RU2020143617A - PHENYL/PYRIDYL-N-PHENYL/PYRIDYL DERIVATIVES FOR THE TREATMENT OF RNA VIRUS INFECTION - Google Patents

Claims (146)

1. Compound of formula (Ie)

(Ie) where ring

and ring

are independently a phenylene or pyridylene group, Y ¹ represents an aryl group selected from a phenyl group, a pyridyl group, a pyrazinyl group, a pyridazinyl or pyrimidinyl group, wherein said aryl group is optionally substituted with one or two substituents selected from a halogen atom, a (C ₁ -C ₄ ) alkyl group, a cyano group , (C ₁ -C ₅ )alkoxy group, trifluoromethyl group, trifluoromethoxy group, -SO ₂ -NR _a R _b group, -SO ₃ H group, -OH group, -O-SO ₂ -OR _c group or -OP(= O)-(OR _c )(OR _d ), R _a , R _b , R _c and R _d independently represent a hydrogen atom or a (C ₁ -C ₄ ) alkyl group, X ² represents group -O-, group -NH-, group -S-, group -CO-NH-, group -NH-CO-NH-, -NH-CO- group, group -CH(OH)-, group -CH(COOH)NH-, group -CH(COOCH ₃ )NH-, -C (OH) (CH ₂ OH) -, group

, a divalent 5-membered heteroaromatic ring containing 1, 2, 3 or 4 heteroatoms such as triazole, tetrazole or oxadiazole, group -SO ₂ - or a -SO ₂ -NH- group, n is 0, 1, 2 or 3, m and m' are independently 0, 1 or 2, Y ² represents hydrogen atom, hydroxyl group, (C ₁ -C ₄ ) alkoxy group, -CHC(OH) ₂ , COOR _f , where R _f represents a hydrogen atom or a (C ₁ -C ₄ )alkyl group, morpholinyl group, dihydropyranyl group, group

, group

, group -PO(OR _f )(OR' _f ), where R _f and R' _f independently represent a hydrogen atom or a (C ₁ -C ₄ )alkyl group, oxetanyl group, group -Si(CH ₃ ) ₃ , -NHCOO-(C ₁ -C ₄ )alkyl group or a -CR ¹ R ² R ³ group, where R ¹ , R ² and R ³ independently represent a hydrogen atom, a fluorine atom or a (C ₁ -C ₄ )alkyl group, with no more than one of R ¹ , R ² and R ³ is a hydrogen atom, or R ¹ and R ² together with the carbon atom that carries them form a (C ₃ -C ₈ )cycloalkyl group, wherein said (C ₃ -C ₈ )cycloalkyl group is optionally substituted with one or two (C ₁ -C ₄ )alkyl groups, a halogen atom or a (C ₁ -C ₄ )alkoxy group, and said (C ₃ -C ₈ )cycloalkyl group is optionally interrupted at said R ¹ and/or R ² by an oxygen atom, or, alternatively, X ² -Y ² is a -CONR _c R _d group, where R _c and R _d together with the nitrogen atom form a heterocyclic group, optionally substituted with a hydroxy group or a (C ₁ -C ₄ ) alkyl group, R and R' are independently (C ₁ -C ₄ )alkyl group, -S-(C ₁ -C ₄ )alkyl group, (C ₃ -C ₆ ) cycloalkyl group, a halogen atom such as a fluorine atom, trifluoromethyl group, -SO ₂ (C ₁ -C ₄ )alkyl group, (C ₃ -C ₆ ) cycloalkenyl group, (C ₁ -C ₅ ) alkoxy group, group -SO ₂ -NR _a R _b , group -SO ₃ H or SO ₂ -CH ₃ , -OH group, -CONHR _g , where R _g represents a hydrogen atom or a (C ₁ -C ₄ )alkyl group, group -O-SO ₂ -OR _c , azetidinyl group, a morpholinyl group, or cyano group, R'' represents a hydrogen atom, a (C ₁ -C ₄ )alkyl group optionally substituted with a -COOH group, or any of its pharmaceutically acceptable salts, with the exception of the connection

