cas 4375-15-9, 3-Methyl-2,3-dihydro-1H-indole

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MILD REDUCTION OF INDOLES TO INDOLINES WITH ZINC BOROHYDRIDE
Mild reduction of indoles to indolines was achieved by using zinc borohydride as a neutral reducing agent.
Kotsuki, Hiyoshizo,Ushio, Yasuyuki,Ochi, Masamitsu
p. 1771 - 1774
(1987)
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Palladium-Catalyzed Direct and Specific C-7 Acylation of Indolines with 1,2-Diketones
The indole scaffold is a ubiquitous and useful substructure, and extensive investigations have been conducted to construct the indole framework and/or realize indole modification. Nevertheless, the direct selective functionalization on the benzenoid core must overcome the high activity of the C-3 position and still remains highly challenging. Herein, a palladium-catalyzed direct and specific C-7 acylation of indolines in the presence of an easily removed directing group was developed. This strategy usually is considered as a practical strategy for the preparation of acylated indoles because indoline can be easily converted to indole under oxidation conditions. In particular, our strategy greatly improved the alkacylation yield of indolines for which only an unsatisfactory yield could be achieved in the previous studies. Furthermore, the reaction can be scaled up to gram level in the standard reaction conditions with a much lower palladium loading (1 mol %).
Xie, Guilin,Zhao, Yuhan,Cai, Changqun,Deng, Guo-Jun,Gong, Hang
supporting information
p. 410 - 415
(2021/01/26)

Stereospecific N-acylation of indoles and corresponding microwave mediated synthesis of pyrazinoindoles using hexafluoroisopropanol
We envisioned a facile construction of diversified pyrazinoindoles by using 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) as the solvent and catalyst, hence eliminating metal catalyzed routes for its development. The process is facilitated by HFIP that has emerged as a powerful tool for development of novel fused heterocycles. This cascade approach blends the asymmetric N-acylation with consecutive intramolecular cyclisation via Pictet-Spengler reaction as an efficient tool forming overall two stereogenic centers. Our approach deals with incorporation of L-amino acid on substituted indoles to provide the chiral N-acylated indole precursor followed by cyclisation to access pyrazinoindole derivatives in high enantiomeric excess up to >99% in good to excellent yields, which have great potential as molecular scaffolds in drug discovery. We have also described the mechanistic course of the reaction based on density functional theory.
Singh, Aarushi,Singh, Snigdha,Sewariya, Shubham,Singh, Nidhi,Singh, Prashant,Kumar, Ajay,Bandichhor, Rakeshwar,Chandra, Ramesh
(2021/02/27)

Covalent Organic Frameworks toward Diverse Photocatalytic Aerobic Oxidations
Photoactive two-dimensional covalent organic frameworks (2D-COFs) have become promising heterogenous photocatalysts in visible-light-driven organic transformations. Herein, a visible-light-driven selective aerobic oxidation of various small organic molecules by using 2D-COFs as the photocatalyst was developed. In this protocol, due to the remarkable photocatalytic capability of hydrazone-based 2D-COF-1 on molecular oxygen activation, a wide range of amides, quinolones, heterocyclic compounds, and sulfoxides were obtained with high efficiency and excellent functional group tolerance under very mild reaction conditions. Furthermore, benefiting from the inherent advantage of heterogenous photocatalysis, prominent sustainability and easy photocatalyst recyclability, a drug molecule (modafinil) and an oxidized mustard gas simulant (2-chloroethyl ethyl sulfoxide) were selectively and easily obtained in scale-up reactions. Mechanistic investigations were conducted using radical quenching experiments and in situ ESR spectroscopy, all corroborating the proposed role of 2D-COF-1 in photocatalytic cycle.
Liu, Shuyang,Tian, Miao,Bu, Xiubin,Tian, Hua,Yang, Xiaobo
supporting information
p. 7738 - 7744
(2021/05/07)

Hydrogenation or Dehydrogenation of N-Containing Heterocycles Catalyzed by a Single Manganese Complex
A highly chemoselective base-metal catalyzed hydrogenation and acceptorless dehydrogenation of N-heterocycles is presented. A well-defined Mn complex operates at low catalyst loading (as low as 2 mol %) and under mild reaction conditions. The described catalytic system tolerates various functional groups, and the corresponding reduced heterocycles can be obtained in high yields. Experimental studies indicate a metal-ligand cooperative catalysis mechanism.
Borghs, Jannik C.,Rueping, Magnus,Zubar, Viktoriia
supporting information

(2020/05/19)

