- CHEMICAL COMPOUNDS
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The present disclosure describes novel compounds, or their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and their medical uses. Compounds of the disclosure have activity as dual modulators of Janus kinase (JAK), alone, or in combination with one or more of an additional mechanism, including a tyrosine kinase, such as TrkA or Syk, and PDE4, and are useful in the in the treatment or control of inflammation, auto-immune diseases, cancer, and other disorders and indications where modulation of JAK would be desirable. Also described herein are methods of treating inflammation, auto-immune diseases, cancer, and other conditions susceptible to inhibition of JAK and PDE4 by administering a compound herein described.
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Paragraph 0286-0288
(2021/01/23)
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- Gold(I)-Catalyzed Cascade Cyclization Reactions of Allenynes for the Synthesis of Fused Cyclopropanes and Acenaphthenes
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A gold-catalyzed reaction of phenylene-tethered allenynes with benzofurans gave 1-(naphth-1-yl)cyclopropa[b]benzofuran derivatives, whereas the reaction of 1-allenyl-2-ethynyl-3-methylbenzene derivatives in the absence of benzofurans gave acenaphthenes in good yields. These results can be rationalized by nucleophilic attack of the alkyne moiety on an activated allene to form a vinyl cation intermediate.
- Ikeuchi, Takaya,Inuki, Shinsuke,Oishi, Shinya,Ohno, Hiroaki
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supporting information
p. 7792 - 7796
(2019/05/15)
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- Efficient synthesis of chiral benzofuryl β-amino alcohols via a catalytic asymmetric Henry reaction
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Chiral β-amino alcohol ligands were found effective for the copper(ii)-catalyzed asymmetric Henry reaction of benzofuran-2-carbaldehydes with nitromethane, which led to the formation of (S)-enriched benzofuryl β-nitro alcohols with satisfactory enantioselectivities (up to 98% ee). Using this catalytic protocol, bioactive (S)-benzofuryl β-amino alcohols could be conveniently prepared in short steps.
- Chen, Wei,Zhou, Zhao-Hui,Chen, Hong-Bin
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supporting information
p. 1530 - 1536
(2017/02/15)
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- THIOSEMICARBAZONES INHIBITORS OF LYSOPHOSPHATIDIC ACID ACYLTRANSFERASE AND USES THEREOF
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Lysophosphatidic acid acyltransferase-beta (LPAAT-β) catalyzes the production of phosphatidic acid (PA) from lysophosphatidic acid (LPA). The lipid cofactor PA contributes to the activation of c-Raf, BRAF, mTOR and PKC-ζ. LPAAT-β expression is a prognostic factor in gynecologic malignancies and is being investigated as a therapeutic target in a variety of tumor types. A class of thiosemicarbazones was identified as inhibitors of LPAAT-β from a screen of a library of small molecules. A focused library of thiosemicarbazones derivatives was prepared and led to the development of compounds which potently inhibit LPAAT-β and inhibit the growth of MiaPaCa2 human pancreatic cancer cells.
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Page/Page column 15
(2015/11/17)
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- New chemo-enzymatic approaches for the synthesis of (R)- and (S)-bufuralol
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Both enantiomers of bufuralol are pharmaceutically important molecules. While the (S)-isomer with a higher β-blocking activity is recommended for hypertension treatment, the (R)-enantiomer can be used as marker of hepatic activity. In this paper two new a
- Nagy, Botond,Dima, Norbert,Paizs, Csaba,Brem, Jürgen,Irimie, Florin Dan,Toa, Monica Ioana
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p. 1316 - 1322
(2015/01/09)
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- Expeditious synthesis of benzopyrans via lewis acid-catalyzed C-H functionalization: Remarkable enhancement of reactivity by an ortho substituent
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An expeditious construction of a benzopyran skeleton via Lewis acid-catalyzed C-H functionalization was achieved. In this process, a [1,5] hydride shift and 6-endo cyclization successively occurred to give benzopyrans. The presence of substituents ortho to the alkoxy group significantly enhanced the reactivity, affording the desired compounds in excellent chemical yields with short reaction times.
- Mori, Keiji,Kawasaki, Taro,Sueoka, Shosaku,Akiyama, Takahiko
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supporting information; experimental part
p. 1732 - 1735
(2010/09/05)
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- Enantioselective synthesis of (R)-bufuralol via dynamic kinetic resolution in the key step
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(Figure presented) An enantioselective synthesis of (R)-bufuralol via a ruthenium- and enzyme-catalyzed dynamic kinetic resolution (DKR) has been achieved. The synthesis starts from readily available 2-ethylphenol and provides (R)-bufuralol in high ee and a good overall yield of 31%.
