- MONOACYLGLYCEROL LIPASE INHIBITORS
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Provided are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof: Also provided are compositions comprising compounds of formula (I). The compounds and compositions are also provided for use as medicaments, for example as medicaments useful in the treatment of a condition modulated by monoacylglycerol lipase (MAGL). Also provided are the use of compounds and compositions for the inhibition of monoacylglycerol lipase (MAGL).
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Paragraph 0111-0112; 0141; 0153-0154; 0181-0182
(2021/09/09)
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- Novel piperazine based compounds as potential inhibitors for SARS-CoV-2 Protease Enzyme: Synthesis and molecular docking study
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Structurally diverse piperazine-based compounds hybrid with thiadiazole, isatin or with sulfur/nitrogen, functionalities were synthesized. The structures of the new compounds were established based on their spectral data and elemental analysis. The physicochemical, bioactivity scores and pharmacokinetic behavior of all the prepared ligands were evaluated using in silico computational tools. The new piperazine ligands have been screened for their inhibition activity against SARS-CoV-2 protease enzyme using molecular docking analysis. The docking studies showed that all the ligands have been docked with negative dock energy onto the target protease protein. Moreover, Molecular interaction studies revealed that SARS-CoV-2 protease enzyme had strong hydrogen bonding interactions with piperazine ligands. The present in silico study thus, provided some guidance to facilitate drug design targeting the SARS-CoV-2 main protease.
- El-atawy, Mohamed,El-sadany, Samer K.,Hamed, Ezzat A.,Mosa, Tawfik M.,Omar, Alaa Z.
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- COMPOUND SIMULTANEOUSLY INHIBITING LSD1 AND HDAC TARGETS AND APPLICATION THEREOF
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A compound having a general structural formula as shown in Formula I: X-AB-Y (Formula I); in the above Formula I, X is selected from any one of -CO2H, -CONHZ, -CH=CH-CO2H, -CH=CH-CONHZ, wherein Z is selected from any one of substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted aryl, and hydroxyl; Y = -NR1R2, wherein NR1R2 is a substituted or unsubstituted 3- to 9-membered nitrogen-containing heterocycloalkyl; A and B are each independently selected from substituted or unsubstituted phenylene, substituted or unsubstituted azaphenylene. The compound or corresponding pharmaceutical salt thereof can inhibit LSD1 and HDAC target proteins at the same time, thus inhibit the proliferation of many kinds of tumor cells and have good antitumor effect.
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Paragraph 0041-0043
(2020/11/26)
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- ANTI-PAIN COMPOUND AND PREPARATION METHOD THEREFOR
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Disclosed are a compound represented by the general Formula (I), or a stereisomer, tautomer, derivative, prodrug or pharmaceutically acceptable salt thereof, and a method for preparing the compound and use of the compound in manufacture of a medicament for treating a neuropathic pain and/or neuropathic pain syndrome or a medicament for combating an inflammation: wherein R1 is selected from hydrogen, halogen, alkyl, cyano and haloalkyl, R2 and R3 are independently selected from hydrogen, halogen, alkyl, haloalkyl and nitro, and R1, R2 and R3 are not hydrogen at the same time; furthermore, when either R2 or R3 is nitro or halogen, the other two of R1, R2 and R3 are not hydrogen at the same time. The compound has good effects in treating a neuropathic pain and/or neuropathic pain syndrome and good effects in combating an inflammation, and has not side effects such as addiction.
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- Ni-Catalyzed Reductive Cyanation of Aryl Halides and Phenol Derivatives via Transnitrilation
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Herein, we report a Ni-catalyzed reductive coupling for the synthesis of benzonitriles from aryl (pseudo)halides and an electrophilic cyanating reagent, 2-methyl-2-phenyl malononitrile (MPMN). MPMN is a bench-stable, carbon-bound electrophilic CN reagent that does not release cyanide under the reaction conditions. A variety of medicinally relevant benzonitriles can be made in good yields. Addition of NaBr to the reaction mixture allows for the use of more challenging aryl electrophiles such as aryl chlorides, tosylates, and triflates. Mechanistic investigations suggest that NaBr plays a role in facilitating oxidative addition with these substrates.
- Mills, L. Reginald,Graham, Joshua M.,Patel, Purvish,Rousseaux, Sophie A. L.
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supporting information
p. 19257 - 19262
(2019/12/02)
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- Design, synthesis and antimycobacterial activity of novel imidazo[1,2-a]pyridine-3-carboxamide derivatives
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We report herein the design and synthesis of “novel imidazo [1,2-a]pyridine-3-carboxamides (IPAs)” bearing a variety of different linkers, based on the structure of IMB-1402 discovered in our lab. Results reveal that 2,6-dimethyl-N-[2-(phenylamino)ethyl] IPAs with an electron-donating group on the benzene ring as a potent scaffold. Compounds 26g and 26h have considerable activity (MIC: 0.041–2.64 μM) against drug-sensitive/resistant MTB strains, and they have acceptable safety indices against MTB H37Rv with the SI values of 4395 and 1405, respectively. Moreover, N-[2-(piperazin-1-yl)ethyl] moiety was also identified as a potentially alternative linker (compound 31), opening a new direction for further SAR studies.
