- Design, synthesis, biological evaluation and cellular imaging of imidazo[4,5-b]pyridine derivatives as potent and selective TAM inhibitors
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The TAM kinase family arises as a new effective and attractive therapeutic target for cancer therapy, autoimmune and viral diseases. A series of 2,6-disubstituted imidazo[4,5-b]pyridines were designed, synthesized and identified as highly potent TAM inhib
- Baladi, Tom,Aziz, Jessy,Dufour, Florent,Abet, Valentina,Stoven, Véronique,Radvanyi, Fran?ois,Poyer, Florent,Wu, Ting-Di,Guerquin-Kern, Jean-Luc,Bernard-Pierrot, Isabelle,Garrido, Sergio Marco,Piguel, Sandrine
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Read Online
- Halogenation of 2-unsubstituted and 2-methylimidazo[4,5-b]pyridine derivatives
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Halogenation of 2-unsubstituted and 2-methylimidazo[4,5-b]pyridines and their N-methyl derivatives with bromine and chlorine in acetic acid takes different pathways, depending on the acetic acid concentration. The bromination in 50% aqueous acetic acid gives only 6-bromoimidazo[4,5-b]pyridines; bromination and chlorination of 2-unsubstituted imidazo[4,5-b]pyridines in glacial acetic acid leads to 5,6-dibromo(dichloro)imidazo[4,5-b]pyridin-2-ones, and bromination of 2-methylimidazo[4,5-b]pyridines in glacial acetic acid involves both the pyridine ring and the 2-methyl group to afford the corresponding 6-bromo-2-tribromomethylimidazo[4,5-b]pyridines.
- Yutilov,Lopatinskaya,Smolyar,Gres'Ko
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Read Online
- Convenient synthesis of imidazo[1,5-a]pyrimidine derivatives and their unusual recyclization into 3H-imidazo[4,5-b]pyridine derivatives
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[Figure not available: see fulltext.] New derivatives of imidazo[1,5-a]pyrimidine have been synthesized by cyclization of in situ generated 1H-imidazol-4(5)-amine with 1,3-diketones or malondialdehyde derivatives. Utilization of asymmetrical 1,3-diketones leads to the formation of a mixture of regioisomers. The discovered conversion of imidazo[1,5-a]pyrimidine core into 3H-imidazo[4,5-b]pyridine that takes place only under acidic conditions can be considered as a new version of Dimroth rearrangement involving cleavage of C–N bond and formation of C–C bond.
- Smirnova, Olga V.,Tolkunov, Andrew S.,Tolkunov, Sergei V.,Tolkunov, Valery S.
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p. 554 - 559
(2021/06/14)
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- Synthesis, biological properties and structural study of new halogenated azolo[4,5-b]pyridines as inhibitors of CK2 kinase
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The new halogenated 1H-triazolo[4,5-b]pyridines and 1H-imidazo[4,5-b]pyridines were synthesised as analogues of known CK2 inhibitors: 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) and 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi). Their influence on the activity of recombinant human CK2α, CK2α’ and PIM1 kinases was determined. The most active inhibitors were di- and trihalogenated 1H-triazolo[4,5-b]pyridines (4a, 5a and 10a) with IC50 values 2.56, 3.82 and 3.26 μM respectively for CK2α. Furthermore, effect on viability of cancer cell lines MCF-7 (human breast adenocarcinoma) and CCRF-CEM (T lymphoblast leukemia) of all final compounds was evaluated. Finally, three crystal structures of complexes of CK2α1-335 with inhibitors 4a, 5a and 10a were obtained. In addition, new protocol was used to obtain high-resolution crystal structures of CK2α’Cys336Ser in complex with four inhibitors (4a, 5a, 5b, 10a).
- Chojnacki,Lindenblatt,Wińska,Wielechowska,Toelzer,Niefind,Bretner
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- Cu@U-g-C3N4 Catalyzed Cyclization of o-Phenylenediamines for the Synthesis of Benzimidazoles by Using CO2 and Dimethylamine Borane as a Hydrogen Source
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Abstract: This work reports a green and sustainable route for the synthesis of benzimidazoles via C–N bond formation using carbon dioxide (CO2) as a C1 carbon source. In this work, Cu@U-g-C3N4 catalyst was prepared from urea derived porous graphitic carbon?nitride (U-g-C3N4) and CuCl2 and characterized by FT-IR, XRD, XPS, SEM, TPD etc. The Cu@U-g-C3N4 as a heterogeneous recyclable catalyst has been employed first time for the cyclization of o-phenylenediamines (OPD) with CO2 to benzimidazoles using dimethylamine borane (DMAB). The proposed protocol becomes sustainable and efficient due to the use of propylene carbonate/water as a suitable biodegradable, economical and environmentally benign solvent system. The proposed catalytic system showed a wide range of substrate scope for the synthesis of benzimidazoles in good to excellent yields. Graphical Abstract: [Figure not available: see fulltext.]
