- PROCESS OF MAKING CFTR MODULATORS
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The disclosure provides processes for synthesizing Compound I, and pharmaceutically acceptable salts thereof.
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Paragraph 0471-0475
(2021/02/19)
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- BICYCLIC HETEROARYL COMPOUNDS AND USES THEREOF
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The present disclosure is directed to modulators of SOS1 and their use in the treatment of disease. Also disclosed are pharmaceutical compositions comprising the same.
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Paragraph 0827-0829
(2021/05/14)
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- OXADIAZOLE COMPOUNDS
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Provided herein are compounds and pharmaceutical compositions comprising said compounds that are useful for treating cancers. Specific cancers include those that are mediated by YAP/TAZ or those that are modulated by the interaction between YAP/TAZ and TEAD.
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Paragraph 00390
(2019/12/04)
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- Olefin-Migrative Cleavage of Cyclopropane Rings through the Nickel-Catalyzed Hydrocyanation of Allenes and Alkenes
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A nickel-catalyzed hydrocyanation triggered by hydronickelation of the carbon-carbon double bonds of allenes followed by cyclopropane cleavage is described. The observed regio- and stereochemistries in the products are strongly influenced by the initial hydronickelation step, and allenyl- and methylenecyclopropanes reacted smoothly to promote the cleavage of cyclopropane. In contrast, this cleavage was not observed with vinylidenecyclopropanes, because the initial hydronickelation does not give a suitable intermediate for cleavage of the cyclopropanes. (Figure presented.).
- Hori, Hiroto,Arai, Shigeru,Nishida, Atsushi
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supporting information
p. 1170 - 1176
(2017/04/13)
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- Cycloaddition of Fluorenone N-Aryl Nitrones with Methylenecyclopropanes and Sequential 1,3-Rearrangement: An Entry to Synthesis of Spirofluorenylpiperidin-4-ones
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A facile synthesis of various spirofluorenylpiperidin-4-ones has been achieved in good yields from fluorenone N-aryl nitrones and methylenecyclopropanes. This method involved an initial cycloaddition to form a 5-spirocyclopropane-isoxazoline, which underwent a highly selective 1,3-rearrangement to give the desired product. The stereochemistry of the spirofluorenylpiperidin-4-one could be controlled by the cycloaddition and sequential rearrangement strategy. Furthermore, the spirofluorenylpiperidin-4-ones could be not only prepared in one-pot procedure but also converted to useful scaffolds by reduction or oxidation conditions.
- Ma, Xiao-Pan,Zhu, Jie-Feng,Wu, Si-Yi,Chen, Chun-Hua,Zou, Ning,Liang, Cui,Su, Gui-Fa,Mo, Dong-Liang
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p. 502 - 511
(2017/04/26)
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- NOVEL PROCESS FOR PREPARATION OF SPIRO[2.5]OCTANE-5,7-DIONE AND SPIRO[3.5]NONANE-6,8-DIONE
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This invention relates to methods for the synthesis of spiro[2.5]octane-5, 7-dione and spiro[3.5]nonane-6, 8-dione which are useful as intermediates in the manufacture of pharmaceutically active ingredients.
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Page/Page column 18
(2016/04/20)
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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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- Short and tandem syntheses of spiro[2.5]octane-5,7-dione and spiro[3.5]nonane-6,8-dione via diethyl acetonedicarboxylate
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A general synthetic route to spiro[2.5]octane-5,7-dione and spiro[3.5]nonane-6,8-dione that involves cyclization of the related acrylates and diethyl acetonedicarboxylate, followed by decarboxylation, has been developed. Compared with previous synthetic methods, the developed protocol avoids the use of column chromatography in each of the synthetic steps. Therefore, it can be readily scaled-up. The use of diethyl acetonedicarboxylate under mild conditions to build the skeleton of 1,3-cyclohexanedione has proved to be very efficient.
- Jin, Xiangle,Xu, Wei,Yang, Jinsong,Lu, Jun,Fu, Yan,Xie, Le,Zhu, Qian,Dong, Weitong
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supporting information
p. 6287 - 6289
(2015/10/20)
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- Bicyclic-Fused Heteroaryl or Aryl Compounds
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Compounds, tautomers and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula Ia, as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
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Paragraph 0812
(2015/10/28)
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- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included.
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Page/Page column 61
(2015/07/15)
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- INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included.
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Page/Page column 60
(2015/07/15)
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- Five-And-Six-Membered Heterocyclic Compound, And Preparation Method, Pharmaceutical Composition And Use Thereof
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A five-and-six-membered heterocyclic compound as represented by general formula I, pharmaceutically acceptable salt, metabolite, metabolic precursors or drug precursors thereof, preparation method, pharmaceutical composition, and use thereof; the five-and-six-membered heterocyclic compound has activity as a Janus kinase (JAK) inhibitor, and can be used to prepare drugs for treating diseases caused by the abnormal activity of kinase, such as cell proliferation diseases like cancer.
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Paragraph 0461; 0462
(2015/12/07)
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- Rhodium-catalyzed carbonylative [3 + 2 + 1] cycloaddition of alkyne-tethered alkylidenecyclopropanes to phenols in the presence of carbon monoxide
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A novel Rh-catalyzed carbonylative [3 + 2 + 1] cycloaddition of alkyne-tethered alkylidenecyclopropanes for the facile synthesis of bicyclic phenols in high yields has been developed. The reaction tolerated carbon and heteroatoms in the tether.
