- Ruthenium-catalyzed intramolecular arene C(sp2)-H amidation for synthesis of 3,4-dihydroquinolin-2(1 H)-ones
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We report the [Ru(p-cymene)(l-proline)Cl] ([Ru1])-catalyzed cyclization of 1,4,2-dioxazol-5-ones to form dihydroquinoline-2-ones in excellent yields with excellent regioselectivity via a formal intramolecular arene C(sp2)-H amidation. The reactions of the 2- and 4-substituted aryl dioxazolones proceeds initially through spirolactamization via electrophilic amidation at the arene site, which is para or ortho to the substituent. A Hammett correlation study showed that the spirolactamization is likely to occur by electrophilic nitrenoid attack at the arene, which is characterized by a negative ρ value of -0.73.
- Au, Chi-Ming,Ling, Cho-Hon,Sun, Wenlong,Yu, Wing-Yiu
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supporting information
p. 3310 - 3314
(2021/05/29)
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- A solid-phase synthetic route to N-acylated α-alkyl-D,L-homoserine lactones
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A synthetic route to N-acylated α-alkyl-D,L-homoserine lactones was established using solid-phase unnatural peptide synthesis (UPS) and combinatorial chemistry. The application of UPS methodology allowed access to racemic N-acylated homoserine lactones (D,L-AHLs) and their α-alkyl structural analogs (α-R1-D,L-AHLs). The synthesis and characterization of a library of five D,L-AHLs and ten α-R1-D,L-AHLs prepared from resin-bound amino acids is reported.
- Ali, Ahmed I. M.,O'Donnell, Martin J.,Samaritoni, J. Geno,Scott, William L.
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supporting information
(2020/09/04)
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- Decarboxylative Borylation of mCPBA-Activated Aliphatic Acids
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A decarboxylative borylation of aliphatic acids for the synthesis of a variety of alkylboronates has been developed by mixing m-chloroperoxybenzoic acid (mCPBA)-activated fatty acids with bis(catecholato)diboron in N,N-dimethylformamide (DMF) at room temperature. A radical chain process is involved in the reaction which initiates from the B-B bond homolysis followed by the radical transfer from the boron atom to the carbon atom with subsequent decarboxylation and borylation.
- Wei, Dian,Liu, Tu-Ming,Zhou, Bo,Han, Bing
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supporting information
p. 234 - 238
(2020/01/02)
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- Copper-Catalyzed Oxidative Benzylic C(sp3)?H Cyclization for the Synthesis of β-Lactams
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β-Lactams are important structural motifs because of their ubiquity in natural products and pharmaceuticals. We report herein a Cu-catalyzed intramolecular oxidative C(sp3)?H amidation for the synthesis of β-lactams using tBuOOtBu. This method
- Nozawa-Kumada, Kanako,Saga, Satoshi,Matsuzawa, Yuta,Hayashi, Masahito,Shigeno, Masanori,Kondo, Yoshinori
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supporting information
p. 4496 - 4499
(2020/04/10)
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- Cyclohexyl-Fused, Spirobiindane-Derived, Phosphine-Catalyzed Synthesis of Tricyclic ?3-Lactams and Kinetic Resolution of ?3-Substituted Allenoates
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A C2-symmetric chiral phosphine catalyst, NUSIOC-Phos, which can be easily derived from cyclohexyl-fused spirobiindane, was introduced. A highly enantioselective domino process involving pyrrolidine-2,3-diones and γ-substituted allenoates catalyzed by NUSIOC-Phos has been disclosed. Diastereospecific tricyclic γ-lactams containing five contiguous stereogenic centers were obtained in high yields and with nearly perfect enantioselectivities. A kinetic resolution process of racemic γ-substituted allenoates was developed for the generation of optically enriched chiral allenoates.
