- Rhodium-Catalyzed Electrooxidative C?H Olefination of Benzamides
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Metal-catalyzed chelation-assisted C?H olefinations have emerged as powerful tools for the construction of functionalized alkenes. Herein, we describe the rhoda-electrocatalyzed C?H activation/alkenylation of arenes. The olefinations of challenging electron-poor benzamides were thus accomplished in a fully dehydrogenative fashion under electrochemical conditions, avoiding stoichiometric chemical oxidants, and with H2 as the only byproduct. This versatile alkenylation reaction also features broad substrate scope and used electricity as a green oxidant.
- Ackermann, Lutz,Struwe, Julia,Zhang, Yan
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Read Online
- Friedel-Crafts Chemistry. Part 53. Divergent and Diversity-Oriented Synthesis of Condensed Indole Scaffolds via Friedel-Crafts Ring Closure Approach
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A series of indole-fused medium-sized N-heterocyclic systems 10a-h were prepared from laboratory-synthesized indole-based esters 9a-h via intramolecular Friedel-Crafts cyclizations induced by both trifluoromethanesulfonic acid and AlCl3/CH
- Abd El-Aal, Hassan A. K.,Khalaf, Ali A.
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- Synthesis of substituted azepino[3,4-b]indole-1,5-diones
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Cyclic β-amino esters 4, obtained from lactams, were condensed with indole-2-carbonyl chloride to afford the corresponding amides. Similarly, unusual conditions led to cyclisation at the 3-position of the indole moiety in the presence of pTSA and ethylene glycol to afford previously unknown pentacyclic derivatives 12 and 15. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Perron, Julien,Joseph, Benoit,Merour, Jean-Yves
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- THE SYNTHESES OF POLYCYCLIC MOLECULES CONTAINING β-CARBOLINE UNITS BY THE PHOTOCHEMICALLY INDUCED RING CLOSURE OF ENAMIDES
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The syntheses of 5-methyl-5,8,9,14-tetrahydroindolo(2,3-c)indolo(2,3-g)quinolizin-6-one and 15-methyl-7,8,13,15-tetrahydroindolo(3,2-c)indolo(2,3-g)quinolizin-5-one from the photochemical cyclisation of 1-methylene-2-(N'-methylindole-2'-carbonyl)1,2,3,4-tetrahydro-β-carboline and 1-methylene-2-(N'-methylindole-3'-carbonyl)1,2,3,4-tetrahydro-β-carboline are described.Attempts to prepare indolo(2,3-c)isoquinolines from the photochemical cyclisation of 2-benzamidoindoles were unsuccessful.
- Hutchins, Michael,Sainsbury, Malcolm,Scopes, David
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- Calcium-Catalyzed Formal [5 + 2] Cycloadditions of Alkylidene β-Ketoesters with Olefins: Chemodivergent Synthesis of Highly Functionalized Cyclohepta[ b]indole Derivatives
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The calcium-catalyzed, formal [5 + 2] cycloaddition of indolyl alkylidene β-ketoesters with mono- A nd disubstituted aryl olefins to form cyclohepta[b]indole derivatives has been established. Unanticipated chemodivergence with phenyl vinyl sulfide/ether revealed a double [5 + 2] cycloaddition cascade providing ethano-bridged cyclohepta[b]indoles. Overall, the method's highlights include: (1) use of a green, calcium-based catalyst (2.5 mol % loading); (2) reaction times under 1 h; (3) mild reaction conditions; (4) substrate-derived chemodivergence; (5) functional group tolerance; and (6) examples of derivatization.
- Parker, Ariel N.,Martin, M. Cynthia,Shenje, Raynold,France, Stefan
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- Discovery of PHGDH inhibitors by virtual screening and preliminary structure–activity relationship study
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Phosphoglycerate dehydrogenase (PHGDH) is abnormally expressed in numerous malignant tumor cells and catalyzes the first step of serine biosynthesis, thus becoming a key drug target for antitumor treatment. In this study, compound B2 bearing a benzene-1,3-diamine scaffold was identified by structure-based virtual screening as a novel PHGDH inhibitor with moderate enzymatic activity. The structure–activity relationship study led to the discovery of compound C25 possessing improved enzymatic inhibitory activity and potent inhibitory activity on the proliferation of cells overexpressing PHGDH. The enzyme kinetic assay confirmed that C25 inhibited PHGDH in a nicotinamide adenine dinucleotide (NAD+) competitive manner. Molecular docking and mutagenesis experiment on PHGDH collectively revealed the binding site and key interaction residues of C25 in the PHGDH catalytic site. Taken together, this study provides information on the structural diversity for a further development of potent PHGDH inhibitors.
