- Design, Synthesis, and Biological Evaluation of Novel Pyrimido[4,5-b]indole Derivatives against Gram-Negative Multidrug-Resistant Pathogens
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Due to the poor permeability across Gram-negative bacterial membranes and the troublesome bacterial efflux mechanism, only a few GyrB/ParE inhibitors with potent activity against Gram-negative pathogens have been reported. Among them, pyrimido[4,5-b]indol
- Kong, Qidi,Pan, Wei,Xu, Heng,Xue, Yaru,Guo, Bin,Meng, Xin,Luo, Cheng,Wang, Ting,Zhang, Shuhua,Yang, Yushe
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supporting information
p. 8644 - 8665
(2021/06/28)
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- Cobalt-Catalyzed Diastereo- And Enantioselective Reductive Allyl Additions to Aldehydes with Allylic Alcohol Derivatives via Allyl Radical Intermediates
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Catalytic generation of ambiphilic π-allyl-metal complexes and their utility in enantioselective transformations constitutes a powerful approach for introduction of allyl groups to a molecule. Herein an unprecedented cobalt-catalyzed highly site-, diastereo-, and enantioselective protocol for stereoselective formation of nucleophilic allyl-Co(II) complexes followed by addition to aldehydes is presented. The reaction features diastereo- and enantioconvergent conversion of easily accessible allylic alcohol derivatives to diversified enantioenriched homoallylic alcohols with a remarkably broad scope of allyl groups that can be introduced. Mechanistic studies indicated that allyl radical intermediates were involved in this process. These new discoveries establish a new strategy for development of enantioselective transformations through capture of radicals by chiral Co complexes, pushing forward the frontier of Co complexes for enantioselective catalysis.
- Wang, Lei,Wang, Lifan,Li, Mingxia,Chong, Qinglei,Meng, Fanke
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supporting information
p. 12755 - 12765
(2021/08/30)
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- SPIROPIPERIDINE ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS
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The present disclosure relates to compounds of formula (I) that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation.
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Page/Page column 45
(2021/05/15)
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- Visible-Light-Promoted Intramolecular α-Allylation of Aldehydes in the Absence of Sacrificial Hydrogen Acceptors
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We report herein an unprecedented protocol for radical cyclization of aldehydes with pendant alkenes via synergistic photoredox, cobaloxime, and amine catalysis. The transformation was achieved in the absence of external oxidants, providing a variety of 5-, 6-, and 7-membered ring products with alkene transposition in satisfactory yields. The reaction exhibits wide functional group compatibility and occurs under mild conditions with extrusion of H2.
- Liu, Feng,Liu, Jia-Li,tu, Jia-Lin
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supporting information
p. 7369 - 7372
(2020/10/05)
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- SPIROPIPERIDINE ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS
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The present disclosure relates to compounds of formula (I) that are useful as modulators of 7α nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation.
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Page/Page column 50
(2020/11/12)
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- Pd-catalyzed regioselective C?H alkenylation and alkynylation of allylic alcohols with the assistance of a bidentate phenanthroline auxiliary
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A Pd-catalyzed regioselective C?H alkenylation of allylic alcohols with electron-deficient alkenes has been developed. The key to success is the introduction of bidentately coordinating phenanthroline directing group, which enables the otherwise challenging and regioselective C?H activation at the proximal alkenyl C?H bonds over the conceivably competitive allylic C?O bond activation. The same Pd/phenanthroline system is efficient for the C?H alkynylation of allylic alcohols with alkynyl bromides.
- Hirano, Koji,Miura, Masahiro,Xu, Shibo
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supporting information
p. 9059 - 9064
(2020/12/02)
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- SPIROPIPERIDINE ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS
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The present disclosure relates to compounds of formula I that are useful as modulators of 7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation (I).
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Page/Page column 66-67
(2019/11/19)
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- Copper-Catalyzed Enantio-, Diastereo-, and Regioselective [2,3]-Rearrangements of Iodonium Ylides
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The first highly enantioselective, diastereoselective, and regioselective [2,3]-rearrangement of iodonium ylides has been developed as a general solution to catalytic onium ylide rearrangements. In the presence of a chiral copper catalyst, substituted allylic iodides couple with α-diazoesters to generate metal-coordinated iodonium ylides, which undergo [2,3]-rearrangements with high selectivities (up to >95:5 r.r., up to >95:5 d.r., and up to 97 % ee). The enantioenriched iodoester products can be converted stereospecifically into a variety of onium ylide rearrangement products, as well as compounds that are not accessible by classical onium ylide rearrangements.
