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

Patent metadata

Field	Value
Publication number	US-12247018-B2
Application number	US-201917259370-A
Country	US
Kind code	B2
Filing date	Jul 9, 2019
Priority date	Jul 9, 2018
Publication date	Mar 11, 2025
Grant date	Mar 11, 2025

Abstract

A compound of formula (Ic)

wherein X 2 represents a —CO—NR k — group, wherein R k represents a hydrogen atom or a methyl group, a —NH—CO—NH— group, a —OCH 2 — group, a —CH(OH)— group, a —NH—CO— group, a —O— group, a —O—(CH 2 ) s —O—, a —CO— group, a —SO 2 — group, a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms, a —NH—SO 2 — or a —SO 2 —NH— group; Y 2 represents a hydrogen atom, a halogen atom, a hydroxyl group, a (C 1 -C 4 )alkoxy group, a

a

group, a

group, a morpholinyl group, optionally substituted by a (C 1 -C 4 )alkyl group, a piperazinyl group, a piperidinyl group, or a —CR 1 R 2 R 3 group, or any of its pharmaceutically acceptable salt.

First claim

The invention claimed is:

1. A compound of formula (Ic) or a pharmaceutically acceptable salt thereof:

Z is phenylene or pyridylene,
Z′ is phenylene or pyridylene, where the ring is connected to the adjacent —C(O)— and —N(H)— in the para-orientation,
Z″ is —CH 2 — or —CO—,
R g and R h are each independently H or (C 1 -C 4 )alkyl,
X 2 is —CO—NR k —, —NH—CO—NH—, —OCH 2 —, —CH(OH)—, —NH—CO—, —O—, —O—(CH 2 ) s —O—, —CO—, —SO 2 —, —NH—SO 2 —, —NH—, —SO 2 —NH—, or a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms,
wherein R k is H or methyl,
n is 0, 1, 2, or 3,
s is 2 or 3,
R and R′ are each independently (C1-C4)alkyl optionally interrupted by —SO2- or —SO—, (C 3 -C 6 )cycloalkyl, trifluoromethyl, halogen, (C 1 -C 5 )alkoxy, —SO 2 —NR a R b , —SO 3 H, —OH, —O—SO 2 —OR c , or —O—P(═O)—(OR c )(OR d ),
wherein m and m′ are independently 0, 1, or 2 and
R a , R b , R c and R d are independently H or (C 1 -C 4 )alkyl;
and
Y 2 is H, halogen, hydroxyl, (C i -C 4 )alkoxy, piperazinyl, piperidinyl, —CR 1 R 2 R 3 ,

or morpholinyl optionally substituted by (C 1 -C 4 )alkyl,
wherein R f is (C 1 -C 4 )alkyl or cyano,
R q and R′ q are each independently H or methyl, and
R 1 , R 2 , and R 3 are each independently H, F, or (C 1 -C 4 )alkyl, said (C 1 -C 4 )alkyl optionally substituted by trifluoromethyl and/or hydroxyl, with the proviso that no more than one of R 1 , R 2 , and R 3 is a hydrogen atom,
or R 1 and R 2 are taken together with the carbon atom bearing them form a (C 3 -C 8 )cycloalkyl optionally interrupted by 1 or 2 oxygen ring atom(s) and optionally substituted by one or two (C 1 -C 4 )alkyl, halogen, hydroxy, or (C 1 -C 4 )alkoxy.

2. A compound of formula (Ic) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms is selected from a triazole, an imidazole, a tetrazole and an oxadiazole.

3. The compound of formula (Ic) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Z and Z′ both are phenylene or Z is pyridylene and Z′ is phenylene.

4. The compound of formula (Ic) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R g is H and R h is H or (C 1 -C 4 )alkyl.

5. The compound of formula (Ic) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein X 2 is —CO—NR k —, —NH—CO—, —O—, —CO—, —CH(OH)—, —SO 2 —, —NH—, —NH—SO 2 —, —SO 2 —NH—, or a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms.

6. The compound of formula (Ic) or a pharmaceutically acceptable salt thereof according to claim 5 , wherein the divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms is selected from triazole, imidazole, tetrazole, and oxadiazole.

7. The compound of formula (Ic) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Y 2 is H, halogen, (C 1 -C 4 )alkoxy, —CR 1 R 2 R 3 ,

or morpholinyl optionally substituted by (C 1 -C 4 )alkyl.

8. The compound of formula (Ic) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R and R′ are each independently (C1-C4)alkyl optionally interrupted by —SO2- or —SO—, (C 3 -C 6 )cycloalkyl, trifluoromethyl, or halogen.

9. The compound of formula (Ic) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Z and Z′ both are phenylene or Z is pyridylene and Z′ is phenylene,
m and n are each independently 0 or 1,
X 2 is —CO—NH—, —CO—N(CH 3 )—, —NH—, —NH—CO—, —O—, —CO—, —CH(OH)—, —SO 2 —, divalent triazole, divalent imidazole, divalent tetrazole, or divalent oxadiazole;
Y 2 is H, —CR 1 R 2 R 3 ,

or morpholinyl optionally substituted by (C 1 -C 4 )alkyl; and
R and R′ are each independently (C1-C4)alkyl, (C 3 -C 6 )cycloalkyl, trifluoromethyl, or halogen.

10. The compound of formula (Ic) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Z and Z′ both are phenylene,
m is 0 and n is 1,
X 2 is —CO—NH—, —O—;
Y 2 is —CR 1 R 2 R 3 , wherein R 1 , R 2 , and R 3 are each independently H or (C 1 -C 4 )alkyl with the proviso that no more than one of R 1 , R 2 , and R 3 is a hydrogen atom,
or R 1 and R 2 are taken together with the carbon atom bearing them form a (C 3 -C 8 )cycloalkyl; and
R′ is (C 1 -C 4 )alkyl or (C 3 -C 6 )cycloalkyl.

11. A compound of formula (Ic) according to claim 1 selected from

(Ic)

19

20

21

22

23

24

25

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

• C07D403/12

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

• C07D239/22

  with hetero atoms directly attached to ring carbon atoms · CPC title

• C07D239/16

  acylated on said nitrogen atoms · CPC title

• C07D241/12

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07D239/42

  One nitrogen atom (nitro radicals C07D239/30) · CPC title