- Feng, Kai-Rui,Gao, Dingding,Huang, Cheng,Huang, Min,Lan, Xiaojing,Lin, Guo-Qiang,Shi, Xin-Wei,Tang, Shuai,Tian, Ping,Yuan, Liang,Zhang, Fu-Mao
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- Structure-based discovery of 1H-indole-2-carboxamide derivatives as potent ASK1 inhibitors for potential treatment of ulcerative colitis
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Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase (MAPK) family, is implicated in many human diseases. Here, we describe the structural optimization of hit compound 7 and conduct further structure-activity relationship (SAR) studies that result in the development of compound 19 with a novel indole-2-carboxamide hinge scaffold. Compound 19 displays potent anti-ASK1 kinase activity and stronger inhibitory effect on ASK1 in AP1-HEK293 cells than previously described ASK1 inhibitor GS-4997. Besides improved in vitro activity, compound 19 also exhibits an appropriate in vivo PK profile. In a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC), compound 19 shows significant anti-UC efficacy and markedly attenuates DSS-induced body weight loss, colonic shortening, elevation in disease activity index (DAI) and inflammatory cell infiltration in colon tissues. Mechanistically, compound 19 represses the phosphorylation of ASK1-p38/JNK signaling pathways and suppresses the overexpression of inflammatory cytokines. Together, these findings suggest that ASK1 inhibitors can potentially be used as a therapeutic strategy for UC.
- Hou, Shaohua,Yang, Xiping,Tong, Yu,Yang, Yuejing,Chen, Quanwei,Wan, Boheng,Wei, Ran,Wang, Yuchen,Zhang, Yanmin,Kong, Bo,Huang, Jianhang,Chen, Yadong,Lu, Tao,Hu, Qinghua,Du, Ding
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- Copper-mediated C–H thiolation of (hetero)arenes using weakly coordinating directing group
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We have developed a copper-mediated C–H thiolation of (hetero)arenes by using monodentate amide as weakly coordinating directing group. This protocol features excellent functional group tolerance and shows satisfactory compatibility with various heterocycles, such as indole, pyrrole, imidazole, pyridine, thiophene and quinoline. The robust nature of this protocol renders that it has potential value in the synthetic application.
- Wu, Peng,Cheng, Tai-Jin,Lin, Hai-Xia,Xu, Hui,Dai, Hui-Xiong
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supporting information
(2020/06/17)
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- Synthesis method and applications of N heteroatom polysubstituted benzoquaternary cycloketone
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The invention discloses an N heteroatom polysubstituted benzoquaternary cycloketone synthesis method. According to the invention, the synthetic route starts from a known aniline compound A, the hundred g-scale preparation can be achieved, the yield can ac
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Paragraph 0075-0080
(2020/03/12)
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- 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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- Asymmetric Nazarov Cyclizations Catalyzed by Chiral-at-Metal Complexes
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The application of Lewis acidic chiral-at-metal complexes of iridium(III) and rhodium(III) as catalysts for the asymmetric polarized Nazarov cyclization of dihydropyran- and indole-functionalized α-unsaturated β-ketoesters is reported (overall 24 examples). For both substrate classes, catalyst loadings of 2 mol% were found to be sufficient for achieving high yields and high stereoselectivities. The cyclized dihydropyran products were isolated in 85–98% yield, with 89%–>99% ee, and trans/cis ratios of 15:1–50:1 (9 examples). The cyclized indole products were typically isolated in more than 70% yield and in up to 93% yield, typically with more than 90% ee and in up to 97% ee, and trans/cis ratios of 12:1–28:1 (15 examples). (Figure presented.).
- Mietke, Thomas,Cruchter, Thomas,Larionov, Vladimir A.,Faber, Tabea,Harms, Klaus,Meggers, Eric
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p. 2093 - 2100
(2018/04/19)
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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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- Decarbonylative Methylation of Aromatic Esters by a Nickel Catalyst
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A Ni-catalyzed decarbonylative methylation of aromatic esters was achieved using methylaluminums as methylating agents. Dimethylaluminum chlorides uniquely worked as the methyl source. Because of the Lewis acidity of aluminum reagents, less reactive alkyl esters could also undergo the present methylation. By controlling the Lewis acidity of aluminum reagents, a chemoselective decarbonylative cross-coupling between alkyl esters and phenyl esters was successful.