- Xu, Bin,Tambar, Uttam K.
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supporting information
p. 9868 - 9871
(2017/08/08)
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- PYRROLO AND PYRAZOLOPYRIMIDINES AS UBIQUITIN-SPECIFIC PROTEASE 7 INHIBITORS
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The invention relates to inhibitors of USP7 inhibitors useful in the treatment of cancers, neurodegenerative diseases, immunological disorders, inflammatory disorders, cardiovascular diseases, ischemic diseases, viral infections and diseases, and bacterial infections and diseases, having the Formula: where m, n, X1, X2, R1-R5, R5′ and R6 are described herein.
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-
Paragraph 2280; 2281
(2016/08/03)
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- The synthesis of α,α-disubstituted α-amino acids via ichikawa rearrangement
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An approach to α,α-disubstituted α-amino acids is reported. The key step is allyl cyanate-to-isocyanate rearrangement. As demonstrated, the resultant allyl isocyanates can be directly trapped with various nucleophiles, for instance, alcohols, amines, and organometallic reagents, to provide a broad range of N-functionalized allylamines. The developed method has been successfully applied in the synthesis of two bioactive peptides: 2-aminoadamantane-2-carboxylic acid derived P2X7-evoked glutamate release inhibitor and 4-amino-tetrahydropyranyl-4-carboxylic acid derived dipeptide GSK-2793660, which is currently in clinical trials as cathepsin C inhibitor for the treatment of cystic fibrosis, noncystic fibrosis bronchiectasis, ANCA-associated vasculitis and bronchiectasis.
- Szczes?niak, Piotr,Pieczykolan, Micha?,Stecko, Sebastian
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p. 1057 - 1074
(2016/02/19)
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- 7-(4-Alkylidenylpiperidinyl)-quinolone bacterial topoisomerase inhibitors
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Novel antibacterial fluoroquinolone agents bearing a 4-alkylidenylpiperidine 7-position substituent are active against quinolone-susceptible and quinolone-resistant gram-positive bacteria, including Streptococcus pneumoniae and MRSA. Analogs 22b, 23c, and 24 demonstrated superior in vitro and in vivo efficacy to ciprofloxacin against these cocci.
- Grant, Eugene B.,Foleno, Barbara D.,Goldschmidt, Raul,Hilliard, Jamese J.,Lin, Shu-Chen,Morrow, Brian,Paget, Steven D.,Weidner-Wells, Michele A.,Xu, Xiaodong,Xu, Xiaoqing,Murray, William V.,Bush, Karen,Macielag, Mark J.
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p. 5502 - 5506
(2015/01/08)
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- Efficient one-to-one coupling of easily available 1,3-dienes with carbon dioxide
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An efficient one-to-one coupling reaction of atmospheric pressure carbon dioxide with 1,3-dienes is realized for the first time through PSiP-pincer type palladium-catalyzed hydrocarboxylation. The reaction is applicable to various 1,3-dienes including easily available chemical feedstock such as 1,3-butadiene and isoprene. This protocol affords a highly useful method for the synthesis of β,γ-unsaturated carboxylic acid derivatives from CO2.
- Takaya, Jun,Sasano, Kota,Iwasawa, Nobuharu
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supporting information; experimental part
p. 1698 - 1701
(2011/05/04)
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- 6-PHENYL-LH-IMIDAZO [4, 5-C] PYRIDINE-4-CARBONITRILE DERIVATIVES AS CATHEPSIN S AND/OR CATHEPSIN K INHIBITORS
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The present invention relates to 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives having the general Formula (I) to pharmaceutical compositions comprising the same as well as to the use of these derivatives for the preparation of a medicament
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Page/Page column 57-58
(2010/08/08)
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- 6-PHENYL-1H-IMIDAZO[4,5-c]PYRIDINE-4-CARBONITRILE DERIVATIVES
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The present invention relates to 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives having the general Formula I to pharmaceutical compositions comprising the same as well as to the use of these derivatives for the preparation of a medicament f
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Page/Page column 31
(2010/08/07)
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- Synthesis of 2-isoxazolines: Enantioselective and racemic methods based on conjugate additions of oximes
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The formation of 3-unsubstituted 2-isoxazolines by means of condensation reactions between α,β-unsaturated aldehydes and oximes proceeds readily in the presence of catalytic amounts of anilinium salts. Mechanistically, the process involves a fast conjugate addition of the oxime and a slower intramolecular oxime-transfer reaction. The rate of oxime transfer was found to correlate with the acidity of the catalyst. This finding enabled us to discover an enantioselective process in which the fragile conjugate-addition product generated in the first stage is rapidly cyclized into the stable isoxazo-line under acidic conditions, with conservation of enantiomeric excess. In summary, herein we describe synthetically useful protocols for accessing 3-unsubstituted 2-isoxazolines in both the enantioselective and racemic manner. The mechanism of the condensation reaction catalyzed by the anilinium salt was also investigated by NMR spectroscopy experiments in which the effect of differently substituted aldehydes and oximes as well as water on the reaction rate was studied. The results point to the rate-limiting elimination of water from the 3-hydroxy-2-iso-xazolidine intermediate.
