- BICYCLIC HETEROARENES AND METHODS OF THEIR USE
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Disclosed are compounds useful in the treatment of neurological disorders. The compounds described herein, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological diseases.
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Page/Page column 67-68
(2021/12/30)
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- A Unified Strategy for the Synthesis of Difluoromethyl- And Vinylfluoride-Containing Scaffolds
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Here, we report a general method for the synthesis of quaternary and tertiary difluoromethylated compounds and their vinylfluoride analogues. The strategy, which relies on a two-step sequence featuring a C-selective electrophilic difluoromethylation and either a palladium-catalyzed decarboxylative protonation or a Krapcho decarboxylation, is practical, scalable, and high yielding. Considering the generality of the method and the attractive properties offered by the difluoromethyl group, this approach provides a valuable tool for late-stage functionalization and drug development.
- Duchemin, Nicolas,Buccafusca, Roberto,Daumas, Marc,Ferey, Vincent,Arseniyadis, Stellios
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supporting information
p. 8205 - 8210
(2019/10/16)
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- Pyrrolidines and Piperidines by Ligand-Enabled Aza-Heck Cyclizations and Cascades of N-(Pentafluorobenzoyloxy)carbamates
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Ligand-enabled aza-Heck cyclizations and cascades of N-(pentafluorobenzoyloxy)carbamates are described. These studies encompass the first examples of efficient non-biased 6-exo aza-Heck cyclizations. The methodology provides direct and flexible access to carbamate protected pyrrolidines and piperidines.
- Hazelden, Ian R.,Carmona, Rafaela C.,Langer, Thomas,Pringle, Paul G.,Bower, John F.
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supporting information
p. 5124 - 5128
(2018/03/26)
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- Enantioselective phase-transfer catalytic α-benzylation and α-allylation of α-tert-butoxycarbonyllactones
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A new enantioselective α-benzylation and α-allylation of α-tert-butoxycarbonyllactones was devloped. α-Benzylation and α-allylation of α-tert-butoxycarbonylbutyrolactone and α-tert-butoxycarbonylvalerolactone under phase-transfer catalytic conditions (50% cesium hydroxide, toluene, -60 °C) in the presence of (S,S)-3,4,5-trifluorophenyl-NAS bromide (1 mol%) afforded the corresponding α-substituted α-tert-butoxycarbonyllactones in very high chemical yields (up to 99%) and optical yields (up to 99% ee). The synthetic potential of this method has been successfully demonstrated by the asymmetric synthesis of unnatural α-quaternary homoserines, 3-alkyl-3-carboxypyrrolidine and 3-alkyl-3-carboxypiperidine. Copyright
- Ha, Min Woo,Lee, Heejin,Yi, Hye Yeong,Park, Yohan,Kim, Sori,Hong, Suckchang,Lee, Myungmo,Kim, Mi-Hyun,Kim, Taek-Soo,Park, Hyeung-Geun
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supporting information
p. 637 - 642
(2013/04/10)
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- Lead optimization of a dihydropyrrolopyrimidine inhibitor against phosphoinositide 3-kinase (PI3K) to improve the phenol glucuronic acid conjugation
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Our lead compound for a phosphoinositide 3-kinase (PI3K) inhibitor (1) was metabolically unstable because of rapid glucuronidation of the phenol moiety. Based on structure-activity relationship (SAR) information and a FlexSIS docking simulation score, aminopyrimidine was identified as a bioisostere of phenol. An X-ray structure study revealed a hydrogen bonding pattern of aminopyrimidine derivatives. Finally, aminopyrimidine derivatives 33 showed strong tumor growth inhibition against a KPL-4 breast cancer xenograft model in vivo.
- Kawada, Hatsuo,Ebiike, Hirosato,Tsukazaki, Masao,Nakamura, Mitsuaki,Morikami, Kenji,Yoshinari, Kiyoshi,Yoshida, Miyuki,Ogawa, Kotaro,Shimma, Nobuo,Tsukuda, Takuo,Ohwada, Jun
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supporting information
p. 673 - 678
(2013/02/23)
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- HETEROCYCLIC AMIDES AS ROCK INHIBITORS
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The present invention relates to new kinase inhibitors of formula (I), more specifically ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In particular, the present invention relates to new ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In addition, the invention relates to methods of treatment and use of said compounds in the manufacture of a medicament for the application to a number of therapeutic indications including sexual dysfunction, inflammatory diseases, ophthalmic diseases and Respiratory diseases.
