Pyrazole derivatives and their uses thereof

Patent metadata

Field	Value
Publication number	US-10130609-B2
Application number	US-201414775449-A
Country	US
Kind code	B2
Filing date	Mar 12, 2014
Priority date	Mar 13, 2013
Publication date	Nov 20, 2018
Grant date	Nov 20, 2018

Abstract

The present disclosure relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof; wherein U, R1, R2, R3 and Q are as defined herein. The disclosure also provides a method for treating or preventing a method for the prevention, treatment and/or alleviation of one or more autoimmune or alloimmune disease, pharmaceutical compositions and combination comprising a therapeutically effective amount of a compound, as defined herein.

First claim

The invention claimed is:

1. A compound of formula:

or a pharmaceutically acceptable salt thereof; wherein
U is an alkylene residue of 1-4 members wherein one or two non-consecutive carbon atom is optionally independently replaced by O or NR10;
Q is

wherein each R1 is independently H, alkyl, amino or halogen;
each R2 is H;
each R3 is independently aryl, -alkyl-aryl, cycloalkyl, or -alkyl-cycloalkyl; and
R4 is hydroxyl, hydroxyalkyl or halogen;
R10 is H or a lower alkyl;
wherein each of the alkyl and aryl is optionally substituted.

2. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein R1 is H or alkyl.

3. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein R1 is C1-3 alkyl.

4. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein R3 is C6-10-aryl, —C1-2alkyl-C6-10aryl, C5-6-cycloalkyl, or —C1-2alkyl-C5-6cycloalkyl.

5. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein R3 is phenyl, CH 2 -phenyl; cyclopentyl; cyclohexyl, CH 2 -cyclopentyl; CH 2 -cyclohexyl; CH 2 —COOH or CH 2 CH 2 NH 2 .

6. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein U is an alkylene residue of 1-4 members wherein one carbon atom is optionally independently replaced by O.

7. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein U is an alkylene residue of 2-3 members, wherein one carbon atom is replaced by O or NR10.

8. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein U is CH 2 —CH 2 , CH 2 ; CH 2 —O, O—CH 2 ; or CH 2 —NH—CH 2 .

9. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein Q is

and R4 is hydroxyl.

10. A pharmaceutical composition comprising a compound as defined in claim 1 or a pharmaceutically acceptable salt thereof; in combination with one or more pharmaceutically acceptable carrier or excipient.

11. A compound of formula:

or a pharmaceutically acceptable salt thereof; wherein
U is CH 2 —CH 2 or CH 2 ;
R1 is independently an alkyl of 1-3 carbon atoms,
R2 is H;
R3 is phenyl, or benzyl; and
R4 is hydroxyl ;
wherein each of the alkyl is optionally substituted.

12. The compound or a pharmaceutically acceptable salt thereof of claim 1 , having the formula:

wherein:
U is CH 2 , CH 2 —CH 2 , CH 2 —O, O—CH 2 ; or CH 2 —NH—CH 2 ;
each R1 is independently an alkyl of 1-3 carbon atoms;
R2 is H;
R3 is independently C6-10-aryl, —C1-2alkyl-C6-10aryl, C5-6-cycloalkyl, —C1-2alkyl-C5-6cycloalkyl or C1-6 substituted alkyl; and
R4 is hydroxyl;
wherein each of the alkyl and aryl is optionally substituted.

13. A compound having the formula

Cpd #
Formula

14

15

18

20

24

28

32

37

41

47

48

50

Assignees

• Canadian Blood Services
• Univ Health Network

Inventors

• Branch Donald R
• Kotra Lakshmi P

Classifications

• C07D403/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/4155 Primary

  non condensed and containing further heterocyclic rings · CPC title

• C07D231/12

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

• C07D403/12

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