groups, especially trifluoromethyl groups at 2-position on the phenyl ring (moiety B) were more effective. In this study, a promising compound 17 (c-Met IC50= 2.20 nM, a multi-target tyrosine kinase inhibitor) showed the most potent antitumor activities with IC50values of 0.14 μM, 0.18 μM, 0.09 μM, 0.03 μM, and 1.06 μM against HT-29, H460, A549, MKN-45, and U87MG cell lines, respectively.
- Zhou, Shunguang,Ren, Jianguo,Liu, Mingmei,Ren, Lixiang,Liu, Yajing,Gong, Ping
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- Synthesis and evaluation in vitro of 1-[2-(10-dihydroartemisininoxy) ethyl]-3-phenylurea derivatives as potential agents against cancer
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In order to develop potent and selective anticancer agents, a series of novel artemisinin derivatives bearing urea moiety 1a-n were facilely synthesized herein and screened for their activities in vitro against ten human tumor cell lines (HeLa, MCF-7, U937, K562, HL60, HCT116, HepG2, A549, A375-S2, and HT1080). The pharmacological results indicated that some compounds showed excellent activity against cancer cell lines and good selectivity, especially the compound 1c which proved to be the most active against the cancer cells as well as distinctive patterns of selectivity.
- Luo, Wei,Xia, Ming-Yu,Ikejima, Takashi,Li, Li-Hua,Guo, Chun
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p. 3170 - 3176
(2013/07/19)
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- Synthesis and biological evaluation of 4-phenoxy-6,7-disubstituted quinolines possessing semicarbazone scaffolds as selective c-Met inhibitors
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Novel quinoline derivatives bearing acyclic semicarbazones were prepared and their chemical structures as well as the relative stereochemistry were confirmed. All the synthesized compounds were evaluated for their c-Met kinase inhibitory activity and their cytotoxicity against the cell lines HT-29, MKN-45, and MDA-MB-231 in vitro. Several potent compounds were further evaluated against A549 cells. Most compounds displayed moderate to excellent activity, and the structure-activity relationship studies identified the most promising compound 35 as a selective c-Met kinase inhibitor (IC50 = 4.3 nM). Compound 35 showed a 3.5- and 18.8-fold increase in cytotoxicity in vitro against HT-29 and A549 cells, respectively, compared to that of foretinib. Poor off-target effects of compound 35 were further confirmed by the antiproliferative activity against the c-Met inhibition less sensitive MDA-MB-231 cell line (IC50 = 0.77 μM). Copyright
- Qi, Baohui,Tao, Haiyan,Wu, Di,Bai, Jinying,Shi, Yandan,Gong, Ping
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p. 596 - 609
(2013/09/02)
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- Synthesis and biological activities of novel artemisinin derivatives as cysteine protease falcipain-2 inhibitors
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A series of novel artemisinin derivatives were synthesized from artemisinin and different anilines. All compounds were obtained as β-isomers. The target compounds were evaluated for inhibition activity against Plasmodium falciparum falcipain-2 in vitro, and most of them exhibited potent inhibition in the low micromolar range and proved to be new types of falcipain-2 inhibitors.
- Liu, Yang,Lu, Wei-Qiang,Cui, Kun-Qiang,Luo, Wei,Wang, Jian,Guo, Chun
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p. 1525 - 1531
(2013/03/14)
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- Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism
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The incidence of life-threatening fungal infections is increasing dramatically. In an attempt to develop novel antifungal agents, our previously synthesized phenoxyalkylpiperazine triazole derivatives were used as lead structures for further optimization. By means of structure-based bioisosterism, triazolone was used as a new bioisostere of oxygen atom. This type of bioisosteric replacement can improve the water solubility without loss of hydrogen-bonding interaction with the target enzyme. A series of triazolone-containing triazoles were rationally designed and synthesized. As compared with fluconazole, several compounds showed higher antifungal activity with broader spectrum, suggesting their potential for further evaluations.