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Page/Page column 80
(2011/10/03)
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- PYRIMIDINE DERIVATIVE AS PI3K INHIBITOR AND USE THEREOF
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A drug is provided that is useful as a preventive or therapeutic for cancer as a result of having superior PI3K inhibitory effects as well as superior stability in the body and water-solubility. A compound, or pharmaceutically acceptable salt thereof, rep
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Page/Page column 147
(2009/05/29)
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- SYNTHESIS OF TETRAHYDRO-1,2-OXAZINES BY THE CYCLOADDITION OF NITRONES WITH CYCLOPROPANES
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One aspect of the present invention relates to a method of preparing tetrahydro-1,2- oxazines comprising the step of combining a nitrone and a cyclopropane in the presence of a Lewis acid. Another aspect of the present invention relates to a method of preparing a tetrahydro-1,2-oxazine, comprising the step of combining an aldehyde and a hydroxylamine in the presence of a Lewis acid to generate a nitrone in situ, then admixing a cyclopropane. Another aspect of the present invention relates to converting a tetrahydro-l,2-oxazine to a pyrrolidine comprising the step of admixing a tetrahydro-1,2-oxazine and a reducing agent.
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- NOVEL PURINE- OR PYRROLOL[2,3-d]PYRIMIDINE-2-CARBONITILES FOR TREATING DISEASES ASSOCIATED WITH CYSTEINE PROTEASE ACTIVITY
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The present invention therefore provides a compound of formula (I) and compositions for treating diseases associated with cysteine protease activity. The compounds are reversible inhibitors of cysteine proteases S, K, F, L and B. Of particular interest ar
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- -Alkoxystannyl ethers in organic synthesis: Synthesis of functionalised γ-butyrolactones
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Ozonolysis of a variety of (tetraydrofuran-2-yl)tri-n-butylstannanes affords the corresponding γ-butyrolactones in good to excellent yields. This reaction is tolerant to a range of other functional groups and provides access to substituted γ-butyrolactone
- Gilbert, Philip,Lewis, Mark L.,Quayle, Peter,Zhao, Yuekun,Mills, Keith
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p. 9115 - 9118
(2007/10/03)
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- Cyclopropane Derivatives, 2. - Self-Acylation of α-Alkyl-γ-lactones To Give Bis(1-alkylcyclopropyl)ketones via Spiroacetals
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High-yield synthetic ways are recommended for the title lactones 1.The coupling of two 2-alkyl-4-butanolides is possible in an inter-(1b, c) or intramolecular fashion (4c) to give spiroacetals 8 or 9, respectively, in the absence of hindering substituents.Symmetrically substituted bis(1-alkylcyclopropyl)ketones 12 and 13 may be prepared by acidic cleavage of those spiroacetals lacking 2,7-substituents.
- Boehrer, Gerald,Knorr, Rudolf,Boehrer, Petra
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p. 2161 - 2166
(2007/10/02)
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- A CONVENIENT PREPARATION OF 2-CARBOXY- AND 2-ALKOXYCARBONYL-γ-BUTYROLACTONES FROM CYCLOPROPANE-1,1-DICARBOXYLIC ACID
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A convenient method for the preparation of 2-carboxy and 2-alkoxycarbonyl-γ-butyrolactones from cyclopropane-1,1-dicarboxylic acid and their mode of formation is described.A possible conformation for the ring is suggested based on the proton coupling data.
- Rao, Vanga S.
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p. 1389 - 1394
(2007/10/02)
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- Hydroxyalkylation and Lactone Formation from Dialkyl Malonate by Means of a EuIII/EuII Photoredox System
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A EuIII/EuII photoredox system in alcohol induced an effective hydroxyalkylation at an α-position of a dialkyl malonate.The alcohol adduct was then converted to the lactone.A step-by-step hydroxyalkylation mechanism was suggested in which the Eu ion is used as a photocatalyst and also as a condensation catalyst for the reaction of dialkyl malonates and aldehydes.
- Ishida, Akito,Yamashita, Shinya,Takamuku, Setsuo
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p. 2229 - 2231
(2007/10/02)
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- Protolysis of Cyclopropanes with Geminal Electronegative Substituents
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Cyclopropanes with geminal ester substituents decompose in anhydrous HClO4/benzene solutions to give substituted γ-lactones; e.g. dimethyl 3,3-dimethyl-2-phenylcyclopropane-1,1-dicarboxylate (1e) is stereospecifically transformed to trans-γ,γ-dimethyl-α-m
- Kolsaker, Per,Jensen, Ann Kristin
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p. 345 - 353
(2007/10/02)
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