Condensed ring pyridine compounds as subtype-selective modulators of sphingosine-1-phosphate-2 (S1P2) receptors
AssigneeAllergan, Inc.
InventorsWenkiu K. Fang, Liming Wang, Evelyn G. Corpuz, Ken Chow, Wha-Bin Im
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Abstract
The invention provides compounds represented by the formula I, each of which compounds may have sphingosine-1-phosphate receptor agonist and or antagonist biological activity, wherein these compounds selected from the group consisting of wherein A, B, C, D, X, Y, Z and R3 are defined in the specification. Said compounds are useful for treating a disease or condition of a mammal selected from the group consisting of ocular diseases; systemic vascular barrier related diseases; allergies and other inflammatory diseases; cardiac diseases or conditions; fibrosis; pain and wounds.
Claims7
Compounds represented by the formula I having sphingosine-1-phosphate receptor antagonist biological activity:
- wherein:
- wherein A is a direct bond or (CR) and B, C and D are independently selected from the group consisting of (CR) and N, wherein R is H or alkyl, provided however, not all, of B, C and D are N and, when A is a direct bond, D is (CR);
- R3 is selected from the group consisting of alkyl:
- X is selected from the group consisting of O, NR4 and CR4R5, wherein R4 and R5 are independently selected from the group consisting of H and alkyl,
- Y is selected from the group consisting of O or S and
- Z is a substituted aryl ring.
A compound represented by the formula II, or a pharmaceutically acceptable salt thereof:
- wherein R1 and R2 are independently selected from the group consisting of H and alkyl, methoxy, hydroxyl, halogen, nitrile, and trifluoromethyl;
- R3 is independently selected from the group consisting of alkyl, methoxy, hydroxyl, halogen, nitrile, and trifluoromethyl;
- D is CR or N;
- R is H or alkyl;
- X is O, NR4, CR4R5, where R4 and R5 are independently selected from the group consisting of H and alkyl, e.g. lower alkyl and may have from 1 to 10 carbons, and may be cyclic or branched chain alkyl having 3 to 10 carbons, methoxy, hydroxyl, F, Br, I, nitrile, and trifluoromethyl;
- Y is O or S,
- Z is a substituted aryl ring, having the following structure:
- wherein R6 and R7 are independently selected from the group consisting of alkyl and may include from 1 to 10 carbons, and may be cyclic or branched chain alkyl having 3 to 10 carbons, methoxy, hydroxyl, halogen, nitrile, and trifluoromethyl;
- and
- E is N or CR.
A compound represented by the formula III, or a pharmaceutically salt thereof:
- wherein R1 and R2 are independently selected from the group consisting of H and alkyl, methoxy, hydroxyl, halogen, nitrile, and trifluoromethyl;
- R3 is independently selected from the group consisting of alkyl, methoxy, hydroxyl, halogen, nitrile, and trifluoromethyl;
- X is O, NR4, CR4R5, where R4 and R5 are independently selected from the group consisting of H and alkyl, e.g. lower alkyl and may have from 1 to 10 carbons, and may be cyclic or branched chain alkyl having 3 to 10 carbons, methoxy, hydroxyl, F, Br, I, nitrile, and trifluoromethyl;
- Y is O or S;
- R is H, methoxy or alkyl;
- Z is a substituted aryl ring, having the following structure:
- wherein R6 and R7 are independently selected from the group consisting of alkyl and may include from 1 to 10 carbons, and may be cyclic or branched chain alkyl having 3 to 10 carbons, methoxy, ethoxy, propoxy, butoxy, hydroxyl, halogen, nitrile, and trifluoromethyl;
- and
- E is N or CR.
Dependencies are inferred from the claim text.