Aerobic Dehydrogenation of N-Heterocycles with Grubbs Catalyst: Its Application to Assisted-Tandem Catalysis to Construct N-Containing Fused Heteroarenes
An aerobic dehydrogenation of nitrogen-containing heterocycles catalyzed by Grubbs catalyst is developed. The reaction is applicable to various nitrogen-containing heterocycles. The exceptionally high functional group compatibility of this method was confirmed by the oxidation of an unprotected dihydroindolactam V to indolactam V. Furthermore, by taking advantage of the oxygen-mediated structural change of the Grubbs catalyst, we integrated ring-closing metathesis and subsequent aerobic dehydrogenation to develop the novel assisted-tandem catalysis using molecular oxygen as a chemical trigger. The utility of the assisted-tandem catalysis was demonstrated by the concise synthesis of N-containing fused heteroarenes including a natural antibiotic, pyocyanine.
Kawauchi, Daichi,Noda, Kenta,Komatsu, Yoshiyuki,Yoshida, Kei,Ueda, Hirofumi,Tokuyama, Hidetoshi
supporting information
p. 15793 - 15798
(2020/10/12)

Transition-Metal-Free Stereospecific Oxidative Annulative Coupling of Indolines with Aziridines
Tandem C-N bond formation for the oxidative annulation of indolines with aziridines is accomplished employing the combination of DDQ and NaOCl at ambient conditions. Optically active aziridine can be coupled with high enantiomeric purity (>99% ee). The substrate scope, stereocontrol with the enantioenriched substrate, and scale-up are the important practical advantages.
Karjee, Pallab,Sarkar, Tanumay,Kar, Subhradeep,Punniyamurthy, Tharmalingam
p. 8261 - 8270
(2020/07/25)

SULFONYL-SUBSTITUTED BICYCLIC COMPOUND WHICH ACTS AS ROR INHIBITOR
Provided is a sulfonyl-substituted bicyclic compound (A) which acts as a RORγ inhibitor, said compound has good RORγ inhibitory activity and is expected to be used for treating diseases mediated by a RORγ receptor in mammals.
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(2020/08/16)

Monoamine Oxidase (MAO-N) Biocatalyzed Synthesis of Indoles from Indolines Prepared via Photocatalytic Cyclization/Arylative Dearomatization
The biocatalytic aromatization of indolines into indole derivatives exploiting monoamine oxidase (MAO-N) enzymes is presented. Indoline substrates were prepared via photocatalytic cyclization of arylaniline precursors or via arylative dearomatization of unsubstituted indoles and in turn chemoselectively aromatized by the MAO-N D11 whole cell biocatalyst. Computational docking studies of the indoline substrates in the MAO-N D11 catalytic site allowed for the rationalization of the biocatalytic mechanism and experimental results of the biotransformation. This methodology represents an efficient example of biocatalytic synthesis of indole derivatives and offers a facile approach to access these aromatic heterocycles under mild reaction conditions.
Black, Gary W.,Brancale, Andrea,Castagnolo, Daniele,Colonna, Serena,Ferla, Salvatore,Masci, Domiziana,Turner, Nicholas J.,Varricchio, Carmine,Zhao, Fei
p. 6414 - 6421
(2020/07/09)

Exploiting the radical reactivity of diazaphosphinanes in hydrodehalogenations and cascade cyclizations
The remarkable reducibility of diazaphosphinanes has been extensively applied in various hydrogenations, based on and yet limited by their well-known hydridic reactivity. Here we exploited their unprecedented radical reactivity to implement hydrodehalogenations and cascade cyclizations originally inaccessible by hydride transfer. These reactions feature a broad substrate scope, high efficiency and simplicity of manipulation. Mechanistic studies suggested a radical chain process in which a phosphinyl radical is generated in a catalytic cycle via hydrogen-atom transfer from diazaphosphinanes. The radical reactivity of diazaphosphinanes disclosed here differs from their well-established hydridic reactivity, and hence, opens a new avenue for diazaphosphinane applications in organic syntheses.
Cheng, Jin-Pei,Yang, Jin-Dong,Zhang, Jingjing
p. 4786 - 4790
(2020/06/18)

Re-Catalyzed Annulations of Weakly Coordinating N-Carbamoyl Indoles/Indolines with Alkynes via C?H/C?N Bond Cleavage
Described herein are rhenium-catalyzed [3+2] annulations of N-carbamoyl indoles with alkynes via C?H/C?N bond cleavage, which provide rapid access to fused-ring pyrroloindolone derivatives. For the first time, the weakly coordinating O-directing group was successfully employed in rhenium-catalyzed C?H activation reactions, enabled by the unique catalytic trio of Re2(CO)10, Me2Zn and ZnCl2. Mechanistic studies revealed that aminozinc species plays an important role in the reaction. Based on the mechanistic understanding, a more powerful catalytic trio of Re2(CO)10, [MeZnNPh2]2 and Zn(OTf)2 was devised and applied successfully in the [4+2] annulations of indolines and alkynes affording pyrroloquinolinone derivatives.
Yang, Yunhui,Wang, Congyang
supporting information
p. 8245 - 8248
(2019/05/28)

