- SUBSTITUTED FUSED AROMATIC RING DERIVATIVE, COMPOSITION AND USE THEREOF
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Provided are a substituted fused aromatic ring derivative, a composition containing the compound, and a use thereof. The substituted fused aromatic ring derivative is a compound represented by formula (I) or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof. The compound and the composition can be used to treat various protein tyrosine kinase-mediated diseases or disorders.
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Paragraph 0152-0154
(2021/11/04)
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- NOVEL IMIDAZO-PYRAZINE DERIVATIVES
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The invention provides novel imidazo-pyrazine derivatives having the general formula (I), and pharmaceutically acceptable salts thereof, wherein X, m, n, and R1to R3 are as described herein: formula (I). Further provided are pharmace
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Page/Page column 45; 78
(2021/12/31)
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- Selective Halogenation of Pyridines Using Designed Phosphine Reagents
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Halopyridines are key building blocks for synthesizing pharmaceuticals, agrochemicals, and ligands for metal complexes, but strategies to selectively halogenate pyridine C-H precursors are lacking. We designed a set of heterocyclic phosphines that are installed at the 4-position of pyridines as phosphonium salts and then displaced with halide nucleophiles. A broad range of unactivated pyridines can be halogenated, and the method is viable for late-stage halogenation of complex pharmaceuticals. Computational studies indicate that C-halogen bond formation occurs via an SNAr pathway, and phosphine elimination is the rate-determining step. Steric interactions during C-P bond cleavage account for differences in reactivity between 2- and 3-substituted pyridines.
- Alegre-Requena, Juan V.,Levy, Jeffrey N.,Liu, Renrong,McNally, Andrew,Paton, Robert S.
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supporting information
p. 11295 - 11305
(2020/07/13)
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- COMPOUND USED AS AUTOPHAGY REGULATOR, AND PREPARATION METHOD THEREFOR AND USES THEREOF
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It is related to compounds used as autophagy modulators and a method for preparing and using the same, specifically providing a compound of general formula (I), or pharmaceutically acceptable salts thereof, which is a type of autophagy modulators, particularly mammalian ATG8 homologues modulators.
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Paragraph 0241-0242
(2020/07/07)
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- Alkynyl (hetero) aromatic compounds for inhibiting activity of protein kinase
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The invention relates to alkynyl (hetero) aromatic compounds for inhibiting activity of protein tyrosine kinase. The invention further relates to a pharmaceutical composition containing the alkynyl (hetero) aromatic compounds, and preparation and application of the alkynyl (hetero) aromatic compounds. Specifically, the invention discloses the alkynyl (hetero) aromatic compound shown in an equation (I) and pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, crystal forms, prodrugs and isotopic variants of the alkynyl (hetero) aromatic compound shown in the equation (I). The alkynyl (hetero) aromatic compounds can be used for treating and/or preventing protein tyrosine kinase-related diseases, such as preventing tumors.
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Paragraph 0590; 0593-0595
(2019/10/07)
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- Novel and selective TLR7 antagonists among the imidazo[1,2- a]pyrazines, Imidazo[1,5- a]quinoxalines, and Pyrazolo[1,5- a]quinoxalines Series
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The Toll-like receptors (TLRs) 7 and 8 play an important role in the immune system activation, and their agonists may therefore serve as promising candidate vaccine adjuvants. However, the chronic immune activation by excessive TLR stimulation is a hallmark of several clinically important infectious and autoimmune diseases, which warrants the search for TLR antagonists. In this study, we have synthesized and characterized a variety of compounds belonging to three heterocyclic chemical series: imidazo[1,2-a]pyrazine, imidazo[1,5-a]quinoxaline, and pyrazolo[1,5-a]quinoxaline. These compounds have been tested for their TLR7 or TLR8 agonistic and antagonistic activities. Several of them are shown to be selective TLR7 antagonists without any TLR7 or TLR8 agonistic activity. The selectivity was confirmed by a comparative ligand-docking study in TLR7 antagonist pocket. Two compounds of the pyrazolo[1,5-a]quinoxaline series (10a and 10b) are potent selective TLR7 antagonists and may be considered as promising starting points for the development of new therapeutic agents.
