- Imidazole hydrochloride promoted synthesis of 3,5-disubstituted-1,2,4-oxadiazoles
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Imidazole hydrochloride as an additive promotes the reaction of amidoximes and DMA derivatives to generated 3,5-disubstituted-1,2,4-oxadiazoles in low to excellent yields without the use of coupling reagents, oxidants, strong acids or bases and other additives.
- Wang, Xuetong,Wang, Yin,Liu, Xiaoling,He, Tingshu,Li, Lingli,Wu, Huili,Zhou, Shangjun,Li, Dan,Liao, Siwei,Xu, Ping,Huang, Xing,Yuan, Jianyong
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supporting information
(2021/10/14)
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- SO2F2-Mediated one-pot cascade process for transformation of aldehydes (RCHO) to cyanamides (RNHCN)
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A simple, mild and practical cascade process for the direct conversion of aldehydes to cyanamides was developed featuring a wide substrate scope and great functional group tolerability. This method allows for transformations of readily available, inexpensive, and abundant aldehydes to highly valuable cyanamides in a pot, atom, and step-economical manner with a green nitrogen source. This protocol will serve as a robust tool for the installation of the cyanamide moiety in various complicated molecules.
- Ding, Chengrong,Ge, Shuting,Wei, Junjie,Zhang, Guofu,Zhao, Yiyong
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p. 17288 - 17292
(2020/05/18)
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- KCNT1 INHIBITORS AND METHODS OF USE
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The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.
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Paragraph 000649
(2020/11/23)
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- 1-CYANO-PYRROLIDINE DERIVATIVES AS DUB INHIBITORS
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The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The novel compounds have formula (I): (Formula (I)) or are pharmaceutically acceptable salts thereof, wherein: R1a, R1b, R1c, R1d, R1e and R1f each independently represent hydrogen, optionally substituted C1-C6 alkyl or optionally substituted C3-C4 cycloalkyl, or R1b and R1c together form an optionally substituted C3-C6 cycloalkyl ring, or R1d and R1e together form an optionally substituted C3-C6 cycloalkyl ring; R2 represents hydrogen or optionally substituted C1-C6 alkyl; A represents an optionally further substituted 5 to 10 membered monocyclic or bicyclic heteroaryl, heterocyclyl or aryl ring; L represents a covalent bond or linker; B represents an optionally substituted 3 to 10 membered monocyclic or bicyclic heterocyclyl, heteroaryl, cycloalkyl or aryl ring; and when -A-L-B is at position x attachment to A is via a carbon ring atom of A, and either: A cannot be triazolopyridazinyl, triazolopyridinyl, imidazotriazinyl, imidazopyrazinyl or pyrrolopyrimidinyl; or B cannot be substituted with phenoxyl; or B cannot be cyclopentyl when L is an oxygen atom.
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Paragraph 0955-0956
(2020/11/30)
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- A cascade process for directly converting nitriles (RCN) to cyanamides (RNHCN) via SO2F2-activated Tiemann rearrangement
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A simple, mild and practical process for the direct conversion of nitriles to cyanamides was newly discovered and exhibited a wide substrate scope as well as great functional group-tolerability (36 examples). In this efficient strategy, the in situ generated amidoximes obtained from the reaction of nitriles with hydroxylamine subsequently underwent Tiemann rearrangement, producing the corresponding cyanamides with great isolated yields under SO2F2. Additionally, the control experiments reportedly shed light on the tentative mechanism involved in the formation and elimination of the key intermediate: a sulfonyl ester.
- Zhang, Guofu,Zhao, Yiyong,Ding, Chengrong
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supporting information
p. 7684 - 7688
(2019/08/30)
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- NOVEL TRIAZOLONE DERIVATIVES OR SALTS THEREOF AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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The present technology provides triazolone derivatives or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and the use thereof. The triazolone derivatives or their pharmaceutically acceptable salts exhibit selective inhibitory activity on VAP-1 and therefore can be usefully applied, e.g., for the treatment and prophylaxis of nonalcoholic hepatosteatosis (NASH).