. 2. The compound of formula (Ie) according to claim 1, where ring

and ring

both are a phenylene group, or a ring

is a pyridylene group, and the ring

is a phenylene group, or any of its pharmaceutically acceptable salts. 3. The compound of formula (Ie) according to claim 1 or 2, where R" represents a hydrogen atom, or any of its pharmaceutically acceptable salts. 4. The compound of formula (Ie) according to any one of paragraphs. 1-3, where Y ¹ represents an aryl group selected from a phenyl group, a pyridyl group, a pyrazinyl group, a pyridazinyl or pyrimidinyl group, wherein said aryl group is optionally substituted with one or two substituents selected from a halogen atom, a (C ₁ -C ₄ ) alkyl group, a cyano group , (C ₁ -C ₅ )alkoxy group, trifluoromethyl group, trifluoromethoxy group, or any of its pharmaceutically acceptable salts. 5. The compound of formula (Ie) according to any one of paragraphs. 1-4, where X ² represents group -O-, group -NH-, group -S-, group -CO-NH-, group -NH-CO-NH-, -NH-CO- group, a divalent 5-membered heteroaromatic ring containing 1, 2, 3 or 4 heteroatoms such as triazole, tetrazole or oxadiazole, group -SO ₂ - or -SO ₂ -NH- group, or any of its pharmaceutically acceptable salts. 6. The compound of formula (Ie) according to any one of paragraphs. 1-5, where Y ² represents hydrogen atom, hydroxyl group, a group -PO(OR _f )(R' _f ), where R _f and R' _f independently represent a hydrogen atom or a (C ₁ -C ₄ )alkyl group, or a -CR ¹ R ² R ³ group, where R ¹ , R ² and R ³ independently represent a hydrogen atom, a fluorine atom or a (C ₁ -C ₄ )alkyl group, with no more than one of R ¹ , R ² and R ³ is a hydrogen atom, or R ¹ and R ² together with the carbon atom that carries them form a (C ₃ -C ₈ )cycloalkyl group, wherein said (C ₃ -C ₈ )cycloalkyl group is optionally substituted with one or two (C ₁ -C ₄ )alkyl groups, a halogen atom or a (C ₁ -C ₄ )alkoxy group, and said (C ₃ -C ₈ )cycloalkyl group is optionally interrupted at said R ¹ and/or R ² by an oxygen atom, or any of its pharmaceutically acceptable salts. 7. The compound of formula (Ie) according to any one of paragraphs. 1-6, where R and R' are independently (C ₁ -C ₄ )alkyl group, (C ₃ -C ₆ ) cycloalkyl group, a halogen atom such as a fluorine atom, a trifluoromethyl group, or group -SO ₃ H or SO ₂ -CH ₃ , or any of its pharmaceutically acceptable salts. 8. The compound of formula (Ie) according to any one of paragraphs. 1-6, where ring

and ring

both are a phenylene group, R" represents a hydrogen atom, Y ¹ represents an aryl group selected from a phenyl group, a pyridyl group, a pyrazinyl group, a pyridazinyl or pyrimidinyl group, wherein said aryl group is optionally substituted with one or two substituents selected from a halogen atom, a (C ₁ -C ₄ ) alkyl group, a cyano group , (C ₁ -C ₅ )alkoxy group, trifluoromethyl group, trifluoromethoxy group, X ² represents group -O-, group -CO-NH-, group -NH-CO-NH-, -NH-CO- group, a divalent 5-membered heteroaromatic ring containing 1, 2, 3 or 4 heteroatoms such as triazole, tetrazole or oxadiazole, or -SO ₂ -NH- group, Y ² represents hydrogen atom, hydroxyl group, a group -PO(OR _f )(R' _f ), where R _f and R' _f independently represent a hydrogen atom or a (C ₁ -C ₄ )alkyl group, or a -CR ¹ R ² R ³ group, where R ¹ , R ² and R ³ independently represent a hydrogen atom, a fluorine atom or a (C ₁ -C ₄ )alkyl group, with no more than one of R ¹ , R ² and R ³ is a hydrogen atom, or R ¹ and R ² together with the carbon atom that carries them form a (C ₃ -C ₈ )cycloalkyl group, wherein said (C ₃ -C ₈ )cycloalkyl group is optionally substituted with one or two (C ₁ -C ₄ )alkyl groups, a halogen atom or a (C ₁ -C ₄ )alkoxy group, and said (C ₃ -C ₈ )cycloalkyl group is optionally interrupted at said R ¹ and/or R ² by an oxygen atom, and R and R' are independently (C ₁ -C ₄ )alkyl group, (C ₃ -C ₆ ) cycloalkyl group, a halogen atom such as a fluorine atom, trifluoromethyl group, group -SO ₃ H or SO ₂ -CH ₃ or morpholinyl group, or any of its pharmaceutically acceptable salts. 9. The compound of formula (Ie) according to any one of paragraphs. 1-3, where ring