- Kim, Seyun,Chung, Young Keun
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supporting information
p. 4352 - 4355
(2015/01/09)
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- USE OF CONDENSED BENZO[B]THIAZINE DERIVATIVES AS CYTOPROTECTANTS
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The present invention relates to arylthiazine compounds, metabolites, N-oxides, amides, esters,pharmaceutically acceptable salts, hydrates and solvates thereof and their use as cytoprotectants in the treatment or prophylaxis of diseases or states, either acute or chronic, involving aberrant cellular lipid peroxidation in the central nervous system or in the periphery of the body. The present invention also relates to a method for their preparation and to pharmaceutical composition comprising as an active ingredient one or more of the aforementioned compounds.
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- Catalytic dicyanative [4 + 2] cycloaddition triggered by cyanopalladation using ene-enynes and cyclic enynes with methyl acrylate
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Palladium-catalyzed dicyanative [4 + 2] cycloaddition using various ene-enynes was investigated. The key species in this process is a cyanoallene intermediate that is obtained by the cyanopalladation of conjugated enynes followed by 5-exo-cyclization. To
- Arai, Shigeru,Koike, Yuka,Hada, Hirohiko,Nishida, Atsushi
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supporting information; experimental part
p. 7573 - 7579
(2011/02/25)
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- Cyclopropylacetic Acid Derivatives and Use Thereof
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The present application relates to novel cyclopropylacetic acid derivatives, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis
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Page/Page column 11-12
(2009/12/05)
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- Diastereoselective Diels-Alder reactions of a novel cyclopropenyl- containing chiral auxiliary
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(Chemical Equation Presented) A novel cyclopropenyl-containing 1,3-spiroaminoalcohol auxiliary has been used in a variety of asymmetric Diels-Alder reactions providing endo adducts with diastereomeric ratios ranging from 2:1 up to >99:1. In addition, unexpected regiochemistry was observed for a Diels-Alder reaction between cyclopropenyl dienophile and 4-vinyl-1,2-dihydronapthalene.
- Henderson, Jeff R.,Parvez, Masood,Keay, Brian A.
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p. 5167 - 5170
(2008/09/17)
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- [4 + 2] Cycloaddition of thiophene S-monoxides to activated methylenecyclopropanes
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Thiophene S-oxides 4 have been shown to undergo [4 + 2] cycloadditions with methylenecyclopropanes 2 with one or two electron acceptor substituents, i.e. even the tetrasubstituted 2-chloro-2-cyclopropylideneacetate 2c reacted well. However, for the tetrasubstituted alkene bi(cyclopropylidene) 2f high pressure had to be applied to make it react with 4. Only one diastereoisomer was formed in all the reactions. X-Ray crystal structure analyses of two of the cycloadducts, 3a and 3f, have been performed, their relative configuration determined as being endo,syn. The Wittig olefination of cyclopropanone hemiacetal to generate the methylenecyclopropanes and the subsequent cycloaddition can be carried out in a one-pot operation. This procedure is one of many potential one-pot or multi-component reactions involving stabilized phosphoranes. A further example of this type of reaction is shown in the novel desilylation-Wittig olefination of 1-ethoxy-1-trimethylsilyloxycyclopropane 5 to yield in one step cyclopropylideneacetates, e.g. 2a. The Royal Society of Chemistry 2000.
- Thiemann, Thies,Ohira, Daisuke,Li, Yuanqiang,Sawada, Tsuyoshi,Mataka, Shuntaro,Rauch, Karsten,Noltemeyer, Mathias,De Meijere, Armin
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p. 2968 - 2976
(2007/10/03)
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- AKZEPTOREN FUER DIE DOPPELTE MICHAEL-REAKTION, EINE VERBESSERTE SYNTHESE VON CYCLOPROPYLIDENCARBONSAEUREESTERN UND DEREN REAKTIVITAET GEGENUEBER CYCLOHEXADIENOLATEN
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Ethyl cyclopropylidene acetate and analoges are prepared in good yield by an acid catalyzed Wittig reaction.They are used as equivalents of senecioic acid esters in the aprotic double Michael reaction to give spirocyclopropyl substituted bicyclooctanes.
- Spitzner, Dietrich,Swoboda, Harald
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p. 1281 - 1284
(2007/10/02)
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- Reactions of the Cyclopropanone Hemiketal Magnesium Salt with Some Nucleophilic Reagents
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Cyclopropanol (5), 1-(arylethynyl)cyclopropanol (7), 1-(3-hydroxypropyl)cyclopropanol derivative 10, 1-(2-propynyl)cyclopropanol (14), cyclopropanone cyanohydrin (19), 1-(aminomethyl)cyclopropanol (21) derivatives, benzylidenecyclopropanes 32, and ethyl cyclopropylideneacetate (38) have been prepared from the magnesium salt of cyclopropanone hemiketal 3. 3-Cyclopropylidene-1-propanol (12) and 3-cyclopropylidene-1-propyne (16) have been obtained from the cyclopropanols 10 and 14, respectively. Some reactions of this new synthon were specific. On the other hand, 3 did not undergo the nucleophilic addition of sulfur and nitrogen ylides; it underwent oxidizing ring opening with BrZnCH2COOEt and induced the decomposition of diazomethane.
- Salauen, Jacques,Bennani, Fatima,Compain, Jean-Claude,Fadel, Antoine,Ollivier, Jean
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p. 4129 - 4135
(2007/10/02)
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