- Synthesis and Biological Evaluation of Pyrroloindolines as Positive Allosteric Modulators of the α1β2γ2 GABAAReceptor
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γ-Aminobutyric acid type A (GABAA) receptors are key mediators of central inhibitory neurotransmission and have been implicated in several disorders of the central nervous system. Some positive allosteric modulators (PAMs) of this receptor prov
- Blom, Annet E. M.,Su, Justin Y.,Repka, Lindsay M.,Reisman, Sarah E.,Dougherty, Dennis A.
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supporting information
p. 2204 - 2211
(2020/12/17)
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- Enantioselective Synthesis of Pyrroloindolines via Noncovalent Stabilization of Indole Radical Cations and Applications to the Synthesis of Alkaloid Natural Products
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While interest in the synthetic chemistry of radical cations continues to grow, controlling enantioselectivity in the reactions of these intermediates remains a challenge. Based on recent insights into the oxidation of tryptophan in enzymatic systems, we
- Gentry, Emily C.,Rono, Lydia J.,Hale, Martina E.,Matsuura, Rei,Knowles, Robert R.
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supporting information
p. 3394 - 3402
(2018/03/13)
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- A catalytic N-deacylative alkylation approach to hexahydropyrrolo[2,3-b]indole alkaloids
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A versatile unprecedented strategy to diversely functionalized hexahydropyrrolo[2,3-b]indole alkaloids is described in high chemical yields. The synthesis features a key Pd(0)-catalyzed deacylative alkylation of N-acyl 3-substituted indoles using only 1 mol% of Pd(PPh3)4. The scope of this methodology is further defined in the asymmetric synthesis of pyrroloindolines using a diastereoselective approach.
- Kumar, Nivesh,Maity, Arindam,Gavit, Vipin R.,Bisai, Alakesh
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supporting information
p. 9083 - 9086
(2018/08/21)
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- An environmentally friendly protocol for oxidative halocyclization of tryptamine and tryptophol derivatives
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An environmentally friendly and efficient protocol (KX/oxone) for oxidative halocyclization of tryptamine/tryptophol derivatives was developed and demonstrated with 28 examples and concise total synthesis of cyclotryptamine alkaloid protubonines A and B. The distinct advantage of this protocol over all previous methods is that no organic byproduct is generated from a halogenating agent or oxidant, thus greatly reducing the environmental impact of halocyclization and facilitating the post-reaction purification.
- Xu, Jun,Tong, Rongbiao
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p. 2952 - 2956
(2017/07/24)
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- Synthesis and evaluation of oxindoles as promising inhibitors of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1
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Indoleamine 2,3-dioxygenase 1 (IDO1) is considered as an important therapeutic target for the treatment of cancer, chronic infections and other diseases that are associated with immune suppression. Recent developments in understanding the catalytic mechanism of the IDO1 enzyme revealed that conversion of l-tryptophan (l-Trp) to N-formylkynurenine proceeded through an epoxide intermediate state. Accordingly, we synthesized a series of 3-substituted oxindoles from l-Trp, tryptamine and isatin. Compounds with C3-substituted oxindole moieties showed moderate inhibitory activity against the purified human IDO1 enzyme. Their optimization led to the identification of potent compounds, 6, 22, 23 and 25 (IC50 = 0.19 to 0.62 μM), which are competitive inhibitors of IDO1 with respect to l-Trp. These potent compounds also showed IDO1 inhibition potencies in the low-micromolar range (IC50 = 0.33-0.49 μM) in MDA-MB-231 cells. The cytotoxicity of these potent compounds was trivial in different model cancer (MDA-MB-231, A549 and HeLa) cells and macrophage (J774A.1) cells. Stronger selectivity for the IDO1 enzyme (124 to 210-fold) over the tryptophan 2,3-dioxygenase (TDO) enzyme was also observed for these compounds. These results suggest that the oxindole moiety of the compounds could mimic the epoxide intermediate state of l-Trp. Therefore, the structural simplicity and low-micromolar inhibition potencies of these 3-substituted oxindoles make them quite attractive for further investigation of IDO1 function and immunotherapeutic applications.