- Bou Karroum, Nour,Moarbess, Georges,Guichou, Jean-Fran?ois,Bonnet, Pierre-Antoine,Patinote, Cindy,Bouharoun-Tayoun, Hasnaa,Chamat, Soulaima,Cuq, Pierre,Diab-Assaf, Mona,Kassab, Issam,Deleuze-Masquefa, Carine
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p. 7015 - 7031
(2019/08/20)
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- SUBSTITUTED TETRAHYDROQUINOLINONE COMPOUNDS AS ROR GAMMA MODULATORS
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The present invention provides substituted tetrahydroquinolinone and related compounds of formula (I), which are therapeutically useful as modulators of Retinoic acid receptor-related orphan receptors (RORs), more particularly as RORγ modulators. These co
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Page/Page column 38; 39
(2016/12/07)
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- Design and synthesis of new imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrazine derivatives with antiproliferative activity against melanoma cells
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Melanoma is an aggressive form of skin cancer and it is generally associated with poor prognosis in patients with late-stage disease. Due to the increasing occurrence of melanoma, there is a need for the development of novel therapies. A new series of diarylamide and diarylurea derivatives containing imidazo[1,2-a]pyridine or imidazo[1,2-a]pyrazine scaffold was designed and synthesized to investigate their in vitro efficacy against the A375P human melanoma cell line. We found several compounds expressing submicromolar IC50 values against the A375P cells, from which 15d, 17e, 18c, 18h, 18i demonstrated the highest potencies with IC50 below 0.06 μM.
- Garamv?lgyi, Rita,Dobos, Judit,Sipos, Anna,Boros, Sándor,Illyés, Eszter,Baska, Ferenc,Kékesi, László,Szabadkai, István,Szántai-Kis, Csaba,Kéri, Gy?rgy,?rfi, László
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p. 623 - 643
(2015/12/30)
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- 2- and 3-substituted imidazo[1,2-a]pyrazines as inhibitors of bacterial type IV secretion
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A novel series of 8-amino imidazo[1,2-a]pyrazine derivatives has been developed as inhibitors of the VirB11 ATPase HP0525, a key component of the bacterial type IV secretion system. A flexible synthetic route to both 2- and 3-aryl substituted regioisomers has been developed. The resulting series of imidazo[1,2-a]pyrazines has been used to probe the structure-activity relationships of these inhibitors, which show potential as antibacterial agents.
- Sayer, James R.,Walldn, Karin,Pesnot, Thomas,Campbell, Frederick,Gane, Paul J.,Simone, Michela,Koss, Hans,Buelens, Floris,Boyle, Timothy P.,Selwood, David L.,Waksman, Gabriel,Tabor, Alethea B.
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supporting information
p. 6459 - 6470
(2015/01/09)
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- Discovery of a potent, selective, and orally active phosphodiesterase 10A inhibitor for the potential treatment of schizophrenia
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We report the discovery of a series of imidazo[1,2-a]pyrazine derivatives as novel inhibitors of phosphodiesterase 10A (PDE10A). In a high-throughput screening campaign we identified the imidazopyrazine derivative 1, a PDE10A inhibitor with limited select
- Bartolomé-Nebreda, José Manuel,Delgado, Francisca,Martín-Martín, María Luz,Martínez-Viturro, Carlos M.,Pastor, Joaquín,Tong, Han Min,Iturrino, Laura,Macdonald, Gregor J.,Sanderson, Wendy,Megens, Anton,Langlois, Xavier,Somers, Marijke,Vanhoof, Greet,Conde-Ceide, Susana
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p. 4196 - 4212
(2014/06/09)
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- Identification of a series of compounds with potent antiviral activity for the treatment of enterovirus infections
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Rhinovirus (genus enterovirus) infections are responsible for many of the severe exacerbations of asthma and chronic obstructive pulmonary disease. Other members of the genus can cause life-threatening acute neurological infections. There is currently no antiviral drug approved for the treatment of such infections. We have identified a series of potent, broad-spectrum antiviral compounds that inhibit the replication of the human rhinovirus, Coxsackie virus, poliovirus, and enterovirus-71. The mechanism of action of the compounds has been established as inhibition of a lipid kinase, PI4KIIIβ. Inhibition of hepatitis C replication in a replicon assay correlated with enterovirus inhibition.
