- Electrochemical-Oxidation-Promoted Direct N-ortho-Selective Difluoromethylation of Heterocyclic N-Oxides
-
An efficient and green electrochemical N-ortho-selective difluoromethylation method of various quinoline and isoquinoline N-oxides has been developed. In this method, sodium difluoromethanesulfinate (HCF2SO2Na) was used as the source of the difluoromethyl moiety, and various N-ortho-selective difluoromethylation quinoline and isoquinoline N-oxides were obtained in good to excellent yields under a constant current. In addition, the reaction was easy to scale up and maintained a good yield. Preliminary mechanism studies suggested that the reaction undergoes a free-radical addition and hydrogen elimination pathway.
- Zhang, Dong,Cai, Jinlin,Du, Jinze,Wang, Qingdong,Yang, Jinming,Geng, Rongqing,Fang, Zheng,Guo, Kai
-
supporting information
p. 1434 - 1438
(2022/03/01)
-
- Cu(II)-Catalyzed Construction of Heterobiaryls using 1-Diazonaphthoquinones: A General Strategy for the Synthesis of QUINOX and Related P,N Ligands
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An efficient and straightforward method was developed for the synthesis of heterobiaryls using easily available N-oxides and diazonaphthoquinones under cheap Cu(II) catalysis. The developed method offered QUINOX and related congeners in a simple manner. A wide scope of important heterobiaryls was achieved with high site selectivity. The synthesized naphthols were transformed into the privileged related P,N ligands. Suitable resolution methods can directly afford the corresponding axially chiral heterobiaryls.
- Biswas, Aniruddha,Pan, Subarna,Samanta, Rajarshi
-
supporting information
p. 1631 - 1636
(2022/03/14)
-
- Method for preparing sulfone and N-oxygen compound by using green and efficient oxidation system
-
The invention discloses a method for preparing sulfone and N-oxygen compound by using a green and efficient oxidation system. The method comprises the following steps of: by using a tertiary amine compound or aromatic thioether or fatty thioether compound as a raw material, H2O2 as an oxidant, methanol as a reaction solvent and potassium carbonate as an alkali, introducing sulfuryl fluoride 5O2F2gas as an accelerator; performing stirring at room temperature under a sealed condition for oxidation reaction; and after finishing the reaction, filtering to remove solid potassium carbonate, dryingto remove water, filtering to obtain a crude product, and finally carrying out column chromatography separation to obtain a pure product. Tertiary amine is oxidized into an N-oxygen compound, and thethioether is oxidized into sulfone. According to the method, the sulfuryl fluoride (SO2F2) which is very cheap and easy to obtain is used as the reaction promoter, green and environment-friendly hydrogen peroxide (H2O2) is used as an oxidizing agent, and so that the yield of the reaction is generally high; after the reaction, byproducts are only water and inorganic salts (SO4 and F) whichare easy to remove and free of pollution, and the green and efficient oxidation system can be realized, and therefore, the method is suitable for large-scale industrial production.
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-
Paragraph 0036-0038
(2021/01/29)
-
- SO2F2-mediated oxidation of primary and tertiary amines with 30% aqueous H2O2 solution
-
A highly efficient and selective oxidation of primary and tertiary amines employing SO2F2/H2O2/base system was described. Anilines were converted to the corresponding azoxybenzenes, while primary benzylamines were transformed into nitriles and secondary benzylamines were rearranged to amides. For tertiary amine substrates quinolines, isoquinolines and pyridines, their oxidation products were the corresponding N-oxides. The reaction conditions are very mild and just involve SO2F2, amines, 30% aqueous H2O2 solution, and inorganic base at room temperature. One unique advantage is that this oxidation system is just composed of inexpensive inorganic compounds without the use of any metal and organic compounds.
