- Biocatalytic Strategy for the Highly Stereoselective Synthesis of CHF2-Containing Trisubstituted Cyclopropanes
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The difluoromethyl (CHF2) group has attracted significant attention in drug discovery and development efforts, owing to its ability to serve as fluorinated bioisostere of methyl, hydroxyl, and thiol groups. Herein, we report an efficient biocat
- Carminati, Daniela M.,Decaens, Jonathan,Couve-Bonnaire, Samuel,Jubault, Philippe,Fasan, Rudi
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supporting information
p. 7072 - 7076
(2021/02/27)
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- Synthesis of various acylating agents directly from carboxylic acids
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A straightforward synthesis of acylating reagents such as Weinreb and MAP amides from aromatic, aliphatic carboxylic acids, and amino acids using PPh3/NBS combination is described. A chemo-selective modification of the carboxylic acid group into Weinreb amide in the presence of more reactive aldehydes and ketones is presented. All reactions were performed at ambient temperature under air using undried commercial grade solvent. Furthermore, the present methodology could be performed at a gram scale under inert-free reaction conditions. In addition, 7-azaindoline amide auxiliary (used for catalytic asymmetric aldol- and Mannich-type reactions), which behaves like Weinreb amide is also synthesized under similar reaction conditions.
- Pilathottathil, Fathima,Vineet Kumar, Doppalapudi,Kaliyamoorthy, Alagiri
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supporting information
p. 1622 - 1632
(2020/04/27)
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- A small-molecule cell-based screen led to the identification of biphenylimidazoazines with highly potent and broad-spectrum anti-apicomplexan activity
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An in vitro screening of the anti-apicomplexan activity of 51 compounds, stemming from our chemical library and from chemical synthesis, was performed. As a study model, we used Toxoplasma gondii (T. gondii), expressing β-galactosidase for the colorimetric assessment of drug activity on parasites cultivated in vitro. This approach allowed the validation of a new series of molecules with a biphenylimidazoazine scaffold as inhibitors of T. gondii growth in vitro. Hence, 8 molecules significantly inhibited intracellular replication of T. gondii in vitro, with EC50 50 in the submicromolar to nanomolar range, for each parasite. These data, including the broad anti-parasite spectrum of these inhibitors, define a new generation of potential anti-parasite compounds of wide interest, including for veterinary application. Studies realized on E. tenella suggest that these molecules act during the intracellular development steps of the parasite. Further experiments should be done to identify the molecular target(s) of these compounds.
- Moine, Espérance,Denevault-Sabourin, Caroline,Debierre-Grockiego, Fran?oise,Silpa, Laurence,Gorgette, Olivier,Barale, Jean-Christophe,Jacquiet, Philippe,Brossier, Fabien,Gueiffier, Alain,Dimier-Poisson, Isabelle,Enguehard-Gueiffier, Cécile
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p. 386 - 400
(2014/12/11)
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- Copper-catalyzed synthesis of weinreb amides by oxidative amidation of alcohols
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A simple and efficient protocol has been developed for the oxidative amidation of alcohols to Weinreb amides using tert-butyl hydroperoxide as an oxidant and an inexpensive and air stable copper catalyst. The present protocol is advantageous as it uses commercially affordable alcohols as starting materials. The developed protocol also tolerates various substituted alcohols as starting materials to provide good to excellent yields of the desired products.
- Yedage, Subhash L.,Bhanage, Bhalchandra M.
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p. 526 - 532
(2015/02/19)
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- Synthesis and structure-activity relationships of benzophenone-bearing diketopiperazine-type anti-microtubule agents
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KPU-105 (4), a potent anti-microtubule agent that contains a benzophenone was derived from the diketopiperazine-type vascular disrupting agent (VDA) plinabulin 3, which displays colchicine-like tubulin depolymerization activity. To develop derivatives wit
- Hayashi, Yoshio,Yamazaki, Yuri,Sumikura, Makiko,Masuda, Yurika,Hayashi, Yoshiki,Yasui, Hiroyuki,Kiso, Yoshiaki,Chinen, Takumi,Usui, Takeo,Yakushiji, Fumika,Potts, Barbara,Neuteboom, Saskia,Palladino, Michael,Lloyd, George Kenneth
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experimental part
p. 4279 - 4289
(2012/09/08)
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- A Weinreb amide approach to the synthesis of trifluoromethylketones
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A novel route to access trifluoromethylketones (TFMKs) from Weinreb amides is reported. This represents the first documented case of the Ruppert-Prakash reagent (TMS-CF3) reacting in a constructive manner with an amide and enables synthesis of TMFKs without risk of over-trifluoromethylation.
- Rudzinski, Diandra M.,Kelly, Christopher B.,Leadbeater, Nicholas E.
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supporting information
p. 9610 - 9612
(2012/10/29)
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- Ru-catalyzed hydrogenation of 3,5-diketo amides: Simultaneous control of chemo- and enantioselectivity
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By modulating the chelating priorities of the different directing groups in 3,5-diketo amides with the assistance from coordinating solvent, highly chemo- and enantioselective hydrogenation of the C3-carbonyls was achieved in the presence of [RuCl(benzene)(S)-SunPhos]Cl in THF.
