- Ni-catalyzed direct carboxylation of an unactivated C-H bond with CO2
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The transition-metal-catalyzed direct carboxylation of an unactivated C-H bond is rarely reported, and no example of catalysis using abundant and cheap nickel has been reported. In this work, the first Ni-catalyzed direct carboxylation of an unactivated C-H bond under an atmospheric pressure of CO2 is reported. This method affords moderate to high carboxylation yields of various methyl carboxylates under mild conditions. Preliminary mechanistic studies reveal that a Ni(0)-Ni(II)-Ni(I) catalytic cycle may be involved in this reaction.
- Pei, Chunzhe,Zong, Jiarui,Han, Shanglin,Li, Bin,Wang, Baiquan
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Read Online
- Pd(II)-Catalyzed asymmetric oxidative annulation of N-alkoxyheteroaryl amides and 1,3-dienes
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The first Pd(II)-catalyzed asymmetric oxidative annulation of N-alkoxyaryl amides and 1,3-dienes is reported, which features particular applicability for quick assembly of different types of chiral heterocycles with high yields and enantioselectivities. A novel chiral pyridine-oxazoline bearing a methoxyl group at the C-5 position and a gem-dimethyl group on the oxazoline moiety was found to be crucial for conversion.
- Zhang, Tao,Shen, Hong-Cheng,Xu, Jia-Cheng,Fan, Tao,Han, Zhi-Yong,Gong, Liu-Zhu
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supporting information
p. 2048 - 2051
(2019/03/29)
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- Novel inhibitors of Staphylococcus aureus RnpA that synergize with mupirocin
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We recently discovered RnpA as a promising new drug discovery target for methicillin-resistant S. aureus (MRSA). RnpA is an essential protein that is thought to perform two required cellular processes. As part of the RNA degrasome Rnpa mediates RNA degradation. In combination with rnpB it forms RNase P haloenzymes which are required for tRNA maturation. A high throughput screen identified RNPA2000 as an inhibitor of both RnpA-associated activities that displayed antibacterial activity against clinically relevant strains of S. aureus, including MRSA. Structure-activity studies aimed at improving potency and replacing the potentially metabotoxic furan moiety led to the identification of a number of more potent analogs. Many of these new analogs possessed overt cellular toxicity that precluded their use as antibiotics but two derivatives, including compound 5o, displayed an impressive synergy with mupirocin, an antibiotic used for decolonizing MSRA whose effectiveness has recently been jeopardized by bacterial resistance. Based on our results, compounds like 5o may ultimately find use in resensitizing mupirocin-resistant bacteria to mupirocin.
- Lounsbury, Nicole,Eidem, Tess,Colquhoun, Jennifer,Mateo, George,Abou-Gharbia, Magid,Dunman, Paul M.,Childers, Wayne E.
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supporting information
p. 1127 - 1131
(2018/02/21)
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- ANTI-HIV COMPOUNDS
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Thiazole derivatives represented by Formula (I) are disclosed, where R1, R2, R3, A, X, Y, Z, R6 and R7 are disclosed herein. These thiazole derivatives and pharmaceutical compositions comprising these derivatives are useful in the treatment of HIV mediated diseases and conditions.
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Page/Page column 47-48; 52; 60; 75; 80
(2009/08/14)
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- Design and synthesis of 2-(3-benzo[b]thienyl)-6,7-methylenedioxyquinolin-4- one analogues as potent antitumor agents that inhibit tubulin assembly
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As part of our continuing investigation of azo-flavonoid derivatives as potential anticancer drug candidates, a series of 2-aryl-6,7- methylenedioxyquinolin-4-one analogues was designed and synthesized. The design combined structural features of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4- one (CHM-1), a previously discovered compound with potent in vivo antitumor activity, and 2-arylquinolin-4-ones, identified by CoMFA models. The newly synthesized analogues were evaluated for cytotoxicity against seven human cancer cell lines, and structure -activity relationship (SAR) correlations were established. Analogues 1, 37, and 39 showed potent cytotoxicity against different cancer cell lines. Compound 1 demonstrated selective cytotoxicity against Hep 3B (hepatoma) cells. Compound 37 was cytotoxic against HL-60 (leukemia), HCT-116 (colon cancer), Hep 3B (hepatoma), and SK-MEL-5 (melanoma) cells. Compound 39 exhibited broad cytotoxicity against all seven cancer cell lines, with IC50 values between 0.07 and 0.19 μM. Results from mechanism of action studies revealed that these new quinolone derivatives function as antitubulin agents.