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Paragraph 0204-0205
(2019/10/15)
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- Novel 5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazoles to investigate the activation of the α7 nicotinic acetylcholine receptor subtype: Synthesis and electrophysiological evaluation
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α7 nicotinic acetylcholine receptors (nAChRs) are relevant therapeutic targets for a variety of disorders including neurodegeneration, cognitive impairment, and inflammation. Although traditionally identified as an ionotropic receptor, the α7 subtype showed metabotropic-like functions, mainly linked to the modulation of immune responses. In the present work, we investigated the structure-activity relationships in a set of novel α7 ligands incorporating the 5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazole scaffold, i.e. derivatives 21a-34a and 21b-34b, aiming to identify the structural requirements able to preferentially trigger one of the two activation modes of this receptor subtype. The new compounds were characterized as partial and silent α7 nAChR agonists in electrophysiological assays, which allowed to assess the contribution of the different groups towards the final pharmacological profile. Overall, modifications of the selected structural backbone mainly afforded partial agonists, among them tertiary bases 27a-33a, whereas additional hydrogen-bond acceptor groups in permanently charged ligands, such as 29b and 31b, favored a silent desensitizing profile at the α7 nAChR.
- Quadri, Marta,Silnovi?, Almin,Matera, Carlo,Horenstein, Nicole A.,Stokes, Clare,De Amici, Marco,Papke, Roger L.,Dallanoce, Clelia
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p. 207 - 228
(2018/10/23)
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- Pharmacophore requirements for HIV-1 reverse transcriptase inhibitors that selectively “Freeze” the pre-translocated complex during the polymerization catalytic cycle
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Reverse transcriptase (RT) is responsible for replicating the HIV-1 genome and is a validated therapeutic target for the treatment of HIV infections. During each cycle of the RT-catalyzed DNA polymerization process, inorganic pyrophosphate is released as the by-product of nucleotide incorporation. Small molecules were identified that act as bioisosteres of pyrophosphate and can selectively freeze the catalytic cycle of HIV-1 RT at the pre-translocated stage of the DNA- or RNA-template-primer-enzyme complex.
- Lacbay, Cyrus M.,Menni, Michael,Bernatchez, Jean A.,G?tte, Matthias,Tsantrizos, Youla S.
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p. 1713 - 1726
(2018/02/27)
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- Focused microwave irradiation-assisted synthesis of N-cyclohexyl-1,2,4-oxadiazole derivatives with antitumor activity
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A facile synthesis of 3,5-disubstituted 1,2,4-oxadiazole derivatives under focused microwave irradiation (FMWI) is reported. Arylamidoximes 1a–i and dicyclohexylcarbodiimide (DCC) were carried out in DMF under FMWI to obtain 1,2,4-oxadiazoles 2a–i in 61–8
- de Oliveira, Valentina Nascimento Melo,dos Santos, Franciane Gon?alves,Ferreira, Vanessa Pinheiro Gon?alves,Araújo, Héverton Mendes,do ó Pessoa, Cláudia,Nicolete, Roberto,de Oliveira, Ronaldo Nascimento
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p. 2522 - 2532
(2018/10/15)
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- Synthesis, characterisation and photophysical studies of oxadiazolyl coumarin: A new class of blue light emitting fluorescent dyes
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A library of novel 1, 2, 4-oxadiazole linked coumarin dyes have been synthesised via condensation of corresponding acid 6 and N’-hydroxybenzimidamide 8. This new class of organic compounds were examined for their fluorescent properties and found to emit blue light in the visible region of the spectrum with very high Stoke's shift values. Most of these compounds demonstrated high quantum yields and fluorescence life time in nano-second range which makes them quite lucrative to be used as new fluorescent probes. The highest quantum yield of 0.68 was shown by compound 9j which also shows high Stoke's shift value. The electronic structure of these coumarin-based donor–π–acceptor (D–π–A)-type organic dyes have been examined by Density Functional Theory (DFT). TGA analysis of few of the compounds show that they are stable up to temperature range of 0–245?°C. The synthesised compounds were characterised by NMR and mass spectrometry and the structure of two of these compounds have been confirmed by X-ray crystallography.