and ring

both are a phenylene group, R" represents a hydrogen atom, Y ¹ represents a phenyl group or a pyridyl group, X ² represents group -O-, group -CO-NH-, -NH-CO- group, or a divalent 5-membered heteroaromatic ring containing 1, 2, 3 or 4 heteroatoms such as triazole, tetrazole or oxadiazole, Y ² represents a group -PO(OR _f )(R' _f ), where R _f and R' _f independently represent a hydrogen atom or a (C ₁ -C ₄ )alkyl group, or a -CR ¹ R ² R ³ group, where R ¹ , R ² and R ³ independently represent a hydrogen atom, a fluorine atom or a (C ₁ -C ₄ )alkyl group, with no more than one of R ¹ , R ² and R ³ represents a hydrogen atom, or R ¹ and R ² together with the carbon atom bearing them form a (C ₃ -C ₈ )cycloalkyl group, and R and R' are independently (C ₁ -C ₄ )alkyl group, (C ₃ -C ₆ )cycloalkyl group or morpholinyl group, or any of its pharmaceutically acceptable salts. 10. The compound of formula (Ie) according to claim 1, selected from 36

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or any of its pharmaceutically acceptable salts. 11. The use of compounds of formula (Ie) according to any one of paragraphs. 1-9 or any of the compounds (36)-(206) as defined in paragraph 10, or any of its pharmaceutically acceptable salts for the treatment and/or prevention of an RNA viral infection caused by an RNA virus belonging to group IV or V according to the Baltimore classification. 12. Use according to claim 12, where the compound is a compound of formula (Ie) according to any one of paragraphs. 1-9, and wherein the RNA viral infection caused by an RNA virus belonging to Baltimore Group IV or V is selected from RSV (respiratory syncytial virus), chikungunya, influenza, and dengue, and in particular from RSV , chikungunya and dengue. 13. Pharmaceutical composition containing at least one compound according to any one of paragraphs. 1-9 or any of its pharmaceutically acceptable salts, or at least any of the compounds (36)-(206) as defined in paragraph 10, or any of its pharmaceutically acceptable salts, and at least one pharmaceutically acceptable excipient . 14. The method of synthesis to obtain compounds of formula (Ie) according to any one of paragraphs. 1-9 or any of its pharmaceutically acceptable salts, or a compound as defined in claim 10, or any of its pharmaceutically acceptable salts, comprising at least the step of coupling a compound of formula (IIe)

(IIe) with a compound of formula (IIIe)

(IIIe), where Y ¹ , R, R', m, m', ring

, ring

, X ² , Y ² R _a and R _b are as defined in paragraph 1, X represents a chlorine atom, an iodine atom or a bromine atom, and Y ¹ represents a phenyl group, a pyridine group, a pyrazine group, a pyridazine group, or a pyrimidine group, in the presence of an inorganic base and diphosphine and in the presence of an organometallic catalyst, to obtain a compound of formula (Ie) according to any one of paragraphs. 1-9 or any of its pharmaceutically acceptable salts, or compounds as defined in paragraph 10, or any of its pharmaceutically acceptable salts.