- WDR5-MYC INHIBITORS
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Substituted N-phenyl sulfonamide compounds inhibit WDR5-MYC interactions, and the compounds and their pharmaceutical compositions are useful for treating disorders and conditions in a subject, such as cancer cell proliferation.
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Paragraph 00492; 00540; 001241-001242
(2021/02/05)
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- HETEROCYCLIC CARBOXYLIC ACID AMIDE LIGAND AND APPLICATIONS THEREOF IN COPPER CATALYZED COUPLING REACTION OF ARYL HALOGENO SUBSTITUTE
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Provided are a heterocyclic carboxylic acid amide ligand and applications thereof in a copper catalyzed coupling reaction. Specifically, provided are uses of a compound represented by formula (I), definitions of radical groups being described in the specifications. The compound represented by formula (I) can be used as the ligand in the copper catalyzed coupling reaction of the aryl halogeno substitute, and is used or catalyzing the coupling reaction for forming the aryl halogeno substitute having C—N, C—O, C—S and other bonds.
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Paragraph 0293-0294
(2019/05/15)
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- Aromatic C-H amination in hexafluoroisopropanol
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We report a direct radical aromatic amination reaction that provides unprotected anilines with an improvement in the substrate scope compared to prior art. Hydrogen bonding by the solvent hexafluoroisopropanol to anions of cationic species is responsible for increased reactivity and can rationalize the enhancement in substrate scope. Our findings may have bearings on radical additions to arenes for direct C-H functionalization in general.
- D'Amato, Erica M.,B?rgel, Jonas,Ritter, Tobias
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p. 2424 - 2428
(2019/02/28)
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- NOVEL INHIBITORS OF MAP4K1
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The invention relates to novel inhibitors of MAP4K1 (HPK1) useful for the treatment of diseases or disorders characterised by dysregulation of the signal transduction pathways associated with MAPK activation, including hyperproliferative diseases, diseases of immune system dysfunction, inflammatory disorders, neurological diseases, and cardiovascular diseases. The invention further relates to pharmaceutical compositions comprising the same and methods of treatment of said diseases and disorders. The inhibitors are of formula (I) wherein the definitions for A, D, E, F, R5, R6, R7, Z, ring Q, n, x and y are as given in the application.
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Page/Page column 67; 114
(2018/12/13)
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- A Class of Amide Ligands Enable Cu-Catalyzed Coupling of (Hetero)aryl Halides with Sulfinic Acid Salts under Mild Conditions
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The amide derived from 4-hydroxy-l-proline and 2,6-dimethylaniline is a powerful ligand for Cu-catalyzed coupling of (hetero)aryl halides with sulfinic acid salts, allowing the formation of a wide range of (hetero)aryl sulfones from the corresponding (hetero)aryl halides at considerably low catalytic loadings. The coupling of (hetero)aryl iodides and sodium methanesulfinate proceeds at room temperature with only 0.5 mol % CuI and ligand, representing the first example for Cu-catalyzed arylation at both low catalytic loading and room temperature.
- Zhao, Jinlong,Niu, Songtao,Jiang, Xi,Jiang, Yongwen,Zhang, Xiaojing,Sun, Tiemin,Ma, Dawei
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p. 6589 - 6599
(2018/05/31)
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- BENZAMIDE COMPOUNDS AND RELATED METHODS OF USE
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Benzamide compounds and derivatives thereof, as can be used for selective inhibition of the SIRT2 enzyme and/or therapeutic use in the treatment of Huntington's disease.
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Paragraph 0080; 0232
(2014/07/08)
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- ANTIVIRAL PYRIMIDINES
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Disclosed herein are novel compounds comprising substituted pyrimidines, pyrazolopyrimtdines, and imidazolopyrimidines, the syntheses thereof, and compositions thereof, including pharmaceutical compositions, comprising the novel pyrimidines, pyrazolopyrimtdines, imidazolpyrimidines and related compounds. Such compounds function to inhibit entry of viruses of the Flaviviridae family, including Hepatitis C virus (HCV), into cells that are susceptible to virus infection. These compounds are useful for the treatment, therapy and/or prophylaxis of viral diseases and infection, including HCV infection.
