Compounds useful for treating diseases caused by retroviruses

Patent metadata

Field	Value
Publication number	US-9827237-B2
Application number	US-201414902935-A
Country	US
Kind code	B2
Filing date	Jul 4, 2014
Priority date	Jul 5, 2013
Publication date	Nov 28, 2017
Grant date	Nov 28, 2017

Abstract

Methods for preventing or treating retroviral infection not HIV and/or for preventing, inhibiting or treating a disease caused by the retroviral infection include contacting a cell with compound (I)

wherein:

means a pyridazine, pyrimidine or pyrazine group, R independently represent a hydrogen atom, halogen atom or group chosen among a —CN, hydroxyl, —COOR 1 , (C 1 -C 3 )fluoroalkyl, (C 1 -C 3 )fluoroalkoxy, —NO 2 , —NR 1 R 2 , (C 1 -C 4 )alkoxy, phenoxy and (C 1 -C 3 )alkyl group, the alkyl being optionally mono-substituted by hydroxyl group, n is 1, 2 or 3, n′ is 1 or 2, R′ is a hydrogen atom, halogen atom or group chosen among (C 1 -C 3 )alkyl group, hydroxyl group, —COOR 1 group, —NO 2 group, —NR 1 R 2 group, morpholinyl or morpholino group, N-methylpiperazinyl group, (C 1 -C 3 )fluoroalkyl group, (C 1 -C 4 )alkoxy group and —CN group, Z is N or C, Y is N or C, X is N or C, W is N or C, T is N or C, U is N or C.

First claim

The invention claimed is:

1. A method for inhibiting RNA splicing of HTLV-1 comprising administering a compound to a subject in need thereof, at least one compound of formula (I):

wherein:

is an aromatic ring wherein V is C or N and when V is N, V is in an ortho, meta or para position with respect to Z such that the ring respectively forms a pyridazine, a pyrimidine or a pyrazine,
R independently represents a hydrogen atom, a halogen atom or a group chosen among a —CN group, a hydroxyl group, a —COOR 1 group, a (C 1 -C 3 )fluoroalkyl group, a (C 1 -C 3 )fluoroalkoxy group, a —NO 2 group, a —NR 1 R 2 group, a (C 1 -C 4 )alkoxy group, a phenoxy group and a (C 1 -C 3 )alkyl group, said alkyl group being optionally mono-substituted by a hydroxyl group,
R 1 and R 2 are independently a hydrogen atom or a (C 1 -C 3 )alkyl group,
n is 1, 2 or 3,
n′ is 1 or 2,
R′ is a hydrogen atom, a halogen atom or a group chosen among a (C 1 -C 3 )alkyl group, a hydroxyl group, a —COOR 1 group, a —NO 2 group, a —NR 1 R 2 group, a morpholinyl or a morpholino group, a N-methylpiperazinyl group, a (C 1 -C 3 )fluoroalkyl group, a (C 1 -C 4 )alkoxy group and a —CN group,
R″ is a hydrogen atom or a (C 1 -C 4 )alkyl group,
Z is N or C,
Y is N or C,
X is N or C,
W is N or C,
T is N or C,
U is N or C,
and wherein at most four of the groups V, T, U, Z, Y, X and W are N,
and at least one of the groups T, U, Y, X and W is N,
or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein
Z is N, V is C, Y is N, X is C, T is C, U is C and W is C,
Z is C, V is C, Y is N, X is C, T is C, U is C and W is C,
Z is N, V is C, Y is C, X is N, T is C, U is C and W is C,
Z is N, V is C, Y is C, X is C, T is C, U is C and W is N,
Z is N, V is N and is in the para position with respect to Z, Y is N, X is C, T is C, U is C and W is C
Z is C, V is N and is in the para position with respect to Z, Y is C, X is N, T is C, U is C and W is C,
Z is C, V is N and is in the meta position with respect to Z and is in a para position with respect to the bond linked to NR″, Y is N, X is C, T is C, U is C and W is C,
Z is C, V is N and is in the meta position with respect to Z and is in the para position with respect to the bond linked to NR″, Y is C, X is N, T is C, U is C and W is C,
Z is C, V is C, Y is C, X is N, T is C, U is C and W is C,
Z is C, V is C, Y is N, X is N, T is C, U is C and W is C,
Z is N, V is N and is in the meta position with respect to Z and in an ortho position with respect to the bond linked to NR″, Y is N, X is C, T is C, U is C and W is C,
Z is N, V is N and is in the para position with respect to Z, Y is C, X is C, T is C, U is C and W is N,
Z is N, V is N and is in the para position with respect to Z, Y is C, X is N, T is C, U is C and W is C,
Z is N, V is C, Y is N, X is N, T is C, U is C and W is C,
Z is N, V is N and is in the meta position with respect to Z and is in the ortho position with respect to the bond linked to NR″, Y is N, X is N, T is C, U is C and W is C,
Z is C, V is C, Y is C, X is C, T is N, U is C and W is C,
Z is N, V is C, Y is C, X is C, T is N, U is C and W is C, or
Z is N, V is C, Y is C, X is C, T is C, U is N and W is C.

