- SUBSTITUTED OXOPYRIDINE DERIVATIVES
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The invention relates to substituted oxopyridine derivatives and to processes for their preparation, and also to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular cardiovascular disorders, preferably thrombotic or thromboembolic disorders, and o edemas, and also ophthalmic disorders.
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Page/Page column 75
(2017/02/09)
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- New 6-Aminoquinoxaline Derivatives with Neuroprotective Effect on Dopaminergic Neurons in Cellular and Animal Parkinson Disease Models
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Parkinson's disease (PD) is a neurodegenerative disorder of aging characterized by motor symptoms that result from the loss of midbrain dopamine neurons and the disruption of dopamine-mediated neurotransmission. There is currently no curative treatment for this disorder. To discover druggable neuroprotective compounds for dopamine neurons, we have designed and synthesized a second-generation of quinoxaline-derived molecules based on structure-activity relationship studies, which led previously to the discovery of our first neuroprotective brain penetrant hit compound MPAQ (5c). Neuroprotection assessment in PD cellular models of our newly synthesized quinoxaline-derived compounds has led to the selection of a better hit compound, PAQ (4c). Extensive in vitro characterization of 4c showed that its neuroprotective action is partially attributable to the activation of reticulum endoplasmic ryanodine receptor channels. Most interestingly, 4c was able to attenuate neurodegeneration in a mouse model of PD, making this compound an interesting drug candidate for the treatment of this disorder.
- Le Douaron, Gael,Ferrié, Laurent,Sepulveda-Diaz, Julia E.,Amar, Majid,Harfouche, Abha,Séon-Méniel, Blandine,Raisman-Vozari, Rita,Michel, Patrick P.,Figadère, Bruno
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p. 6169 - 6186
(2016/07/26)
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- 6- endo -dig Cycloisomerization of N -Propargyl Aminoquinoxalines: A New Route to 1,4,8-Triazaphenanthrenes
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We report the preparation of novel 1,4,8-triazaphenanthrenes and show that the target compounds are efficiently obtained from the corresponding 6-aminoquinoxalines after N-propargylation followed by copper-catalyzed 6-endo-dig cycloisomerization and aroma
- Vallerotto, Sara,Douaron, Gael Le,Bernadat, Guillaume,Ferrié, Laurent,Figadère, Bruno
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p. 3232 - 3240
(2016/09/12)
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- HETEROCYCLIC DERIVATIVES THAT ARE USED IN THE TREATMENT OF NEURODEGENERATIVE DISEASES
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The present invention relates to compounds of Formula (I) below, to their pharmaceutically acceptable salts and to their isomers or mixtures of isomers: HetAr—X—CHR1R2 (I) in which: -HetAr represents a group chosen from: —X represents a linear, saturated or unsaturated, hydrocarbon-based chain comprising from 8 to 22 carbon atoms, optionally interrupted by an —NH— or —NH—CO— group, —R1 represents a hydrogen atom or an —OH, —O(C1-C6)alkyl, —OCO((C1-C6)alkyl), —OSO2((C1-C6)alkyl) or —OSO3H group, and —R2 represents a hydrogen atom or a (C2-C6)alkynyl, (C2-C6)alkenyl or (C3-C6)cycloalkyl group. The present invention also relates to a process for preparing the compounds of Formula (I), and also to the use thereof, especially in the treatment of neurodegenerative diseases.
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Page/Page column 8
(2011/06/10)
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- Bicyclic aromatic substituted pyridone derivative
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Disclosed is a compound represented by the formula (I): Wherein R1 and R2 independently represent a hydrogen atom, a lower alkyl group or the like; X1, X2 and X3 independently represent a methine group or a nitrogen atom; Y1 and Y3 independently represent a single bond, —O— or the like; Y2 represents a lower alkylene group or the like; W1 to W4 independently represent a single bond, a methylene group or the like; L represents a single bond, a methylene group or the like; Z1 and Z2 independently represent a single bond, a C1-4 alkylene group or the like; Ar1 represents an aromatic carbocyclic ring or the like; and Ar2 represents a bicyclic aromatic carbocyclic ring or the like. The compound is useful as a pharmaceutical for a central disease, a cardiovascular disease or a metabolic disease.
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Page/Page column 43
(2009/10/30)
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- Novel highly regioselective syntheses of unsymmetrical 2,3-disubstituted quinoxalines
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Non-symmetrical 2,3-disubstituted quinoxalines are not easily obtained in good yields because of the lack of regioselectivity of the Hinsberg condensation, or the large number of steps required for achieving their preparation. Two efficient methods leadin
- Hui, Xu,Schmidt, Fanny,Fakhfakh, Mohammed Akram,Franck, Xavier,Figadère, Bruno
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p. 353 - 361
(2008/03/12)
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- Synthesis and antiprotozoal activity of some new synthetic substituted quinoxalines
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A series of 29 new quinoxalines was synthesized and evaluated in vitro against several parasites (Leishmania donovani, Trypanosoma brucei brucei, and Trichomonas vaginalis). Several of them displayed interesting activities, and particularly four quinoxaline amides showed in vitro antileishmanial properties (IC50 less than 20 μM).