- Phatake, Vishal V.,Bhanage, Bhalchandra M.
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p. 347 - 359
(2018/11/23)
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- TRICYCLIC DLK INHIBITORS AND USES THEREOF
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The invention relates to compounds of formula (I) and salts thereof, wherein ring A and R1-R2 have any of the values defined in the specification. The compounds and salts are useful for treating DLK mediated disorders. The invention also provides pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as well as methods of using said compounds, salts, or compositions as DLK inhibitors and for treating neurodegeneration diseases and disorders.
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Page/Page column 86-87
(2016/09/26)
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- HETEROCYCLIC COMPOUNDS AND USE THEREOF AS MODULATORS OF TYPE III RECEPTOR TYROSINE KINASES
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Provided herein are heterocyclic compounds for treatment of CSF1R, FLT3, KIT, and/or PDGFRβ kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.
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Paragraph 0737
(2016/08/03)
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- Microwave-Assisted C-2 Direct Alkenylation of Imidazo[4,5-b]pyridines: Access to Fluorescent Purine Isosteres with Remarkably Large Stokes Shifts
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We describe herein the first C-2 direct alkenylation of the valuable 3H-imidazo[4,5-b]pyridine promoted by microwave-assisted Pd/Cu co-catalysis. The reaction is rapid and compatible with a wide range of functional groups either on the imidazo[4,5-b]pyridine ring or on the styryl bromides thereby leading to the isolation of 23 compounds with moderate to good yields. The relevance of this method is demonstrated by its application to the synthesis of new cross-conjuguated push-pull 2-vinyl- and 2-alkynylimidazo[4,5-b]pyridines characterized by satisfactory fluorescence quantum yields and remarkable solvatofluorochromic properties.
- Baladi, Tom,Granzhan, Anton,Piguel, Sandrine
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p. 2421 - 2434
(2016/06/01)
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- Direct Alkynylation of 3H-Imidazo[4,5-b]pyridines Using gem-Dibromoalkenes as Alkynes Source
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C2 direct alkynylation of 3H-imidazo[4,5-b]pyridine derivatives is explored for the first time. Stable and readily available 1,1-dibromo-1-alkenes, electrophilic alkyne precursors, are used as coupling partners. The simple reaction conditions include an inexpensive copper catalyst (CuBr·SMe2 or Cu(OAc)2), a phosphine ligand (DPEphos) and a base (LiOtBu) in 1,4-dioxane at 120 °C. This C-H alkynylation method revealed to be compatible with a variety of substitutions on both coupling partners: heteroarenes and gem-dibromoalkenes. This protocol allows the straightforward synthesis of various 2-alkynyl-3H-imidazo[4,5-b]pyridines, a valuable scaffold in drug design.
- Aziz, Jessy,Baladi, Tom,Piguel, Sandrine
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p. 4122 - 4133
(2016/06/09)
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- 2-AMINO-BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS 5-LIPOXYGENASE AND/OR PROSTAGLANDIN E SYNTHASE INHIBITORS
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The present invention relates to benzimidazole derivatives having the general formula I, wherein n is 0 or 1; X1 and X2 are independently, at each occurrence, CR5 or N; Y is C1-C6 alkylene, wherein alkylene is optionally substituted with one to two C1-C3 alkyl groups; R1 is selected from the group consisting of hydrogen, halogen, C1-C6 alkoxy, -NH2, -NHR6, -NR7R8 and -NH-(R9)n-R10, n being 0 or 1; R2 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, -NH2, -NHR6, - NR7R8 and -NH-(R9)n-R10; R3 is selected from the group consisting of hydrogen, hydroxyl, OR11, -NR7R8, C1-C6 alkoxy, C1-C6 alkyl, C3-C10 cycloalkyl, C1-C3 haloalkyl, -C(O)NHR11, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups; and R4 is selected from the group consisting of -NH2, -N(R12)(V)pR13, - NH(V)p-OR14, -NHC(O)R15, and groups of formula la shown below, and their use in the treatment of diseases, in particular inflammatory diseases, cancer, stroke and/or Alzheimer's disease.
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Page/Page column 57
(2016/03/12)
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- Expedient synthesis of benzimidazoles using amides
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In the present report an efficient, rapid, facile and inexpensive route for the synthesis of benzimidazoles using 1,2-arylenediamines and N,N-dimethylformamide in acidic medium under thermal/microwave condition is developed. This reaction was further explored with the different amides to afford a library of 2-substituted benzimidazoles. The advantage of the present synthetic method includes shorter reaction time, easy work up and excellent yields without using catalysts.
- Kattimani, Pramod P.,Kamble, Ravindra R.,Meti, Gangadhar Y.
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p. 29447 - 29455
(2015/04/14)
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- HETEROCYCLIC COMPOUNDS AS INHIBITORS OF FATTY ACID BIOSYSNTHESIS FOR BACTERIAL INFECTIONS
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The present invention relates to novel heterocyclic compounds which specifically inhibit bacterial FabI and can be used for the treatment of Staphylococcal infections.