Sustainable Radical Cascades to Synthesize Difluoroalkylated Pyrrolo[1,2-a]indoles
We disclose herein a photocatalytic difluoroalkylation and cyclization cascade reaction of N-(but-2-enoyl)indoles with broad substrate scopes in up to 90% isolated yield. This method provides sustainable and efficient access to synthesize difluoroalkylated pyrrolo[1,2-a]indoles with a quaternary carbon center under mild conditions.
Huang, Honggui,Yu, Menglin,Su, Xiaolong,Guo, Peng,Zhao, Jia,Zhou, Jiabing,Li, Yi
p. 2425 - 2437
(2018/02/23)

Ru(ii)-Catalyzed C7-acyloxylation of indolines with carboxylic acids
Ruthenium(ii)-catalyzed site-selective C7-acyloxylation of indolines with carboxylic acids is presented. The substrate scope and functional group tolerance are important practical features. The kinetic isotope studies suggest that C-H bond activation may be the rate-determining step.
De, Pinaki Bhusan,Banerjee, Sonbidya,Pradhan, Sourav,Punniyamurthy, Tharmalingam
p. 5889 - 5898
(2018/08/21)

Expedient cobalt(II)-catalyzed site-selective C7-arylation of indolines with arylboronic acids
Cobalt(ii)-catalyzed pyrimidyl directing group-assisted C7 arylation of indolines with arylboronic acids has been developed using Mn(OAc)2·4H2O as an oxidant. The use of cobalt(ii)-PCy3 as a catalyst and broad substrate scope are the important practical features.
De, Pinaki Bhusan,Pradhan, Sourav,Banerjee, Sonbidya,Punniyamurthy, Tharmalingam
supporting information
p. 2494 - 2497
(2018/03/21)

STABILIZATION OF ACTIVE METAL CATALYSTS AT METAL-ORGANIC FRAMEWORK NODES FOR HIGHLY EFFICIENT ORGANIC TRANSFORMATIONS
Metal-organic framework (MOFs) compositions based on post?synthetic metalation of secondary building unit (SBU) terminal or bridging OH or OH2 groups with metal precursors or other post-synthetic manipulations are described. The MOFs provide a versatile family of recyclable and reusable single-site solid catalysts for catalyzing a variety of asymmetric organic transformations, including the regioselective boryiation and siiylation of benzyiic C—H bonds, the hydrogenation of aikenes, imines, carbonyls, nitroarenes, and heterocycles, hydroboration, hydrophosphination, and cyclization reactions. The solid catalysts can also be integrated into a flow reactor or a supercritical fluid reactor.
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Paragraph 0349

(2019/01/07)

Asymmetric Cycloisomerization of o-Alkenyl-N-Methylanilines to Indolines by Iridium-Catalyzed C(sp3)?H Addition to Carbon–Carbon Double Bonds
Highly enantioselective cycloisomerization of N-methylanilines, bearing o-alkenyl groups, into indolines is established. An iridium catalyst bearing a bidentate chiral diphosphine effectively promotes the intramolecular addition of the C(sp3)?H bond across a carbon–carbon double bond in a highly enantioselective fashion. The reaction gives indolines bearing a quaternary stereogenic carbon center at the 3-position. The reaction mechanism involves rate-determining oxidative addition of the N-methyl C?H bond, followed by intramolecular carboiridation and subsequent reductive elimination.
Torigoe, Takeru,Ohmura, Toshimichi,Suginome, Michinori
supporting information
p. 14272 - 14276
(2017/10/23)

B(C6F5)3-Promoted hydrogenations of N-heterocycles with ammonia borane
A transition-metal-free method for the B(C6F5)3-promoted hydrogenations of N-heterocycles using ammonia borane under mild reaction conditions has been developed. The reaction affords a broad range of hydrogenated products in moderate to good yields. The enantioselective versions for the corresponding products were also investigated via our approach, showing good feasibility.
Ding, Fangwei,Zhang, Yiliang,Zhao, Rong,Jiang, Yanqiu,Bao, Robert Li-Yuan,Lin, Kaifeng,Shi, Lei
supporting information
p. 9262 - 9264
(2017/08/21)

Cascade radical cyclization of N-propargylindoles: Substituents dictate stereoselective formation of N-fused indolines versus indoles
An efficient protocol for the synthesis of pyrrolo[1, 2- a]indole derivatives having sulfide functionality using cascade radical cyclization on propargylindole is described. The nature of the substituents at the propargylic carbon bearing nitrogen of the indole has a profound effect on the rate, yield, and nature of the product obtained by the cascade radical cyclization. An expeditious one-pot route for cascade radical cyclization-desulfurization is also presented. Products obtained were elaborated to the core of the putative structure of the yuremamine and indoline derivative with five contiguous stereocenters.
Gharpure, Santosh J.,Shelke, Yogesh G.
supporting information
p. 5022 - 5025
(2017/11/06)

Using weak interactions to control C-H mono-nitration of indolines
An unprecedented C-H mononitration of indolines either at the -C5 or -C7 positions under mild condition is reported here. The roles of multiple weak interactions and factors such as steric factors, electronic effects, cation-π interactions, and solvent polarity were established, and we achieved a 100% regioselective electrophilic aromatic (EArS) nitration using Cu(NO3)2 or AgNO3.
Bose, Anima,Mal, Prasenjit
supporting information
p. 11368 - 11371
(2017/10/19)