- Okita, Toshimasa,Muto, Kei,Yamaguchi, Junichiro
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supporting information
p. 3132 - 3135
(2018/05/28)
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- Nickel-Catalyzed Sulfonylation of C(sp2)–H Bonds with Sodium Sulfinates
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The first nickel-catalyzed ortho-sulfonylation of C(sp2)–H bonds with sodium sulfinates directed by (pyridin-2-yl)isopropylamine (PIP-amine) is described. This strategy exhibits a broad substrate scope and good functional group tolerance with high monosulfonylation selectivity. Besides arenes and heteroarenes, the reaction can also be extended to alkenes, providing diverse diaryl and alkyl aryl sulfones in high yields. Furthermore, a plausible Ni(I)/Ni(III) mechanism is outlined based on our experimental results and related precedents. (Figure presented.).
- Liu, Shuang-Liang,Li, Xue-Hong,Zhang, Shu-Sheng,Hou, Sheng-Kai,Yang, Guang-Chao,Gong, Jun-Fang,Song, Mao-Ping
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supporting information
p. 2241 - 2246
(2017/07/07)
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- Discovery, Structure-Activity Relationship, and Antiparkinsonian Effect of a Potent and Brain-Penetrant Chemical Series of Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4
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The metabotropic glutamate receptor 4 (mGluR4) is an emerging target for the treatment of Parkinson's disease (PD). However, since the discovery of its therapeutic potential, no ligand has been successfully developed enough to be tested in the clinic. In the present paper, we report for the first time the medicinal chemistry efforts conducted around the pharmacological tool (-)-PHCCC. This work led to the identification of compound 40, a potent and selective mGluR4 positive allosteric modulator (PAM) with good water solubility and demonstrating consistent activity across validated preclinical rodent models of PD motor symptoms after intraperitoneal administration: haloperidol-induced catalepsy in mouse and the rat 6-hydroxydopamine (6-OHDA) lesion model. Moreover, we also describe the identification of compound 60 a close analogue of compound 40 with improved pharmacokinetic profile after oral administration. On the basis of its favorable and unique preclinical profile, compound 60 (PXT002331, now foliglurax) was nominated as a candidate for clinical development.
- Charvin, Delphine,Pomel, Vincent,Ortiz, Millan,Frauli, Mélanie,Scheffler, Sophie,Steinberg, Edith,Baron, Luc,Deshons, Laurène,Rudigier, Rachel,Thiarc, Delphine,Morice, Christophe,Manteau, Baptiste,Mayer, Stanislas,Graham, Danielle,Giethlen, Bruno,Brugger, Nadia,Hédou, Ga?l,Conquet, Fran?ois,Schann, Stephan
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supporting information
p. 8515 - 8537
(2017/11/03)
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- Visible-Light-Promoted Oxidative [4 + 2] Cycloadditions of Aryl Silyl Enol Ethers
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Visible-light-promoted oxidative [4 + 2] cycloadditions of μ,3-unsaturated silyl enol ethers have been developed to efficiently and diastereoselectively construct polycyclic skeletons under mild conditions. The diastereoselectivities were dependent on the stereoconfiguration of silyl enol ether, substitutions on the link, as well as electric properties of substitutions on aryl rings. The intermediates could be trapped by TEMPO, oxygen or methanol. Mechanistic studies indicated the reaction was initiated by one-electron oxidation of the silyl enol ether.
- Yang, Bo,Lu, Zhan
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p. 7288 - 7300
(2016/08/30)
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- Transition-Metal-Free Synthesis of N-Aryl Hydroxamic Acids via Insertion of Arynes
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An efficient and transition-metal-free N-arylation of amides via the insertion of arynes into the N-H bonds in the N-alkoxy amides is described. A variety of the reactive functional groups including the reactive aldehyde carbonyl group, furan ring, carbon-carbon double bonds, and free N-H bond of indole are found to be compatible with this process. In particular, the protocol is applicable in the synthesis of structurally diverse N-aryl hydroxamates and hydroxamic acids derived from N-protecting amino acids and peptides. In the presence of multiple amide N-H bonds, the N-arylation reaction can proceed selectively in the N-H bonds of terminal N-OBn amides giving rise to the desired N-aryl hydroxamates.