- Paul, Saurav,Roy, Ashalata,Deka, Suman Jyoti,Panda, Subhankar,Srivastava, Gopal Narayan,Trivedi, Vishal,Manna, Debasis
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p. 1640 - 1654
(2017/08/22)
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- Convergent and Biomimetic Enantioselective Total Synthesis of (-)-Communesin F
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The first biomimetic enantioselective total synthesis of (-)-communesin F based on a late-stage heterodimerization and aminal exchange is described. Our synthesis features the expedient diazene-directed assembly of two advanced fragments to secure the con
- Lathrop, Stephen P.,Pompeo, Matthew,Chang, Wen-Tau T.,Movassaghi, Mohammad
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supporting information
p. 7763 - 7769
(2016/07/06)
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- Synthesis of naked amino-pyrroloindoline via direct aminocyclization of tryptamine
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The first direct access to unprotected amino-pyrroloindoline via aminocyclization of tryptamine and tryptophan has been described. A variety of structurally diverse amino-pyrroloindolines are furnished by the use of O-(2,4-dinitrophenyl)hydroxylamine (DPH
- Shen, Zhigao,Xia, Zilei,Zhao, Huijun,Hu, Jiadong,Wan, Xiaolong,Lai, Yisheng,Zhu, Chen,Xie, Weiqing
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supporting information
p. 5381 - 5384
(2015/05/20)
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- Aerobic palladium(II)-catalyzed 5-endo-trig cyclization: An entry into the diastereoselective C-2 alkenylation of indoles with tri- and tetrasubstituted double bonds
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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
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supporting information; experimental part
p. 1265 - 1269
(2012/03/08)
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- INHIBITION OF BACTERIAL BIOFILMS WITH ARYL CARBAMATES
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Disclosure is provided for carbamate compounds that prevent, remove and/or inhibit the formation of biofilms, compositions including these compounds, devices including these compounds, and methods of using the same.
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Page/Page column 33-34
(2012/02/01)
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- An excellent method for Cbz-protection of amines
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Cbz-protection of aliphatic and aromatic amines can be accomplished with benzylchloroformate using a catalytic amount of dodecatungstophosphoric acid hydrate (0.05 equiv). The reaction is simple, fast, does not require aqueous work-up and gives excellent yields.
- Vanlaldinpuia, Khiangte,Sema, H. Atoholi,Rokhum, Lalthazuala,Bez, Ghanashyam
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experimental part
p. 228 - 229
(2010/08/20)
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- Synthesis of indoleamine 2,3-dioxygenase inhibitory analogues of the sponge alkaloid exiguamine A
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Synthetic analogues of the sponge natural product exiguamine A (3) have been prepared and evaluated for their ability to inhibit indoleamine 2,3-dioxygenase in vitro.
- Carr, Gavin,Chung, Marco K. W.,Mauk, A. Grant,Andersen, Raymond J.
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p. 2634 - 2637
(2008/12/22)
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- SUBSTITUTED QUINONE INDOLEAMINE 2,3-DIOXYGENASE (IDO) INHIBITORS AND SYNTHESES AND USES THEREFOR
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The present invention relates to substituted mdoloqumone compounds of the general formula (A) and (B) and pharmaceutical compositions thereof that are inhibitors of mdoleamme-2,3-dioxygenase (IDO) More specifically, the invention relates to said compounds
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Page/Page column 60; 62-63
(2008/12/05)
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- A mild and efficient chemoselective protection of amines as N-benzyloxycarbonyl derivatives in the presence of La(NO3)3·6H2O under solvent-free conditions
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A facile and versatile method for the chemoselective N-benzyloxycarbonylation of amines has been developed by treatment with benzyloxycarbonyl chloride (Cbz-Cl) in the presence of lanthanum(III) nitrate hexahydrate under solvent-free conditions. The metho
- Chinni Mahesh,Narasimhulu,Srikanth Reddy,Suryakiran,Venkateswarlu
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- Synthetic studies toward diazonamide A. Preparation of the benzofuranone-indolyloxazole fragment
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The benzofuranone-indolyloxazole fragment of the polycyclic marine natural product diazonamide A was prepared from tryptamine. The oxazole ring was synthesized from an α keto-indole via cyclodehydration with Ph3P/Cl3CCCl3,
- Wipf, Peter,Yokokawa, Fumiaki
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p. 2223 - 2226
(2007/10/03)
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- Mannich biscyclizations. Total synthesis of (-)-ajmalicine
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A concise enantioselective total synthesis of the cardiovascular agent (-)-ajmalicine and an approach toward the synthesis of (+)-19-epiajmalicine are described. The key step of the (-)-ajmalicine synthesis is a carboxylate-terminated N-acyliminium ion biscyclization (74 → 67), which assembles the D and E rings of this heteroyohimbine alkaloid in one step. A related carboxylate-terminated iminium ion biscyclization (28 → 29) is the central step in the approach to (+)-epiajmalicine.