- Liao, Xudong,Zhou, Yi,Ai, Chengmei,Ye, Cuijiao,Chen, Guanghui,Yan, Zhaohua,Lin, Sen
-
supporting information
(2021/11/01)
-
- Synthetic method of drug intermediate nitrogen-containing heterocycle-containing brominated compound
-
The invention relates to a method for synthesizing a pharmaceutical intermediate nitrogen heterocyclic bromo-compound. The method comprises that 6-bromoisoquinoline, dichloromethane and m-chloroperoxybenzoic acid as raw materials undergo a reaction to produce a mixture 6-bromoisoquine oxynitride, phosphorus oxychloride is added into the mixture so that solid and water phase products are obtained,the solid products are dried, the water phase products are repeatedly washed and are extracted multiple times, the organic phase is spin-dried, the solid and water phases are treated so that 6-bromo-1-chloroisoquinoline is obtained, the solid crude product and the water crude product are mixed, the mixture is treated through a silica gel column of 100-200 meshes, the mixture is eluted through a petroleum ether PE: ethyl acetate EA eluent A to form a pure product 6-bromo-1-chloroisoquinoline, trimethylbromosilane, acetonitrile and 6-bromo-1-chloroisoquinoline undergo a reaction, pH of the reaction product is adjusted to 7 so that 1, 6-dibromoisoquinoline is obtained, and the 1, 6-dibromoisoquinoline is added into dichloroditriphenyl phosphine and a homemade Grignard reagent so that a finalproduct 6-bromo-1-methylisoquinoline is obtained. The method has the advantages of clear processes, less waste, high yield, raw material saving and operation easiness.
- -
-
Paragraph 0018; 0020; 0021; 0027; 0028; 0034; 0035
(2020/03/29)
-
- Light-induced [2 + 2] cycloadditions for the construction of cyclobutane-fused pyridinyl sulfonyl fluorides
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Cyclobutanes are an important class of motifs present in a wide range of natural products and other biologically significant molecules. A photocatalytic [2 + 2] cycloaddition between pyridones or isoquinolones and ethenesulfonyl fluoride was achieved, providing a portal to a class of unique cyclobutane-fused pyridinyl sulfonyl fluorides with quaternary rigid rings (30 examples). Further applications of these novel sulfonyl fluoride molecules in SuFEx click chemistry were also accomplished, providing the corresponding sulfonates and sulphonamides with reasonable yields.
- Liu, Jing,Wang, Shi-Meng,Qin, Hua-Li
-
supporting information
p. 4019 - 4023
(2020/06/09)
-
- Discovery of VU2957 (Valiglurax): An mGlu4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease
-
Herein, we report the discovery of a novel potent, selective, CNS penetrant, and orally bioavailable mGlu4 PAM, VU0652957 (VU2957, Valiglurax). VU2957 possessed attractive in vitro and in vivo pharmacological and DMPK properties across species.
- Panarese, Joseph D.,Engers, Darren W.,Wu, Yong-Jin,Bronson, Joanne J.,Macor, John E.,Chun, Aspen,Rodriguez, Alice L.,Felts, Andrew S.,Engers, Julie L.,Loch, Matthew T.,Emmitte, Kyle A.,Castelhano, Arlindo L.,Kates, Michael J.,Nader, Michael A.,Jones, Carrie K.,Blobaum, Anna L.,Conn, P. Jeffrey,Niswender, Colleen M.,Hopkins, Corey R.,Lindsley, Craig W.
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p. 255 - 260
(2018/10/25)
-
- The discovery of VU0652957 (VU2957, Valiglurax): SAR and DMPK challenges en route to an mGlu4 PAM development candidate
-
This letter describes the first account of the chemical optimization (SAR and DMPK profiling) of a new series of mGlu4 positive allosteric modulators (PAMs), leading to the identification of VU0652957 (VU2957, Valiglurax), a compound profiled a
- Panarese, Joseph D.,Engers, Darren W.,Wu, Yong-Jin,Guernon, Jason M.,Chun, Aspen,Gregro, Alison R.,Bender, Aaron M.,Capstick, Rory A.,Wieting, Joshua M.,Bronson, Joanne J.,Macor, John E.,Westphal, Ryan,Soars, Matthew,Engers, Julie E.,Felts, Andrew S.,Rodriguez, Alice L.,Emmitte, Kyle A.,Jones, Carrie K.,Blobaum, Anna L.,Jeffrey Conn,Niswender, Colleen M.,Hopkins, Corey R.,Lindsley, Craig W.