Rh(III)-Catalyzed C7-Thiolation and Selenation of Indolines
The rhodium(III)-catalyzed intermolecular C7-thiolation and selenation of indolines with disulfides and diselenides were developed. This protocol relies on the use of a removable pyrimidyl directing group to access valuable C-7 functionalized indoline scaffolds with ample substrate scope and broad functional group tolerance.
Xie, Wucheng,Li, Bin,Wang, Baiquan
p. 396 - 403
(2016/01/25)

Single-Site Cobalt Catalysts at New Zr8(μ2-O)8(μ2-OH)4 Metal-Organic Framework Nodes for Highly Active Hydrogenation of Alkenes, Imines, Carbonyls, and Heterocycles
We report here the synthesis of robust and porous metal-organic frameworks (MOFs), M-MTBC (M = Zr or Hf), constructed from the tetrahedral linker methane-tetrakis(p-biphenylcarboxylate) (MTBC) and two types of secondary building units (SBUs): cubic M8(μ2-O)8(μ2-OH)4 and octahedral M6(μ3-O)4(μ3-OH)4. While the M6-SBU is isostructural with the 12-connected octahedral SBUs of UiO-type MOFs, the M8-SBU is composed of eight MIV ions in a cubic fashion linked by eight μ2-oxo and four μ2-OH groups. The metalation of Zr-MTBC SBUs with CoCl2, followed by treatment with NaBEt3H, afforded highly active and reusable solid Zr-MTBC-CoH catalysts for the hydrogenation of alkenes, imines, carbonyls, and heterocycles. Zr-MTBC-CoH was impressively tolerant of a range of functional groups and displayed high activity in the hydrogenation of tri- and tetra-substituted alkenes with TON > 8000 for the hydrogenation of 2,3-dimethyl-2-butene. Our structural and spectroscopic studies show that site isolation of and open environments around the cobalt-hydride catalytic species at Zr8-SBUs are responsible for high catalytic activity in the hydrogenation of a wide range of challenging substrates. MOFs thus provide a novel platform for discovering and studying new single-site base-metal solid catalysts with enormous potential for sustainable chemical synthesis.
Ji, Pengfei,Manna, Kuntal,Lin, Zekai,Urban, Ania,Greene, Francis X.,Lan, Guangxu,Lin, Wenbin
supporting information
p. 12234 - 12242
(2016/09/28)

Selective Catalytic Hydrogenation of Heteroarenes with N-Graphene-Modified Cobalt Nanoparticles (Co3O4-Co/NGratα-Al2O3)
Cobalt oxide/cobalt-based nanoparticles featuring a core-shell structure and nitrogen-doped graphene layers on alumina are obtained by pyrolysis of Co(OAc)2/phenanthroline. The resulting core-shell material (Co3O4-Co/NGratα-Al2O3) was successfully applied in the catalytic hydrogenation of a variety of N-heteroarenes including quinolines, acridines, benzo[h], and 1,5-naphthyridine as well as unprotected indoles. The peculiar structure of the novel heterogeneous catalyst enables activation of molecular hydrogen at comparably low temperature. Both high activity and selectivity were achieved in these hydrogenation processes, to give important building blocks for bioactive compounds as well as the pharmaceutical industry.
Chen, Feng,Surkus, Annette-Enrica,He, Lin,Pohl, Marga-Martina,Radnik, J?rg,Topf, Christoph,Junge, Kathrin,Beller, Matthias
supporting information
p. 11718 - 11724
(2015/09/28)

Palladium-catalyzed C-7 alkenylation of indolines using molecular oxygen as the sole oxidant
A general and efficient method for the intermolecular direct C-7-selective C-H alkenylation of indolines using palladium(ii) as the catalyst and molecular oxygen as the sole oxidant has been developed. The reaction showed complete regio- and stereoselectivity. All products were E-isomers at the C-7 position, and no Z-isomers or other position substituted products could be detected. The approach also presented an efficient route for the synthesis of C-7 alkenylated indoles.
Yang, Dong,Mao, Shuai,Gao, Ya-Ru,Guo, Dong-Dong,Guo, Shi-Huan,Li, Bin,Wang, Yong-Qiang
p. 23727 - 23736
(2015/04/14)

A simple iridicycle catalyst for efficient transfer hydrogenation of n-heterocycles in water
A cyclometalated iridium complex is shown to catalyse the transfer hydrogenation of various nitrogen heterocycles, including but not limited to quinolines, isoquinolines, indoles and pyridinium salts, in an aqueous solution of HCO2H/HCO2Na under mild conditions. The catalyst shows excellent functional-group compatibility and high turnover number (up to 7500), with catalyst loadings as low as 0.01 mol % being feasible. Mechanistic investigation of the quinoline reduction suggests that the transfer hydrogenation proceeds via both 1,2- and 1,4-addition pathways, with the catalytic turnover being limited by the step of hydride transfer. An easily accessible iridicycle catalyst effects the transfer hydrogenation of a wide variety of N-heterocycles in water, including quinolines, isoquinolines, indoles, quinoxalines, and pyridines. The catalyst shows excellent functional-group compatibility and high turnover number (up to 7500), even with low catalyst loadings.
Talwar, Dinesh,Li, Ho Yin,Durham, Emma,Xiao, Jianliang
supporting information
p. 5370 - 5379
(2015/03/30)