- Zhang, Lanlan,Geng, Yu,Jin, Zhong
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p. 3542 - 3552
(2016/05/24)
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- Iron-Catalyzed Directed C(sp2)-H and C(sp3)-H Functionalization with Trimethylaluminum
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Conversion of a C(sp2)-H or C(sp3)-H bond to the corresponding C-Me bond can be achieved by using AlMe3 or its air-stable diamine complex in the presence of catalytic amounts of an inorganic iron(III) salt and a diphosphine along with 2,3-dichlorobutane as a stoichiometric oxidant. The reaction is applicable to a variety of amide substrates bearing a picolinoyl or 8-aminoquinolyl directing group, enabling methylation of a variety of (hetero)aryl, alkenyl, and alkyl amides. The use of the mild aluminum reagent prevents undesired reduction of iron and allows the reaction to proceed with catalyst turnover numbers as high as 6500.
- Shang, Rui,Ilies, Laurean,Nakamura, Eiichi
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supporting information
p. 7660 - 7663
(2015/06/30)
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- Pd(OAc)2-catalyzed dehydrogenative C-H activation: An expedient synthesis of uracil-annulated β-carbolinones
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An intramolecular dehydrogenative C-H activation enabled an efficient synthesis of an uracil-annulated β-carbolinone ring system. The reaction is simple, efficient and high yielding (85-92%).
- Mondal, Biplab,Hazra, Somjit,Panda, Tarun K.,Roy, Brindaban
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supporting information
p. 1360 - 1366
(2015/08/19)
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- Catalytic Asymmetric Nazarov Cyclization of Heteroaryl Vinyl Ketones through a Crystallographically Defined Chiral Dinuclear Nickel Complex
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A Ni(NTf2)2 and tetradentate bisimino-bisquinoline ligand complex catalyzed the enantioselective Nazarov cyclization of heteroaryl vinyl ketones. An X-ray-quality crystal was obtained from a mixture of the Ni complex and the substrat
- Takeda, Takuya,Harada, Shinji,Nishida, Atsushi
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supporting information
p. 5184 - 5187
(2015/11/18)
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- Cu(II)-mediated C-H amidation and amination of arenes: Exceptional compatibility with heterocycles
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A Cu(OAc)2-mediated C-H amidation and amination of arenes and heteroarenes has been developed using a readily removable directing group. A wide range of sulfonamides, amides, and anilines function as amine donors in this reaction. Heterocycles present in both reactants are tolerated, making this a broadly applicable method for the synthesis of a family of inhibitors including 2-benzamidobenzoic acids and N-phenylaminobenzoates.
- Shang, Ming,Sun, Shang-Zheng,Dai, Hui-Xiong,Yu, Jin-Quan
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supporting information
p. 3354 - 3357
(2014/03/21)
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- HYDROPHOBICALLY TAGGED SMALL MOLECULES AS INDUCERS OF PROTEIN DEGRADATION
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Provided are bifunctional small molecules of Formula (I): or pharmaceutically acceptable salts thereof, wherein M represents a small organic molecule which binds, covalently or non-covalently, a kinase, such as Her3 protein kinase; L1 represents a linker; and RH represents a hydrophobic group. An example of a compound of Formula (I) is a compound of Formula (II): Also provided are pharmaceutical compositions comprising a compound of Formula (I) or (II) and methods of using such compounds for treating proliferative diseases.
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Paragraph 00359
(2014/05/07)
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- Iron-catalyzed C(sp2)-H bond functionalization with organoboron compounds
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We report here that an iron-catalyzed directed C-H functionalization reaction allows the coupling of a variety of aromatic, heteroaromatic, and olefinic substrates with alkenyl and aryl boron compounds under mild oxidative conditions. We rationalize these results by the involvement of an organoiron(III) reactive intermediate that is responsible for the C-H bond-activation process. A zinc salt is crucial to promote the transfer of the organic group from the boron atom to the iron(III) atom.
- Shang, Rui,Ilies, Laurean,Asako, Sobi,Nakamura, Eiichi
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supporting information
p. 14349 - 14352
(2014/12/11)
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- Mild rhodium(III)-catalyzed C-H allylation with 4-vinyl-1,3-dioxolan-2-ones: Direct and stereoselective synthesis of (E)-allylic alcohols
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A rhodium(III)-catalyzed C-H direct allylation reaction with 4-vinyl-1,3-dioxolan-2-ones has been developed. The reaction provides a facile and stereoselective access to substituted-(E)-allylic alcohols under mild and redox-neutral reaction conditions. Olefinic C-H activation is applicable, giving multifunctionalized skipped dienes in good yields. Minimal double-bond migration was observed.
