IP Library › Granted Patent US 9,550,794
Granted Patent B2
US 9,550,794 · App. 14/766,291 · Granted Jan 24, 2017

Macrocyclic pyridazinone derivatives

Inventors: Catherine Jorand-Lebrun (Contamine-Sarzin, FR); Santosh Kulkarni (Bangalore, IN); Serge Christmann-Franck (Geneva, CH)
Assignee: MERCK PATENT GmbH
C07D498/18A61K31/504A61K45/06C07D471/22C07D487/18C07D487/22
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Quick Facts
Patent No.
US 9,550,794
App. No.
14/766,291
Granted
Jan 24, 2017
Kind
B2
Abstract

The present invention relates to compounds of formula (I) Wherein R1, R2, R3, R4, L and Z have the meaning given in claim 1 , and their use in the prophylaxis and treatment of diseases.

Claims (31)

1. A compound of formula (I):

wherein

R1, R3 denote each, independently of one another H, (CH 2 ) p CON(R5) 2 , OA, Hal, COOH, COOA, (CH 2 ) p NHCOA, (CH 2 ) p Het1, (CH 2 ) p NR2R5, or OH;

R2 denotes H or linear or branched alkyl with 1, 2 or 3 C atoms, wherein one or two H atoms of the alkyl group are optionally replaced by OR6, NR5R6, NHCOR5, CONR5R6;

R4 denotes H or A;

R5 denotes H or linear or branched alkyl with 1, 2 or 3 C atoms;

R6 denotes H or linear or branched alkyl with 1, 2 or 3 C atoms;

Z is absent or denotes Ar-diyl or Het-diyl;

L denotes (CH 2 ) n wherein one or two CH 2 groups are optionally replaced by O and/or a CH═CH-group, and/or wherein one or two H atoms are optionally replaced by OR2, NR2R5 or Het1;

Ar-diyl denotes 1,2-, 1,3- or 1,4-phenylen optionally substituted with from 1 to 5 groups independently selected from the group consisting of Hal, CN, —CF 3 , —OCF 3 , OH, O-A, SO 2 -A, COOH, COOA, —CO-A, O-phenyl, SO 2 -phenyl, SO 2 —CF 3 , Het2 and A;

Het-diyl denotes an unsaturated, saturated or aromatic 5- or 6-membered heterocycle having 1 to 2 N, O and/or S atoms, which are optionally unsubstituted or mono-, di- or trisubstituted by Hal, CN, —CF 3 , —OCF 3 , O-A, SO 2 -A, COOH, COOA, —CO-A, O-phenyl, SO 2 -phenyl, SO 2 —CF 3 , Het2 and/or A;

A denotes an unbranched or branched alkyl having 1 to 10 C atoms, in which 1 to 5 H atoms are optionally replaced by F and/or in which one or two non-adjacent CH 2 groups are optionally replaced by O;

Het1 denotes morpholinyl, piperidinyl or pyrrolidinyl;

Het2 denotes morpholinyl, piperidinyl or pyrrolidinyl;

Hal denotes F, Cl, Br, I;

n denotes 1, 2, 3, 4, 5 or 6;

p denotes 0, 1 or 2

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R4 is H or methyl.

3. The compound of claim 1 , wherein Het-diyl denotes pyridine-diyl, pyrimidine-diyl, pyridazin-diyl, pyrazol-diyl, imidazol-diyl, piperidin-diyl or pyrrolidin-diyl, each of which is unsubstituted or disubstituted by A.

4. The compound of claim 1 , wherein Z is 1,3-phenylen, which is unsubstituted or monosubstituted by A, Hal, OH, or OA.

5. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition, comprising: the compound of claim 1 and at least one pharmaceutically acceptable carrier or excipient.

7. A kit consisting of separate packs of:

(a) an effective amount of the compound of claim 1 , and

(b) an effective amount of a further medicament active ingredient.

8. The pharmaceutical composition of claim 6 , further comprising: a medicament effective for treatment of an inflammatory disease or an immune disorder.

9. The pharmaceutical composition of claim 8 , further comprising an immunomodulating agent.

10. A process for synthesizing the compound of claim 1 , the process comprising:

macrocyclizing a compound of formula (II) to obtain the compound of claim 1 , wherein R1, R2, R3, R4, Z and L are the same as in claim 1 and A1 is H, Li, Na or K:

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 1, 2015
From: JORAND-LEBRUN, CATHERINE; KULKARNI, SANTOSH; CHRISTMANN-FRANCK, SERGE
To: MERCK PATENT GMBH
Reel/Frame 037173/0459 →
Priority Claims (1)
EP 13154391 · Feb 7, 2013 · regional
Continuity (1)
Related Publication 20150376206A1 · Dec 31, 2015