- Insertion of Diazo Esters into C-F Bonds toward Diastereoselective One-Carbon Elongation of Benzylic Fluorides: Unprecedented BF3Catalysis with C-F Bond Cleavage and Re-formation
-
Selective transformation of C-F bonds remains a significant goal in organic chemistry, but C-F insertion of a one-carbon-atom unit has never been established. Herein we report the BF3-catalyzed formal insertion of diazo esters as one-carbon-atom sources into C-F bonds to accomplish one-carbon elongation of benzylic fluorides. A DFT calculation study revealed that the BF3 catalyst could contribute to both C-F bond cleavage and re-formation. This elongation provided α-fluoro-α,β-diaryl esters with a high level of diastereoselectivity. Various benzylic fluorides and diazo esters were applicable. The synthetic utility of this method was demonstrated by the synthesis of a fluoro analogue of a compound that is used as a transient receptor and potential canonical channel inhibitor.
- Wang, Fei,Nishimoto, Yoshihiro,Yasuda, Makoto
-
supporting information
p. 20616 - 20621
(2021/11/23)
-
- PYRAZOLOTRIAZOLOPYRIMIDINE DERIVATIVES AS A2A RECEPTOR ANTAGONIST
-
Disclosed herein is a pyrazolotriazolopyrimidine derivative or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof useful as A2A receptor antagonist, and a pharmaceutical composition comprising the same. Also disclosed herein is a method of treating cancer using the pyrazolotriazolopyrimidine derivative or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as A2A receptor antagonist.
- -
-
Paragraph 0699-0701
(2020/02/16)
-
- Pd-Catalyzed Decarboxylative Olefination: Stereoselective Synthesis of Polysubstituted Butadienes and Macrocyclic P-glycoprotein Inhibitors
-
The efficient and stereoselective synthesis of polysubstituted butadienes, especially the multifunctional butadienes, represents a great challenge in organic synthesis. Herein, we wish to report a distinctive Pd(0) carbene-initiated decarboxylative olefination approach that enables the direct coupling of diazo esters with vinylethylene carbonates (VECs), vinyl oxazolidinones, or vinyl benzoxazinones to afford alcohol-, amine-, or aniline-containing 1,3-dienes in moderate to high yields and with excellent stereoselectivity. This protocol features operational simplicity, mild reaction conditions, a broad substrate scope, and gram-scalability. Notably, a structurally unique allylic Pd(II) intermediate was isolated and characterized. DFT calculation and control experiments demonstrated that a rare Pd(0) carbene intermediate could be involved in this reaction. Moreover, the polysubstituted butadienes as novel building blocks were unprecedentedly assembled into macrocycles, which efficiently inhibited the P-glycoprotein and dramatically reversed multidrug resistance in cancer cells by 190-fold.
- Chen, Xiangyang,Hao, Jiping,Houk, K. N.,Li, Yingzi,Lou, Liguang,Quan, Haitian,Song, Bichao,Wang, Lu,Xia, Yuanzhi,Xie, Peipei,Xu, Zhongliang,Yang, Weibo
-
supporting information
p. 9982 - 9992
(2020/06/27)
-
- ARYL-SUBSTITUTED ACETAMIDE AND PYRROLIDIN-2-ONE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF SEIZURES
-
Aryl-substituted acetamide and pyrrolidin-2-one (γ-butyrolactam) derivatives have useful activity in the inhibition, prevention, or treatment of seizures. The derivatives may be useful in the treatment of epilepsy, including medically refractory epilepsy, and nerve agent poisoning.
- -
-
Paragraph 0068; 0069
(2019/06/09)
-
- Synthesis and bio-evaluation of natural butenolides-acrylate conjugates
-
A series of novel 3-aryl-4-hydroxy-2(5H) furanone-acrylate hybrids were designed and synthesized based on the natural butenolides and acrylates scaffolds. The structures of the prepared compounds were characterized by 1H-NMR, 13C-NMR and electrospray ionization mass spectrometry (ESI-MS), and the bioactivity of the target compounds against twelve phytopathogenic fungi was investigated. The preliminary in vitro antifungal activity screening showed that most of the target compounds had moderate inhibition on various pathogenic fungi at the concentration of 100 mg·L?1, and presented broad-spectrum antifungal activities. Further studies also indicated that compounds 7e and 7k still showed some inhibitory activity against Pestallozzia theae, Sclerotinia sclerotiorum and Gibberella zeae on rape plants at lower concentrations, which could be optimized as a secondary lead for further research.