3. The method of claim 1 , wherein
Z is N, V is C, Y is N, X is C, T is C, U is C and W is C,
Z is C, V is C, Y is N, X is C, T is C, U is C and W is C,
Z is N, V is C, Y is C, X is N, T is C, U is C and W is C,
Z is N, V is N and is in the para position with respect to Z, Y is N, X is C, T is C, U is C and W is C, or
Z is N, V is C, Y is N, X is N, T is C, U is C and W is C.

4. The method of claim 1 , wherein the compound of formula (I) is selected from the group consisting of:

wherein:
R independently represents a hydrogen atom, a halogen atom or a group chosen among a (C 1 -C 3 )alkyl group, a —CN group, a hydroxyl group, a —COOR 1 group, a (C 1 -C 3 )fluoroalkyl group, a —NO 2 group, a —NR 1 R 2 group and a (C 1 -C 3 )alkoxy group,
R′ is a hydrogen atom, a halogen atom or a group chosen among a (C 1 -C 3 )alkyl group, a —NO 2 group, a (C 1 -C 3 )alkoxy group and a —NR 1 R 2 group,
R 1 and R 2 are a hydrogen atom or a (C 1 -C 3 )alkyl group,

wherein:
R independently represents a hydrogen atom, a halogen atom or a group chosen among a (C 1 -C 3 )alkyl group, a —NR 1 R 2 group, a (C 1 -C 3 )fluoroalkoxy group, a —NO 2 group, a phenoxy group and a (C 1 -C 4 )alkoxy group,
R 1 and R 2 are independently a hydrogen atom or a (C 1 -C 3 )alkyl group,
R′ is a hydrogen atom, a halogen atom or a group chosen among a (C 1 -C 3 )alkyl group and a (C 1 -C 4 )alkoxy group,

wherein:
R independently represents a hydrogen atom or a group chosen among a (C 1 -C 3 )alkyl group, a (C 1 -C 3 )fluoroalkyl group, a —NR 1 R 2 group, a —COOR 1 group, a —NO 2 group and a (C 1 -C 3 )alkoxy group,
R′ is a hydrogen atom,
R 1 and R 2 are independently a hydrogen atom or a (C 1 -C 3 )alkyl group,

wherein:
R independently represents a hydrogen atom or a group chosen among a (C 1 -C 3 )alkyl group, a (C 1 -C 3 )fluoroalkyl group and a (C 1 -C 3 )alkoxy group,
R′ is a hydrogen atom,

wherein:
R is a hydrogen atom,
R′ is a hydrogen atom, a halogen atom or a group chosen among a (C 1 -C 3 )alkyl group and a (C 1 -C 3 )alkoxy group,

wherein:
R is a hydrogen atom,
R′ is a hydrogen atom,

wherein:
R is a hydrogen atom,
R′ is a hydrogen atom or a halogen atom,

wherein:
R is a hydrogen atom,
R′ is a hydrogen atom,

wherein:
R independently represents a hydrogen atom or a group chosen among a (C 1 -C 3 )fluoroalkoxy group and a (C 1 -C 3 )alkoxy group,
R′ is a hydrogen atom,

wherein:
R independently represents a hydrogen atom or a group chosen among a (C 1 -C 3 )fluoroalkoxy group and a (C 1 -C 3 )alkyl group,
R′ is a hydrogen atom,

wherein:
R is a hydrogen atom,
R′ is a hydrogen atom, a halogen atom or a (C 1 -C 3 )alkyl group,

wherein:
R is a hydrogen atom,
R′ is a hydrogen atom,

Assignees

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

Inventors

• Tazi Jamal
• Mahuteau-Betzer Florence
• Najman Romain
• Scherrer Didier
• Campos Noëlie
• Garcel Aude

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P31/14

  for RNA viruses · CPC title