- Sheng, Chunquan,Che, Xiaoying,Wang, Wenya,Wang, Shengzheng,Cao, Yongbing,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Wannian
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experimental part
p. 5276 - 5282
(2011/12/03)
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- Synthesis and characterization of vanillin semicarbazones
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Semicarbazones have a great interest because of their chemistry and biological activities for the treatment of various human ailments. A series of seven vanillin semicarbazones (3a-g) were synthesized by reflux of aryl semicarbazides with appropriate carbonyl compound in the presence of glacial acetic acid. The aryl semicarbazides (2a-g) were synthesized from aryl carbamates by reacting with hydrazine hydrate and ethanol on hydrazinolysis. The aryl carbamates (1a-g) were obtained by the reaction between phenyl chloro formate and aniline/substituted aniline in anhydrous ether in the presence of sodium hydroxide. The structure of the newly synthesized compounds was established by various analytical techniques such as IR, 1H NMR and MASS spectral studies.
- Venkateshhan,Ravichandiran,Selvakumar,Lavakumar
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experimental part
p. 4632 - 4634
(2012/02/04)
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- Phenyl 4,5-dichloro-6-oxopyridazine-1(6H)-carboxylate as carbonyl source: Facile and selective synthesis of carbamates and ureas under mild conditions
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The selective syntheses of carbamates, symmetric -ureas, and unsymmetrical ureas have been accomplished by the -reaction of amines with phenyl 4,5-dichloro-6-oxopyridazine-1(6H)-carboxylate as a carbonyl source under mild conditions. It is noteworthy that this process is mild, economic, and convenient.
- Lee, Hyung-Geun,Kim, Min-Jung,Park, Song-Eun,Kim, Jeum-Jong,Kim, Bo Ram,Lee, Sang-Gyeong,Yoon, Yong-Jin
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experimental part
p. 2809 - 2814
(2010/03/03)
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- PROCESS FOR PREPARING CARBAMATES
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A process for the preparation of carbamates from organic urea and organic carbonate in presence of a solid base catalyst is disclosed. The process works at the milder reaction conditions and utilizes inexpensive catalysts that can be recycled several times.
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Page/Page column 16
(2008/06/13)
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- Process for preparing carbamates
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A process for the preparation of carbamates from organic urea and organic carbonate in presence of a solid base catalyst is disclosed. The process works at the milder reaction conditions and utilizes inexpensive catalysts that can be recycled several times.
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Page/Page column 7
(2008/06/13)
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- Preparation of N-substituted aryl and alkyl carbamates and their inhibitory effect on oat seed germination.
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A series of N-substituted aryl and alkyl carbamates (RNHCOOR'; R: aryl, alkyl; R': aryl, alkyl) was prepared and screened for inhibitory activity toward the germination of oat seeds. The activity of each compound was compared with that of chlorpropham (isopropyl 3-chlorocarbanilate). Some of the synthetic carbamates possessing the N-(phenylthio)methyl group, PhSCH2NHCOOR', showed inhibitory activity close or comparable to that of chlorpropham.
- Alizadeh, Babak Heidary,Sugiyama, Takeyoshi,Oritani, Takayuki,Kuwahara, Shigefumi
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p. 422 - 425
(2007/10/03)
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- Carbamate synthesis by solid-base catalyzed reaction of disubstituted ureas and carbonates
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A simple and efficient methodology to prepare carbamates has been demonstrated for the first time from symmetrical ureas and organic carbonates in the presence of solid base catalysts.
- Gupte,Shivarkar,Chaudhari
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p. 2620 - 2621
(2007/10/03)
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- Nucleophilic substitution reactions of phenyl chloroformates
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Methanolysis and aminolysis of phenyl chloroformates in acetonitrile have been investigated.The rates are slow due to initial-state stabilization by strong resonance electron donation from the phenoxy group.In both reactions the large positive values of ρY = 0.8-1.6 and low ΔH(excit.) and ΔS(excit.) values show that the transition state is strongly associative with little bond breaking.This mechanism is supported by the relatively large solvent isotope effect, kMeOH/kMeOD = ca. 2.3-2.5, and by the relatively strong inverse secondary kinetic isotope effect, kH/kD =/ca. 0.74-0.94, involving deuteriated aniline nuclephiles, in addition to a negative value of ρXY.The dependence on aniline basicity, βx(βnuc) =/ca. 0.8, and the ρX values of -2.3 are similar to those corresponding values for the reactions of benzoyl chlorides which have been predicted to react by an associative SN2 mechanism.These observations are consistent with a concerted displacement mechanism for the methanolysis and aminolysis of phenyl chloroformates.
- Yew, Kyoung Han,Koh, Han Joong,Lee, Hai Whang,Lee, Ikchoon
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p. 2263 - 2268
(2007/10/03)
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