- Chang, Yu-Hsun,Hsu, Mei-Hua,Wang, Sheng-Hung,Huang, Li-Jiau,Qian, Keduo,Morris-Natschke, Susan L.,Hamel, Ernest,Kuo, Sheng-Chu,Lee, Kuo-Hsiung
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experimental part
p. 4883 - 4891
(2010/02/28)
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- Further structure-activity relationships in the series of tropanyl esters endowed with potent antinociceptive activity
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Several analogs of the α-tropanyl esters of 2-(4-chlorophenoxy)butyric acid (SM21) and 2-phenylthiobutyric acid (SM32), endowed with potent antinociceptive and cognition enhancing activity, were synthesized, aimed at obtaining more potent and safe drug candidates. Variation of the acyl moiety, as well as the conformational restriction of atropine to give the α-tropanyl ester of 2,3-dihydrobenzofurane-3-carboxylic acid (18), practically abolished activity. In the case of 18, the antimuscarinic activity was also severely affected by the conformation restrain. On the contrary, conformational restriction of phenoxybutyric and phenylthiobutyric acid derivatives to give the α-tropanyl ester of 2,3-dihydro-benzofurane-2-carboxylic acid and 2,3-dihydro-benzothiophene-2-carboxylic acid, afforded potent analgesic drugs that unfortunately were too toxic to be reliable drug candidates. A series of related esters of benzofurane-3-carboxylic acid and benzothiophene-3-carboxylic acid were also studied and found to be potent but toxic analgesics.
- Scapecchi, Serena,Giorgi, Antonella,Bellucci, Cristina,Dei, Silvia,Ghelardini, Carla,Manetti, Dina,Romanelli, M. Novella,Teodori, Elisabetta
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p. 764 - 772
(2007/10/03)
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- Aminoalkylindoles: Structure - Activity Relationships of Novel Cannabinoid Mimetics
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Aminoalkylindoles (AAIs) are a novel series of cannabinoid receptor ligands.In this report we disclose the structural features of AAIs which are important for binding to this receptor as measured by inhibition of binding of 3H>Win 55212-2 (5).Functional activity in the mouse vas deferens is also noted and used to distinguish agonists from potential antagonists.The key structural features for potent cannabinoid activity in this series are a bicyclic (naphthyl) substituent at the 3-position, a small (H) substituent at the 2-position, and an aminoethyl (morpholinoethyl) substituent at the 1-position.A 6-bromo analog, Win 54461 (31), has been identified as a potential cannabinoid receptor antagonist.Modeling experiments were done to develop a pharmacophore and also to compare AAI structures with those of classical cannabinoids.The fact that the cannabinoid AAIs arose out of work on a series of cyclooxygenase inhibitors makes sense now that an endogenous cannabinoid ligand has been identified which is a derivative of arachidonic acid.Because of their unique structures and physical properties, AAIs provide useful tools to study the structure and function of the cannabinoid receptor(s).
- Eissenstat, Michael A.,Bell, Malcolm R.,D'Ambra, Thomas E.,Alexander, E. John,Daum, Sol J.,et al.
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p. 3094 - 3105
(2007/10/02)
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- Conformational Analysis of Organic Carbonyl Compounds. Part 5. p-Methoxybenzoyl Derivatives of Benzofuran, Benzothiophene, and Naphthalene
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The conformational analysis of 2- and 3-(p-methoxybenzoyl)-benzofuran and -benzothiophene and 1- and 2-(p-methoxybenzoyl)naphthalene was performed by the n.m.r. lanthanide-induced shift (LIS) method on 1H and 13C chemical shifts with Yb(fod)3 as shi
- Benassi, Rois,Folli, Ugo,Iarossi, Dario,Schenetti, Luisa,Taddei, Ferdinando
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p. 351 - 358
(2007/10/02)
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