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Paragraph 0137; 0138
(2014/09/16)
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- Regioselective C2-arylation of imidazo[4,5-b]pyridines
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We show that N3-MEM-protected imidazo[4,5-b]pyridines undergo efficient C2-functionalisation via direct C-H arylation. Twenty-two substituted imidazo[4,5-b]pyridines are prepared and iterative, selective elaboration of functionalised imidazo[4,5-b]pyridin
- Macdonald, Jonathan,Oldfield, Victoria,Bavetsias, Vassilios,Blagg, Julian
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supporting information
p. 2335 - 2347
(2013/04/23)
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- HETEROCYCLIC COMPOUNDS AS INHIBITORS OF FATTY ACID BIOSYNTHESIS FOR BACTERIAL INFECTIONS
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The present invention relates to novel heterocyclic compounds which specifically inhibit bacterial Fab I and can be used for the treatment of Staphylococcal infections.
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Page/Page column 31
(2013/04/10)
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- A simple and convenient two-step, one-pot synthesis of hetero-imidazoles from nitroaminoaryls catalyzed by Ytterbium triflate
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A mild two-step one-pot procedure for the conversion of ortho-nitroamino aromatic heterocycles into corresponding benzo and heteroaromatic fused imidazoles is described. The procedure utilizes iron powder, acetic acid, triethylorthoformate, and a catalytic amount of Ytterbium triflate at 75 C for the nitro group reduction and cyclization reaction. The optimum stoichiometry of each component is highlighted and the broad utility is demonstrated with high compatibility to numerous functional groups.
- Wang, Fen,Tran-Dubé, Michelle,Scales, Stephanie,Johnson, Sarah,McAlpine, Indrawan,Ninkovic, Sacha
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p. 4054 - 4057
(2013/07/25)
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- Synthesis and in vitro and in vivo evaluation of phosphoinositide-3-kinase inhibitors
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Phospoinositide-3-kinases (PI3K) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. A series of 2-morpholino, 4-substituted, 6-(3-hydroxyphenyl) pyrimidines have been reported as potent inh
- Burger, Matthew T.,Knapp, Mark,Wagman, Allan,Ni, Zhi-Jie,Hendrickson, Thomas,Atallah, Gordana,Zhang, Yanchen,Frazier, Kelly,Verhagen, Joelle,Pfister, Keith,Ng, Simon,Smith, Aaron,Bartulis, Sarah,Merrit, Hanne,Weismann, Marion,Xin, Xiaohua,Haznedar, Joshua,Voliva, Charles F.,Iwanowicz, Ed,Pecchi, Sabina
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supporting information; experimental part
p. 34 - 38
(2011/04/22)
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- BENZOXAZEPINES AS INHIBITORS OF PI3K/m TOR AND METHODS OF THEIR USE AND MANUFACTURE
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The invention is directed to Compounds of Formula (I): the invention provides compounds that inhibit, regulate, and/or modulate P13K and/or mTOR that are useful in the treatment of hyperproliferative diseases, such as cancer, in mammals. This invention al
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Page/Page column 188
(2010/12/26)
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- THIAZOLOPYRIMIDINE PI3K INHIBITOR COMPOUNDS AND METHODS OF USE
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Compounds of Formulas (Ia and Ib), and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed
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Page/Page column 72
(2009/05/29)
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- NOVEL JNK INHIBITORS
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Disclosed are compounds of the formula (I) wherein X is N or CH, and Y is N or CR5. Also disclosed are methods of treating JNK and ERK mediated diseases using the compounds of formula 1.0.
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Page/Page column 107
(2008/12/07)
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- Pharmaceutical compounds
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Compounds of Formulae Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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Page/Page column 100
(2008/06/13)
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- PHOSPHOINOSITIDE 3-KINASE INHIBITOR COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Compounds of Formulas (Ia) and (Ib), and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula (Ia) and (Ib) for in vitro, in situ, and in vivodiagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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Page/Page column 140-141
(2008/06/13)
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- ARYLMETHYL TRIAZOLO AND IMIDAZOPYRAZINES AS C-MET INHIBITORS
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The present invention relates to compounds of the Formulae (I) - (IV), wherein R1 - R6, R11 - R13, X and Y are defined herein, and their pharmaceutically acceptable salts. These compounds modulate the activity of c-Met and are therefore expected to be useful in the prevention and treatment of c-Met related disorders such as cancer.
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Page/Page column 40
(2008/06/13)
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- FAB I INHIBITORS
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Compounds of the formula (I) are disclosed which are Fab I inhibitors and are useful in the treatment of bacterial infections.
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- Amide compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use
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Amide compounds that modulate and/or inhibit the activity of certain protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating tyrosine kinase signal transduction in order to modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer as well as other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.
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