- Zhang, Shang-Shi,Wu, Jia-Qiang,Lao, Ye-Xing,Liu, Xu-Ge,Liu, Yao,Lv, Wen-Xin,Tan, Dong-Hang,Zeng, Yao-Fu,Wang, Honggen
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supporting information
p. 6412 - 6415
(2015/01/09)
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- Rhodium(III)-catalyzed C-H activation/annulation with vinyl esters as an acetylene equivalent
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The behavior of electron-rich alkenes in rhodium-catalyzed C-H activation/annulation reactions is investigated. Vinyl acetate emerges as a convenient acetylene equivalent, facilitating the synthesis of sixteen 3,4-unsubstituted isoquinolones, as well as select heteroaryl-fused pyridones. The complementary regiochemical preferences of enol ethers versus enol esters/enamides is discussed.
- Webb, Nicola J.,Marsden, Stephen P.,Raw, Steven A.
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supporting information
p. 4718 - 4721
(2015/04/27)
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- Rh[III]-catalyzed C-H amidation using aroyloxycarbamates to give N-Boc protected arylamines
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The Rh(III)-catalyzed amidation of C(sp2)-H bonds by the use of electron-deficient aroyloxycarbamates as efficient electrophilic amidation partners is reported. The reaction proceeded under mild conditions with broad functional group tolerance, and pyridine and O-methyl hydroxamic acids serve as efficient directing groups, giving access to valuable N-Boc protected arylamines (also Fmoc and Cbz). Preliminary mechanistic experiments are discussed.
- Grohmann, Christoph,Wang, Honggen,Glorius, Frank
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supporting information
p. 3014 - 3017
(2013/07/26)
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- Synthesis and evaluation of novel anti-proliferative pyrroloazepinone and indoloazepinone oximes derived from the marine natural product hymenialdisine
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The tetrahydroazepinone pharmacophore is a component of many interesting compounds, including several marine natural products, with anti-cancer properties. The synthesis and biological evaluation of a novel series of pyrroloazepinone and indoloazepinone oximes is reported. These compounds showed promising growth inhibition activity against four human cancer cell lines but did not significantly inhibit the cell cycle regulator cyclin dependent kinase 2. The most active compounds in this series displayed improved anti-proliferative activity over the related synthetic indoloazepine kenpaullone. The structure activity relationships exhibited by the azepinone pharmacophore suggests several novel lead compounds for anti-cancer drug discovery.
- White, Alex W.,Carpenter, Nicholas,Lottin, Jerome R. P.,McClelland, Richard A.,Nicholson, Robert I.
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p. 246 - 253,8
(2012/12/11)
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- Synthesis and evaluation of indole-containing 3,5-diarylisoxazoles as potential pro-apoptotic antitumour agents
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A series of novel indole-containing diarylisoxazoles has been synthesised, based on our previous work on the synthesis and pro-apoptotic antitumour activity of indole-based diaryl 1,2,4-oxadiazoles. Concise synthetic routes to both 3-(indol-2-yl)-5-phenylisoxazoles and 5-(indol-2-yl)-3-phenylisoxazoles have been developed with full regiochemical control, bearing substituents on the indole ring, indole nitrogen, and/or phenyl group. Additionally a series of the related 5-(1H-indol-5-yl)-3-phenylisoxazoles has been prepared. In vitro evaluation in human cancer cell lines Colo320 (colon) and Calu-3 (lung) revealed preferential antiproliferative activity within the 5-(indol-5-yl)-3- phenylisoxazole series (low micromolar IC50). Further analysis revealed the ability of the indol-5-yl series to induce expression of effector caspases-3 and -7, and retention of viability of the human bronchial smooth muscle cell (BSMC) control cell population (particularly for compounds 18c and 18e).
- Md Tohid, Siti Farah,Ziedan, Noha I.,Stefanelli, Fabio,Fogli, Stefano,Westwell, Andrew D.
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p. 263 - 270
(2013/01/15)
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- Mild Rh(III)-catalyzed C-H activation and annulation with alkyne MIDA boronates: Short, efficient synthesis of heterocyclic boronic acid derivatives
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Taking advantage of Rh(III)-catalyzed C-H activation reactions, we have developed a mild, short, and efficient method for the synthesis of bench-stable 3-isoquinolone MIDA boronates. The reaction is practical and scalable. The product formed has been applied in the Suzuki-Miyaura reaction with high efficiency. This strategy has also been successfully expanded to the synthesis of MIDA boronate functionalized heterocycles such as isoquinoline, pyrrole, and indole.
- Wang, Honggen,Grohmann, Christoph,Nimphius, Corinna,Glorius, Frank
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supporting information
p. 19592 - 19595
(2013/02/21)
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- Platinum-catalyzed cyclization reaction of alkynes: Synthesis of azepino[3,4-b]indol-1-ones
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Novel azepino[3,4-b]indol-1-ones were synthesized from alkyne-substituted indole-2-carboxamides by catalytic intramolecular cyclization in the presence of PtCl2. The scope and limitations of this straightforward protocol are reported.
