Derivatives of tartaric acid

Patent metadata

Field	Value
Publication number	US-2016326090-A1
Application number	US-201415037667-A
Country	US
Kind code	A1
Filing date	Dec 4, 2014
Priority date	Dec 5, 2013
Publication date	Nov 10, 2016
Grant date	—

Abstract

The present invention relates to novel compounds, e.g. for use as a medicament. In particular, the present invention relates to novel medicaments, preferably in the treatment and/or prevention of systemic diseases, autoimmune diseases, and/or inflammatory diseases, for example multiple sclerosis and psoriasis.

First claim

1 . Compound according to Formula (I) or Formula (II)

wherein R 1 is OR 1′ or NR 1″ R 1′″ wherein R 1′ is hydrogen, alkyl with 1 to 6 carbon atoms or cyclic alkyl with 3 to 6 carbon atoms, or wherein R 1″ and R 1′″ independently are hydrogen, alkyl with 1 to 6 carbon atoms or cyclic alkyl with 3 to 6 carbon atoms, and
R 2 is OR 2′ or NR 2″ R 2′″ wherein R 2′ is hydrogen, alkyl with 1 to 6 carbon atoms or cyclic alkyl with 3 to 6 carbon atoms, or wherein R 2″ and R 2′″ independently are hydrogen, alkyl with 1 to 6 carbon atoms or cyclic alkyl with 3 to 6 carbon atoms
or
wherein R 1 and R 2 together are NR 12 forming a cyclic imide, wherein R 12 is hydrogen, alkyl with 1 to 6 carbon atoms or cyclic alkyl with 3 to 6 carbon atoms;
or

wherein
R 3 and R 4 are each independently —(CH 2 ) n′ —OR 5 or —(CH 2 ) n″ —CO—R 6 , wherein
n′ and n″ are each independently 1, 2 or 3,
R 5 is hydrogen or trans —CO—CH═CH—COOCH 3 ,
R 6 is OR 7 wherein R 7 is hydrogen or alkyl with 1 to 4 carbon atoms, or NR 8 R 9 , wherein R 8 and R 9 are each independently hydrogen or alkyl with 1 to 4 carbon atoms.

2 . Compound according to claim 1 , wherein R 1 and R 2 in Formula (I) are OR 1′ and OR 2′ wherein R 1′ and R 2 ′ can be independently hydrogen, alkyl with 1 to 6 carbon atoms or cyclic alkyl with 3 to 6 carbon atoms.

3 . Compound according to claim 1 , wherein in Formula (I) R 1 and R 2 are OR 1′ and OR 2′ and wherein OR 1′ and OR 2′ are identical.

4 . Compound according to claim 1 , wherein R 1 and R 2 in Formula (I) are OR 1 ′ and OR 2′ and wherein R 1 ′ and R 2′ are hydrogen, ethyl or isopropyl.

5 . Compound according to claim 1 , wherein the compound according to Formula (I) is selected from the compounds according to any one of Formulae (Ia) to (Ic)

6 . Compound according to claim 1 , wherein R 1 and R 2 in Formula (I) are NR 1″ R 1′″ and NR 2″ R 2′″ , wherein R 1″ , R 1′″ , R 2″ and R 2′″ independently are hydrogen, alkyl with 1 to 6 carbon atoms or cyclic alkyl with 3 to 6 carbon atoms.

7 . Compound according to claim 6 , wherein one of R 1″ and R 1′″ and one of R 2″ and R 2′″ are hydrogen.

8 . Compound according to claim 1 , wherein R 1 and R 2 in Formula (I) together are NR 12 forming a cyclic imide, wherein R 12 is hydrogen or alkyl with 1 to 3 carbon atoms.

9 . Compound according to claim 1 , wherein R 1 and R 2 in Formula (II) are not both trans —(CH 2 ) 2 —O—CO—CH═CH—COOCH 3 .

10 . Compound according to claim 1 , wherein one of R 3 and R 4 in Formula (II) is trans —(CH 2 ) 2 —O CO—CH═CH—COOCH 3 .

11 . Compound according to claim 1 represented by Formula (IIa)

12 . Compound according to claim 1 , wherein R 3 and R 4 in Formula (II) are each independently —(CH 2 ) n′ —OR 5 or —(CH 2 ) n″ —CO—R 6 , wherein
n′ and n″ are each independently 1, 2 or 3,
R 5 is hydrogen,
R 6 is OR 7 wherein R 7 is hydrogen or alkyl with 1 to 4 carbon atoms, or NR 8 R 9 , wherein R 8 and R 9 are each independently hydrogen or alkyl with 1 to 4 carbon atoms.

13 . Compound according to claim 1 , wherein in R 3 and R 4 are each independently —(CH 2 ) n′ —OR 5 , wherein
n′ is independently 1, 2 or 3, and
R 5 is hydrogen.

14 . Compound according to claim 1 , wherein in R 3 and R 4 both are —(CH 2 ) 2 —OH represented by Formula (IIb)

15 . Compound according to claim 1 for use as a medicament.

16 . Compound according to claim 1 for use in the treatment of systemic diseases, autoimmune diseases or inflammatory diseases, preferably for the use in the treatment of multiple sclerosis or psoriasis.

17 . Pharmaceutical composition comprising a compound according to claim 1 .

18 . Pharmaceutical composition according to claim 17 , comprising
(i) 0.01 to 10 mmol of a compound according to any one of the claims 1 to 14 and (ii) optionally pharmaceutical excipients.

19 . Pharmaceutical composition according to claim 17 , wherein the composition is a solid oral dosage form.

20 . Pharmaceutical composition according to claim 17 , wherein the in-vitro drug release after 2 hours is less than 10%, measured according to USP, Apparatus II, paddle, 0.1 N HCl, 37° C., 50 rpm.

21 . A method for treating and/or preventing systemic diseases, autoimmune diseases and/or inflammatory diseases, preferably multiple sclerosis or psoriasis, comprising administering to a subject in need thereof a therapeutically effective amount of the compound according to claim 1 .

Assignees

• Rationpharm Gmbh
• Ratiopharm Gmbh

Inventors

• Albrecht Wolfgang
• Selig Roland
• Rabe Sebastian
• Maier Annemarie
• Guserle Richard

Classifications

• C07C219/08

  having at least one of the hydroxy groups esterified by a carboxylic acid having the esterifying carboxyl group bound to an acyclic carbon atom of an acyclic unsaturated carbon skeleton · CPC title

• C07C69/708 Primary

  Ethers · CPC title

• C07C69/60 Primary

  Maleic acid esters; Fumaric acid esters · CPC title

• C07C69/67

  of saturated acids · CPC title