Aryl-n-aryl derivatives for treating a RNA virus infection

Patent metadata

Field	Value
Publication number	US-11739073-B2
Application number	US-201917259483-A
Country	US
Kind code	B2
Filing date	Jul 9, 2019
Priority date	Jul 9, 2018
Publication date	Aug 29, 2023
Grant date	Aug 29, 2023

Abstract

A compound:wherein X1 represents an alkenylene group, a —NH—CO— group, a —CO—NH— group, Y1 represents an aryl group selected from pyridyl, pyrazinyl or pyrimidinyl, X2 represents —O—, —CO—NH—, —NH—CO—NH—, —OCH2—, —NH—CO—, a divalent 5-membered heteroaromatic ring comprising 1 to 4 heteroatoms or —SO2—NH—, and Y2 represents a hydrogen atom, a hydroxyl group, a morpholinyl group, a piperidinyl group, optionally substituted by a (C1-C4)alkyl group, a piperazinyl group, optionally substituted by a (C1-C4)alkyl group, or —CR1R2R3 or alternatively X2—Y2 represents —CONRcRd, wherein Rc and Rd form, together with the nitrogen atom a heterocyclic ring, optionally substituted by one or two (C1-C4)alkyl group, by a cyclopentyl group thus forming a spirocyclopentyl, or by a trifluoromethyl group, or any of its pharmaceutically acceptable salt, for use in the treatment and/or prevention of a RNA virus infection caused by a RNA virus belonging to group IV or V of the Baltimore classification.

First claim

The invention claimed is:

1. A method for treating a subject for a RNA virus infection caused by a virus belonging to group IV or V of the Baltimore classification comprising administering to a patient in need thereof of a therapeutically effective quantity of a compound of formula (I):

wherein:

ring and

ring independently mean a phenylene or a pyridylene group,
X 1 represents an alkenylene group, a —NH—CO— group, a —CO—NH— group,
Y 1 represents an aryl group selected from a pyridyl group, a pyrazinyl group or a pyrimidinyl group,
X 2 represents
a —O— group,
a —CO—NH— group,
a —NH—CO—NH— group,
a —OCH 2 — group,
a —NH—CO— group,
a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms
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
a hydrogen atom,
a hydroxyl group,
a morpholinyl group,
a piperidinyl group, optionally substituted by a (C 1 -C 4 )alkyl group,
a piperazinyl group, optionally substituted by a (C 1 -C 4 )alkyl group,
or
a —CR 1 R 2 R 3 group, wherein R 1 , R 2 and R 3 independently represent a hydrogen atom, a fluorine atom or a (C 1 -C 4 )alkyl group, being understood that no more than one of R 1 , R 2 and R 3 is a hydrogen atom, or R 1 and R 2 form together with the carbon atom bearing them a (C 3 -C 8 )cycloalkyl group, said (C 3 -C 8 )cycloalkyl group being optionally substituted by one or two (C 1 -C 4 )alkyl group, halogen atom or (C 1 -C 4 )alkoxy group and said (C 3 -C 8 )cycloalkyl group being optionally interrupted on said R 1 and/or R 2 by an oxygen atom,

or alternatively X 2 —Y 2 represents a group —C(═O)—NR C R d , wherein R c and R d form, together with the nitrogen atom a saturated heterocyclic ring, optionally substituted by one or two (C 1 -C 4 )alkyl group, by a cyclopentyl group thus forming a spirocyclopentyl derivative, or by a trifluoromethyl group,
R and R′ independently represent
a (C 1 -C 4 )alkyl group,
a (C 3 -C 6 )cycloalkyl group,
a halogen atom,
a (C 1 -C 5 )alkoxy group,
a —SO 2 —NR a R b group,
a —SO 3 H group,
a —OH group, or
a —O—SO 2 —OR c group,

provided that when X 1 is a —NH—CO— group, Y 1 may further be a phenyl group optionally substituted by one or two substituent(s) selected from a halogen atom, a (C 1 -C 4 )alkyl group, a cyano group, a (C 1 -C 5 )alkoxy group, a trifluoromethyl group, a trifluoromethoxy group, a —SO 2 —NR a R b group, a —SO 3 H group, a —OH group, a —O—SO 2 —OR c group or a —O—P(═O)—(OR c )(OR d ) group,

or any pharmaceutically acceptable salt thereof.

2. The method according to claim 1 , wherein the divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms is a triazole or an oxadiazole.

3. The method according to claim 1 , wherein

ring and

ring both represent a phenylene group or

ring represents a pyridylene group and

ring represents a phenylene group.