Palladium on carbon-catalyzed one-pot N-arylindole synthesis: Intramolecular aromatic amination, aromatization, and intermolecular aromatic amination
Indole and indoline derivatives were selectively and temperature dependently synthesized via the intramolecular cross-coupling reaction between the amino and aromatic bromine functionalities of 2-bromophenethylamine derivatives in the presence of 10% palladium on carbon (Pd/C), 1,1-bis(diphenylphosphino)ferrocene (DPPF), and sodium tert-butoxide (NaO-t-Bu) in mesitylene at 140 and 200°C, respectively. The neutralization using acetic acid after formation of the indoline derivatives effectively promoted their aromatization, and the corresponding indole derivatives were obtained at 140°C. Furthermore, various aryl groups were also introduced to the N-1 position of the indole, pyrrole, and carbazole rings by their direct intramolecular arylation with aryl halides and a one-pot protocol for N-arylindole synthesis from 2-bromophenethylamine was developed.
Monguchi, Yasunari,Marumoto, Takahisa,Takamatsu, Haruki,Sawama, Yoshinari,Sajiki, Hironao
supporting information
p. 1866 - 1872
(2014/06/09)

Palladium-catalyzed synthesis of N-tert-prenylindoles
Palladium-catalyzed N-tert-prenylations of indoles, tricarbonylchromium- activated indoles, and indolines that occur in high yields (up to 94%) with high tert-prenyl-to-n-prenyl selectivity (up to 12:1) are reported.
Johnson, Kirsten F.,Van Zeeland, Ryan,Stanley, Levi M.
supporting information
p. 2798 - 2801
(2013/07/19)

Selective anti-markovnikov cyclization and hydrofluorination reaction in superacid HF/SbF5: A tool in the design of nitrogen-containing (fluorinated) polycyclic systems
The selective synthesis of tetrahydroquinolines and fluorinated arylamines was performed in superacid HF/SbF5 through a superelectrophilic ammonium-carbenium activation process. This anti-Markovnikov oriented reaction was applied to the straightforward synthesis of highly valued (fluorinated) nitrogen-containing heterocyclic compounds.
Compain, Guillaume,Bonneau, Celine,Martin-Mingot, Agnes,Thibaudeau, Sebastien
p. 4463 - 4472
(2013/06/05)

NOVEL RHO KINASE INHIBITORS AND METHODS OF USE
The subject invention concerns materials and methods for treating diseases and disorders associated with expression of Rho associated kinases (ROCKs). Examples of diseases and disorders contemplated within the scope of the invention include, but are not limited to, oncological disorders, cardiovascular diseases, CNS disorders, and inflammatory disorders. In one embodiment, a method of the invention comprises administering a therapeutically effective amount of one or more compounds of the present invention, or a composition comprising the compounds, to a person or animal in need of treatment. The subject invention also concerns compounds that inhibit ROCKs, and compositions that comprise the inhibitor compounds of the invention. Compounds contemplated within the scope of the invention include, but are not limited to, those compounds shown in Table (5).
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(2012/10/18)

Aerobic palladium(II)-catalyzed 5-endo-trig cyclization: An entry into the diastereoselective C-2 alkenylation of indoles with tri- and tetrasubstituted double bonds
The endo trick: An endo ring closure onto the trigonal β carbon atom of α,β-unsaturated acceptors that are tethered to the indole nitrogen atom followed by amide cleavage enables the diastereoselective C-2 alkenylation of indoles with fully substituted double bonds. The carboxy group functions as a synthetically useful temporary tether (see scheme). Copyright
Kandukuri, Sandeep R.,Schiffner, Julia A.,Oestreich, Martin
supporting information; experimental part
p. 1265 - 1269
(2012/03/08)

Anti-Markovnikov additions to N-allylic derivatives involving ammonium-carbenium superelectrophiles
Anti-Markovnikov additions to non-conjugated unsaturated amines in superacid are reported. In situ NMR studies, DFT calculations and labelled substrates reactions support the involvement of new ammonium-carbenium superelectrophiles in this original proces
Compain, Guillaume,Martin-Mingot, Agnes,Frapper, Gilles,Bachmann, Christian,Jouannetaud, Marie-Paule,Thibaudeau, Sebastien
p. 5877 - 5879
(2012/08/14)