- Gruit, Marina,Pews-Davtyan, Anahit,Beller, Matthias
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experimental part
p. 1148 - 1159
(2011/04/15)
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- 8-METHYL-1-PHENYL-IMIDAZOL[1,5-A]PYRAZINE COMPOUNDS
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The present invention provides 8-methyl-1 -phenyl-imidazo[1,5-a]pyrazine derivatives according to formula I or pharmaceutically acceptable salts thereof. The compounds of the current invention show inhibitory activity against Lck and can be used for the treatment of Lck-mediated diseases or Lck-mediated conditions such as inflammatory disorders.
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Page/Page column 43
(2011/09/14)
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- Ruthenium-catalyzed isoquinolone synthesis through C-H activation using an oxidizing directing group
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The oxidant directs: A mild, practical, efficient, and regioselective Ru-catalyzed isoquinolone synthesis with a broad substrate scope was reported (see scheme). In this redox neutral process, the aromatic CiH bond functionalization can be performed at room temperature without using any external oxidant. The mechanism of the reaction was probed, and it was found that CiH activation is the turnover-limiting step.
- Li, Bin,Feng, Huiliang,Xu, Shansheng,Wang, Baiquan
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supporting information; experimental part
p. 12573 - 12577
(2011/12/03)
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- Catalytic syntheses of N-heterocyclic ynones and ynediones by in situ activation of carboxylic acids with oxalyl chloride
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Breaking the bottleneck: α-Keto carboxylic acids and N-heterocyclic carboxylic acids are activated in situ with oxalyl chloride then catalytically alkynylated to give ynediones and N-heterocyclic ynones efficiently in a one-pot fashion. 5-Acylpyrazoles and 2-phenylaminopyrimidines, potentially interesting for pharmaceutical applications, are readily synthesized in concise one-pot, three-component syntheses. Copyright
- Boersch, Christina,Merkul, Eugen,Mueller, Thomas J. J.
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supporting information; experimental part
p. 10448 - 10452
(2011/12/05)
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- Synthesis of β- And γ-carbolinones via Pd-catalyzed direct dehydrogenative annulation (DDA) of indole-carboxamides with alkynes using air as the oxidant
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A palladium-catalyzed direct dehydrogenative annulation (DDA) of indolecarboxamides with internal alkynes via C-H and N-H bond cleavage using air as the oxidant was developed. With this method, both β- and γ-carbolinones can be easily prepared under the mild conditions.
- Shi, Zhuangzhi,Cui, Yuxin,Jiao, Ning
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supporting information; experimental part
p. 2908 - 2911
(2010/09/18)
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- Drug design, in vitro pharmacology, and structure-activity relationships of 3-acylamino-2-aminopropionic acid derivatives, a novel class of partial agonists at the glycine site on the N-methyl-D-aspartate (NMDA) receptor complex
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Retaining agonistic activity at the glycine coagonist site of the NMDA receptor in molecules derived from glycine or D-serine has proven to be difficult because in the vicinity of the α-amino acid group little substitution is tolerated. We have solved thi
- Urwyler, Stephan,Floersheim, Philipp,Roy, Bernard L.,Koller, Manuel
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supporting information; experimental part
p. 5093 - 5107
(2010/03/02)
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- Gold-catalyzed cycloisomerization of N-propargylindole-2-carboxamides: Application toward the synthesis of lavendamycin analogues
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(Chemical Equation Presented) A series of N-propargylindole-2-carboxamides were found to undergo a AuCl3-catalyzed cycloisomerization to give β-carbolinones in high yield. The corresponding β-chlorocarboline derivative was prepared and used for
- England, Dylan B.,Padwa, Albert
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supporting information; experimental part
p. 3631 - 3634
(2009/05/07)
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- Intramolecular sulfoxide electrophilic sulfenylation in 2- and 3-indoleanilides
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When N-[2-(alkylsulfinyl)phenyl]-1H-indole-2-carboxamides with varying degrees of indolic and amidic N-alkylation are heated in an inert solvent or treated with trifluoroacetic anhydride; only compounds in which the amidic nitrogen is methylated cyclize t
- Eggers, Mary E.,Jog, Parag V.,Bates, Dallas K.