- Matta, Akanksha,Bahadur, Vijay,Taniike, Toshiaki,Van der Eycken, Johan,Singh, Brajendra K.
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p. 250 - 260
(2017/02/05)
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- Cobalt(III)-Catalyzed Oxadiazole-Directed C-H Activation for the Synthesis of 1-Aminoisoquinolines
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Aromatic heterocycles have been identified as effective directing groups (DGs) in C-H functionalization but can be retained as undesired bulky substituents in the final products. Herein, we report a Co(III)-catalyzed 1-aminoisoquinoline synthesis strategy based on oxadiazole-directed aromatic C-H coupling with alkynes and a subsequent redox-neutral C-N cyclization reaction. This labile N-O bond-based protocol has allowed the toleration of a broad range of functional groups.
- Yang, Fan,Yu, Jiaojiao,Liu, Yun,Zhu, Jin
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supporting information
p. 2885 - 2888
(2017/06/07)
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- BIARYL PYRAZOLES AS NRF2 REGULATORS
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The present invention relates to biaryl pyrazole compounds, methods of making them, pharmaceutical compositions containing them and their use as NRF2 regulators.
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Page/Page column 515; 516
(2017/08/01)
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- PYRAZOLO[1,5-A]PYRIMIDINYL CARBOXAMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
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The invention provides substituted pyrazolo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[1,5-a]pyrimidinyl carboxamide compounds described herein include 2-heterocyclyl-4-alkyl-pyrazolo[1,5-a]pyrirnidine-3-carboxarnide compounds and variants thereof.
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Paragraph 00586
(2017/11/06)
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- Design, synthesis and in vitro activity of phidianidine B derivatives as novel PTP1B inhibitors with specific selectivity
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A series of phidianidine B derivatives were synthesized by introducing various heterocyclic rings. Their inhibitory effects on PTP1B and other PTPs (TCPTP, SHP1, SHP2 and LAR) were evaluated. A majority of them displayed significant inhibitory potency and specific selectivity over PTP1B. The SAR and molecular docking analysis were also described.
- Zhang, Li,Jiang, Cheng-Shi,Gao, Li-Xin,Gong, Jing-Xu,Wang, Zhong-Hua,Li, Jing-Ya,Li, Jia,Li, Xu-Wen,Guo, Yue-Wei
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supporting information
p. 778 - 781
(2016/05/24)
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- A 1, 2, 4-oxadiazole micromolecule the main body material and its preparation method, application
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The invention discloses a 1, 2, 4-oxadiazole micromolecule main body material. The 1, 2, 4-oxadiazole micromolecule main body material contains one or multiple electrophilic 1, 2, 4-oxadiazoles which serve as electron acceptor units, wherein the tail ends of molecules are connected to electron donor units. The invention also discloses a preparation method of the micromolecule main body material. The preparation method is characterized in that a dibromo substituted intermediate, namely a 1, 2, 4-oxadiazole compound is prepared by using bromobenzonitrile as a reaction raw material, and then electron donor units are connected to the dibromo substituted intermediate, namely the 1, 2, 4-oxadiazole compound through Suzuki coupling reaction. The invention also discloses an application of the 1, 2, 4-oxadiazole micromolecule main body material. The 1, 2, 4-oxadiazole micromolecule main body material has relatively good solubility and film-forming property, relatively strong eletrophilicity, relatively low LUMO (Lowest Unoccupied Molecular Orbital) energy level and relatively high electronic mobility.