- Hui, Xu,Desrivot, Julie,Bories, Christian,Loiseau, Philippe M.,Franck, Xavier,Hocquemiller, Reynald,Figadere, Bruno
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p. 815 - 820
(2007/10/03)
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- PHENYL CARBOXAMIDE AND SULFONAMIDE DERIVATIVES FOR USE AS 11-BETA-HYDROXYSTEROID DEHYDROGENASE
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There is provided a compound having Formula (I) R1-Z-R2 Formula (I) wherein R1 is an optionally substituted phenyl ring; R2 is or comprises an optionally substituted aromatic ring; and Z is -X-Y-L- or -Y-X-L- wherein either X is selected from -S(=O)(=O)- and -C(=O)-, and Y is -NR3-; or X is selected from -S(=O)(=O)- and -S-, and Y is -C(R4)(R5)-; L is an optional linker; and R3, R4 and R5 are each independently selected from H and hydrocarbyl; and wherein when R2 comprises the following structural moiety, Formula (II) wherein Q is an atom selected from the group consisting of S, O, N and C; the compound is selected from compounds of the formulae R1-C(=O)-NR3-L-R2; R1-S(=O)(=O)-C(R4)(R5)-L-R2; R1-S-C(R4)(R5)-L-R2; R1-NR3-S(=O)(=O)-L-R2; R1-NR3-C(=O)-L-R2; R1-C(R4)(R5)-S(=O)(=O)-L-R2; and R1-C(R4)(R5)-S-L-R2. These compounds are useful as 11β-hydroxysteriod dehydrogenase inhibitors in the treatment of i.a. diabetes.
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Page/Page column 69
(2010/02/11)
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- FIBROSIS INHIBITOR
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Medicament being useful as a fibrosis inhibitor for organs or tissues, which comprises a compound of the formula (I): wherein Ring Z is optionally substituted pyrrole ring, etc.; W2 is -CO-, -SO2-, optionally substituted C1-C4 alkylene, etc.; Ar2 is optionally substituted aryl, etc.; W1 and Ar1 mean the following (1) and (2):(1) W1 is optionally substituted C1-C4 alkylene, etc.; Ar1 is optionally substituted bicyclic heteroaryl having 1 to 4 nitrogen atoms as ring-forming atoms:(2) W1 is optionally substituted C2-C5 alkylene, optionally substituted C2-C5 alkenylene, etc.; and Ar1 is aryl or monocyclic heteroaryl, which is substituted by carboxyl, alkoxycarbonyl, etc. at the ortho- or meta-position thereof with respect to the binding position of W1, or a pharmaceutically acceptable salt thereof.
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- Pyrrole derivatives
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Pyrrole derivatives represented by the following formula: wherein Ring Z is an optionally substituted pyrrole ring, etc.; W2 is —CO—, —SO2—, an optionally substituted C1-C4 alkylene, etc.; Ar2 is an optionally substituted aryl, etc.; W2 and Ar1 mean the following (1) and (2): (1) W1 is an optionally substituted C1-C4 alkylene, etc.; Ar1 is an optionally substituted bicyclic heteroaryl having 1 to 4 nitrogen atoms as ring-forming atoms: (2) W1 is an optionally substituted C2-C5 alkylene, an optionally substituted C2-C5 alkenylene, etc.; and Ar1 is an aryl or monocyclic heteroaryl, which are substituted by carboxyl, an alkoxycarbonyl, etc. at the ortho- or meta-position thereof with respect to the binding position of W1, or a pharmaceutically acceptable salt thereof These compounds are useful as medicaments such as a fibrosis inhibitor for organs or tissues.
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- Methods for using (2-imidazolin-2-ylamino) quinoxaline derivatives
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A method of treating a mammal comprises administering to a mammal an effective amount to provide a desired therapeutic effect in the mammal of a compound selected from the group consisting of those having the formula: and pharmaceutically acceptable acid addition salts thereof and mixtures thereof, wherein R1and R2each is selected from the group consisting of alkyl radicals containing 1 to 4 carbon atoms and alkoxy radicals containing 1 to 4 carbon atoms, the 2-imidazolin-2-ylamino group may be in any of the 5-, 6-, 7- or 8-positions of the quinoxaline nucleus, and R3, R4and R5each is located in one of the remaining 5-, 6-, 7- or 8-positions of the quinoxaline nucleus and is independently selected from the group consisting of Cl, Br, H and alkyl radicals containing 1 to 3 carbon atoms. Such compounds, when administered to a mammal, provide desired therapeutic effects, such as reduction in peripheral pain.
