- Enantioselective, Catalytic Multicomponent Synthesis of Homoallylic Amines Enabled by Hydrogen-Bonding and Dispersive Interactions
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We report a one-step catalytic, enantioselective method for the preparation of homoallylic N-Boc amines directly from acetals. Reactive iminium ion intermediates are generated in situ through the combination of an acetal, a chiral thiourea catalyst, trialkylsilyl triflate, and N-Boc carbamate and are subsequently trapped by a variety of allylsilane nucleophiles. No homoallylic ether byproducts are detected, consistent with allylation of the iminium intermediate being highly favored over allylation of the intermediate oxocarbenium ion. Acetals derived from aromatic aldehydes possessing a variety of functional groups and substitution patterns yield homoallylic amines with excellent levels of enantiomeric enrichment. Experimental and computational data are consistent with an anchoring hydrogen-bond interaction between the protioiminium ion and the amide of the catalyst in the enantiodetermining transition state, and with stereodifferentiation achieved through specific noncovalent interactions (NCIs) with the catalyst pyrenyl moiety. Evidence is provided that the key NCI in the major pathway is a π-stacking interaction, contrasting with the cation-πinteractions invoked in previously studied reactions promoted by the same family of aryl-pyrrolidino-H-bond-donor catalysts.
- Ronchi, Elisabetta,Paradine, Shauna M.,Jacobsen, Eric N.
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supporting information
p. 7272 - 7278
(2021/05/26)
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- Synthesis of Raputimonoindoles A–C and Congeners
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The first synthesis of raputimonoindole A from the tree Raputia praetermissa (Rutaceae) is reported, starting from indole-5-carbaldehyde. The key step is Braun′s diastereoselective Heck–Suzuki cascade that assembled the prenylated methylenetetrahydrofuran moiety. The unsubstituted indole enamine functionality was tolerated, and the absolute configuration of naturally occurring raputimonoindole A is assigned as (R,R). Raputimonoindole B was accessed by Ir-catalyzed C–H activation/borylation followed by Suzuki–Miyaura cross-coupling. Two biosynthetically related 5-(dihydrofuran-2-yl)indole derivatives from R. simulans were synthesized by ring-closing metathesis, and their absolute configurations were determined.
- Kock, Mario,Fresia, Marvin,Jones, Peter G.,Lindel, Thomas
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supporting information
p. 4061 - 4065
(2019/06/27)
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- PENTAFLUOROPHENYL SULFONAMIDE COMPOUNDS, COMPOSITIONS AND USES THEREOF
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The present application relates to sulfonamide containing compounds of Formulae (I) and (II) and compositions containing said compounds effective in the treatment of cell proliferative disorders, in particular cancer, and various methods of use thereof.
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Paragraph 00134; 00217
(2019/04/16)
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- Structure-guided design, synthesis, and biological evaluation of (2-(1 H-Indol-3-yl)-1 H-imidazol-4-yl)(3,4,5-trimethoxyphenyl) methanone (ABI-231) analogues targeting the colchicine binding site in Tubulin
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ABI-231 is a potent, orally bioavailable tubulin inhibitor that interacts with the colchicine binding site and is currently undergoing clinical trials for prostate cancer. Guided by the crystal structure of ABI-231 in complex with tubulin, we performed structure-activity relationship studies around the 3-indole moiety that led to the discovery of several potent ABI-231 analogues, most notably 10ab and 10bb. The crystal structures of 10ab and 10bb in complex with tubulin confirmed their improved molecular interactions to the colchicine site. In vitro, biological studies showed that new ABI-231 analogues disrupt tubulin polymerization, promote microtubule fragmentation, and inhibit cancer cell migration. In vivo, analogue 10bb not only significantly inhibits primary tumor growth and decreases tumor metastasis in melanoma xenograft models but also shows a significant ability to overcome paclitaxel resistance in a taxane-resistant PC-3/TxR model. In addition, pharmacological screening suggested that 10bb has a low risk of potential off-target function.
- Wang, Qinghui,Arnst, Kinsie E.,Wang, Yuxi,Kumar, Gyanendra,Ma, Dejian,White, Stephen W.,Miller, Duane D.,Li, Wei,Li, Weimin
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p. 6734 - 6750
(2019/08/20)
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- Synthesis of Aldehydes by Organocatalytic Formylation Reactions of Boronic Acids with Glyoxylic Acid
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Reported herein is a conceptually novel organocatalytic strategy for the formylation of boronic acids. New reactivity is engineered into the α-amino-acid-forming Petasis reaction occurring between aryl boronic acids, amines, and glyoxylic acids to prepare aldehydes. The operational simplicity of the process and its ability to generate structurally diverse and valued aryl, heteroaryl, and α,β-unsaturated aldehydes containing a wide array of functional groups, demonstrates the practical utility of the new synthetic strategy.
