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The invention belongs to the field, of pharmaceutical chemistry and particularly provides a quinoxaline signal pathway inhibitor as well as a preparation method and application, of the quinoxaline signal pathway inhibitor. , The preparation method can prepare more quinoxaline compounds, has good anti-cancer effect, both in vitro and in vivo, and has good application prospects, in the aspects of anticancer new drug research and development and the like. (by machine translation)

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Thirty-three quinoxalines bearing an aminobenxoyl or aminobenzoylglutammate group on position 2 and various substituents on position 3,6,7 of the heterocycle were prepared in order to evaluate in vitro anticancer activity. Preliminary screening performed at NCI showed that most derivatives exhibited a moderate to strong growth inhibition activity on various tumor panel cell lines between 10-5 and 10-4 molar concentrations. Interesting selectivities were also recorded between 10-8 and 10-6. Among the series examined one compound (29) which was the most active also exhibited both in vitro anti-HIV protection and antifungal activity while in other two (31.37) the antifungal activity was prevailing.

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The preparation method and, the 3 – application of the diarylamine quinoxaline-3 – 2,formamide derivative disclosed by the invention have the advantages of 3 – high yield and low production cost, and the preparation method and, the application thereof have a high medical value and 3 – a wide market prospect. (by machine translation)

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A novel series of 3-ethoxyquinoxalin-2-carboxamides were designed as per the pharmacophoric requirements of 5-HT3 receptor antagonist using ligand-based approach. The desired carboxamides were synthesized from the key intermediate, 3-ethoxyquinoxalin-2-carboxylic acid by coupling with appropriate amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole (HOBt). The 5-HT 3 receptor antagonism was evaluated in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT3 agonist, 2-methy-5-HT, which was expressed in the form of pA2 values. Compound 6h (3-ethoxyquinoxalin-2-yl)(4-methylpiperazin-1-yl)methanone was found to be the most active compound, which expressed a pA2 value of 7.7. In forced swim test, the compounds with higher pA2 value exhibited good anti-depressant-like activity and compounds with lower pA2 value failed to show activity as compared to the vehicle-treated group.

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We identified a new series of quinoxaline-2-carboxylic acid derivatives, targeting the human proviral integration site for Moloney murine leukemia virus-1 (HsPim-1) kinase. Seventeen analogues were synthesized providing useful insight into structure-activity relationships studied. Docking studies realized in the ATP pocket of HsPim-1 are consistent with an unclassical binding mode of these inhibitors. The lead compound 1 was able to block HsPim-1 enzymatic activity at nanomolar concentrations (IC50 of 74 nM), with a good selectivity profile against a panel of mammalian protein kinases. In vitro studies on the human chronic myeloid leukemia cell line KU812 showed an antitumor activity at micromolar concentrations. As a result, compound 1 represents a promising lead for the design of novel anticancer targeted therapies.

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The compounds of this invention are designated as quinoxalinyl esters of carbamimidothioic acids and exhibit the pharmacological properties of preventing gastric ulcers, reducing gastric secretions and lowering blood pressure. The compounds have the following structural formula: STR1 in which Q is hydrogen or nitro;

A is hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, carbomethoxy, carbethoxy, carbopropoxy, carbisopropoxy, carbobutoxy, carbisobutoxy, or carbo-t-butoxy; and< P>

R 1, R 2, and R 3 are, independently, hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, t-butyl, allyl, or R. sup.1 and R 3 may be concatenated with a carbon chain having 4 carbon atoms with R 2 then being hydrogen; except that, when A and Q are hydrogen, R 1, R 2, and R. sup.3 may not all be hydrogen; and with the further exception that, where A is methyl and R 1, R 2, and Q are all hydrogen, R 3 may not be ethyl;

or a pharmaceutically acceptable salt thereof.

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The present invention provides a tri-substituted pyrimidine compound having an excellent PDE10 inhibitory activity. The present invention relates to a tri-substituted pyrimidine compound represented by the following formula [I0] or a pharmaceutically acceptable salt thereof, a method for preparing the same, and use of said compound for PDE10 inhibitor, and a pharmaceutical composition comprising said compounds as an active ingredient: wherein: either one of X1 and X2 is N, and the other of X1 and X2 is CH; A is *-CH?CH?, *-C(Alk)=CH?, *-CH2?CH2? or *-O?CH2? (* is a bond with R1); Alk is a lower alkyl group; Ring B is an optionally substituted nitrogen-containing aliphatic heterocyclic group; R1 is an optionally substituted quinoxalinyl or an optionally substituted quinolyl; Y0 is mono- or di-substituted amino group, or a pharmaceutically acceptable salt thereof.

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A novel series of 3-ethoxyquinoxalin-2-carboxamides were designed as per the pharmacophoric requirements of 5-HT3 receptor antagonist using ligand-based approach. The desired carboxamides were synthesized from the key intermediate, 3-ethoxyquinoxalin-2-carboxylic acid by coupling with appropriate amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole (HOBt). The 5-HT 3 receptor antagonism was evaluated in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT3 agonist, 2-methy-5-HT, which was expressed in the form of pA2 values. Compound 6h (3-ethoxyquinoxalin-2-yl)(4-methylpiperazin-1-yl)methanone was found to be the most active compound, which expressed a pA2 value of 7.7. In forced swim test, the compounds with higher pA2 value exhibited good anti-depressant-like activity and compounds with lower pA2 value failed to show activity as compared to the vehicle-treated group.

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The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit Respiratory Syncytial Virus (RSV). The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from RSV infection. The invention also relates to methods of treating an RSV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

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Among a new series of 28 3-carboxy or carbethoxy quinoxalines bearing a substituted benzylamino or N-[4-(aminomethyl)benzoyl]glutamate group on position 2 of the ring and various substituents at C-6, 7 positions, 21 were selected at the National Cancer Institute for evaluation of their in vitro anticancer activity. The results obtained seem to confirm that the carboxy or carbethoxy group on position 3 is not helpful, with a few exceptions, for the anticancer activity. Copyright (C) 2000 Elsevier Science S.A.

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