4. The method according to claim 1 , wherein
Y 1 represents
a 2-pyridinyl group or a 3-pyridinyl group,
a pyrimidinyl group or a pyrazinyl group, with one of the nitrogen atoms being in ortho position with respect to X 1 ,

provided that when X 1 is a —NH—CO— group, Y 1 may further be a phenyl group.

5. The method according to claim 1 , wherein
X 2 represents
a —O— group,
a —CO—NH— group,
a divalent triazole,
or
a —SO 2 —NH— group.

6. The method according to claim 1 , wherein
Y 2 represents
a hydroxyl group,
a morpholinyl group,
a piperidinyl group, optionally substituted by a (C 1 -C 4 )alkyl group,
a piperazinyl group, optionally substituted by a (C 1 -C 4 )alkyl group,
or
a —CR 1 R 2 R 3 group, wherein R 1 , R 2 and R 3 independently represent a hydrogen atom, a fluorine atom or a (C 1 -C 4 )alkyl group, being understood that no more than one of R 1 , R 2 and R 3 is a hydrogen atom, or R 1 and R 2 form together with the carbon atom bearing them a (C 3 -C 8 )cycloalkyl group.

7. The method according to claim 1 , wherein
R and R′ independently represent
a (C 1 -C 4 )alkyl group,
a (C 3 -C 6 )cycloalkyl group,
a halogen atom, or
a (C 1 -C 5 )alkoxy group.

8. The method according to claim 1 , wherein

ring and

ring both represent a phenylene group,
Y 1 represents a 2-pyridinyl group provided that when X 1 is a —NH—CO— group,
Y 1 may further be a phenyl group,
X 2 represents a —O— group, a —CO—NH— group,
Y 2 represents
a —CR 1 R 2 R 3 group, wherein R 1 , R 2 and R 3 independently represent a hydrogen atom, or a (C 1 -C 4 )alkyl group, being understood that no more than one of R 1 , R 2 and R 3 is a hydrogen atom, or R 1 and R 2 form together with the carbon atom bearing them a (C 3 -C 8 )cycloalkyl group and R 3 represents a hydrogen atom or a (C 1 -C 4 )alkyl group, or a morpholinyl group, and

R and R′ independently represent a hydrogen atom, (C 1 -C 4 )alkyl group, or a (C 3 -C 6 )cycloalkyl group.

9. The method according to claim 1 , wherein the compound of formula (I) is a compound of formula (Ia)

wherein
Y 1 , R, R′, m, m′,

ring, X 2 , n and Y 2 are as defined in claim 1 ,
or any pharmaceutically acceptable salt thereof.

10. The method according to claim 9 , wherein

ring is a phenylene group or a pyridylene group,
Y 1 represents a 2-pyridyl group, a 3-pyridyl group or a pyrazinyl group,
n is 1, 2 or 3, m is 0,
R′ is a halogen atom, a (C 1 -C 2 )alkoxy group or a (C 1 -C 2 )alkyl group,
X 2 represents a —CO—NH— group, a —SO 2 NH— group or a divalent triazole,
Y 2 represents
a morpholinyl group, a piperidinyl group or a piperazinyl group, optionally substituted by a (C 1 -C 4 )alkyl group,
a —CR 1 R 2 R 3 group, wherein R 1 , R 2 and R 3 independently represent a hydrogen atom or a (C 1 -C 2 )alkyl group, being understood that no more than one of R 1 , R 2 and R 3 is a hydrogen atom, or R 1 and R 2 form together with the carbon atom bearing them a (C 3 -C 6 )cycloalkyl group,
or alternatively X 2 —Y 2 represents a group —C(═O)—NR c R d , wherein R c and R d form, together with the nitrogen atom a saturated heterocyclic ring, optionally substituted by one or two (C 1 -C 4 )alkyl group, by a cyclopentyl group thus forming a spirocyclopentyl derivative, or by a trifluoromethyl group.

11. The method according to claim 1 , wherein the compound of formula (I) is a compound of

Assignees

• Abivax
• Centre Nat Rech Scient
• Univ Montpellier
• Inst Curie

Inventors

• Scherrer Didier
• Tazi Jamal
• Mahuteau-Betzer Florence
• Najman Romain
• Santo Julien
• Apolit Cécile

Classifications

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• C07D401/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• A61P31/12

  Antivirals · CPC title

• C07C233/65

  having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals · CPC title

• C07C237/40

  having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring · CPC title