Pyrazole derivatives and their uses thereof

Patent metadata

Field	Value
Publication number	US-11090288-B2
Application number	US-201816141092-A
Country	US
Kind code	B2
Filing date	Sep 25, 2018
Priority date	Mar 13, 2013
Publication date	Aug 17, 2021
Grant date	Aug 17, 2021

Abstract

The present disclosure relates to a compound of formula

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 method for treating or preventing one or more autoimmune or alloimmune disease comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula:

or a pharmaceutically acceptable salt thereof; wherein
U is an alkylene residue of 1-5 members, wherein one or two non-consecutive carbon atom is optionally independently replaced by O or NR 10 ;
Q is

wherein each R 1 is independently H, alkyl, amino or halogen;
each R 2 is independently H, alkyl, amino or halogen;
each R 3 is independently aryl, -alkyl-aryl, cycloalkyl, -alkyl-cycloalkyl or substituted alkyl;
R 4 is hydroxyl, hydroxyalkyl or halogen;
R 10 is H or a lower alkyl;
wherein each alkyl and aryl is optionally substituted; and
wherein immune thrombocytopenia (ITP) is prevented in the subject and/or immune thrombocytopenia, refractory immune thrombocytopenia, autoimmune haemolytic anemia, Graves' disease, myasthenia gravis, bullous pemphigoid, pemphigus vulgaris, rheumatic fever, Goodpasture's syndrome, alloantibody-mediated haemolytic transfusion reaction, disease of the fetus and newborn or pernicious anemia is treated in the subject.

2. The method of claim 1 , wherein R 2 is H.

3. The method of claim 1 , wherein R 1 is H or alkyl.

4. The method of claim 1 , wherein R 3 is C6-10-aryl, —C1-2alkyl-C6-10aryl, C5-6-cycloalkyl, —C1-2alkyl-C5-6cycloalkyl or C1-6 substituted alkyl.

5. The method of claim 1 , wherein U is an alkylene residue of 1-5 members or U is an alkylene residue of 2-5 members, wherein one carbon atom is replaced by 0 or NR 10 .

6. The method of claim 1 , wherein R 3 is phenyl, CH 2 -phenyl, cyclopentyl, cyclohexyl, CH 2 -cyclopentyl, CH 2 -cyclohexyl, CH 2 —COOH or CH 2 CH 2 NH 2 .

7. The method of claim 1 , wherein U is —CH 2 —, CH 2 —CH 2 , CH 2 —O, O—CH 2 , CH 2 —NH—CH 2 , O—CH 2 —CH 2 —O, or O—.

8. The method of claim 1 , wherein Q is

and R 4 is hydroxyl.

9. A method according to claim 1 , wherein said compound is a compound of formula:

or a pharmaceutically acceptable salt thereof; wherein
U is CH 2 —CH 2 , CH 2 —O, O—CH 2 , CH 2 —NH—CH 2 , O—CH 2 —CH 2 —O, or —O—;
each R 1 is independently an alkyl of 1-3 carbon atoms;
R 2 is H;
each R 3 is independently phenyl, or benzyl, and
wherein each alkyl is optionally independently substituted.

10. A method according to claim 1 , wherein said compound is a compound of formula:

or a pharmaceutically acceptable salt thereof; wherein
U is CH 2 —CH 2 or CH 2 ;
R 1 is independently an alkyl of 1-3 carbon atoms,
R 2 is H;
R 3 is phenyl, or benzyl; and
R 4 is hydroxyl;
wherein each alkyl is optionally substituted.

11. A method according to claim 1 , wherein said compound is

Cpd #
Formula

14

15

18

20

24

28

or

32

37

41

47

48

Assignees

• Canadian Blood Services
• Univ Health Network

Inventors

• Branch Donald R
• Kotra Lakshmi P

Classifications

• A61K45/06

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

• C07D403/06

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

• C07D231/20

  One oxygen atom attached in position 3 or 5 · CPC title

• C07D231/22

  with aryl radicals attached to ring nitrogen atoms · CPC title

• A61K31/4155 Primary

  non condensed and containing further heterocyclic rings · CPC title