- L?gers, Michael,Overman, Larry E.,Welmaker, Gregory S.
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p. 9139 - 9150
(2007/10/02)
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- Compounds useful as antiproliferative agents
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Melatonin compounds are disclosed of the formula STR1 where R is hydrogen or C1 to C6 linear or branched alkylene substituted with phenyl; R1 is hydrogen, substituted benzyl, naphthylmethyl or taken together with R2/
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- MANIPULATION OF THE CARBOXYL GROUPS OF α-AMINO-ACIDS AND PEPTIDES USING RADICAL CHEMISTRY BASED ON ESTERS OF N-HYDROXY-2-THIOPYRIDONE
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Photolysis of α-amino-acid or peptide esters derived from N-hydroxy-2-thiopyridone in the presence of t-butylthiol affords the expected decarboxylation products in good yield.The reaction can be applied to the α-carboxyl or to the side chain carboxyl of g
- Barton, Derek H. R.,Herve, Yolande,Potier, Pierre,Thierry, Josiane
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p. 5479 - 5486
(2007/10/02)
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- Psychotomimetic N-Methyl-N-isopropyltryptamines. Effects of Variation of Aromatic Oxygen Substituents
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Eight N-methyl-N-isopropyltryptamines (MIPTs) possessing various aromatic oxygen substituents were prepared, characterized, and evaluated for hallucinogenic activity in man.In at least two instances (the Ar H and the Ar 5-OCH3, 1 and 4) the unsymmetrical nitrogen substitution led to a substantial increase in potency as well as oral activity when compared to the symmetrical dimethyl homologues.Qualitatively, 4-hydroxy-N-methyl-N-isopropyltryptamine (2) was the most interesting in overall effect, producing a classic hallucinogenic profile.The 5-methoxy congeger 4 resulted in a state characterized by heightened conceptual stimulation lacking in visual phenomena.Other members of the series exhibited diminished effects.
- Repke, David B.,Grotjahn, Douglas B.,Shulgin, Alexander T.
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p. 892 - 896
(2007/10/02)
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- Reductive Radical Decarboxylation of Amino-acids and Peptides
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Radicals generated from N-protected α-amino-acids by photolysis of their N-hydroxypyridine-2-thione esters at room temperature are efficiently quenched by t-butyl thiol to give decarboxy-acids; comparable reactions have been carried out on the side chain carboxy groups of suitable protected aspartic and glutamic acids.
- Barton, Derek H. R.,Herve, Yolande,Potier, Pierre,Thierry, Josiane
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p. 1298 - 1299
(2007/10/02)
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- Synthesis of Oxazolylindole Alkaloids from Tryptamine and Tryptophan by Oxidation with 2,3-Dichloro-5,6-dicyanobenzoquinone
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When N-acyl derivatives of tryptamine and L-tryptophan methyl ester were treated with DDQ (2 equiv) in tetrahydrofuran or other anhydrous solvents, four consecutive reactions, dehydrogenation, nucleophilic cyclization, another dehydrogenation, and isomeri
- Yoshioka, Tadao,Mohri, Kunihiko,Oikawa, Yuji,Yonemitsu, Osamu
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p. 2252 - 2281
(2007/10/02)
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