- Optimization of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives as dual inhibitors of BTK and PI3Kδ
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BTK and PI3Kδ play crucial roles in the progression of leukemia, and studies confirmed that the dual inhibition against BTK and PI3Kδ could provide superior anticancer agents to single targeted therapies. Herein, a new series of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives were optimized based on a BTK/PI3Kδ inhibitor 2 designed by our group. Biological studies clarified that compound 6f exhibited the most potent inhibitory activity (BTK: IC50 = 74 nM; PI3Kδ: IC50 = 170 nM) and better selectivity than 2. Moreover, 6f significantly inhibited the proliferation of Raji and Ramos cells with IC50 values of 2.1 μM and 2.65 μM respectively by blocking BTK and PI3K signaling pathways. In brief, 6f possessed of the potency for further optimization as an anti-leukemic drug by inhibiting BTK and PI3Kδ kinase.
- Liu, Linyi,Li, Xinyu,Cheng, Yu,Wang, Lianjian,Yang, Huizhu,Li, Jiurong,He, Siying,shuangjie Wu,Yin, Qianqian,Xiang, Hua
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Read Online
- Development of a pilot-plant process for a nevirapine analogue HIV NNRT inhibitor
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The pilot-plant synthesis of nevirapine analogue 1 is described. The compound was prepared in eight steps from substituted pyridine raw materials and 4-hydroxyquinoline. The key transformation involves a novel one-pot conversion of an arylhalide to arylac
- Busacca, Carl A.,Cerreta, Mike,Dong, Yong,Eriksson, Magnus C.,Farina, Vittorio,Feng, XuWu,Kim, Ji-Young,Lorenz, Jon C.,Sarvestani, Max,Simpson, Robert,Varsolona, Rieh,Vitous, Jana,Campbell, Scot J.,Davis, Mark S.,Jones, Paul-James,Norwood, Daniel,Qiu, Fenghe,Beaulieu, Pierre L.,Duceppe, Jean-Simon,Hache, Bruno,Brong, Jim,Chiu, Fang-Ting,Curtis, Tom,Kelley, Jason,Lo, Young S.,Powner, Tory H.
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- NOVEL COMPOUNDS FOR THE TREATMENT OF HEPATITIS C
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The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.
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(2016/09/26)
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- Synthesis of pyridodiazepinediones by using the ugi multicomponent reaction
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Benzodiazepines show a broad spectrum of biological activities. In an ongoing effort to extend molecular diversity in this type of systems, we developed a strategy for synthesizing 3,4-dihydro-1H-pyrido[2,3-e][1,4] diazepine-2,5-dione compounds starting from 2-hydroxynicotinic acid and by using an Ugi reaction as a key step in the synthesis. We opted to use 2isocyanophenyl benzoate instead of Armstrong's convertible isocyanide in this multicomponent reaction.
- Van Den Bogaert, An M.,Nelissen, Jo,Ovaere, Margriet,Van Meervelt, Luc,Compernolle, Frans,De Borggraeve, Wim M.
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scheme or table
p. 5397 - 5401
(2010/11/18)
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- HETEROCYCLIC UREA DERIVATIVES AND METHODS OF USE THEREOF
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Compounds of formula (IA) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.
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Page/Page column 112
(2010/12/26)
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- Novel naphthyridines are histamine H3 antagonists and serotonin reuptake transporter inhibitors
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A series of novel tetrahydronaphthyridine-based histamine H3 ligands that have serotonin reuptake transporter inhibitor activity is described. The 1,2,3,4-tetrahydro-2,6-naphthyridine scaffold is assembled via the addition of a nitrostyrene to a metalated pyridine followed by reduction and cyclization to form the naphthyridine. In vitro biological data for these novel compounds are discussed.
- Letavic, Michael A.,Keith, John M.,Ly, Kiev S.,Barbier, Ann J.,Boggs, Jamin D.,Wilson, Sandy J.,Lord, Brian,Lovenberg, Timothy W.,Carruthers, Nicholas I.
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p. 2566 - 2569
(2008/02/01)
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- NAPHTHYRIDINE COMPOUNDS
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Certain naphthyridine compounds are histamine H3 receptor and serotonin transporter modulators useful in the treatment of histamine H3 receptor- and serotonin-mediated diseases.
