- Cobalt-Catalyzed Enantioselective C–H Arylation of Indoles
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Atropoisomeric (hetero)biaryls are scaffolds with increasing importance in the pharmaceutical and agrochemical industries. Although it is the most obvious disconnection to construct such compounds, the direct enantioselective C–H arylation through the concomitant induction of the chiral information remains extremely challenging and uncommon. Herein, the unprecedented earth-abundant 3d-metal-catalyzed atroposelective direct arylation is reported, furnishing rare atropoisomeric C2-arylated indoles. Kinetic studies and DFT computation revealed an uncommon mechanism for this asymmetric transformation, with the oxidative addition being the rate- and enantio-determining step. Excellent stereoselectivities were reached (up to 96% ee), while using an unusual N-heterocyclic carbene ligand bearing an essential remote substituent. Attractive dispersion interactions along with positive C–H-π interactions exerted by the ligand were identified as key factors to guarantee the excellent enantioselection.
- Ackermann, Lutz,Jacob, Nicolas,Oliveira, Jo?o C. A.,Wencel-Delord, Joanna,Zaid, Yassir
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supporting information
p. 798 - 806
(2022/02/03)
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- Electrochemically Enabled C3-Formylation and -Acylation of Indoles with Aldehydes
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Reported herein is an effective strategy for oxidative cross-coupling of indoles with various aldehydes. The strategy is based on a two-step transformation via a well-known Mannich-type reaction and a C-N bond cleavage for carbonyl introduction. The key step - the C-N bond cleavage of the Mannich product - was enabled by electrochemistry. This strategy (with over 40 examples) ensures excellent functional-group tolerance as well as late-stage functionalization of pharmaceutical molecules.
- Yang, Liquan,Liu, Zhaoran,Li, Yujun,Lei, Ning,Shen, Yanling,Zheng, Ke
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supporting information
p. 7702 - 7707
(2019/10/19)
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- I2-mediated C3-formylation of indoles by tertiary amine and H2O
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An I2-promoted 3-formylation of free (N-H) and N-substituted indoles with tetramethylethylenediamine (TMEDA) and H2O as the carbonyl source is achieved, providing 3-formylindole in moderate to excellent yields with good functional gr
- Zhang, Bo,Liu, Bin,Chen, Jianbin,Wang, Jiehui,Liu, Miaochang
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supporting information
p. 5618 - 5621
(2014/12/11)
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- The ammonium-promoted formylation of indoles by DMSO and H2O
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DMSO and H2O is an efficient combination in the NH 4OAc-promoted formylation of indole, where DMSO serves as a C1 carbon source. The mechanism study reveals that the procedure involves a usual and unusual Pummerer reaction.
- Fei, Haiyang,Yu, Jintao,Jiang, Yan,Guo, Huan,Cheng, Jiang
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supporting information
p. 7092 - 7095
(2013/10/22)
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- Identification of trans-4-[1-[[7-fluoro-2-(1-methyl-3-indolyl)-6- benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid as a potent, orally active VLA-4 antagonist
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For the purpose of obtaining orally potent VLA-4 inhibitors, we have carried out structural modification of the (N′-phenylureido)phenyl group in compound 1, where the group was found to be attributed to poor pharmacokinetic profile in our previous research. Through modification, we have identified several compounds with both potent in vitro activity and improved oral exposure. In particular, compound 7e with 7-fluoro-2-(1-methyl-1H-indol-3- yl)-1,3-benzoxazolyl group as a novel replacement of the (N′-phenylureido) phenyl group significantly inhibited eosinophil infiltration into bronchoalveolar lavage fluid at 15 mg/kg in an Ascaris-antigen-induced murine bronchial inflammatory model, and its efficacy was comparable to that of the anti-mouse α4 antibody (R1-2).
- Setoguchi, Masaki,Iimura, Shin,Sugimoto, Yuuichi,Yoneda, Yoshiyuki,Chiba, Jun,Watanabe, Toshiyuki,Muro, Fumihito,Iigo, Yutaka,Takayama, Gensuke,Yokoyama, Mika,Taira, Tomoe,Aonuma, Misato,Takashi, Tohru,Nakayama, Atsushi,MacHinaga, Nobuo
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p. 1201 - 1212
(2012/03/26)
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- The copper-catalyzed C-3-formylation of indole C-H bonds using tertiary amines and molecular oxygen
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A copper-catalyzed formylation reaction has been developed by employing oxygen (O2) as the clean oxidant. The C-H bonds of indoles were C-3-formylated by tetramethylethylenediamine (TMEDA) and water (H2O; in situ formed and external added water) as the carbonyl source in moderate to good yields with good functional group tolerance. Thus, it represents a facile procedure leading to 3-formylindoles. Copyright
- Chen, Jianbin,Liu, Bin,Liu, Dongfang,Liu, Shan,Cheng, Jiang
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supporting information
p. 2438 - 2442
(2012/11/07)
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- Synthesis and cytotoxicity studies of achiral azaindole-substituted titanocenes
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From the reaction of 1-methyl-1 H-pyr-rolo[2,3-b]pyridine (1a),1-(methoxymethyl)-1 H-pyrrolo[2,3-b]pyridine (1b), 1-isopropyl-1 H-pyrrolo[2,3-b]pyridine (1c), and 1-(4-methoxybenzyl)-1 H-pyrrolo[2,3-b] pyridine (1d) under Vilsmeier-Haak conditions, the co
- Mendez, Luis Miguel Menendez,Deally, Anthony,O'Shea, Donal F.,Tacke, Matthias
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p. 148 - 157
(2011/10/08)
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- A rapid method toward the synthesis of new substituted tetrahydro α-carbolines and α-carbolines
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A rapid and efficient method for stereoselective synthesis of new substituted tetrahydro-α-carbolines using Diels-Alder reaction under microwave irradiation has been developed. Further, dehydrogenation of these adducts resulted in synthesis of new substit
- Chavan, Neelam L.,Nayak, Sandip K.,Kusurkar, Radhika S.
