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- Nachgewiesen in: USPTO Patent Applications
- Sprachen: English
- Document Number: 20120184557
- Publication Date: July 19, 2012
- Appl. No: 13/203427
- Application Filed: March 11, 2010
- Assignees: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (PARIS, FR), INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) (PARIS, FR), UNIVERSITE CLAUDE BERNARD LYON 1 (VILLEURBANNE, FR), UNIVERSITE PARIS DESCARTES (PARIS, FR)
- Claim: 1. A compound of formula (I) below, or a pharmaceutically acceptable salt thereof: [chemical expression included] where: R1 is a (C1-C6)alkyl group or a (C3-C6)cycloalkyl group; R2 is: a (C1-C6)alkyl group, a (C3-C6)cycloalkyl group, a (C1-C6)alkenyl group, a (C1-C6)fluoroalkyl group, a (C1-C3)fluoroalkoxy group, or a (C1-C6)alkoxy(C1-C6)alkyl group, substituted: (i) with one to three hydroxyl groups, or (ii) with an NRaRb group, where Ra and Rb are independently a hydrogen atom or a (C1-C3)alkyl group: or a pyrrolidinylmethyl group substituted with one to three hydroxyl groups; R2 is: hydrogen, a (C1-C6)alkyl group, a (C3-C6)cycloalkyl group, a (C1-C6)alkenyl group, a (C1-C6)fluoroalkyl group, a (C1-C3)fluoroalkoxy group, or a (C1-C6)alkoxy(C1-C6)alkyl group, substituted: (i) with one to three hydroxyl groups, or with an NRaRb group; or a pyrrolidinylmethyl group substituted with one to three hydroxyl groups; said R2 group and R9 group independently being optionally substituted with an —OCOR3 group, in which R3 is a natural or unnatural amino acid derivative or a piperidyl group of formula (B): [chemical expression included] where: R4 is a hydrogen, a halogen atom, a (C1-C3)alkyl group, a hydroxy(C1-C3)alkyl group or an —NRaRb group; and R5 is a hydrogen, a (C1-C3)alkyl group, an —N(Me)2 group, a piperidyl group or a morpholinyl, group; alternatively, R2 and R9 together form, with the nitrogen atom which bears them, a heterocycle selected from the group consisting of a pyrrolidinyl group, a piperidinyl group, a piperazinyl group, and a piperidinylpiperidinyl group, the heterocycles optionally being substituted with one to three groups selected from the group consisting of: hydroxyl; and (C1-C6)alkyl or (C1-C6)alkoxy(C1-C6)alkyl substituted with: (i) one to three hydroxyl groups, or (ii) an NRaRb group; X and Y are independently a phenyl group or a heteroaryl group, said heteroaryl and phenyl groups optionally being substituted with one or two groups independently selected from the group consisting of a (C1-C2)alkyl group, a (C1-C2)alkoxy group, a halogen atom, a (C1-C2)fluoroalkyl group, a (C1-C2)fluoroalkoxy group, a hydroxyl group, a —COOH group, a —CONHR6 group, and an —NRaRb group; R6 is a hydrogen or a (C1-C3)alkyl group; and said heteroaryl group is selected from the group consisting of a thienyl group, a pyridyl group, a pyrimidinyl group, a thiazolyl group, a pyrrolyl group, and a furanyl group.
- Claim: 2. The compound as claimed in claim 1, wherein R3 is one of the following formulae (a-1) to (a-5), or enantiomers thereof: [chemical expression included] where Boc is a tert-butoxycarbonyl group and Ac is an acetyl group.
- Claim: 3. The compound as claimed in claim 1, wherein at least one of the X and Y groups is substituted with one or two substitution groups, said substitution group being selected from the group consisting, of a (C1-C2)alkyl group, a (C1-C2)fluoroalkyl group, a (C1-C2)alkoxy group, a (C1-C2)fluoroalkoxy group, a halogen atom, a hydroxyl group, and a —COOH group.