INDOLINE DERIVATIVES AND THEIR USE AS FLAVOURING AGENTS
Organic compounds of formula (I) wherein: X is N, or C, R1 -R6 may be independently selected from the group consisting of, H, substituted, unsubstituted, branched or unbranched C1-C4 alkyl, methoxy, ethoxy, Br,
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Page/Page column 12

(2011/05/11)

Molecular modeling studies, synthesis, configurational stability and biological activity of 8-chloro-2,3,5,6-tetrahydro-3,6-dimethyl-pyrrolo[1,2,3- de]-1,2,4-benzothiadiazine 1,1-dioxide
The potential therapeutic benefit of compounds able to activate AMPA receptors (AMPArs) has led to a search for new AMPAr positive modulators. Among them, 8-chloro-2,3,5,6-tetrahydro-3,6-dimethyl-pyrrolo[1,2,3-de]-1,2,4- benzothiadiazine 1,1-dioxide (1) has attracted particular attention, because it is one of the most active benzothiadiazine-derived positive modulators of the AMPA receptor. It possesses two stereogenic centers, C3 and C6, thus it can exist as four stereoisomers. In this work, preliminary in silico studies suggested that 1 interacts stereoselectively with AMPArs. Single stereoisomers of 1 were prepared in order to evaluate their biological activity. However, studies regarding the configurational stability of the investigated compounds suggested a rapid epimerization at C3 in aqueous solvents, and we can expect the same reaction in vivo. Thus, electrophysiological experiments were performed on the two epimeric mixtures, (3*,6R)- and (3*, 6S)- 8-chloro-2,3,5,6-tetrahydro-3,6-dimethyl-pyrrolo[1,2,3-de]-1,2,4- benzothiadiazine 1,1-dioxide, in order to evaluate their activities as positive allosteric modulators of AMPArs. The obtained data suggest that the (3 *,6S) epimeric mixture is the most active in positively modulating AMPArs, confirming in silico results.
Battisti, Umberto M.,Carrozzo, Marina M.,Cannazza, Giuseppe,Puia, Giulia,Troisi, Luigino,Braghiroli, Daniela,Parenti, Carlo,Jozwiak, Krzysztof
scheme or table
p. 7111 - 7119
(2012/01/14)

NOVEL COMPOUNDS
The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R1, R2, R3 and R4 are defined as in the description, the tautomers, the isomers, the diastereomers, the enantiomers, the hydrates, the mixtures thereof and the salts thereof and the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, medicaments containing these compounds, their use and processes for preparing them.
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(2011/02/18)

ORGANIC COMPOUNDS
Organic compounds of formula (I), wherein: X is C, R1 to R6 may be independently selected from the group consisting of, H, C1-C3 alkyl, Br, F, Cl, R7 is O R8 is NH R9 is a group having 5 to12 carbons selected from the group consisting of cycloalkyl or substituted alkyl, wherein the substituent is selected from the group consisting of aryl or cycloalkyl. The compounds create / modify flavour, in particular sweet flavour and may be used in compositions and consumable products.
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(2011/05/11)

1-(Indolin-1-yl)-1-phenyl-3-propan-2-olamines as potent and selective norepinephrine reuptake inhibitors
Efforts to identify new selective and potent norepinephrine reuptake inhibitors (NRIs) for multiple indications by structural modification of the previous 3-(arylamino)-3-phenylpropan-2-olamine scaffold led to the discovery of a novel series of 1-(indolin-1-yl)-1-phenyl-3-propan-2-olamines (9). Investigation of the structure-activity relationships revealed that small alkyl substitution at the C3 position of the indoline ring enhanced selectivity for the norepinephrine transporter (NET) over the serotonin transporter (SERT). Several compounds bearing a 3, 3-dimethyl group on the indoline ring, 9k, 9o,p, and 9s,t, exhibited potent inhibition of NET (IC50= 2.7-6.5 nM) and excellent selectivity over both serotonin and dopamine transporters. The best example from this series, 9p, a potent and highly selective NRI, displayed oral efficacy in a telemetric rat model of ovariectomized-induced thermoregulatory dysfunction, a mouse p-phenylquinone (PPQ) model of acute visceral pain, and a rat spinal nerve ligation (SNL) model of neuropathic pain.
Vu, An T.,Cohn, Stephen T.,Zhang, Puwen,Kim, Callain Y.,Mahaney, Paige E.,Bray, Jenifer A.,Johnston, Grace H.,Koury, Elizabeth J.,Cosmi, Scott A.,Deecher, Darlene C.,Smith, Valerie A.,Harrison, James E.,Leventhal, Liza,Whiteside, Garth T.,Kennedy, Jeffrey D.,Trybulski, Eugene J.
experimental part
p. 2051 - 2062
(2010/08/22)

HETEROCYCLIC DERIVATIVES FOR MODULATION OF CALCIUM CHANNELS
Heterocyclic derivatives act as Ca channel antagonists. The compositions are useful for treating or relieving Ca channel mediated conditions.
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(2008/06/13)