- Bao, Longzhu,Wang, Shuangshuang,Song, Di,Wang, Jingjing,Cao, Xiufang,Ke, Shaoyong
-
-
- Dehydroxymethylation of alcohols enabled by cerium photocatalysis
-
Dehydroxymethylation, the direct conversion of alcohol feedstocks as alkyl synthons containing one less carbon atom, is an unconventional and underexplored strategy to exploit the ubiquity and robustness of alcohol materials. Under mild and redox-neutral reaction conditions, utilizing inexpensive cerium catalyst, the photocatalytic dehydroxymethylation platform has been furnished. Enabled by ligand-to-metal charge transfer catalysis, an alcohol functionality has been reliably transferred into nucleophilic radicals with the loss of one molecule of formaldehyde. Intriguingly, we found that the dehydroxymethylation process can be significantly promoted by the cerium catalyst, and the stabilization effect of the fragmented radicals also plays a significant role. This operationally simple protocol has enabled the direct utilization of primary alcohols as unconventional alkyl nucleophiles for radical-mediated 1,4-conjugate additions with Michael acceptors. A broad range of alcohols, from simple ethanol to complex nucleosides and steroids, have been successfully applied to this fragment coupling transformation. Furthermore, the modularity of this catalytic system has been demonstrated in diversified radical-mediated transformations including hydrogenation, amination, alkenylation, and oxidation.
- Zhang, Kaining,Chang, Liang,An, Qing,Wang, Xin,Zuo, Zhiwei
-
supporting information
p. 10556 - 10564
(2019/08/20)
-
- Dehydroxymethylation of Alcohols Enabled by Cerium Photocatalysis
-
Dehydroxymethylation, the direct conversion of alcohol feedstocks as alkyl synthons containing one less carbon atom, is an unconventional and underexplored strategy to exploit the ubiquity and robustness of alcohol materials. Under mild and redox-neutral reaction conditions, utilizing inexpensive cerium catalyst, the photocatalytic dehydroxymethylation platform has been furnished. Enabled by ligand-to-metal charge transfer catalysis, an alcohol functionality has been reliably transferred into nucleophilic radicals with the loss of one molecule of formaldehyde. Intriguingly, we found that the dehydroxymethylation process can be significantly promoted by the cerium catalyst, and the stabilization effect of the fragmented radicals also plays a significant role. This operationally simple protocol has enabled the direct utilization of primary alcohols as unconventional alkyl nucleophiles for radical-mediated 1,4-conjugate additions with Michael acceptors. A broad range of alcohols, from simple ethanol to complex nucleosides and steroids, have been successfully applied to this fragment coupling transformation. Furthermore, the modularity of this catalytic system has been demonstrated in diversified radical-mediated transformations including hydrogenation, amination, alkenylation, and oxidation.
- Zhang, Kaining,Chang, Liang,An, Qing,Wang, Xin,Zuo, Zhiwei
-
supporting information
p. 10556 - 10564
(2019/08/28)
-
- Palladium-Catalyzed Tandem Reaction of Three Aryl Iodides Involving Triple C-H Activation
-
A novel palladium-catalyzed tandem reaction of N-(2-iodoaryl)acrylamides with two aryl iodides for the synthesis of spirooxindole has been achieved. The reaction underwent the process of triple C-H activation and four C-C bond formations based on the double trapping of transient spirocyclic palladacycles which are obtained through remote C-H activation.
- Luo, Xiai,Xu, Yankun,Xiao, Genhua,Liu, Wenjuan,Qian, Cheng,Deng, Guobo,Song, Jianxin,Liang, Yun,Yang, Chunming
-
supporting information
p. 2997 - 3000
(2018/05/28)
-
- Stereoselective synthesis of 3,4-di-substituted mercaptolactones via photoredox-catalyzed radical addition of thiophenols
-
A visible light mediated radical addition of thiophenols on 4-phenylbut-3-enoic acids to give diastereoselective synthesis of 3,4-disubstituted γ-lactones is reported. The reaction precludes the conventional prerequisite of conjugate addition. Furthermore, the lactones were successfully utilized in the synthesis of γ-ketoamides.