- Claim: 4. The compound as claimed in claim 1, wherein R2 is one of the following formulae: [chemical expression included] [chemical expression included] [chemical expression included] [chemical expression included] or R2 and R9 together form, with the nitrogen atom which bears them, one of the following formulae: [chemical expression included] [chemical expression included]
- Claim: 5. The compound as claimed in claim 1, wherein the compound is of a formula (Ia), or a pharmaceutically acceptable salt thereof: [chemical expression included] where: R2 and R9 are independently a (C1-C6)alkyl group, a (C1-C6)fluoroalkyl group, a (C1-C3)fluoroalkoxy group, or a (C1-C6)alkoxy(C1-C6)alkyl group, said group being substituted with one to three hydroxyl groups, R9 optionally being a hydrogen atom; or R2 and R9 together form, with the nitrogen atom which bears them, a piperidin-1-yl or piperidin-4-ylpiperidin-1-yl group, said group being substituted with one to three (C1-C6)alkyl groups substituted with a hydroxyl group; R7 and R8 are independently a hydrogen atom, a (C1-C2)alkyl group, a (C1-C2)fluoroalkyl group, a (C1-C2)alkoxy group, a (C1-C2)fluoroalkoxy group, a halogen atom, a hydroxyl group, or a —COOH group; G is —CH═ or —N═; and when G is —CH═, W and Z are either simultaneously —CH═, or one is —N═ and the other is —CH═, and when G is —N═, then W and Z are —CH═.
- Claim: 6. The compound as claimed in claim 1, wherein the compound is of a formula (Ib), or a pharmaceutically acceptable salt thereof: [chemical expression included] where: R2 is a (C1-C6)alkyl group, a C1-C6)fluoroalkyl group, a (C1-C3)fluoroalkoxy group, or a (C1-C6)alkoxy(C1-C6)alkyl group, said group being substituted with one to three hydroxyl groups; and R7 and C8 are independently a hydrogen atom, a (C1-C2)alkyl group, a (C1-C2)fluoroalkyl group, a (C1-C2)alkoxy group, a (C1-C2)fluoroalkoxy group, a halogen atom, a hydroxyl group, or a —COOH group.
- Claim: 7. The compound as claimed in claim 1, wherein the compound is of a formula (Ic), or a pharmaceutically acceptable salt thereof: [chemical expression included] where: R9 is a hydrogen atom and R2 is a (C1-C6)alkyl group, a (C1-C6)fluoroalkyl group, a (C1-C3)fluoroalkoxy group, or a (C1-C6)alkoxy(C1-C6)alkyl group, said group being substituted with one to three hydroxyl groups; or R2 and R9 together form, with the nitrogen atom which bears them, a piperidin-1-yl or piperidin-4-ylpiperidin-1-yl group, said group being substituted with one to three (C1-C6)alkyl groups substituted with a hydroxyl groups; and R7 and R8 are independently a hydrogen atom, a (C1-C2)alkyl group, a (C1-C2)fluoroalkyl group, a (C1-C2)alkoxy group, a (C1-C2)fluoroalkoxy group, a halogen atom, a hydroxyl group, or a —COOH group.
- Claim: 8. The compound as claimed in claim 1, wherein the compound is of a formula (Id), or a pharmaceutically acceptable salt thereof: [chemical expression included] where: R2 group, a (C1-C6)alkyl group, a (C1-C6)fluoroalkoxy group, or a (C1-C6)alkoxy(C1-C6)alkyl group, said group being substituted with one to three hydroxyl groups, R9 optionally being a hydrogen atom; and R7 is a hydrogen atom, a (C1-C2)alkyl group, a (C1-C2)fluoroalkoxy group, a (C1-C2)alkoxy group, a (C1-C2)fluoroalkoxy group, a halogen atom, a hydroxyl group, or a —COOH group.
- Claim: 9. The compound as claimed in claim 1, wherein: the compound is of a formula (Ie): [chemical expression included] where: R2 is a (C1-C6)alkyl group, a (C1-C6)fluoroalkyl group, a (C1-C3)fluoroalkoxy group, or a (C1-C6)alkoxy(C1-C6)alkyl group, said group being substituted with one to three hydroxyl groups; or the compound is of a formula (If): [chemical expression included] where: R2 is a (C1-C6)alkyl group, a (C1-C6)fluoroalkyl group, a (C1-C3)fluoroalkoxy group, or a (C1-C6)alkoxy(C1-C6)alkyl group, said group being substituted with one to three hydroxyl groups.