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Paragraph 0079 - 0081
(2017/02/24)
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- An efficient one-pot synthesis of 3-aryl-5-(dialkoxymethyl)-1,2,4-oxadiazoles under solvent-free conditions
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An efficient and simple synthesis of 3-aryl-5-(dialkoxymethyl)-1,2,4-oxadiazoles is described. The in situ prepared amidoximes from the reaction between nitriles and hydroxylamine are condensed with alkyl 2,2-dialkoxyacetates under solvent-free conditions
- Adib, Mehdi,Saeedi, Sara,Soheilizad, Mehdi,Bayanati, Maryam,Tajbakhsh, Mahmood,Amanlou, Massoud
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p. 314 - 317
(2016/07/06)
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- METABOTROPIC GLUTAMATE RECEPTOR NEGATIVE ALLOSTERIC MODULATORS (NAMS) AND USES THEREOF
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Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor negative allosteric modulators (NAMs), compositions comprising the compounds, and methods of using the compounds and compositions.
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Page/Page column 119
(2016/01/01)
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- Synthesis of new bipolar host materials based on 1,2,4-oxadiazole for blue phosphorescent OLEDs
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Two novel bipolar host materials, namely 3,5-bis(4-(9H-carbazol-9-yl) phenyl)-1,2,4-oxadiazole (pCzmOXD) and 3,5-bis(3-(9H-carbazol-9-yl)phenyl)-1,2, 4-oxadiazole (mCzmOXD) were designed and synthesized, by incorporating a new block 1,2,4-oxadiazole as th
- Li, Qian,Cui, Lin-Song,Zhong, Cheng,Yuan, Xiao-Dong,Dong, Shou-Cheng,Jiang, Zuo-Quan,Liao, Liang-Sheng
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p. 142 - 149
(2013/11/19)
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- Asymmetric design of bipolar host materials with novel 1,2,4-oxadiazole unit in blue phosphorescent device
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The intrinsic asymmetry of 1,2,4-oxadiazole was utilized to synthesize three isomers, DCzmOXD-1, DCzmOXD-2, and mCzmOXD, and high triplet energies over 2.80 eV made them good candidates for host materials in blue OLEDs. The best efficiencies of 23.0 cd A
- Li, Qian,Cui, Lin-Song,Zhong, Cheng,Jiang, Zuo-Quan,Liao, Liang-Sheng
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supporting information
p. 1622 - 1625
(2014/04/17)
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- Design, synthesis and SAR of piperidyl-oxadiazoles as 11β- hydroxysteroid dehydrogenase 1 inhibitors
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The potential roles of 11β-HSD1 inhibitors in metabolic syndrome, T2D and obesity were well established and currently several classes of 11β-HSD1 inhibitors have been developed as promising agents against metabolic diseases. To find potent compounds with good pharmacokinetics, we used the bioisosterism approach, and designed the compound 2 and 3 bearing an 1,2,4-oxadiazole ring to replace the amide group in compound 1. Guided by docking study, we then transformed compound 3 into a potent lead compound 4a by changing sulfonamide group to amide. To elaborate this series of piperidyl-oxadiazole derivatives as human 11β-HSD1 inhibitors, we explored the structure-activity relationship of several parts of the lead compound. Based on their potency toward human 11β-HSD1 two compounds 4h and 4q were advanced to pharmacokinetic study. It was found that 4h and 4q are potent and selective human 11β-HSD1 inhibitors with better pharmacokinetic properties than those of the original piperidine-3-carboxamide compound 1, and suitable for further in vivo preclinical study in primate model.