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Page/Page column 89
(2010/11/03)
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- UREA DERIVATIVES USEFUL AS CALCIUM RECEPTOR MODULATORS
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The present invention provides compounds of formula (I): in which Y is oxygen or sulphur; R1 and R”1 are optionally substituted aryl, heteroaryl or a fused ring structure, R2and R'2 are each H, or optionally substituted alkyl, alkylaminoalkyl or dialkylaminoalkyl, or R2 and R'2 and their N form a saturated or unsaturated optionally substituted heterocycle, R3 represents a group of formula -(CH2)P-Ar-Rn, wherein p is 0 or 1 and, when p is 1, is optionally substituted, Ar is aryl or heteroaryl, and each R is H, halogen; hydroxyl; trifiuoromethyl; linear and branched alkyl, alkenyl, alkynyl, and alkoxyl groups, all optionally further substituted by one or more of hydroxy groups, halogen atoms, alkoxy groups, amino groups, and alkylthio groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; aryl groups; aralkyl groups; aralkoxy groups; aryloxy groups; perfluoroalkyl; -CN; -NR4R5, -C(=X)NR4R5,-O-C(=X)NR4R5, -SO2NR4R5, - Alk-NR4R5, -NZC(=X)(NH)qR6, -Alk-NZC(=X)(NH)qR6, -C(=X)R6, -Alk-C(=X)(NH)qR6, -NHSO2R7, -SO2R7, -SOR7, -SR7, or is a saturated or unsaturated heterocyclyl group, and salts and esters thereof, are useful in the treatment of conditions susceptible to modulating ion channels, to a process for their preparation, their application by way of medicaments, and to pharmaceutical compositions containing them.
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Page/Page column 49-50
(2008/06/13)
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- Rational design of 6-methylsulfonylindoles as selective cyclooxygenase-2 inhibitors
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The introduction of 3-arylmethyl, 3-aryloxy and 3-arylthio moieties into a 6-methylsulfonylindole framework using rational drug design led to potent, selective COX-2 inhibitors having efficacy in a rat carrageenan air pouch model. Incorporation of a conformationally more rigid 3-aroyloxy substituent onto the 6-methylsulfonylindole scaffold led to selective, but considerably less potent COX-2 inhibitors. Variation of the hydrophilicity and size of the indole 2-substituent of 3-arylthio-6-methylsulfonylindole inhibitors led to modulation of the COX-2 human whole blood (HWB) potency and selectivity. The introduction of 3-arylmethyl, 3-aryloxy and 3-arylthio moieties into a 6-methylsulfonylindole framework using rational drug design led to potent, selective COX-2 inhibitors having efficacy in a rat carrageenan air pouch model. Incorporation of a conformationally more rigid 3-aroyloxy substituent onto the 6- methylsulfonylindole scaffold led to selective, but considerably less potent COX-2 inhibitors. Variation of the hydrophilicity and size of the indole 2-substituent of 3-arylthio-6-methylsulfonylindole inhibitors led to modulation of the COX-2 human whole blood (HWB) potency and selectivity.
- Campbell, Jeffrey A.,Bordunov, Viola,Broka, Chris A.,Browner, Michelle F.,Kress, James M.,Mirzadegan, Tara,Ramesha, Chakk,Sanpablo, Bong F.,Stabler, Russell,Takahara, Patricia,Villasenor, Armando,Walker, Keith A.M.,Wang, Jin-Hai,Welch, Mary,Weller, Paul
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p. 4741 - 4745
(2007/10/03)
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- Herbicidally active phenylsubstituted 5-and 6-membered heterocyclic compounds
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A compound of formula (I): STR1 where E is oxygen or sulphur; A is CR3 or N where R3 is hydrogen or hydrocarbyl; D completes a 5 or 6-membered non-aromatic heterocyclic ring which optionally contains additional heteroatoms selected from oxygen, nitrogen or sulphur and which is optionally substituted by an optionally substituted lower hydrocarbyl group, or an optionally substituted heteroaryl group; R1 and R2 are each independently hydrogen; optionally substituted lower hydrocarbyl, or optionally substituted heteroaryl, or R1 and R2 together with the nitrogen atom to which they are attached, form a heterocyclic ring; Z represents halogen optionally substituted lower hydrocarbyl, optionally substituted lower hydocarbyloxy, optionally substituted lower hydrocarbylthio, hydrocarbylsulphinyl or hydrocarbylsulphonyl, cyano, nitro, CHO, NHOH, ONR7' R7", SF5 ; CO (optionally substituted lower hydrocarbyl), acylamino, COOR7, SO2 NR8 R9, CONR10 R11, OR12 or NR13 R14 where R7, R7', R7", R8, R9, R10 and R11 are independently hydrogen or lower hydrocarbyl; R12 is hydrogen; SO2 lower hydrocarbyl or COR15 ; R13 and R14 are independently lower hydrocarbyl, lower hydrocarbyloxy or a group R12 ; R15 is OR16, NR17 R18, hydrogen or lower hydrocarbyl; R16 is lower hydrocarbyl; R17 and R18 are independently hydrogen or lower hydrocarbyl; provided that when there are two or more substituents Z, they may be the same or different; and m is 0 or an integer from 1 to 5.