- Claim: 10. The compound as claimed in claim 1, wherein the compound is chosen from one of the following compounds: (R)-2-(1-hydroxybut-2-ylamino)-8-isopropyl-4-(4 phenylbenzylamino)pyrazolo[1,5-a]-1,3,5-triazine; (R)-2-(1-hydroxybut-2-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; Fumarate salt of (R)-2-(1-hydroxybut-2-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (S)-2-(1-hydroxybut-2-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; Fumarate salt of (S)-2-(1-hydroxybut-2-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (R)-2-(1-hydroxybut-2-ylamino)-8-isopropyl-4-[4-(thiophen-3-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (S)-2-(1-hydroxybut-2-ylamino)-8-isopropyl-4-[4-(thiophen-3-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (S)-2-(1,2-dihydroxypropan-3-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; Fumarate salt of (S)-2-(1,2-dihydroxypropan-3-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (R)-2-(1,2-dihydroxypropan-3-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; Fumarate salt of (R)-2-(1,2-dihydroxypropan-3-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (2R,3R)-2-(1,3-dihydroxybut-2-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; Fumarate salt of (2R,3R)-2-(1,3-dihydroxybut-2-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (2S,3S)-2-(1,3-dihydroxybut-2-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; Fumarate salt of (2S,3S)-2-(1,3-dihydroxybut-2-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (2R,3R)-2-(1,3-dihydroxybut-2-ylamino)-8-isopropyl-4-[4-(thiophen-3-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; 2-(1,3-dihydroxyprop-2-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; Fumarate salt of 2-(1,3-dihydroxyprop-2-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; 2-(1,3-dihydroxyprop-2-ylamino)-8-isopropyl-4-[4-(pyridin-3-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (S)-2-(1-hydroxybut-2-ylamino)-8-isopropyl-4-[4-(pyridin-3-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (2S,3S)-2-(1,3-dihydroxybut-2-ylamino)-8-isopropyl-4-[4-phenyl(pyridin-3-yl)methylamino]pyrazolo[1,5-a]-1,3,5-triazine; (S)-2-(1-hydroxybut-2-ylamino)-8-isopropyl-4-[4-phenyl(pyridin-3-yl)methylamino]pyrazolo[1,5-a]-1,3,5-triazino; (2R,3R)-2-(1,3-dihydroxybut-2-ylamino)-8-isopropyl-4-[4-phenyl(pyridin-3-yl)methylamino]pyrazolo[1,5-a]-1,3,5-triazine; 2-(1,3-dihydroxyprop-2-ylamino)-8-isopropyl-4-[4-phenyl(pyridin-3-yl)methylamino]pyrazolo[1,5-a]-1,3,5-triazine; (R)-2-(1-hydroxy-4-methylpent-2-ylamino)-8-isopropyl-4-[4-phenyl(pyridin-3-yl)methylamino]pyrazolo[1,5-a]-1,3,5-triazine; (S)-2-(1-hydroxy-4-methylpent-2-ylamino)-8-isopropyl-4-[4-phenyl(pyridin-3-yl)methylamino]pyrazolo[1,5-a]-1,3,5-triazine; (S)-2-(1-hydroxy-3,3-dimethylbut-2-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (S)-2-(1-hydroxy-3-methylbut-2-ylamino)-8-isopropyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; 2-[4-[1-[8-isopropyl-4-[[4-(pyridin-2-yl)phenyl]methylamino]pyrazolo[1,5-a]-1,3,5-triazin-2-yl]piperidin-4-yl]piperidin-1-yl]ethanol; 2-[4-[8-isopropyl-4-[[4-(pyridin-2-yl)phenyl]methylamino]pyrazolo[1,5-a]-1,3,5-triazin-2-yl]piperazin-1-yl]ethanol; (R)-2-(1,2-dihydroxypropan-3-ylamino)-8-ethyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; [(2R)-3-[[8-ethyl-4-[[4-(2-pyridyl)phenyl]methylamino]pyrazolo[1,5-a][1,3,5]triazin-2-yl]amino]-2-hydroxypropyl](2R)-2-Bocamino-3-methylbutanoate; [(2R)-3-[[8-ethyl-4-[[4-(2-pyridyl)phenyl]methylamino]pyrazolo[1,5-a][1,3,5]triazin-2-yl]amino]-2-hydroxypropyl](2R)-2-amino-3-methylbutanoate