-
p. 342 - 346
(2018/12/05)
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- Wnt SIGNALING INHIBITOR, COMPOSITION, AND COMPOUND AS USE THEREFOR
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PROBLEM TO BE SOLVED: To provide an inhibitor for Wnt signaling route. SOLUTION: The present invention provides a compound represented by formula I, and a composition comprising the compound (X1-X8 independently represent CR4 or N; Y1 is H or C (R4)3; Y2 and Y3 independently represent H, halogen or C (R3)3; R1 and R2 independently represent H, halogen, C1-6 alkyl, quinolinyl or the like; R3s independently represent H, halogen, cyano, C1-6 alkyl or the like; R4s independently represent H, halogen, cyano, C1-6 alkoxy or the like). SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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-
Paragraph 0119; 0120
(2017/08/15)
-
- Inhibiting WNT signal conduction of compound, composition and use thereof (by machine translation)
-
The invention relates to a having the general formula (1) compounds and compositions thereof, and the use of the compound or composition thereof to inhibit WNT signal transmission method. The compounds of this invention and its composition can effectively inhibit the secretion of WNT protein, inhibit WNT signal conduction, so the WNT-mediated disease with a very good therapeutic effect. . (by machine translation)
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-
Paragraph 0216; 0219; 0220; 0221
(2017/12/27)
-
- Iodine/TBHP-Promoted One-Pot Deoxygenation and Direct 2-Sulfonylation of Quinoline N-Oxides with Sodium Sulfinates: Facile and Regioselective Synthesis of 2-Sulfonylquinolines
-
A highly efficient iodine/TBHP-mediated one-pot deoxygenative and regioselective 2-sulfonylation of quinoline N-oxides with sodium sulfinate salts has been developed. This metal-, base-, and phosphorus-free protocol employs readily accessible and easy-to-handle reagents and can be conveniently carried out at room temperature under mild conditions, providing an alternative access to a series of 2-sulfonylquinolines and other related heteroaryl sulfone products in moderate-to-excellent yields within a short reaction time.
- Sumunnee, Ladawan,Buathongjan, Chonchanok,Pimpasri, Chaleena,Yotphan, Sirilata
-
supporting information
p. 1025 - 1032
(2017/02/15)
-
- Method for preparing 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-formic acid
-
The invention relates to a method for synthesizing 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-formic acid. The 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-formic acid is made of 6-bromoisoquinoline. The method includes adding meta-chloroperoxybenzoic acid into the 6-bromoisoquinoline and carrying out reaction on the 6-bromoisoquinoline and the meta-chloroperoxybenzoic acid under room-temperature conditions overnight to obtain a mixture which is bromoisoquinoline nitrogen oxide; adding the mixture into phosphoryl chloride in batches, carrying out temperature reaction on the mixture and the phosphoryl chloride to obtain reaction products, cooling the reaction products to precipitate a large quantity of solid and washing and drying the solid to obtain 6-bromine-1-chloroisoquinoline; extracting aqueous phases and directly carrying out spin dry on organic phases to obtain 6-bromine-1-chloroisoquinoline with the purity higher than 95%; placing the 6-bromine-1-chloroisoquinoline into THF (tetrahydrofuran) and adding n-butyl lithium and carbon dioxide gas into the 6-bromine-1-chloroisoquinoline and the THF to obtain 1-chloroisoquinoline-6-formic acid; placing the 1-chloroisoquinoline-6-formic acid into concentrated hydrochloric acid to obtain white solid which is 1-oxo-1, 2-dihydroisoquinolines-6-formic acid; placing the 1-oxo-1, 2-dihydroisoquinolines-6-formic acid into solvents, adding cesium carbonate into the 1-oxo-1, 2-dihydroisoquinolines-6-formic acid and the solvents and dropwise adding methyl iodide into the 1-oxo-1, 2-dihydroisoquinolines-6-formic acid and the solvents to obtain 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-methyl formate; adding the 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-methyl formate into methyl alcohol, adding NaOH solution into the 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-methyl formate and the methyl alcohol, removing the methyl alcohol by means of reduced-pressure distillation to obtain mixtures, regulating the PH (potential of hydrogen) of the mixtures until the PH of the mixtures is equal to 2, precipitating solid, carrying out suction filtration and washing and drying the solid to obtain a product which is the 2-methyl-1-oxo-1, 2-dihydroisoquinolines-6-formic acid. The method has the advantages of reasonable route, little wastage, high yield, easiness in operation and capability of saving raw materials.