- Huang, He,Yu, Chenguang,Li, Xiangmin,Zhang, Yongqiang,Zhang, Yueteng,Chen, Xiaobei,Mariano, Patrick S.,Xie, Hexin,Wang, Wei
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supporting information
p. 8201 - 8205
(2017/06/30)
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- Visible-Light-Promoted Nickel- and Organic-Dye-Cocatalyzed Formylation Reaction of Aryl Halides and Triflates and Vinyl Bromides with Diethoxyacetic Acid as a Formyl Equivalent
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A simple formylation reaction of aryl halides, aryl triflates, and vinyl bromides under synergistic nickel- and organic-dye-mediated photoredox catalysis is reported. Distinct from widely used palladium-catalyzed formylation processes, this reaction proceeds by a two-step mechanistic sequence involving initial in situ generation of the diethoxymethyl radical from diethoxyacetic acid by a 4CzIPN-mediated photoredox reaction. The formyl-radical equivalent then undergoes nickel-catalyzed substitution reactions with aryl halides and triflates and vinyl bromides to form the corresponding aldehyde products. Significantly, besides aryl bromides, less reactive aryl chlorides and triflates and vinyl halides serve as effective substrates for this process. Since the mild conditions involved in this reaction tolerate a plethora of functional groups, the process can be applied to the efficient preparation of diverse aromatic aldehydes.
- Huang, He,Li, Xiangmin,Yu, Chenguang,Zhang, Yueteng,Mariano, Patrick S.,Wang, Wei
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supporting information
p. 1500 - 1505
(2017/02/05)
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- MAP4K4 (HGK) Inhibitors
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The invention provides mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) inhibitors, and pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant diminution of tumor cell growth, cancer or metastasis.
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- GAMMA-DIKETONES AS WNT/BETA -CATENIN SIGNALING PATHWAY ACTIVATORS
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The present disclosure provides γ-diketones or analogs thereof, that activate Wnt/β-catenin signaling and thus treat or prevent diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries or spine injuries, brain atrophy/neurological disorders related to the differentiation and development of the central nervous system, including Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; otic disorders like cochlear hair cell loss; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, such as hair loss, hematopoiesis related diseases and tissue regeneration related diseases.
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Paragraph 1755; 1756; 1757; 1758
(2014/09/03)
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- Design of new antifungal agents: synthesis and evaluation of 1-[(1H-indol-5-ylmethyl)amino]-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan- 2-ols
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We previously reported on the design and synthesis of 1-[((hetero)aryl- or piperidinylmethyl)amino]-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols showing various degrees of antifungal activity against Candida albicans and Aspergillus fumigatus strains. N
- Guillon, Remi,Giraud, Francis,Loge, Cedric,Le Borgne, Marc,Picot, Carine,Pagniez, Fabrice,Le Pape, Patrice
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scheme or table
p. 5833 - 5836
(2010/04/28)
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- PESTICIDAL CONDENSED - RING ARYL COMPOUNDS
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Condensed-ring aryl compounds of formula (I) and use of the same as a agrochemical for controlling noxious organisms wherein (X)mQ, A, R1, (Y)n and the grouping -W1-W2-W3-W4- are as defined herein.
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Page/Page column 132
(2009/10/22)
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- Sulfonamide bicyclic compounds
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The invention encompasses compounds of Formula I, including pharmaceutically acceptable salts and solvates, their pharmaceutical compositions, and their uses in inhibiting β-amyloid peptide (β-AP) production.
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Page/Page column 7
(2010/10/20)
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- A concise synthesis of a novel antiangiogenic tyrosine kinase inhibitor
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(Chemical Equation Presented). An efficient synthesis of the potent KDR inhibitor 3-[5-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-1H-indole-2-yl] quinolin-2(1H)-one (1) is described. The process features a noncryogenic indole boronation and a dicyclohexylamine-mediated Suzuki coupling.
- Payack, Joseph F.,Vazquez, Enrique,Matty, Louis,Kress, Michael H.,McNamara, James
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p. 175 - 178
(2007/10/03)
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- FORMULATIONS FOR TYROSINE KINASE INHIBITORS
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The present invention is related to a powder, powder blend or granulation formulation of 3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one, a tyrosine kinase inhibitor, which is adapted for reconstitution with a diluent. This invention is also related to a prepared aqueous suspension, or dispersion, formulation, particularly to a stable oral pharmaceutical formulation, comprising granules of 3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one mixed with a diluent. Additionally, the present invention is related to the method of preparing these formulations.
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- Sulfonamide hydroxamates
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A compound of the Formula (I): wherein Z, R1, R, and Ar2are as defined in the specification. This invention also relates to sulfonamide compounds of the Formula (I) that are inhibitors of procollagen C-proteinase, pharmaceutical compositions containing them, methods for their use, and methods for preparing the compounds.
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- Catalytic asymmetric synthesis of protected tryptophan regioisomers
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Tryptophan 1 (Trp) is superior to all other naturally occurring peptide residues in its ability to bind cations (the cation - π interaction). In an effort to expand the toolbox of Trp-like amino acids, in this note we report catalytic asymmetric syntheses of Trp regioisomers 2a - e, where the alanine unit is attached not to C-3 of indole but to C-2, C-4, C-5, C-6, or C-7. Excellent asymmetric induction is obtained in each case (generally >97% ee). Ab initio calculations suggest that the indole nuclei of 2a-e will bind Na+ with the same affinity as that of Trp.
- Carlier, Paul R.,Lam, Polo C.-H.,Wong, Dawn M.
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p. 6256 - 6259
(2007/10/03)
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