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experimental part
p. 1827 - 1831
(2010/04/06)
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- Green N-methylation of electron deficient pyrroles with dimethylcarbonate
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The N-methylation of electron-deficient pyrroles was affected using dimethyl carbonate in the presence of DMF and catalytic DABCO. This alkylation methodology has proven useful for the alkylation of a variety of pyrroles in 72-98% yields and is considered to be green chemistry relative to the more common use of methyl halides or dimethyl sulfate.
- Laurila, Michael L.,Magnus, Nicholas A.,Staszak, Michael A.
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experimental part
p. 1199 - 1201
(2010/04/22)
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- PIPERAZINYL OXOALKYL TETRAHYDRO-BETA-CARBOLINES AND RELATED ANALOGUES
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Piperazinyl oxoalkyl tetrahydro-beta-carbolines and related analogues of the formula (I): are provided, as are methods for their preparation and use. Such compounds may generally be used to modulate ligand binding to histamine H3 receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of disorders in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and therapeutic methods are provided, as are methods for using such ligands for detecting histamine H3 receptors (e.g., receptor localization studies).
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Page/Page column 61-62
(2009/03/07)
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- THERAPEUTIC AGENTS I
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Compounds of formula(I), processes for preparing such compounds, their use in the treatment of obesity, psychiatric disorders, cognitive disorders, memory disorders, schizophrenia, epilepsy, and related conditions, and neurological disorders such as dementia, multiple sclerosis, Parkinson's disease, Huntington's chorea and Alzheimer's disease and pain related disorders, and pharmaceutical compositions containing them.
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Page/Page column 66
(2010/02/12)
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- FAB I INHIBITORS
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Compounds of the formula (I) are disclosed which are Fab I inhibitors and are useful in the treatment of bacterial infections.
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- VLA-4 INHIBITORS
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The present invention relates to a compound represented by the following formula (I): (wherein, W represents WA-A1 -WB - (in which, WA is substituted or unsubstituted aryl, etc., A1 is -NR1-, single bond, -C(O)-, etc., and WB is substituted or unsubstituted arylene, etc.), R is single bond, -NH-, -OCH2-, alkenylene, etc., X is -C(O) -CH2-, etc., and M is, for example, the following formula: (in which, R11, R12 and R13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R14 is hydrogen or lower alkyl, Y represents -CH2-O-, etc., Z is substituted or unsubstituted arylene, etc., A2 is single bond, etc, and R10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.
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- Excited-state double proton transfer in 3-formyl-7-azaindole: role of the nπ* state in proton-transfer dynamics
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3-Formyl-7-azaindole (3FAI) and its derivatives have been synthesized to study the role of the nπ* state in the excited-state double proton transfer (ESDPT) reaction. In 3FAI monomer as well as its associated hydrogenbonded complexes the lowest excited singlet state has been concluded to be in the nπ* configuration. The association constants incorporating the hydrogen bonding formation were determined to be 1.9 × 104 (313 K), 2.2 × 104 (298 K) and 1.8 × 105 M-1 (298 K) for 3FAI dimer, 3FAI/azacyclohexanone and 3FAI/acetic acid, respectively, in cyclohexane. In alcohols, the rate of solvent (e.g., methanol) diffusional migration, forming a 'correct' precursor for ESDPT, is concluded to be much slower than the rate of Sππ(*) → Snπ(*) internal conversion which has been deduced to be 4.37 × 1012 s-1. ESDPT is prohibited in the Snπ(*) state of which the relaxation dynamics are dominated by the rate of Snπ(*) → Tππ(*) intersystem crossing. In contrast, for 3FAI dimer or 3FAI/acetic acid complex possessing intact dual hydrogen bonds the intrinsic ESDPT is competitive with the rate of Sππ(*) → Snπ(*) internal con version, resulting in a prominent imine-like tautomer emission. The results provide the first model among 7AI analogues in which the fast rate of Sππ(*) → Snπ(*) internal conversion serves as an internal clock to examine the mechanism of guest molecules (including the bulk alcohols) assisted ESDPT.
- Chou, Pi-Tai,Wu, Guo-Ray,Wei, Ching-Yen,Shiao, Mei-Ying,Liu, Yun-I
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p. 8863 - 8871
(2007/10/03)
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- New 5-HT3 (serotonin-3) receptor antagonists. IV. Synthesis and structure-activity relationships of azabicycloalkaneacetamide derivatives.
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The synthesis and structure-activity relationships of a series of new azabicycloalkanes as 5-HT3 (serotonin-3) receptor antagonists are described. Our study on the azabicycloalkaneacetamide derivatives showed that 2,3-dihydroindole as the aromatic ring mo
- Kato,Ito,Nishino,Yamakuni,Takasugi
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p. 1351 - 1357
(2007/10/02)
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