- Li, Wanfang,Fan, Weizheng,Ma, Xin,Tao, Xiaoming,Li, Xiaoming,Xie, Xiaomin,Zhang, Zhaoguo
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supporting information
p. 8976 - 8978
(2012/11/07)
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- Palladium-catalyzed carbonylation reactions of aryl bromides at atmospheric pressure: A general system based on xantphos
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(Chemical Equation Presented) A method for the Pd-catalyzed carbonylation of aryl bromides has been developed using Xantphos as the ligand. This method is effective for the direct synthesis of Weinreb amides, 1° and 2° benzamides, and methyl esters from the corresponding aryl bromides at atmospheric pressure. In addition, a putative catalytic intermediate, (Xanphos)Pd(Br)benzoyl, was prepared and an X-ray crystal structure was obtained revealing an unusual cis-coordination mode of Xantphos in this palladium-acyl complex.
- Martinelli, Joseph R.,Watson, Donald A.,Freckmann, Dominique M. M.,Barder, Timothy E.,Buchwald, Stephen L.
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supporting information; experimental part
p. 7102 - 7107
(2009/05/09)
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- PYRIDAZINONE COMPOUNDS AS CALCILYTICS
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Various calcilytic compounds and pharmaceutical compositions containing these compounds are disclosed. Calcilytic compounds are compounds capable of inhibiting calcium receptor activity. Methods for preparing calcilytic compounds, oral bioavailability of calcilytic compounds, and their use as calcium receptor antagonists are also disclosed.
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Page/Page column 48
(2010/11/27)
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- Convenient method for the preparation of weinreb amides via PD-catalyzed aminocarbonylation of aryl bromides at atmospheric pressure
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(Chemical Equation Presented) The direct transformation of aryl bromides into the corresponding Weinreb amides via Pd-catalyzed aminocarbonylation at atmospheric pressure is reported.
- Martinelli, Joseph R.,Freckmann, Dominique M. M.,Buchwald, Stephen L.
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p. 4843 - 4846
(2007/10/03)
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- Calcium receptor antagonist
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A compound of the formula [I] wherein R1 is optionally substituted aryl group or optionally substituted heteroaryl group; R2 is optionally substituted C1-6 alkyl group, C3-7 cycloalkyl group and the like; R3 is hydrogen atom, C1-6 alkyl group, hydroxyl group and the like; R4 is hydrogen atom, C1-6 alkyl group and the like; R5 and R6 are each C1-6 alkyl group and the like; R7 is optionally substituted aryl group or optionally substituted heteroaryl group; X1, X2 and X3 are each C1-6 alkylene group and the like; and X4 and X5 are each a single bond, methylene group and the like, a salt thereof, a solvate thereof or a prodrug thereof, and a pharmaceutical composition containing the compound, particularly a calcium receptor antagonist and a therapeutic agent for osteoporosis, are provided. The compound of the present invention is useful as a therapeutic drug of diseases accompanied by abnormal calcium homeostasis, or osteoporosis, hypoparathyreosis, osteosarcoma, periodontal disease, bone fracture, steoarthrosis, chronic rheumatoid arthritis, Paget's disease, humoral hypercalcemia, autosomal dominant hypocalcemia and the like. In addition, an intermediate for the compound is provided.
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- Imidazole derivatives and their use as cytokine inhibitors
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As cytokine inhibitors 2,4,5-triarylimidazole compounds and compositions for use as cytokine inhibitors.
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- Regulation of stress-induced cytokine production by pyridinylimidazoles inhibition of CSBP kinase
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Members of three classes of pyridinylimidazoles bind with varying affinities to CSBP (p38) kinase which is a member of a stress-induced signal transduction pathway. Based upon SAR and protein homology modeling, the pharmacophore and three potential modes of binding to the enzyme are presented. For a subset of pyridinylimidazoles, binding is shown to correlate with inhibition of CSBP kinase activity, whereas no significant inhibition of PKA, PKα and ERK kinase activity is observed.
- Gallagher, Timothy F.,Seibel, George L.,Kassis, Shouki,Laydon, Jeffrey T.,Blumenthal, Mary Jane,Lee, John C.,Lee, Dennis,Boehm, Jeffrey C.,Fier-Thompson, Susan M.,Abt, Jeffrey W.,Soreson, Margaret E.,Smietana, Juanita M.,Hall, Ralph F.,Garigipati, Ravi S.,Bender, Paul E.,Erhard, Karl F.,Krog, Arnold J.,Hofmann, Glenn A.,Sheldrake, Peter L.,McDonnell, Peter C.,Kumar, Sanjay,Young, Peter R.,Adams, Jerry L.
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- A CONVENIENT METHOD FOR THE PREPARATION OF N-METHOXYAMIDES
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A variety of N-methoxyamides is easily prepared from carboxylic acids and N,O-dimethylhydroxylamine hydrochloride in the presence of triphenylphosphine and carbon tetrabromide.
- Einhorn, J.,Einhorn, C.,Luche, J.-L.
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p. 1105 - 1112
(2007/10/02)
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