- -
-
Paragraph 0017; 0020; 0026; 0032
(2017/08/29)
-
- ISOQUINILINE AND NAPTHALENE-SUBSTITUTED COMPOUNDS AS MGLUR4 ALLOSTERIC POTENTIATORS, COMPOUNDS, AND METHODS OF TREATING NEUROLOGICAL DYSFUNCTION
-
Compounds which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); pharmaceutical compositions comprising the compounds; and methods of using the compounds, for example, in treat
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-
Page/Page column 63; 70; 71
(2016/08/23)
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- Regioselective Chlorination of Quinoline N-Oxides and Isoquinoline N-Oxides Using PPh3/Cl3CCN
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A novel method for the regioselective C2-chlorination of heterocyclic N-oxides has been developed. PPh3/Cl3CCN were used as chlorinating reagents and the desired N-heterocyclic chlorides were obtained smoothly in satisfactory yields. The reactions proceeded in a highly efficient and selective manner across a broad range of substrates demonstrating excellent functional group tolerance. In addition, this chlorination reaction can be used for the modification of N-heterocyclic scaffolds of appealing ligands and pharmaceuticals.
- Qiao, Kai,Wan, Li,Sun, Xiaoning,Zhang, Kai,Zhu, Ning,Li, Xin,Guo, Kai
-
p. 1606 - 1611
(2016/04/05)
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- Palladium(II)-catalyzed C-C and C-O bond formation for the synthesis of C1-benzoyl isoquinolines from isoquinoline: N -oxides and nitroalkenes
-
C1-Benzoyl isoquinolines can be generated via a palladium(ii)-catalyzed C-C and C-O coupling of isoquinoline N-oxides with aromatic nitroalkenes. The reaction proceeds through remote C-H bond activation and subsequent intramolecular oxygen atom transfer (OAT). In this reaction, the N-O bond was designed as a directing group in the C-H bond activation as well as the source of an oxygen atom.
- Li, Jiu-Ling,Li, Wei-Ze,Wang, Ying-Chun,Ren, Qiu,Wang, Heng-Shan,Pan, Ying-Ming
-
supporting information
p. 10028 - 10031
(2016/08/15)
-
- Benzylation of heterocyclic N-oxides via direct oxidative cross-dehydrogenative coupling with toluene derivatives
-
A novel cross-dehydrogenative coupling (CDC) of heterocyclic N-oxides with toluene derivatives has been discussed, allowing for the facile synthesis of a broad range of structurally diverse C1-benzyl quinoline N-oxides, isoquinoline N-oxides and pyridine N-oxides, including two methylated quinoline N-oxides in particular. This protocol not only extends the application of toluenes in synthetic organic chemistry, but also offers an alternative method to prepare benzylated heterocyclic N-oxides without any metal involved, which is important in medicinal chemistry.
- Wan,Qiao,Sun,Di,Fang,Li,Guo
-
supporting information
p. 10227 - 10232
(2016/12/07)
-
- TUMOR BIOMARKERS AND USE THEREOF
-
Disclosed herein are biomarkers related to WNT signal transduction pathway, as well as methods and kits comprising the same. Further, the present disclosure relates to the use of the biomarkers in patient selection, companion diagnostics, and treatment of cancer.
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-
Paragraph 0255-0256
(2016/12/22)
-
- Compound as WNT Signaling Inhibitor, Composition, and Use Thereof
-
The present invention relates to a compound having the structure of Formula I as inhibitor of WNT signal transduction pathways, as well as a composition comprising the compound. Further, the present invention relates to the use of the compound and the method of inhibiting the WNT signal transduction pathways.
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-
Paragraph 0201; 0202
(2015/05/05)
-
- CARBONITRILE DERIVATIVES AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
-
The present invention relates to a compound of Formula 1, 2 or 3: I II III wherein A is N or -CR0--, where R0 is hydrogen, C1-C6 linear or branched chain alkyl, etc., Z is -CRe --, or, -N--, where Re is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R1 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R2 are independently hydrogen or C1-C6 linear or branched chain alkyl; R3 and R4 are independently hydrogen, C1C6 linear or branched chain alkyl, etc.;. R5 and R6 are independently hydrogen or C1-C6 linear or branched chain alkyl, etc.; R8 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R9 and R10 are independently hydrogen or C1- C6 linear or branched chain alkyl, etc.; Q is --CO--, --(CH2)q--, --(CHRs)q--, or -(CRsRt)q- -, where Rs and Rt are independently C1-C6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to compbinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.