- Johnston, Eric V.,Bogar, Krisztian,Baeckvall, Jan-E.
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experimental part
p. 4596 - 4599
(2010/09/30)
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- Asymmetric Henry reaction catalyzed by a copper tridentate chiral schiff-base complex
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A series of copper-tridentate chiral Schiff-base complexes were prepared and employed in an asymmetric Henry reaction, affording the corresponding adducts in good yields and with high enantioselectivities (up to 96% ee).
- Lai, Guoyin,Wang, Sujing,Wang, Zhiyong
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p. 1813 - 1819
(2008/12/22)
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- CHEMICAL COMPOUNDS
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This invention relates to non-steroidal compounds that are modulators of androgen receptor, and also to the methods for the making and use of such compounds.
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Page/Page column 27
(2008/12/04)
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- Synthesis of substituted salicylamines and dihydro-2H-1,3-benzoxazines
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Phenols were converted to their magnesium salts with the MgCl2-Et3N base system and subsequently reacted with Eschenmoser's salt, affording N,N-dimethyl substituted benzylamines in high to excellent yields. A series of mono N-substituted benzylamines were prepared in one-pot syntheses by ortho-formylation of phenols to corresponding salicylaldehydes, which in turn reacted with amines to imines. The imines were subsequently reduced to mono N-substituted benzylamines. Some of these benzylamines were further converted, without work-up, to mono N-substituted dihydro-2H-1,3-benzoxazines.
- Anwar, Hany F.,Skatteb?l, Lars,Hansen, Trond Vidar
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p. 9997 - 10002
(2008/02/13)
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- Development of a scalable process for CI-1034, an endothelin antagonist
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A concise, convergent multikilogram synthesis of CI-1034 (1), a potent endothelin receptor antagonist, is described. A 15-step preparation from commercially available o-vanillin and benzenesulfonyl chloride employs a remarkably robust Suzuki coupling between a boronic acid and an aromatic sulfonate ester as the key synthetic step. A scalable route capable of producing multikilogram quantities of CI-1034 with no chromatographic steps is described in this contribution. Improvements to the process included using a 4-fluorobenzenesulfonate ester as a suitable substitute for the triflate group in the Suzuki reaction and the use of MgCl2 as a substitute for TiCl4 in a Dieckmann condensation to provide the benzothiazine dioxide core.
- Jacks, Thomas E.,Belmont, Daniel T.,Briggs, Christopher A.,Horne, Nicole M.,Kanter, Gerald D.,Karrick, Greg L.,Krikke, James J.,McCabe, Richard J.,Mustakis, Jason G.,Nanninga, Thomas N.,Risedorph, Guy S.,Seamans, Ronald E.,Skeean, Richard,Winkle, Derick D.,Zennie, Thomas M.
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p. 201 - 212
(2013/09/04)
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- Non-metallocene compounds, method for the production thereof and use of the same for the polymerisation of olefins
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The invention relates to a method for producing special transition metal compounds, to novel transition metal compounds and to the use of the same for the polymerisation of olefins.
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- 1,2-AZOLE DERIVATIVES WITH HYPOGLYCEMIC AND HYPOLIPIDEMIC ACTIVITY
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A compound represented by the formula (1) wherein ring A is a ring optionally having 1 to 3 substituents; ring B is a 1,2-azole ring which may further have 1 to 3 substituents; Xa, Xb and Xc are the same or different and each is a bond, - O -, - S - and the like; Ya is a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms; Yb and Yc are the same or different and each is a bond or a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms; ring C is a monocyclic aromatic ring which may further have 1 to 3 substituents; and R represents -OR4 (R4 is hydrogen atom or optionally substituted hydrocarbon group) and the like, or a salt thereof or a prodrug thereof is useful as an agent for the prophylaxis or treatment of diabetes and the like.
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- Asymmetric synthesis of (S)-bufuralol and a propafenone analogue
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Asymmetric synthesis of (S)-bufuralol of 87% ee from 3-ethyl-2-hydroxybenzaldehyde, via the reduction of 2-bromo-1-(7-ethylbenzofuran-2-yl)ethanone with (-)-B-chlorodiisopinocampheylborane as the key step, followed by cyclization of the product bromohydrin to the corresponding epoxide and treatment with tert-butylamine, is described. (S)-1-(3-Phenethylbenzofuran-2-yl)-2-propylaminoethanol of 73% ee, a propafenone analogue, was prepared following the same approach.
- Zaidlewicz, Marek,Tafelska-Kaczmarek, Agnieszka,Prewysz-Kwinto, Andrzej,Chechlowska, Aldona
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p. 1659 - 1664
(2007/10/03)
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