in the form of a base or of a salt; (S)-2-(1,2-dihydroxypropan-3-ylamino)-8-ethyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (S)-8-ethyl-2-(1-hydroxybut-2-ylamino)-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; (R)-8-ethyl-2-(1-hydroxybut-2-ylamino)-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; 2-(1,3-dihydroxyprop-2-ylamino)-8-ethyl-4-[4-(pyridin-2-yl)benzylamino]pyrazolo[1,5-a]-1,3,5-triazine; 2-[(2S)-1-[8-ethyl-4-[[4-(2-pyridyl)phenyl]methylamino]pyrazolo[1,5-a][1,3,5]triazin-2-yl]-2-piperidyl]ethanol; 2-[[8-ethyl-4-[[4-(2-pyridyl)phenyl]methylamino]pyrazolo[1,5-a][1,3,5]triazin-2-yl]-(2-hydroxyethyl)amino]ethanol; (2R,3R)-2-[[8-ethyl-4-[[4-(2-pyridyl)phenyl]methylamino]pyrazolo[1,5-a][1,3,5]triazin-2-yl]amino]butane-1,3-diol; (2S,3S)-2-[[8-ethyl-4-[[4-(2-pyridyl)phenyl]methylamino]pyrazolo[1,5-a][1,3,5]triazin-2-yl]amino]butane-1,3-diol; and their optional salts of pharmaceutically acceptable acids.
- Claim: 11. A process for preparing a compound of formula (I) as claimed in claim 1, comprising: reacting a compound of formula (IIa) with meta-chloroperbenzoic acid in an oxidation reaction to obtain a sulfone: [chemical expression included] directly using the sulfone obtained in a nucleophilic substitution reaction in the presence of a primary amine of formula NH—R2R9 at a temperature of from 100 to 180° C., to produce a compound of formula (I); or reacting a compound of formula (IIb) with a metal, to give a compound of formula (IIa): [chemical expression included] reacting the compound of formula (IIb) with meta-chloroperbenzoic acid in an oxidation reaction, directly using the sulfone obtained in a nucleophilic substitution reaction in the presence of a primary amine of formula NH—R2R9, so as to give a compound of formula (III): [chemical expression included] and subjecting the compound to a coupling reaction catalyzed by a metal, to produce a compound of formula (I).
- Claim: 12. A compound of formula (II): [chemical expression included] where: R1 is a (C1-C6)alkyl group or a (C3-C6)cycloalkyl group; and X and Y are independently a phenyl group or a heteroaryl group, said heteroaryl and phenyl groups optionally being substituted with one or two groups independently selected from the group consisting of a (C1-C2)alkyl group, a (C1-C2)alkoxy group, a halogen atom, a (C1-C2)fluoroalkyl group, a (C1-C2)fluoroalkoxy group, a hydroxyl group, a —COOH group, a —CONHR6 group, and an —NRaRb group.
- Claim: 13. A medicament comprising a compound of formula (I) as claimed in claim 1.
- Claim: 14. A pharmaceutical composition comprising a compound of formula (I) as claimed in claim 1, and at least one pharmaceutically acceptable excipient.
- Claim: 15. A method for treating or preventing the following diseases: cancers, chronic neurodegenerative diseases, acute neurodegenerative diseases, stroke, epilepsy, pulmonary inflammations, arthritis, viral infections (AIDS, Herpes), pain treatment, diabetes, kidney diseases leukemias, or parasites, the method comprising administering to a patient in need thereof the compound of formula (I) as claimed in claim 1.
- Current U.S. Class: 514/245
- Current International Class: 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 07; 61
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