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Page/Page column 133
(2015/12/17)
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- COMPOUNDS FOR TREATMENT OF CANCER
-
The present invention relates to compounds as inhibitor of WNT signal transduction pathway, as well as a composition comprising the same. Further, the present invention relates to the use of the compounds in the treatment of cancer.
- -
-
Paragraph 0200; 0201
(2014/10/18)
-
- COMPOUNDS FOR TREATMENT OF FIBROSIS DISEASES
-
The present invention relates to compounds as inhibitor of WNT signal transduction pathway, as well as a composition comprising the same. Further, the present invention relates to the use of the compounds in the treatment of fibrosis. Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli including persistent infections, autoimmune reactions, allergic responses, chemical insults, radiation, and tissue injury.
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-
Paragraph 0186-0187
(2014/10/15)
-
- COMPOUND AS WNT SIGNALING INHIBITOR, COMPOSITION, AND USE THEREOF
-
The present invention relates to a compound having the structure of Formula I as inhibitor of WNT signal transduction pathways, as well as a composition comprising the compound. Further, the present invention relates to the use of the compound and the method of inhibiting the WNT signal transduction pathways.
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Page/Page column 26; 27
(2014/01/08)
-
- ISOQUINOLINE DERIVATIVE, AND PDE INHIBITOR COMPRISING SAME AS ACTIVE INGREDIENT
-
The present invention provides a novel isoquinoline derivative which is useful as a pharmaceutical agent having a phosphodiesterase inhibitory activity. The isoquinoline derivative of the present invention is represented by the following general formula (
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Page/Page column 53
(2011/08/08)
-
- Amino-substituted heterocycles, compositions thereof, and methods of treatment therewith
-
Provided herein are Heterocyclic Compounds having the following structure: wherein R1, R2, X, Y and Z are as defined herein, compositions comprising an effective amount of a Heterocyclic Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heterocyclic Compound to a patient in need thereof.
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-
Page/Page column 39
(2008/12/07)
-
- SUBSTITUTED ISOQUINOLINE AND ISOQUINOLINONE DERIVATIVES
-
The invention relates to 6-substituted isoquinoline and isochinolone derivatives of the formula (I) useful for the treatment and/or prevention of diseases associated with Rho-kinase and/or Rho-kinase mediated phosphorylation of myosin light chain phosphatase, and compositions containing such compounds.
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Page/Page column 53
(2008/12/06)
-
- CYCLOALKYLAMINE SUBSTITUTED ISOQUINOLONE AND ISOQUINOLINONE DERIVATIVES
-
The invention relates to 6-substituted isoquinoline and isoquinolinone derivatives of the formula 1 useful for the treatment and prevention of diseases associated with Rho-kinase and Rho- kinase mediated phosphorylation of myosin light chain phosphatase, and composition containing such compound
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Page/Page column 42
(2008/12/06)
-
- Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-Isoquinolinylguanidines
-
A series of 1-isoquinolinylguanidines are shown to be potent inhibitors of uPA with selectivity over tPA and plasmin. Potency is enhanced by the presence of a 4-halo and a 7-aryl substituent, particularly when substituted by a 3-carboxylic acid group. Compound 13j (UK-356,202) combines excellent potency and selectivity, and has been selected as a candidate for clinical evaluation.
- Barber, Christopher G.,Dickinson, Roger P.,Fish, Paul V.
-
p. 3227 - 3230
(2007/10/03)
-
- HEPATITIS C VIRUS INHIBITORS
-
Hepatitis C virus inhibitors are disclosed having the general formula:(I) wherein R1, R2, R3, R', B, Y and X are described in the description. Compositions comprising the compounds and methods for using the compounds toinhibit HCV are also disclosed.
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-
-
- Isoquinolines as urokinase inhibitors
-
Compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein one of R1 and R2 is H and the other is N=C(NH2)2 or NHC(=NH)NH2, and the other substituents are as defined herein, are urokinase (uPA) inhibitors.
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-