- Wu, Mingyue,Han, Zhaobin,Li, Kaizhi,Wu, Ji'En,Ding, Kuiling,Lu, Yixin
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p. 16362 - 16373
(2019/10/16)
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- Synthesis and antitumor activity of aza-brazilan derivatives containing imidazolium salt pharmacophores
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The synthesis of a series of novel aza-brazilan derivatives containing imidazolium salt pharmacophores is presented. The biological activity of such imidazolium salts was further evaluated in vitro against a panel of human tumor cell lines. The results suggest that the electron-withdrawing group on the aza-brazilan moiety, substituted 5,6-dimethyl-benzimidazole ring and substitution of the imidazolyl-3-position with a 4-methylbenzyl group were essential for modulating the cytotoxic activity. Compounds 55 and 39, bearing a 4-methylbenzyl substituent at position-3 of 5,6-dimethyl-benzimidazole, were found to be the most potent compounds with IC50 values of 0.52-1.30 μM and 0.56-1.51 μM against four human tumor cell lines investigated. Particularly, compound 57 exhibited inhibitory activity against the MCF-7 cell line with an IC50 value of 0.35 μM and was 56-fold more sensitive than DDP. Moreover, compound 55 inhibited cell proliferation through inducing G0/G1 cell cycle arrest and apoptosis in SMMC-7721 cells.
- Huang, Mingqin,Duan, Shengzu,Ma, Xueqiong,Cai, Bicheng,Wu, Dongmei,Li, Yan,Li, Liang,Zhang, Hongbin,Yang, Xiaodong
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supporting information
p. 1027 - 1036
(2019/06/27)
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- Ligand-Assisted Palladium(II)/(IV) Oxidation for sp3C H Fluorination
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The direct functionalization of inert sp3C H bonds is limited to a few bond types. Although the activation of sp3C H bonds can be accomplished under mild conditions using palladium catalysts, the subsequent functionalization is not trivial due to the high energy required to convert palladium(II) to palladium(IV). We have systematically studied the palladium oxidation using computation-guided experiments for reactions involving strong chelation control. We find that a mild external ligand could significantly accelerate the oxidation of palladium(II) to palladium(IV) for strong bidentate directing groups. The acceleration is believed to be a result of ligand stabilization of both the palladium(II) and palladium(IV) intermediates. (Figure presented.) .
- Sun, Huan,Zhang, Yi,Chen, Ping,Wu, Yun-Dong,Zhang, Xinhao,Huang, Yong
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p. 1946 - 1957
(2016/07/06)
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- SUBSTITUTED BENZAMIDES AND THEIR USES
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Provided herein are Substituted Benzamides, compositions, and method of their manufacture and use.
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- Synthesis of Alkyl-Substituted Pyridines by Directed Pd(II)-Catalyzed C-H Activation of Alkanoic Amides
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A general alkylation protocol for substituted iodopyridines was developed (32 examples, 44-97% yield). The reaction is based on the Pd(II)-catalyzed C-H activation of 8-aminoquinoline-derived alkanoic amides and it employs a catalyst cocktail of Pd(OAc)2 (10 mol%), NaI (30 mol%), and (BuO)2POOH (20 mol%), with Ag2CO3 as base.
- Hu, Peng,Bach, Thorsten
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supporting information
p. 2853 - 2857
(2015/12/18)
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- SUBSTITUTED BENZAMIDES AND THEIR USES
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Provided herein are Substituted Benzamides, compositions, and method of their manufacture and use.
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- INHIBITORS OF BETA-SECRETASE
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The present invention is directed to a compound represented by the following structural formula or a pharmaceutically acceptable salt thereof. Pharmaceutical compositions and method of use of the compounds are also described.
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Page/Page column 77
(2010/10/03)
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- BICYCLO-SUBSTITUTED PYRAZOLON AZO DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF
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The bicyclo-substituted pyrazolon-azo derivatives of formula (I) or pharmaceutical acceptable salts, hydrates or solvates thereof, methods for their preparation, pharmaceutical compositions containing the same and their use as a therapeutic agent, especially as thrombopoietin (TPO) mimetics and their use as agonists of thrombopoietin receptor are disclosed. The definition of substituents in formula (I) are the same as defined in the description.
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Page/Page column 58
(2010/10/19)
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- An investigation into the electrophilic cyclisation of N-acyl-pyrrolidinium ions: A facile synthesis of Pyrrolo-tetrahydroisoquinolones and Pyrrolo-benzazepinones
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The triflic acid-mediated cyclisation of N-arylmethyl- and N-arylethyl-acylpyrrolidinium ions gave moderate to good yields of pyrrolo-tetrahydroisoquinolones and pyrrolo-benzazepinones respectively. Electron-donating R substituents enhanced the rate of reaction and gave higher yields than electron-withdrawing substituents. Substituents on the methyl or ethyl chain in general enhanced the reaction, unless sterically encumbered. The equivalent acylpiperidinium ions cyclised much slower and in lower yield.