- Kouser, Farzana,Sharma, Vijay Kumar,Rizvi, Masood,Sultan, Shaista,Chalotra, Neha,Gupta, Vivek K.,Nandi, Utpal,Shah, Bhahwal Ali
-
supporting information
p. 2161 - 2166
(2018/05/05)
-
- HETEROCYCLIC COMPOUNDS
-
The present invention relates to compounds of the general formula (1) wherein the variables are defined as given in the description and claims. The invention further relates to uses of and to, processes and intermediates related to compounds of the general formula (I), wherein Q is wherein the substituents of I, Ia and Ib are as defined in description and claims.
- -
-
Page/Page column 91
(2018/07/29)
-
- Pd-Catalyzed Three-Component Domino Reaction of Vinyl Benzoxazinanones for Regioselective and Stereoselective Synthesis of Allylic Sulfone-Containing Amino Acid Derivatives
-
A Pd-catalyzed, highly regioselective and stereoselective three-component domino allylic substitution/N-H carbene insertion reaction under mild conditions is described. This reaction demonstrates a wide substrate scope and satisfactory functional group tolerance, providing a broad range of allylic sulfone-containing amino acid derivatives. Moreover, DBU mediates highly diastereoselective cross-dehydrogenative coupling annulation of allylic sulfones without using peroxides or any metal oxidants. This developed protocol affords 7-membered ring heterocyclic compounds incorporating both sulfone-containing amino acid esters and one quaternary carbon center. Mechanistic studies indicate that an unusual umpolung of glycine occurred in this annulation.
- Hao, Jiping,Xu, Yi,Xu, Zhongliang,Zhang, Zhiqiang,Yang, Weibo
-
supporting information
p. 7888 - 7892
(2019/01/04)
-
- The computer-aided discovery of novel family of the 5-HT6 serotonin receptor ligands among derivatives of 4-benzyl-1,3,5-triazine
-
The work describes a discovery of new chemical family of potent ligands for the 5-HT6 serotonin receptors. During the search for new histamine H4 receptor antagonists among 1,3,5-triazine derivatives, compound 2 (4-benzyl-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine) was found. Compound 2, weakly active for the H4 receptor but fitted in 3/4 of pharmacophore features of the 5-HT6R ligand, occurred to be a moderate 5-HT6R agent, useful as a lead structure for further modifications. A series of new derivatives (3–19) of the lead 2 was synthesized, evaluated in the radioligand binding assay (RBA) and explored in comprehensive molecular modelling, including both pharmacophore- and structure-based approaches with docking to the homology model of 5-HT6R. The most active compounds displayed a potent affinity for the 5-HT6R in the nanomolar range (Ki?=?20–30?nM), some of them (4, 11 and 19) were tested in the rat forced swim test that revealed their antidepressant-like effect. SAR-analysis on the basis of both, RBA and docking results, indicated that action on the receptor is related to the hydrophobicity and the size of aromatic moiety substituted by a methylene linker at the position 4 of 1,3,5-triazine.
- ?a?ewska, Dorota,Kurczab, Rafa?,Wi?cek, Ma?gorzata,Kamińska, Katarzyna,Sata?a, Grzegorz,Jastrz?bska-Wi?sek, Magdalena,Partyka, Anna,Bojarski, Andrzej J.,Weso?owska, Anna,Kie?-Kononowicz, Katarzyna,Handzlik, Jadwiga
-
supporting information
p. 117 - 124
(2017/04/26)
-
- Discovery, synthesis, and structure-activity relations of 3,4-dihydro-1H-spiro(naphthalene-2,2′-piperidin)-1-ones as potassium-competitive acid blockers
-
With the aim to discover a gastric antisecretory agent more potent than the existing proton pump inhibitors, novel 3,4-dihydro-1H-spiro(naphthalene-2,2′-piperidin)-1-one derivatives, which could occupy two important lipophilic pockets (described as LP-1 and LP-2) of H+,K+-ATPase and can strongly bind to the K+-binding site, were designed based on a docking model. Among the compounds synthesized, compound 4d showed a strong H+,K+-ATPase-inhibitory activity and a high stomach concentration in rats, resulting in potent inhibitory action on histamine-stimulated gastric acid secretion in rats. Furthermore, 4d exerted significant inhibitory action on histamine-stimulated gastric-acid secretion in rats with a rapid onset and moderate duration of action after the administration. These findings may lead to a new insight into the drug design of potassium-competitive acid blockers.