- Macleod, Angus M.,Mitchell, Dale R.,Palmer, Nicholas J.,Van De Poel, Herve,Conrath, Katja,Andrews, Martin,Leyssen, Pieter,Neyts, Johan
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supporting information
p. 585 - 589
(2013/07/26)
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- IMIDAZOPYRAZINES FOR USE AS MPS-1 AND TKK INHIBITORS IN THE TREATMENT HYPERPROLIFERATIVE DISORDERS
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The present invention relates to substituted imidazopyrazine compounds of general formula (I) : in which R1, R2, R3, R4 and R5 are as defined in the claims, to methods of and intermediates for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.
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Page/Page column 39-40
(2012/06/30)
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- FUSED IMIDAZOLE DERIVATIVE HAVING TTK INHIBITORY ACTION
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Provided are a compound represented by general formula (1) and having a TTK inhibitory action and a medicine containing the compound. In formula (1), (X, Y, V, W) is (—N═, ═CR1—, ═N—, —CR7═), (—CR2═, ═N—, ═N—, —CR7═), etc.; A is an (un)substituted aromatic hydrocarbon ring, etc.; L is a single bond, —C(═O)—NRA—, etc.; Z is a group represented by the formula —NR3R4 or a group represented by the formula —OR5; R1 to R3, R6, and R7 each is a hydrogen atom, etc.; R4 and R5 each is an (un)substituted alkyl, etc.; and R8 is an (un)substituted cycloalkyl, etc.
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Page/Page column 38-39
(2012/03/26)
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- IMIDAZO[1,2-a]PYRAZINE DERIVATIVES AND THEIR USE FOR THE PREVENTION OR TREATMENT OF NEUROLOGICAL, PSYCHIATRIC AND METABOLIC DISORDERS AND DISEASES
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The present invention relates to novel imidazo[1,2-a]pyrazine derivatives which are inhibitors of the phosphodiesterase 10 enzyme (PDE10) and which are useful for the treatment or prevention of neurological, psychiatric and metabolic disorders in which the PDE10 enzyme is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, to the use of such compounds or pharmaceutical compositions for the prevention or treatment of neurological, psychiatric and metabolic disorders and diseases.
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Page/Page column 33
(2013/02/28)
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- IMIDAZO [1, 2 -A] PYRAZINE DERIVATIVES AND THEIR USE FOR THE PREVENTION OR TREATMENT OF NEUROLOGICAL, PSYCHIATRIC AND METABOLIC DISORDERS AND DISEASES
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The present invention relates to novel imidazo[1,2-a]pyrazine derivatives which are inhibitors of the phosphodiesterase 10 enzyme (PDE10) and which are useful for the treatment or prevention of neurological, psychiatric and metabolic disorders in which the PDE10 enzyme is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, to the use of such compounds or pharmaceutical compositions for the prevention or treatment of neurological, psychiatric and metabolic disorders and diseases.
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Page/Page column 73
(2011/10/05)
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- Discovery of imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors
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The synthesis and structure-activity relationships (SAR) of novel, potent imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors are described. The X-ray crystal structure of imidazo[1,2-a]pyrazine Aurora inhibitor 1j is disclosed. Compound 10i was identified as lead compound with a promising overall profile.