Chemoenzymatic preparation of optically active secondary amines: a new efficient route to enantiomerically pure indolines
An efficient chemoenzymatic route for the synthesis of optically active substituted indolines has been developed. Different lipases have been tested in the alkoxycarbonylation of these secondary amines, Candida antarctica lipase A (CAL-A) was found to be the best biocatalyst for 2-substituted-indolines, and C. antarctica lipase B (CAL-B) for 3-methylindoline. The combination of lipases with a variety of allyl carbonates and tert-butyl methyl ether (TBME) as solvent has allowed the isolation of the carbamate and amine derivatives with a high level of enantiopurity.
Gotor-Fernandez, Vicente,Fernandez-Torres, Pedro,Gotor, Vicente
p. 2558 - 2564
(2007/10/03)

Preparation of differentially 1,3-disubstituted indolines by intramolecular carbolithiation
The ether-soluble dilithio species (2), derived from N-allyl-2-bromoaniline (1) upon treatment with t-BuLi at -78°C, cyclizes when warmed to +5°C in the presence of TMEDA to give a (1-lithio-3-indolinyl)methyllithium (3) that may be differentially functio
Bailey, William F.,Luderer, Matthew R.,Mealy, Michael J.
p. 5303 - 5305
(2007/10/03)

Benzylpiperazinyl-indolinylethanones
Disclosed are benzylpiperazinyl-indolinylethanone compounds which are useful for the treatment and/or prevention of neuropsychological disorders including, but not limited to, schizophrenia, mania, dementia, depression, anxiety, compulsive behavior, substance abuse, Parkinson-like motor disorders and motion disorders related to the use of neuroleptic agents. Pharmaceutical compositions, including packaged pharmaceutical compositions, are further provided. Compounds of the invention are also useful as probes for the localization of GABAAreceptors in tissue samples.
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Page column 22-23

(2010/11/30)

Indoles
A 1,4-substituted cyclic amine derivative represented by the following formula or a pharmacologically acceptable salt thereof: wherein A, B, C, D, T, Y, and Z each represent a methine or a nitrogen linkage; R1, R2, R3, R4, and R5 each represent a substituent; n represents 0 or an integer of 1 to 3; m represents 0 or an integer of 1 to 6; and p represents an integer of 1 to 3. The compounds have serotonin antagonism. They are therefore clinically useful as medicaments, in particular, for treating, ameliorating, and preventing spastic paralysis. They are also useful as central muscle relaxants for ameliorating myotonia.
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(2008/06/13)

Indoline and piperazine containing derivatives as a novel class of mixed D2/D4 receptor antagonists. Part 1: Identification and structure-activity relationships
Optimization of the lead compound 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2,3-dihydro-indol-1-yl)-ethanone 1 by systematic structure-activity relation (SAR) studies lead to two potent compounds 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)- ethanone 2n and 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)- ethanone 7b. Their related synthesis was also reported.
Zhao, He,Thurkauf, Andrew,He, Xiaoshu,Hodgetts, Kevin,Zhang, Xiaoyan,Rachwal, Stanislaw,Kover, Renata X.,Hutchison, Alan,Peterson, John,Kieltyka, Andrzej,Brodbeck, Robbin,Primus, Renee,Wasley, Jan W.F.
p. 3105 - 3109
(2007/10/03)

5'-alkyl-benzothiadiazides: a new subgroup of AMPA receptor modulators with improved affinity.
AMPA receptors form a major subdivision of the glutamate receptor family that mediates excitatory synaptic transmission in the brain. Currents through AMPA receptors can be up- or down-regulated by compounds that allosterically modulate receptor kinetics through binding sites distinct from that for glutamate. One of those modulators is the benzothiadiazide IDRA-21 which has been reported to enhance synaptic transmission and be effective in behavioral tests, but typically requires threshold concentrations of at least 100 microM to be active in vitro. In this study, new benzothiadiazides were developed with IDRA-21 as lead compound and examined for their potency in modulating AMPA receptor kinetics. A significant increase in drug affinity was obtained by alkyl substitution at the 5'-position of IDRA-21; substitutions at other positions of the benzothiadiazide core generally did not yield a further gain in affinity and in some cases abolished drug binding. The 5'-ethyl derivative exhibited an EC(50) value in the order of 22 microM which represents about a 30-fold gain in affinity over that of IDRA-21. The EC(50) value is comparable to that of cyclothiazide, the most potent benzothiadiazide drug, but the effects on AMPA receptors differed substantially between these two compounds in that the 5'-ethyl derivative of IDRA-21 greatly increased the binding affinity for receptor agonists whereas cyclothiazide is known to reduce agonist binding. The structure--activity relationships reported here thus offer to provide new insights how receptor kinetics is linked to particular aspects of receptor--drug interactions.
Phillips, Dean,Sonnenberg, Jennifer,Arai, Amy C,Vaswani, Rishi,Krutzik, Peter O,Kleisli, Thomas,Kessler, Markus,Granger, Richard,Lynch, Gary,Richard Chamberlin
p. 1229 - 1248
(2007/10/03)