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- METHODS FOR USING (2-IMIDAZOLIN-2-YLAMINO) QUINOXALINE DERIVATIVES
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A method of treating a mammal comprises administering to a mammal an effective amount to provide a desired therapeutic effect in the mammal of a compound selected from the group consisting of those having the formula: STR1 and pharmaceutically acceptable acid addition salts thereof and mixtures thereof, wherein R 1 and R 2 each is independently selected from the group consisting of alkyl radicals containing 1 to 4 carbon atoms and alkoxy radicals containing 1 to 4 carbon atoms, the 2-imidazolin-2-ylamino group may be in any of the 5-, 6-, 7-or 8-positions of the quinoxaline nucleus, and R 3, R 4 and R 5 each is located in one of the remaining 5-, 6-, 7-or 8-positions of the quinoxaline nucleus and is independently selected from the group consisting of Cl, Br, H and alkyl radicals containing 1 to 3 carbon atoms. Such compounds, when administered to a mammal, provide treatment for ischemia.
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- Methods for using (2-imidazolin-2-ylamino) quinoxaline derivatives
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A method of treating a mammal comprises administering to a mammal an effective amount to provide a desired therapeutic effect in the mammal of a compound selected from the group consisting of those having the formula: STR1 , pharmaceutically acceptable acid addition salts thereof and mixtures thereof, wherein R1 and R4 are independently selected from the group consisting of H and alkyl radicals having 1 to 4 carbon atoms; the R2 s are independently selected from H or alkyl radicals having 1 to 4 carbon atoms or are, together, oxo; the R3 s are independently selected from H or alkyl radicals having 1 to 4 carbon atoms or are, together, oxo; the 2-imidazolin-2-ylamino group may be in any of the 5-, 6, 7- or 8- positions of the quinoxaline nucleus; and R5, R6 and R7 each is located in one of the remaining 5-, 6-, 7- or 8- positions of the quinoxaline nucleus and is independently selected from the group consisting of Cl, Br, H and alkyl radicals having 1 to 3 carbon atoms. Such compounds, when administered to a mammal, provide desired therapeutic effects, such as constriction of one or more blood vessels and decongestion of one or more nasal passages.
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- METHODS FOR USING (2-IMIDAZOLIN-2-YLAMINO) QUINOXALINE DERIVATIVES
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A method of treating a mammal comprises administering to a mammal an effective amount to provide a desired therapeutic effect in the mammal of a compound selected from the group consisting of those having the formula: STR1 ,pharmaceutically acceptable acid addition salts thereof and mixtures thereof, wherein R 1 and R 4 are independently selected from the group consisting of H and alkyl radicals having 1 to 4 carbon atoms; the R 2 s are independently selected from H or alkyl radicals having 1 to 4 carbon atoms or are, together, oxo; the R 3 s are independently selected from H or alkyl radicals having 1 to 4 carbon atoms or are, together, oxo; the 2-imidazolin-2-ylamino group may be in any of the 5-, 6, 7-or 8-positions of the quinoxaline nucleus; and R 5, R 6 and R 7 each is located in one of the remaining 5-, 6-, 7-or 8-positions of the quinoxaline nucleus and is independently selected from the group consisting of Cl, Br, H and alkyl radicals having 1 to 3 carbon atoms. Such compounds, when administered to a mammal, provide desired therapeutic effects, such as reduction in peripheral pain, anesthetization of the central nervous system, constriction of one or more blood vessels, reduction in or prevention of at least one effect of ischemia, decongestion of one or more nasal passages, and reduction of at least one effect of an inflammatory disorder.
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- (2-imidazolin-2-ylamino) tetrahydroquinoxalines and methods for using same
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A compound selected from the group consisting of those having the formula: STR1 and pharmaceutically acceptable acid addition salts thereof, wherein R1 wherein R1 and R4 are independently selected from the group consisting of H and alkyl radicals containing 1 to 4 carbon atoms, R2 and R3 are independently selected from the group consisting of H, OXO, and alkyl radicals containing 1 to 4 carbon atoms, the 2-imidazolin-2-ylamino group may be in any of the 5-, 6-, 7- or 8- positions of the quinoxaline nucleus, and R5, R6 and R7 each is located in one of the remaining 5-, 6-, 7- or 8- positions of the qunioxaline nucleus and is selected from the group consisting of Cl, Br, H and alkyl radicals containing 1 to 3 carbon atoms. Such compounds, when administered to a mammal, provide desired therapeutic effects, such as alteration in the rate of fluid transport in the gastrointestinal tract, reduction in intraocular pressure, and increase in renal fluid flow.
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- SYNTHESIS OF 2-AMINO-3,8-DIMETHYLIMIDAZOQUINOXALINE (Me-IQx), A POTENT MUTAGEN ISOLATED FROM FRIED BEEF
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A potent mutagen, 2-amino-3,8-dimethylimidazoquinoxaline (Me-IQx), isolated from fried beef and its 3,7-dimethyl derivative were synthesized from 6-amino-3-methylquinoxaline and 6-amino-2-methylquinoxaline, respectively.These compounds showed strong mutagenic activity towards Salmonella typhimurium TA98 in the presence of S9 Mix.
- Kasai, Hiroshi,Shiomi, Tomoko,Sugimura, Takashi,Nishimura, Susumi
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p. 675 - 678
(2007/10/02)
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