Arylsulfonanilide phosphates
AssigneeTularik Inc.
InventorJonathan B. Houze
Life of this patent
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Abstract
The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.
Claims79
A compound having the formula:
- 21
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is a member selected from the group consisting of hydrogen, (C1-C6)alkyl and (C1- C6)heteroalkyl;
- R2 and R3 are each independently selected from the group consisting of hydrogen, halogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, —OR11 and —NR11R12, wherein R11 and R12 are each independently selected from the group consisting of hydrogen, (C1-C8)alkyl and (C1-C8)heteroalkyl;
- or
- R2 and R3, when attached to adjacent carbon atoms, can be linked together to form a fused 5-, 6- or 7-membered ring;
- R4 and R5 are each independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, aryl, heteroaryl, aryl(C1-C4)alkyl, aryl(C1-C4)heteroalkyl, heteroaryl(C1-C4)alkyl and heteroaryl(C1-C4)heteroalkyl, and are optionally linked together to form a 5-, 6- or 7-membered ring;
- or
- R4 represents a single bond to the phenyl ring bearing the phosphoryl group and R5 is selected from the group consisting of hydrogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, aryl, heteroaryl, aryl(C1-C4)alkyl, aryl(C1-C4)heteroalkyl, heteroaryl(C1-C4)alkyl and heteroaryl(C1-C4)heteroalkyl;
- and
- Ar is a substituted aryl group selected from the group consisting of:
- 22
- wherein
- X1 and X2 are each independently selected from the group consisting of F, Cl and Br.
A method of treating or preventing a disease state characterized by abnormally high levels of low density lipoprotein particles or cholesterol in the blood, or by an abnormally high level of cell proliferation, which method comprises administering to a mammalian subject in need thereof a therapeutically effective amount of a composition comprising a compound of formula:
- 37
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is a member selected from the group consisting of hydrogen, (C1-C6)alkyl and (C1-C6)heteroalkyl;
- R2 and R3 are each independently selected from the group consisting of hydrogen, halogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, —OR11 and —NR11R12, wherein R11 and R12 are each independently selected from the group consisting of hydrogen, (C1-C8)alkyl and (C1-C8)heteroalkyl;
- or
- R2 and R3, when attached to adjacent carbon atoms, can be linked together to form a fused 5-, 6- or 7-membered ring;
- R4 and R5 are each independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, aryl, heteroaryl, aryl(C1-C4)alkyl, aryl(C1-C4)heteroalkyl, heteroaryl(C1-C4)alkyl and heteroaryl(C1-C4)heteroalkyl, and are optionally linked together to form a 5-, 6- or 7-membered ring;
- or
- R4 represents a single bond to the phenyl ring bearing the phosphoryl group and R5 is selected from the group consisting of hydrogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, aryl, heteroaryl, aryl(C1-C4)alkyl, aryl(C1-C4heteroalkyl, heteroaryl(C1-C4)alkyl and heteroaryl(C1-C4)heteroalkyl;
- and
- Ar is a substituted aryl group selected from the group consisting of:
- 38
- wherein
- X1 and X2 are each independently selected from the group consisting of F, Cl and Br.
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound having the formula:
- 40
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is a member selected from the group consisting of hydrogen, (C1-C6)alkyl and (C1-C6)heteroalkyl;
- R2 and R3 are each independently selected from the group consisting of hydrogen, halogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, —OR11 and —NR11R12, wherein R11 and R12 are each independently selected from the group consisting of hydrogen, (C1-C8)alkyl and (C1-C8)heteroalkyl;
- or
- R2 and R3, when attached to adjacent carbon atoms, can be linked together to form a fused 5-, 6- or 7-membered ring;
- R4 and R5 are each independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, aryl, heteroaryl, aryl(C1-C4)alkyl, aryl(C1-C4)heteroalkyl, heteroaryl(C1-C4)alkyl and heteroaryl(C1-C4)heteroalkyl, and are optionally linked together to form a 5-, 6- or 7-membered ring;
- or
- R4 represents a single bond to the phenyl ring bearing the phosphoryl group and
- R5 is selected from the group consisting of hydrogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, aryl, heteroaryl, aryl(C1-C4)alkyl, aryl(C1-C4)heteroalkyl, heteroaryl(C1-C4)alkyl and heteroaryl(C1-C4)heteroalkyl;
- and
- Ar is a substituted aryl group selected from the group consisting of:
- 41
- wherein
- X1 and x2 are each independently selected from the group consisting of F, Cl and Br.
Dependencies are inferred from the claim text.