- King, Frank D.,Aliev, Abil E.,Caddick, Stephen,Copley, Royston C. B.
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experimental part
p. 3561 - 3571
(2010/01/06)
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- Reactive trityl derivatives: Stabilised carbocation mass-tags for life sciences applications
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The rational design of novel triarylmethyl (trityl)-based mass tags (MT) for mass-spectrometric (MS) applications is described. We propose a "pKR+ rule" to correlate the stability of trityl carbocations with their MS performance: trityls with higher pKR+ values ionise and desorb better. Trityl blocks were synthesised that have high pKR+ values and are stable in conditions of MS analysis; these MTs can be ionised by matrix as well as irradiation with a 337 nm nitrogen laser. 13C-Labelled tags were prepared for MS quantitation applications. Moreover, the tags were equipped with a variety of functional groups allowing conjugation with different functionalities within (bio)molecules to enhance the MS characteristics of the latter. The MS behaviour of model polycationic trityl compounds with and without the matrix was studied to reveal that poly-trityl clusters are always singly charged under the (MA)LDI-TOF conditions. Several peptide-trityl conjugates were prepared and comparisons revealed a beneficial effect of trityl tags on the conjugate detection in MS. Trityl compounds containing para-methoxy- and dimethylamine groups, as well as a xanthene fragment, showed considerable enhancement in MS detection of model peptides; thus they are promising tools for proteomic applications. Dimethoxytrityl derivatives allow one to distinguish between Arg- and Lys-containing peptides. Maleimido trityl derivatives are suitable for the efficient derivatisation of thiol-containing peptides in pyridine.
- Ustinov, Alexey V.,Shmanai, Vadim V.,Patel, Kaajal,Stepanova, Irina A.,Prokhorenko, Igor A.,Astakhova, Irina V.,Malakhov, Andrei D.,Skorobogatyi, Mikhail V.,Bernad, Pablo L.,Khan, Safraz,Shahgholi, Mona,Southern, Edwin M.,Korshun, Vladimir A.,Shchepinov, Mikhail S.
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supporting information; experimental part
p. 4593 - 4608
(2009/03/12)
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- DISUBSTITUTED THIENYL COMPOUNDS AND THEIR USE AS PHARMACEUTICALS
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The present invention relates to modulators of HM74a receptor, and pharmaceutical compositions thereof. The compounds of the invention can be useful in the treatment of various diseases associated with HM74a receptor.
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Page/Page column 33
(2010/11/25)
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- Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor
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Biaryl anthranilides are reported as potent and selective full agonists for the high affinity niacin receptor GPR109A. The SAR presented outlines approaches to reduce serum shift and both CYPCYP2C8 and CYP2C9 liabilities, while improving PK and maintainin
- Shen, Hong C.,Ding, Fa-Xiang,Luell, Silvi,Forrest, Michael J.,Carballo-Jane, Ester,Wu, Kenneth K.,Wu, Tsuei-Ju,Cheng, Kang,Wilsie, Larissa C.,Krsmanovic, Mihajlo L.,Taggart, Andrew K.,Ren, Ning,Cai, Tian-Quan,Deng, Qiaolin,Chen, Qing,Wang, Junying,Wolff, Michael S.,Tong, Xinchun,Holt, Tom G.,Waters, M. Gerard,Hammond, Milton L.,Tata, James R.,Colletti, Steven L.
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p. 6303 - 6306
(2008/04/12)
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- Derivatised molecules for mass spectrometry
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Compounds of formula (IIa): are provided where:X is a group capable of being cleaved from the α-carbon atom to form an ion of formula (I')C is a carbon atom bearing a single positive charge or a single negative charge; The invention further provides compounds of formula (IIb): where:X is a counter-ion to C. The compounds of formula (IIa) and (IIb) may form ions of formula (I') by either cleaving the C-X bond between X and the α-carbon atoms in the case of the compounds of formula (IIa) or dissociating X in the case of compounds of formula (IIb).