Photochemical generation of iminoquinone methides by 1,4-hydrogen migration in derivatives of o-tolylnitrene
The photochemistry of a series of derivatives of o-tolyl azide, bearing a variety of substituents in the benzylic positions, has been investigated using matrix isolation spectroscopy and density functional calculations. It has been found that introduction of any substituent possessing a lone pair (i.e., R = Br, Cl, MeO, Me2N) allows a 1,4-hydrogen shift to take place, yielding iminoquinone methides. Additional methyl groups in the benzylic position, however, do not promote a photochemical conversion into iminoquinone methides. If the benzylic substituent itself is part of a ring system, the size of this ring plays an important role. Thus, 2-methyl-8-nitrenote-trahydroisoquinoline rearranges very easily, whereas 4-nitrenophthalan does not give the reaction. Density functional calculations [B3LYP/6-31G(d)] have been used to gain an understanding of the reaction. It has been found that the activation energies depend strongly on the nature of the substituent, being lowest if R = NMe2. Incorporation of the benzylic substituent into a ring reduces the flexibility of the system and results in significantly raised barriers.
Bucher, Goetz
p. 2447 - 2462
(2007/10/03)

New nonsteroidal androgen receptor modulators based on 4-(trifluoromethyl)-2(1H)-pyrrolidino[3,2-g]quinolinone
A series of 2(1H)-pyrrolidino[3,2-g]quinolinones was prepared and tested for the ability to modulate the transcriptional activity of the human androgen receptor (hAR). The parent compound, 4-(trifluoromethyl)-2(1H)-pyrrolidino[3,2-g]quinolinone, displayed moderate interaction with hAR, but more substituted analogues, particularly 6,7-disubstituted compounds, were potent hAR agonists in vitro.
Edwards, James P.,West, Sarah J.,Pooley, Charlotte L. F.,Marschke, Keith B.,Farmer, Luc J.,Jones, Todd K.
p. 745 - 750
(2007/10/03)

A versatile synthesis of 3-substituted indolines and indoles
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Zhang, Dawei,Liebeskind, Lanny S.
p. 2594 - 2595
(2007/10/03)

Microbiological Transformations Part 13. Microbiological Transformations of Derivatives of Indoline with the Fungus Cunninghamella elegans
The incubation of N-benzoylindoline and N-benzoyl-3-methylindoline with C. elegans resulted in reductive cleavage to produce the corresponding indoline and benzyl alcohol.N-Benzoyl-2-methylindoline and N-acetyl-2-methylindoline were hydroxylated at the benzylic position to produce a mixture of cis- and trans-substituted products.In contrast aromatic ring hydroxylation of N-acetyl-2-methylindoline occurred to give N-acetyl-5-hydroxy-2-methylindoline.Incubation of N-benzoyl-7-methylindoline also resulted in aromatic ring hydroxylation.
Crabb, Trevor A.,Canfield, Lesley M.
p. 2936 - 2945
(2007/10/03)

SmI2-PROMOTED ARYL RADICAL CYCLIZATION. A NEW SYNTHETIC ENTRY INTO HETEROCYCLES
Benzofuran, naphthofuran, and indole frameworks were expediently constructed at ambient temperature from arene bromides with ortho O- and N-substituents containing double or triple bonds via radical cyclization process promoted by SmI2.
Inanaga, Junji,Ujikawa, Osamu,Yamaguchi, Masaru
p. 1737 - 1740
(2007/10/02)

Reductions des thio- et dithioacides et de leurs derives par le complexe BH3-Me2S; transformations fonctionnelles des dithioacides au moyen du catecholborane
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Jabre, Imad,Saquet, Monique,Truillier, Andre
p. 756 - 784
(2007/10/02)

Phosphate Esters in Organic Synthesis: The Alkylation of Aniline and N-Methylaniline by Allylic Diphenyl Phosphates.
Allylic diphenyl phosphates react with aniline and N-methylaniline to give N-alkylation products.The reaction simulates the role played by pyrophosphate esters in the formation of nitrogen heterocycles in nature, while establishing that allylic phosphate esters can function as efficient alkylating agents in chemical systems.The procedure offers potential for a simple synthesis of quinoline derivatives.
Onyiriuka, Samuel O.
p. 2077 - 2085
(2007/10/02)

STUDIES ON THE REACTION OF PRIMARY AND SECONDARY AMINES WITH PHENYLSELENINIC ANHYDRIDE AND WITH PHENYLSELENINIC ACID
The dehydrogenation under mild conditions of indolines with phenylseleninic anhydride or acid affords good yields of indoles or of 3-phenylselenenyl indoles.Tetrahydroquinoline and -isoquinoline show comparable behaviour.The dehydrogenation of primary amines gives more complicated mixtures from which nitriles and bis-2-phenylselenenylaldehydes can be isolated.
Barton, Derek H. R.,Lusinchi, Xavier,Milliet, Pierre
p. 4727 - 4738
(2007/10/02)