- Imaeda, Toshihiro,Ono, Koji,Nakai, Kazuo,Hori, Yasunobu,Matsukawa, Jun,Takagi, Terufumi,Fujioka, Yasushi,Tarui, Naoki,Kondo, Mitsuyo,Imanishi, Akio,Inatomi, Nobuhiro,Kajino, Masahiro,Itoh, Fumio,Nishida, Haruyuki
-
p. 3719 - 3735
(2017/06/13)
-
- Synthesis and Biological Evaluation of New (-)-Gossypol-Derived Schiff Bases and Hydrazones
-
A series of 14 new (-)-gossypol Schiff bases and hydrazones have been synthesized via an in situ procedure in high yields. Structural data showed that all target compounds exist as the enamine tautomer. Bioassays showed that several compounds exhibited cytotoxic effects against three human cancer cell lines. Compound 8a showed the greatest cytotoxic effect against hepatocellular carcinoma (HepG2), lung carcinoma (LU-1), and breast cancer (MCF-7) cell lines with IC50 values of 20.93, 13.58, and 9.40 μM, respectively. However, in an antibacterial test, compounds 8a and 8b inhibited Staphylococcus aureus and Bacillus cereus and compound 8e inhibited only Staphylococcus aureus at the same MIC values of 1024 μg/ml.
- Vu, Vu Van,Nhung, Trinh Thi,Thanh, Nguyen Thi,Chinh, Luu Van,Tien, Vu Dinh,Thuy, Vu Thu,Thi Thao, Do,Nam, Nguyen Hai,Koeckritz, Angela,Vu, Tran Khac
-
-
- Acetylcholinesterase inhibition activity of some quinolinyl substituted triazolothiadiazole derivatives
-
A series of aralkanoic acids was converted into aralkanoic acid hydrazides through their esters formation. The aralkanoic acid hydrazides upon treatment with carbon disulfide and methanolic potassium hydroxide yielded potassium dithiocarbazinate salts, which on refluxing with aqueous hydrazine hydrate yielded 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles. The target compounds, 3-aralkyl-6-(substitutedquinolinyl) [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, were synthesized by condensing various quinolinyl substituted carboxylic acids with 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles in phosphorus oxychloride. The structures of the newly synthesized triazolothiadiazoles were characterized by IR, 1H NMR, 13C NMR, and elemental analysis studies. The structure of one of the 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles was unambiguously deduced by single crystal X-ray diffraction analysis. All the synthesized compounds were screened for their acetylcholinesterase inhibition activities. Four of the triazolothiadiazoles exhibited excellent acetylcholinesterase inhibition activities as compared to the reference inhibitor.
- Rafiq, Muhammad,Saleem, Muhammad,Hanif, Muhammad,Abbas, Qamar,Lee, Ki Hwan,Seo, Sung-Yum
-
p. 170 - 177
(2015/04/14)
-
- Synthesis and biological activities of some new 3,6-disubstituted 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole derivatives
-
A series of aromatic hydrazides 3a-j were prepared by refluxing esters 2a-j with hydrazine hydrate in methanol, which were prepared by the esterification of 1a-j. Acetohydrazides 3a-j upon treatment with carbon disulfide and methanolic potassium hydroxide yielded potassium dithiocarbazate salts 4a-j, which on refluxing with hydrazine hydrate yielded substituted 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones 5a-j. The target compounds 6a-j were synthesized by condensing furan-3-carboxylic acid in the presence of polyphosphoric acid under reflux. The structures of newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, elemental analysis and mass spectrometric studies. All the synthesized compounds were screened for their urease, acetylcholine esterase inhibition, antioxidant and alkaline phosphatase inhibition activity. Almost all of the compounds 6a-j showed good to excellent activities against urease and acetylcholine esterase more than the reference drugs. Compounds 6f and 6g were more potent scavenger of free radicals than the reference n-propyl gallate. Compound 6b and 6h showed excellent activities of alkaline phosphatase as compare to the reference KH 2PO4.