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- The discovery and synthesis of novel adenosine receptor (A2A) antagonists
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In high throughput screening of our file compounds, a novel structure 1 was identified as a potent A2A receptor antagonist with no selectivity over the A1 adenosine receptor. The structure-activity relationship investigation using 1 as a template lead to identification of a novel class of compounds as potent and selective antagonists of A2A adenosine receptor. Compound 26 was identified to be the most potent A2A receptor antagonist (Ki = 0.8 nM) with 100-fold selectivity over the A1 adenosine receptor.
- Matasi, Julius J.,Caldwell, John P.,Hao, Jinsong,Neustadt, Bernard,Arik, Leyla,Foster, Carolyn J.,Lachowicz, Jean,Tulshian, Deen B.
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p. 1333 - 1336
(2007/10/03)
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- DISUBSTITUTED CHALCONE OXIMES HAVING RARγ RETINOID RECEPTOR ANTAGONIST ACTIVITY
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Compounds of the formula where the variables have the values described in the specification are antagonists of RARγ retinoid receptors.
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Page/Page column 27-28
(2008/06/13)
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- TRICYCLIC PYRAZOLE KINASE INHIBITORS
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Compounds of the present invention are useful for inhibiting protein tyrosine kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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Page/Page column 55
(2008/06/13)
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- 2-(Arylpropionylamino)- and 2-(arylacryloylamino)benzophenones: Farnesyltransferase inhibition and antimalarial activity
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Structural variation of the 2-acylamino moiety of some benzophenone farnesyltransferase inhibitors led to the para-trifluoromethylphenylpropionyl derivative with relatively low farnesyltransferase inhibition but considerable antimalarial activity and no c
- Fucik,Kettler,Wiesner,Ortmann,Unterreitmeier,Krauss,Bracher,Jomaa,Schlitzer, Martin
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p. 744 - 752
(2007/10/03)
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- Indanylidenes. 1. Design and synthesis of (E)-2-(4,6-difluoro-1-indanylidene)acetamide, a potent, centrally acting muscle relaxant with antiinflammatory and analgesic activity
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The design of rigid cyclic analogues derived from cinnamamide 1, (E)-N-cyclopropyl-3-(3-fluorophenyl)prop-2-enamide, and β-methylcinnamamide 2, (E)-N-cyclopropyl-3-(3-fluorophenyl)but-2-enamide, has led to the discovery of the potent, centrally acting muscle relaxant (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 17. Compound 17 also possesses potent antiinflammatory and analgesic activity. This paper describes the synthesis and the muscle relaxant, antiinflammatory, and analgesic structure-activity relationships of 17 and 67 of its analogues. Compound 17 has been taken into phase I clinical trials.
- Musso, David L.,Cochran, Felicia R.,Kelley, James L.,McLean, Ed W.,Selph, Jeffrey L.,Rigdon, Greg C.,Orr, G. Faye,Davis, Ronda G.,Cooper, Barrett R.,Styles, Virgil L.,Thompson, James B.,Hall, William R.
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p. 399 - 408
(2007/10/03)
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- Indenyl compounds for the polymerization of olefins
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Indenyl compound of formula (1) wherein: M is a transition metal from the lanthanides or from group 3, 4, 5 or 6 of the Periodic System of Elements, Q is an anionic ligand to M, k is the number of Q groups, R is a bridging group and Z and X are substituents, wherein R contains at least one sp2-hybridized carbon atom that is bonded to the indenyl group at the 2-position with the exclusion of Ti(deshydronorbiphenacene) dichloride.
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- Synthesis of Biological Markers in Fossil Fuels. 2. Synthesis and 13C NMR Studies of Substituted Indans and Tetralins
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Unambiguous syntheses of all possible methyl, ethyl, n-propyl, and n-butyl derivatives of indan and tetralin were developed using the Kumada coupling procedure involving the reaction of aryl or vinyl halides with Grignard reagents in the presence of nickel(II) chloride.An analysis of the 13C NMR spectra of these compounds was also completed.
- Adamczyk, Maciej,Watt, David S.,Netzel, Daniel A.
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p. 4226 - 4237
(2007/10/02)
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