- Xia, Guangxin,You, Xiaodi,Liu, Lin,Liu, Haiyan,Wang, Jianfa,Shi, Yufang,Li, Ping,Xiong, Bing,Liu, Xuejun,Shen, Jingkang
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- Condensation of Vilsmeier salts, derived from tetraalkylureas, with amidoximes: a novel approach to access N,N-dialkyl-1,2,4-oxadiazol-5-amines
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A novel approach, consendation of vilsmeier salts and amidoximes, to access N,N-dialkyl-1,2,4-oxadiazol-5-amines has been developed. By this approach, a broad range of N,N-dialkyl-1,2,4-oxadiazol-5-amines, including aromatic, heteroaromatic and alphatic s
- Su, Dongshan,Duan, Haifeng,Wei, Zhonglin,Cao, Jungang,Liang, Dapeng,Lin, Yingjie
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supporting information
p. 6959 - 6963
(2019/04/10)
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- Synthesis of amidoximes using an efficient and rapid ultrasound method
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This is a report on an efficient and rapid synthesis of amidoximes using ultrasound irradiation with appropriate nitrile and hydroxylamine hydrochloride in water/ethanol. This new synthetic methodology is compared with previously known methods. The main a
- Barros, Carlos Jonnatan Pimentel,De Freitas, Jucleiton J. Rufino,De Oliveira, Ronaldo N.,De Freitas Filho, Jo?o R.
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experimental part
p. 721 - 722
(2012/05/20)
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- BIARYL CARBOXAMIDES
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This invention provides compounds of Formula (I) which are PAFR antagonists: Formula (I) and the pharmaceutically acceptable salts thereof. The compounds are useful for treating PAF-mediated disorders, and can be used in methods for treating atherosclerosis and preventing or reducing risk for atherosclerotic disease events. The compounds are also useful for treating or ameliorating pain, e.g. inflammatory pain and/or nociceptive pain, and for treating or ameliorating autoimmune and/or inflammatory diseases, among other conditions.
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Page/Page column 35
(2010/08/04)
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- Synthesis, characterization, and antimicrobial activities of clubbed [1,2,4]-oxadiazoles with fluorobenzimidazoles
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(Chemical Equation Presented) In this study, a novel series of substituted 4,6-difluoro-2-{2-[3-(substituted-phenyl)-[1,2,4]-oxadiazol-5-yl]-ethyl} -1H-benzo[d]imidazole derivatives were synthesized by condensation of 2,4-difluoro-6-nitrophenyl amine with 3-(substitutedphenyl-[1,2,4]-oxadiazol- 5yl) propionic acid by using 2,4,6-trichlorobenzoyl chloride in the presence of triethyl amine base. The compounds were evaluated for their preliminary in vitro antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Salmonella typhosa. The antibacterial data of the tested compounds indicated that most of the synthesized compounds showed moderate activity with reference standard Gentamycin.
- Jadhav, Ganesh R.,Shaikh, Mohammad U.,Kale, Rajesh P.,Ghawalkar, Anand R.,Gill, Charansingh H.
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experimental part
p. 980 - 987
(2009/12/05)
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- PTSA-ZnCl2: An efficient catalyst for the synthesis of 1,2,4-oxadiazoles from amidoximes and organic nitriles
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(Chemical Equation Presented) PTSA-ZnCl2 has been proved to be an efficient and mild catalyst for the synthesis of 3,5-disubstituted-1,2,4- oxadiazoles from amidoximes and organic nitriles.
- Augustine, John Kallikat,Akabote, Vani,Hegde, Shrivatsa Ganapati,Alagarsamy, Padma
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supporting information; experimental part
p. 5640 - 5643
(2009/12/08)
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- A novel, one-pot, three-component synthesis of 1,2,4-oxadiazoles under microwave irradiation and solvent-free conditions
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A novel synthesis of 3,5-disubstituted 1,2,4-oxadiazoles is described from a one-pot, three-component reaction between nitriles, hydroxylamine, and Meldrum's acids under microwave irradiation and solvent-free conditions in good to excellent yields. Georg
- Adib, Mehdi,Mahdavi, Mohammad,Mahmoodi, Niusha,Pirelahi, Hooshang,Bijanzadeh, Hamid Reza
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p. 1765 - 1767
(2008/02/04)
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