- Belanger, David B.,Curran, Patrick J.,Hruza, Alan,Voigt, Johannes,Meng, Zhaoyang,Mandal, Amit K.,Siddiqui, M. Arshad,Basso, Andrea D.,Gray, Kimberly
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scheme or table
p. 5170 - 5174
(2010/10/02)
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- COMPOUNDS FOR TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY
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Compounds of formula (I): wherein R1, R2, X1, and X2 are as defined herein, are useful for the treatment or prophylaxis of conditions such as Duchenne muscular dystrophy, Becker muscular dystrophy, and cachexia.
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Page/Page column 96
(2010/08/05)
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- HETEROCYCLIC MODULATORS OF GPR119 FOR TREATMENT OF DISEASE
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Disclosed herein are compounds and methods which may be useful as inhibitors of GPRl 19 for the treatment or prevention of diseases including cardiovascular and metabolic diseases.
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Page/Page column 55
(2010/08/09)
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- IMIDAZOPYRAZINE COMPOUNDS
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Novel imidazopyrazine compounds are disclosed that have a formula represented by the following: Formula (I). The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a viral infection, in particular a HCV, HRV, Sb and/or CVB in a patient in need thereof.
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Page/Page column 46
(2009/04/25)
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- 5-MEMBERED HETEROCYCLIC AMIDES AND RELATED COMPOUNDS
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5-Membered heterocyclic amides and related compounds are provided, of the Formula: wherein variables are as described herein. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly usef
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Page/Page column 90
(2009/03/07)
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- Methods for inhibiting protein kinases
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The present invention provides methods for inhibiting protein kinases selected from the group consisting of AKT, Checkpoint kinase, Aurora kinase, Pim-1 kinase, and tyrosine kinase using imidazo[1,2-a]pyrazine compounds and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with protein kinases using such compounds.
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Page/Page column 121
(2010/11/27)
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- FUSED TRIAZOLE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to novel fused triazole derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DPP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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Page/Page column 53
(2008/06/13)
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- Imidazo[1,2-a]pyrazin-8-ones, imidazo[1,2-d][1,2,4]triazin-8-ones and imidazo[2,1-f][1,2,4]triazin-8-ones as α2/α3 subtype selective GABAA agonists for the treatment of anxiety
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Imidazo[1,2-a]pyrazin-8-ones, imidazo[1,2-d][1,2,4]triazin-8-ones and imidazo[2,1-f][1,2,4]triazin-8-ones are high affinity GABAA agonists. Compound 16d has good oral bioavailability in rat, functional selectivity for the GABAAα2 and
- Goodacre, Simon C.,Hallett, David J.,Carling, Robert W.,Castro, Jose L.,Reynolds, David S.,Pike, Andrew,Wafford, Keith A.,Newman, Robert,Atack, John R.,Street, Leslie J.
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p. 1582 - 1585
(2007/10/03)
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- MIDAZOPYRAZINONES AND IMIDAZOTRIAZINONES DERIVATES AS GABA-A RECEPTOR ANXIOLYTIC
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The present invention discloses a compound of formula I, or a pharmaceutically acceptable salt thereof: (I) wherein -U-V- represents -CH=CH-, or -CH2-CH2-, -N=CH- or -CH=N-; X1 represents hydrogen, halogen, C1-6 alkyl, trifluoromethyl or C1-6 alkoxy; X2 represents hydrogen or halogen; Y represents a chemical bond, an oxygen atom, or a -NH- or -OCH2- linkage; Z represents an optionally substituted aryl or heteroaryl group; R1 represents hydrocarbon, a heterocyclic group, trifluoromethyl, -SO2Ra, -SO2NRaRb, -CORa, -CO2Ra or -CONRaRb; and Ra and Rb independently represent hydrogen, hydrocarbon or a heterocyclic group;pharmaceutical compositions comprising it; its use in methods of treatment; use of it in the manufacture of a medicament for treating and/or preventing anxiety; convulsions or a cognitive disorder; and methods of treatment using it.
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