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p. 12185 - 12194
(2008/02/11)
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- Design and synthesis of novel heterobiaryl amides as metabotropic glutamate receptor subtype 5 antagonists
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A series of heterobiaryl amides was designed and synthesized as novel mGluR5 antagonists. The synthesis using palladium catalyzed Suzuki-Miyaura cross-coupling reactions provided an array of compounds with a range of in vitro activities. In particular, compound 9e, 4(3,5-difluorophenyl)-N-(6-methylpyridin-1-yl)picolinamide, exhibited nanomolar affinity at the mGluR5 and will serve as a template for future drug design.
- Kulkarni, Santosh S.,Newman, Amy Hauck
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p. 2074 - 2079
(2007/10/03)
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- Highly active Au(I) catalyst for the intramolecular exo- hydrofunctionalization of allenes with carbon, nitrogen, and oxygen nucleophiles
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Reaction of benzyl (2,2-diphenyl-4,5-hexadienyl)carbamate (4) with a catalytic 1:1 mixture of Au[P(t-Bu)2(o-biphenyl)]CI (2) and AgOTf (5 mol %) in dioxane at 25 °C for 45 min led to isolation of benzyl 4,4-diphenyl-2-vinylpyrrolidine-1-carboxylate (5) in 95% yield. The Au(l)-catalyzed intramolecular hydroamination of N-allenyl carbamates tolerated substitution at the alkyl and allenyl carbon atoms and was effective for the formation of piperidine derivatives, γ-Hydroxy and δ-hydroxy allenes also underwent Au-catalyzed intramolecular hydroalkoxylation within minutes at room temperature to form the corresponding oxygen heterocycles in good yield with high exoselectivity. 2-Allenyl indoles underwent Au-catalyzed intramolecular hydroarylation within minutes at room temperature to form 4-vinyl tetrahydrocarbazoles in good yield. Au-catalyzed cyclization of N-allenyl carbamates, allenyl alcohols, and 2-allenyl indoles that possessed an axially chiral allenyl moiety occurred with transfer of chirality from the allenyl moiety to the newly formed stereogenic tetrahedral carbon atom.
- Zhang, Zhibin,Liu, Cong,Kinder, Robert E.,Han, Xiaoqing,Qian, Hua,Widenhoefer, Ross A.
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p. 9066 - 9073
(2007/10/03)
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- SUBSTITUTED HETEROCYCLES AND THEIR USE AS CHK1, PDK1 AND PAK INHIBITORS
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This invention relates to novel compounds of Formula (I) and to their pharmaceutical compositions and to their methods of use. These novel compounds possess CHK1 kinase inhibitory activity, PDK1 inhibitory activity and Pak kinase inhibitory activity and are accordingly useful in the treatment and/or prophylaxis of cancer.
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Page/Page column 91
(2008/06/13)
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- Thienopyridine and furopyridine kinase inhibitors
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Compounds having the formula are useful for inhibiting protein tyrosine kinases. The present invention also discloses methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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- Pyrazolopyrimidines as therapeutic agents
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The present invention is directed to pyrazolopyrimidine derivatives of formula (I) wherein the substituents are defined herein, which are useful as kinase inhibitors and as such are useful for affecting angiogenesis and diseases and conditions associated with angiogenesis.
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- A domino amidation route to indolines and indoles: Rapid syntheses of anhydrolycorinone, hippadine, oxoassoanine, and pratosine
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(Chemical Equation Presented) When subjected to palladium-catalyzed amidation conditions, 2-triflyloxy phenethyl carbonates undergo, in addition to the expected aryl cross-coupling, an additional amidation with net displacement of the carbonate. The result is a one-step synthesis of indolines which may be oxidized to indoles. The utility of the procedure is illustrated by the two- or three-step syntheses of anhydrolycorinone, hippadine, oxoassoanine, and pratosine.
- Ganton, Michael D.,Kerr, Michael A.
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p. 4777 - 4779
(2007/10/03)
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- Thienopyridine kinase inhibitors
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Compounds having the formula are useful for inhibiting protein tyrosine kinases. The present invention also discloses methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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- Thienopyridine and furopyridine kinase inhibitors
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Compounds having the formula are useful for inhibiting protein tyrosine kinases. The present invention also discloses methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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Page/Page column 65
(2010/02/10)
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- Platinum-Catalyzed Intramolecular Alkylation of Indoles with Unactivated Olefins
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Reaction of 1-methy-2-(4-pentenyl)indole (1) with a catalytic amount of PtCl2 (2 mol %) in dioxane that contained a trace of HCl (5 mol %) at 60 °C for 24 h led to the isolation of 4,9-dimethyl-2,3,4,9-tetrahydro-1H-carbazole (2) in 92% yield. Platinum-catalyzed cyclization of 2-(4-pentenyl)indoles tolerated substitution at each position of the 4-pentenyl chain. Furthermore, the protocol was applicable to the synthesis of tetrahydro-β-carbolinones and was effective for cyclization of unprotected indoles. 2-(3-Butenyl)indoles underwent platinum-catalyzed cyclization with exclusive 6-endo-trig regioselectivity. Mechanistic studies established a mechanism for the platinum-catalyzed cyclization of 2-alkenyl indoles involving nucleophilic attack of the indole on a platinum-complexed olefin. Copyright
- Liu, Cong,Han, Xiaoqing,Wang, Xiang,Widenhoefer, Ross A.