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(2010/11/25)
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- PYRIDINE N-OXIDES AS ANTIVIRAL AGENTS
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The present invention relates to pyridinone derivatives of formula (I) wherein Z represents C2-6 alkynyl, aryl or heteroaryl, any of which groups may be optionally substituted, and R1 represents hydrogen, C1-6alkyl, C
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- Substituted alkylamine derivatives and methods of use
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Selected heterocyclic compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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- Substituted alkylamine derivatives and methods of use
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Selected amines are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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- PYRIDINE MATRIX METALLOPROTEINASE INHIBITORS
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Selective MMP-13 inhibitors are pyridine derivatives of the formula or a pharmaceutically acceptable salt thereof, wherein: R1 and R2 independently are hydrogen, halo, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, NO 2, NR4R5, CN, or CF3, E is independently O or S; A and B independently are OR4 or NR4R5; R4 and R5 independently are H. C1-C 6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, (CH2)n aryl, (CH 2)n cycloalkyl, (CH2)n heteroaryl, or R4 and R5 when taken together with the nitrogen to which they are attached complete a 3 to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S, or NH, and optionally substituted or unsubstituted, n is an integer of from 0 to 6.
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- Process for the preparation of 5-chloro and 5-bromo-2-hydroxynicotinic acids
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A process for the preparation of 5-halo-2-hydroxynicotinic acids having the formula: STR1 wherein X is chlorine or bromine, Y and Z are selected from hydrogen, loweralkyl or loweralkyl, is described wherein a corresponding 2-hydroxynicotinic acid is halogenated with alkali-metal hypohalite in a strongly alkaline solution pH 12 and above. Certain aspects of the isolation of the product are directed to avoiding replacement of the carboxy group with halogen.
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- HALOGENATION OF 2-HYDROXYNICOTINIC ACID
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A convenient method to prepare 5-halo-2-hydroxynicotinic acid is described.
- Gero, Thomas W.,Jaques, Larry W.,Mays, Richard P.,Reid, Debra H.,Shamblee, Dwight A.,et al.
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p. 553 - 560
(2007/10/02)
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- Benzo- and pyrido-1,4-oxazepin-5-ones and -thiones: Synthesis and structure-activity relationships of a new series of H1 antihistamines
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A series of novel benzo- and pyrido-1,4-oxazepinones and -thiones which represents a new structural class of compounds possessing H1 antihistaminic acitivy was synthesized, and the SARs were evaluated. The antihistamine activity was determined by blockade of histamine-induced lethality in guinea pigs. The sedative potential was determined by comparison of the EEG profiles of the compounds with those of known sedating and nonsedating antihistamines. Several of the compounds were shown to possess potent H1 antihistaminic activity and to be free of the cortical slowing with synchronized waves and spindling activity found in the EEG of sedative antihistamines. One compound, 2-[2-(dimethylamino)ethyl]-3,4-dihydro-4-methylpyrido[3,2-f]-1,4-oxazeN pine-5(2H)-thione (rocastine) is currently undergoing clinical evaluation as a nonsedating H1 antihistamine.
- Cale Jr.,Gero,Walker,Lo,Welstead Jr.,Jaques,Johnson,Leonard,Nolan,Johnson
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p. 2178 - 2199
(2007/10/02)
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- Fused aromatic oxazepinones, thiazepinones, diazepinones and sulfur analogs thereof
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Aromatic azepinones and thiones having the formula STR1 wherein; A is benzene, naphthalene, quinoline or pyridine; B is oxygen or sulfur; E is oxygen, sulfur or STR2 n is 1, 2 or 3; Z is an amino or a heterocyclic nitrogen-containing radical; R is hydrogen, loweralkyl, cycloalkyl or phenylloweralkyl; Y is halo, loweralkyl, loweralkoxy, diloweralkylamino, nitro, amino, loweracetylamino, trifluoromethyl, phenyl or phenyl substituted by one to three Y' radicals selected from halo, loweralkyl, loweralkoxy, diloweralkylamino, nitro, amino, loweracylamino or trifluoromethyl; and having antihistaminic utility, a process for the preparation thereof and chemical intermediates therefor are disclosed.
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- Fused aromatic oxazepinones, thiazepinones, diazepinones and sulfur analogs thereof
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Aromatic azepinones and thiones having the formula STR1 wherein; A is benzene, naphthalene, quinoline or pyridine; B is oxygen or sulfur; E is oxygen, sulfur or STR2 n is 1, 2 or 3; Z is an amino or a heterocyclic nitrogen containing radical; R is hydrogen, loweralkyl, cycloalkyl or phenylloweralkyl; and having antihistaminic utility, a process for the preparation thereof and chemical intermediates therefor are disclosed.
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