- Rafiq, Muhammad,Saleem, Muhammad,Hanif, Muhammad,Maqsood, Muhammad Rizwan,Rama, Nasim Hasan,Lee, Ki-Hwan,Seo, Sung-Yum
-
p. 3943 - 3949
(2013/08/23)
-
- Some pyridyl- and thiophenyl- Substituted 1,2,4-triazolo[3,4-b]1,3,4- thiadiazole derivatives as potent antibacterial
-
The target compounds 6-11a-e were synthesized by condensing 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones 5a-f with various aromatic carboxylic acids in the presence of phosphorous oxychloride. The structures of newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, elemental analysis and mass spectrometric studies. All the synthesized compounds were screened for their antibacterial activity. Almost all the tested compounds were potent against four different strains of bacteria when compared with that of reference drug ciprofloxacin. Compounds 6c, 6e, 8d, 9b, 9e, 11a and 11b showed nearly equal or lower MIC values than standard drug, against all four tested bacterial strains but rest of the compounds showed excellent antibacterial activities.
- Maqsood, Muhammad Rizwan,Hanif, Muhammad,Rafiq, Muhammad,Saleem, Muhammad,Zaib, Sumera,Khan, Aftab Ahmed,Iqbal, Mazhar,Iqbal, Jamshed,Rama, Nasim Hasan,Seo, Sung-Yum,Lee, Ki-Hwan
-
p. 4180 - 4184
(2013/08/23)
-
- SUBSTITUTED AROMATIC CARBOXAMIDE AND UREA DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
-
The invention relates to substituted aromatic carboxamide and urea derivatives, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions (formula (I)).
- -
-
Page/Page column 127; 128
(2010/11/18)
-
- NAPHTHALENONE COMPOUNDS EXHIBITING PROLYL HYDROXYLASE INHIBITORY ACTIVITY, COMPOSITIONS, AND USES THEREOF
-
Compounds of Formula (I) and Formula (II) are useful as inhibitors of HIF prolyl hydroxylases. Compounds of Formula(I) and Formula (II) have the following structures, where the definitions of the variables are provided herein.
- -
-
Page/Page column 107; 209
(2008/12/06)
-
- 1,2-disubstituted-6-oxo-3-phenyl-piperidine-3-carboxamides and combinatorial libraries thereof
-
The invention relates to combinatorial libraries containing two or more novel piperidine-3-carboxamide derivative compounds, methods of preparing the piperidine-3-carboxamide derivative compounds and piperidine-3-carboxamide derivative compounds bound to a resin
- -
-
-
- Cyclohexane derivatives and their use as therapeutic agents
-
The present invention relates compounds of formula (I), wherein ring A is a phenyl or pyridyl ring; X represents a linker selected from the group consisting of formulae: (a), (b), (c), (d), and (e); and R1, R2, R3, R4, R5, R6, R7, R13, R14, R15, R16, R17, R21a and R21b are as defined herein. The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migraine, emesis or postherpetic neuralgia.
- -
-
-
- 3-aroylbenzylpyridazinone derivatives
-
Compounds of formula I: STR1 where: R10 is a group represented by formula (A), (B), or (C): STR2 and the other substituents are as defined in the specification; and their pharmaceutically acceptable salts are inhibitors of prostaglandin G/H synthase and are anti-inflammatory and analgesic agents.
- -
-
-
- 6-Benzyl-2H-pyridazin-3-one derivatives,their preparation and their use as inhibitors of prostaglandin G/H synthase I and II (COX I and COX II)
-
Compounds of formula I: where: the dashed line denotes an optional bond; R1is H, halo, alkyl, alkyloxy, amino, alkylamino, dialkylamino, or acylamino; R3and R4are independently H, halo, alkyl, alkyloxy, or hydroxy; R5
- -
-
-