- Pohjakallio, Antti,Pihko, Petri M.,Laitinen, Ulla M.
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supporting information; experimental part
p. 11325 - 11339
(2010/11/16)
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- Non-nucleoside inhibitors of HCV polymerase NS5B. Part 4: Structure-based design, synthesis, and biological evaluation of benzo[d]isothiazole-1,1-dioxides
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A series of benzo[d]isothiazole-1,1-dioxides were designed and evaluated as inhibitors of HCV polymerase NS5B. Structure-based design led to the incorporation of a high affinity methyl sulfonamide group. Structure-activity relationship (SAR) studies of th
- de Vicente, Javier,Hendricks, Robert T.,Smith, David B.,Fell, Jay B.,Fischer, John,Spencer, Stacey R.,Stengel, Peter J.,Mohr, Peter,Robinson, John E.,Blake, James F.,Hilgenkamp, Ramona K.,Yee, Calvin,Adjabeng, George,Elworthy, Todd R.,Li, Jim,Wang, Beihan,Bamberg, Joe T.,Harris, Seth F.,Wong, April,Leveque, Vincent J.P.,Najera, Isabel,Pogam, Sophie Le,Rajyaguru, Sonal,Ao-Ieong, Gloria,Alexandrova, Ludmila,Larrabee, Susan,Brandl, Michael,Briggs, Andrew,Sukhtankar, Sunil,Farrell, Robert
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scheme or table
p. 5652 - 5656
(2010/04/05)
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- G-PROTEIN COUPLED RECEPTOR AGONISTS
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Compounds of formula (I): or pharmaceutically acceptable salts thereof, are GPCR agonists and are useful as for the treatment of obesity and diabetes.
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Page/Page column 48
(2008/06/13)
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- SPIROPIPERIDINE COMPOUND AND MEDICINAL USE THEREOF
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The present invention relates to a spiro-piperidine compound represented by formula (I): wherein R1 represents hydrogen, an aliphatic hydrocarbon group which may have a substituent(s) or a cyclic group which may have a substituent(s); and ring A represents a 5- to 8-membered cyclic group which may have a substituent(s), a salt thereof, an N-oxide thereof, a quaternary ammonium salt thereof or a solvate thereof, or a prodrug thereof The compounds represented by formula (I) have chemokine antagonistic action, so that they are useful for prevention and/or treatment of various inflammatory diseases, immune diseases such as autoimmune diseases or allergic diseases, or HIV infection.
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Page/Page column 67
(2008/06/13)
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- 7-AMINO ALKYLIDENYL-HETEROCYCLIC QUINOLONES AND NAPHTHYRIDONES
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The present invention relates to compounds having a structure according to Formula I wherein n, m, z, R, R2, R3, R4, R5, R6, A, E, X, Y a and b are as defined above; or an optical isomer, diastereomer or enantiomer thereof; a pharmaceutically acceptable s
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Page/Page column 48
(2008/06/13)
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- Fused imidazopyridine derivatives as antihyperlipidemic agents
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A novel compound of the formula: wherein ring Q is an optionally substituted pyridine ring; One of R0, R1and R2is —Y0—Z0, and the other tow groups are a hydrogen, a halogen, an optionally substituted hydroxy group, a hydrocarbon group that may be an optionally substituted hydrocarbon group or an acyl group; Y0is a bond or an optionally substituted bivalent hydrocarbon group; Z0is a basic group which may be bonded via oxygen, nitrogen, —CO—, —CS—, —SO2N(R3)— (where R3is hydrogen or an optionally substituted hydrocarbon group), or S(O)n(wherein n is to 0, 1 or 2); .........is a single bond or a double bond, or a salt thereof, which has an excellent LDL receptor up-regulating, blood-lipids lowering, blood-sugar lowering and diabetic complication-ameliorating activity.
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