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p. 3700 - 3701
(2007/10/03)
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- Anthranilic acid based CCK1 antagonists: The 2-indole moiety may represent a "needle" according to the recent homonymous concept
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Recently we described an innovative class of non-peptide CCK1 antagonists keeping appropriate pharmacophoric groups on the anthranilic acid employed as a molecular scaffold. The lead compound obtained, VL-0395, characterized by the presence of Phe and the 2-indole moiety at the C- and N-termini of anthranilic acid, respectively, is endowed with submicromolar affinity towards CCK1 receptors. Thus, we have prepared and tested on CCK receptors a library of VL-0395 analogues in order to investigate the precise topological and essential key interactions of the 2-indole group of the lead with the CCK1 receptor. The obtained results confirm that this group establishes very specific interactions with this receptor sub-site and may be viewed as a "needle" group.
- Varnavas, Antonio,Lassiani, Lucia,Valenta, Valentina,Berti, Federico,Tontini, Andrea,Mennuni, Laura,Makovec, Francesco
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- Radical dearomatising spirocyclisations onto the C-2 position of benzofuran and indole
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New spirolactams were obtained in radical dearomatising spirocyclisations of alkyl, vinyl and aryl radicals tethered at the C-2 positions of benzofuran and indole. Spirolactams were obtained via an intramolecular radical ipso-type spirocyclisation in benzofuran and indole systems. Alkyl, vinyl and aryl radicals, tethered at the C-2 position of the heterocycle underwent radical cyclisation to produce novel tricyclic partially dearomatised heterocycles in moderate yields. Fragmentation of the furan ring was observed subsequent to spirocyclisation of a vinyl radical onto a benzofuran.
- Kyei, Afua S.,Tchabanenko, Kirill,Baldwin, Jack E.,Adlington, Robert M.
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p. 8931 - 8934
(2007/10/03)
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- Directed ortho-lithiation of the 2-(N,N-dimethylhydrazinecarbonyl)-1-methylindole. Efficient preparation of tricyclic lactones
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N-Methyl indole-2-hydrazide 1 was lithiated at the 3-position using t-BuLi in the presence of TMEDA in THF. The generated ortho-lithiated intermediate is reacted with a variety of electrophiles to give regioselectively 2,3-disubstituted indoles in good yields. The hydroxyhydrazides were converted to the corresponding lactones after oxidation with MnO2.
- Romero,Pujol
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p. 173 - 178
(2007/10/03)
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- Pyrazolopyrimidines as therapeutic agents
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The present invention provides compounds of Formula I, including pharmaceutically acceptable salts and/or prodrugs thereof, where G, R2, and R3 are defined as described herein.
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- Indoles and pyridazinoindoles as nonnucleoside analog inhibitors of HIV-1 reverse transcriptase
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The synthesis and the study of the activity of new indol-2-carboxamides and pyridazinoindoles as inhibitors of HIV-1 reverse transcriptase (RT) are presented.The activity of the compounds synthesized as inhibitors of different types of HIV-1 RT (wild type enzyme and mutant forms P236L, Y181C and P236L/Y181C) was evaluated.The activity of the most active compounds was investigated in the syncytia reduction in vitro assay, in HIV-1IIIB-infected HT4lacZ-1 cells.Their potential cytotoxicity was determined in parallel.Two lead compounds,N-piperazin>-5,6-methylenedioxy indol-2-carboxamide 7q and N-piperazin>-5,6-methylenedioxyindol-2-carboxamide 7s have been identified. - Keywords: indole; nonnucleoside RT inhibitor; syncytia assay; HIV-1IIIBHT4lacZ-1 cells
- Font, M.,Monge, A.,Cuartero, A.,Ellorriaga, A.,Martinez-Irujo, J.J.,et al.
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p. 963 - 972
(2007/10/03)
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