- Lv, Kai,Li, Linhu,Wang, Bo,Liu, Mingliang,Wang, Bin,Shen, Weiyi,Guo, Huiyuan,Lu, Yu
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p. 117 - 125
(2017/06/05)
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- Synthesis and biological evaluation of novel 3-substituted amino-4-hydroxylcoumarin derivatives as chitin synthase inhibitors and antifungal agents
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A series of novel 3-substituted amino-4-hydroxycoumarin derivatives have been designed and synthesized as chitin synthase (CHS) inhibitors. All the synthesized compounds have been screened for their CHS inhibition activity and antimicrobial activity in vitro. The enzymatic assay indicated that most of the compounds have good inhibitory activity against CHS, in which compound 6o with IC50 of 0.10 mmol/L had stronger activity than that of polyoxins B, which acts as control drug with IC50 of 0.18 mmol/L. As far as the antifungal activity is concerned, most of the compounds possessed moderate to excellent activity against some representative pathogenic fungi. Especially, compound 6b was found to be the most potent agent against Cryptococcus neoformans with minimal inhibitory concentration (MIC) of 4 g/mL. Moreover, the results of antibacterial screening showed that these compounds have negligible actions to some tested bacteria. Therefore, these compounds would be promising to develop selective antifungal agents.
- Ge, Zhiqiang,Ji, Qinggang,Chen, Chunyan,Liao, Qin,Wu, Hualong,Liu, Xiaofei,Huang, Yanrong,Yuan, Lvjiang,Liao, Fei
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p. 219 - 228
(2016/02/03)
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- Selective bromination of pyrrole derivatives, carbazole and aromatic amines with DMSO/HBr under mild conditions
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Bromination of pyrrole derivatives, carbazole and aromatic amines using the DMSO/HBr system affords high yields of the corresponding bromo compounds. Temperature control used in the bromination of anilines helped to promote selective formation of mono- or di-brominated products. Simple operation, low toxicity and high selectivity make this a promising new procedure for the bromination of aromatic compounds.
- Liu, Cong,Dai, Rongji,Yao, Guowei,Deng, Yulin
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p. 593 - 596
(2015/01/09)
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- Palladium-mediated conversion of para-aminoarylboronic esters into para-aminoaryl-11C-methanes
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Cross-couplings are an alternative to conventional 11C- methylations which are generally employed in PET tracer synthesis. Therefore, we set out to develop a general procedure for the synthesis of para- 11CH3 labeled aromatic amines from the corresponding para-aminoarylboronic esters in the presence of free amines. Aryl boronic esters containing primary, secondary, and tertiary amines were successfully converted into corresponding labeled methyl derivatives in sufficient radiochemical yield to apply this method for tracer development. This procedure was applied to the labeling of CIMBI-712, a promising candidate for the in vivo imaging of the 5-HT7 receptor in the CNS.
- Andersen, Valdemar L.,Herth, Matthias M.,Lehel, Szabolcs,Knudsen, Gitte M.,Kristensen, Jesper L.
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supporting information
p. 213 - 216
(2013/02/22)
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- Practical method for parallel synthesis of diversely substituted 1-phenylpiperazines
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A simple and practical method to prepare 'libraries' of substituted 1-phenylpiperazine building blocks in parallel format has been developed.
- Konstantinova, Igor,Bukhryakov, Konstantin,Gezentsvey, Yuri,Krasavin, Mikhail
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experimental part
p. 628 - 630
(2012/05/21)
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- Substituted piperazines
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Compounds are provided that act as potent antagonists of the CCR1 receptor, and which have been further confirmed in animal testing for inflammation, one of the hallmark disease states for CCR1. The compounds are generally aryl piperazine derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR1-mediated diseases, and as controls in assays for the identification of competitive CCR1 antagonists.
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- 1-ARYL-4-SUBSTITUTED PIPERAZINES DERIVATIVES FOR USE AS CCR1 ANTAGONISTS FOR THE TREATMENT OF INFLAMMATION AND IMMUNE DISORDERS
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Compounds are provided that act as potent antagonists of the CCR1 receptor, and which have been further confirmed in animal testing for inflammation, one of the hallmark disease states for CCR1. The compounds are generally aryl piperazine derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR1-mediated diseases, and as controls in assays for the identification of competitive CCR1 antagonists.
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- Fused heterocyclic compounds and pharmaceutical applications thereof
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The present invention relates to a fused heterocyclic compound of the formula (I) wherein each symbol is as defined in the specification, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing a compound of the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive, and a medicament containing a compound of the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof. The compound of the present invention is a useful antipsychotic agent effective not only for positive symptoms centering on hallucination and delusion characteristic of the acute stage of schizophrenia, but also negative symptoms of apathy, abulia and autism. The inventive compound is expected to make a highly safe antipsychotic agent associated with less side effects, such as extrapyramidal symptoms and endocrine disturbance, which are observed when a conventional antipsychotic agent having a D2receptor blocking action is administered. Therefore, the inventive compound can be used as a therapeutic agent for the diseases such as schizophrenia.
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