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- Antirhinovirus activity of 6-anilino-9-benzyl-2-chloro-9H-purines
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A series of 6-anilino-9-benzyl-2-chloropurines was synthesized and tested for antirhinovirus activity. Most of the compounds were prepared by reaction of the appropriate aniline with 9-benzyl-2,6-dichloro-9H-purine. Structure-activity relationship studies
- Kelley,Linn,Selway
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p. 1360 - 1363
(2007/10/02)
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- Hypoxia-Selective Antitumor Agents. 3. Relationships between Structure and Cytotoxicity against Cultured Tumor Cells for Substituted N,N-Bis(2-chloroethyl)anilines
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A series of aniline mustards with a wide range of electron-donating and -withdrawing substituents in the 3- and 4-positions has been synthesized and evaluated for cytotoxicity in cell culture to examine the potential of using nitro group deactivated nitrogen mustards for the design of novel hypoxia-selective anticancer drugs (Denny, W.A.; Wilson, W.R.J.Med Chem. 1986, 29, 879).Hydrolytic half-lives in tissue culture media, determined by bioassay against a cell line (UV4) defective in the repair of DNA interstrand cross-links showed the expected dependence on the Hammett electronic parameter, ?, varying from 0.13 h for the 4-amino analogue to >100 h for analogues with strongly electron-withdrawing substituents.Cytotoxic potencies in aerobic UV4 cultures showed a similar dependence on ?.This dependence predicted that the 4-nitroaniline mustard would be 7200-fold less potent than its potential six-electron reduction product, the 4-amino compound, in growth inhibition assays using a 1-h drug exposure.The measured differential was much lower (225-fold) because of the instability of the latter compound, but a differential of 17500-fold was observed in the initial rate of killing by using a clonogenic assay.The potential for formation of reactive mustards by reduction to the amine or hydroxylamine was demonstrated by the 4-nitroso compound, which had an aerobic toxicity similar to that of the amine.Although these features confirmed the original rationale, the 3-nitro- and 4-nitroaniline mustards had only minimal hypoxic selectivity against UV cells.Toxicity to hypoxic cells appears to be limited by the low reduction potentials of these compounds and consequent lack of enzymatic nitroreduction.However, this study has demonstrated that nitro groups can be used to latentiate aromatic nitrogen mustards and indicates that examples with higher reduction potentials could provide useful hypoxia-selective therapeutic agents.
- Palmer, Brian D.,Wilson, William R.,Pullen, Susan M.,Denny, William A.
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p. 112 - 121
(2007/10/02)
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- Syntheses of Some Alkyl, Cycloalkyl and Aryl 3-Aminophenyl Sulfones
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Syntheses of alkyl (1a-1i, 1m), cycloalkyl (1j, 1k) and aryl (1l) 3-aminophenyl sulfones were achieved by ethanolic Bechamp-reduction of the appropriate 3-nitrophenyl sulfones (3a-3m).The alkyl (3a-3i) and cycloalkyl (3j, 3k) 3-nitrophenyl sulfones were p
- Courtin, Alfred
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p. 1849 - 1853
(2007/10/02)
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