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US 6,583,161 B1Granted
Benzenesulfonamides and benzamides as therapeutic agents
AssigneeTularik Inc.
InventorJulio C. Medina
Life of this patent
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Abstract
The invention provides compounds, compositions and methods relating to novel aromatic 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.
Claims50
A compound having the formula:
- wherein,
- A is C—R1;
- B is N;
- wherein R1 is selected from the group consisting of hydrogen, halogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, —OR6, —NR6R7, —S(O)mR6, —CN, —NO2, —S(O)nNR6R7, and —N3, wherein R6 and R7 are independently selected from hydrogen, (C1-C8)alkyl, and (C1-C8)heteroalkyl;
- subscript m is an integer of from 0 to 3;
- and subscript n is an integer of from 1 to 2;
- R2 and R3 are members independently selected from the group consisting of —OR8, —SR8 and —NR8R9, wherein R8 and R9 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl and (C1-C6)heteroalkyl;
- R4 is a member selected from the group consisting of hydrogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, —OR10, —SR10 and —NR10R11, wherein R10 and R11 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl and (C1-C6)heteroalkyl;
- and optionally, R1 is linked to R2 to form a fused ring, R2 is linked to R3 to form a fused ring, or R2 is linked to both of R1 and R3 to form two additional fused rings;
- X is a member selected from the group consisting of —S(O)p— and —C(O)—, wherein subscript p is 1 or 2;
- Y is a member selected from the group consisting of a single bond, —CH2— and —N(R12)—, wherein R12 is selected from the group consisting of hydrogen, (C1-C6)alkyl, (C1-C6)heteroalkyl and arylalkyl;
- and
- Z is a member selected from the group consisting of aryl and arylalkyl, optionally having from 1 to 5 substituents independently selected from the group consisting of halogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, —CN, —NO2, —OR′, —SR′, —OC(O)NR′R″, NR″C(O)R′, —NR″C(O)2R′, —NH—C(NH2)═NH, —NR′C(NH2)═NH, —NH—C(NH2)═NR′, —NR′R″, perfluoro(C1-C8)alkoxy, and perfluoro(C1-C8)alkyl, wherein R′ and R″ are independently selected from the group consisting of hydrogen, (C1-C8)alkyl, and (C1-C8)heteroalkyl.
10 more elements
A composition comprising a pharmaceutically acceptable excipient and a compound having the formula:
- wherein,
- A is C—R1;
- B is N;
- wherein R1 is selected from the group consisting of hydrogen, halogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, —OR, —NR6R7, —S(O)mR6, —CN, —NO2, —S(O)nNR6R7, and —N3, wherein R6 and R7 are independently selected from hydrogen, (C1-C8)alkyl, and (C1-C8)heteroalkyl;
- subscript m is an integer of from 0 to 3;
- and subscript n is an integer of from 1 to 2;
- R2 and R3 are members independently selected from the group consisting of —OR8, —SR8 and —NR8R9, wherein R8 and R9 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl and (C1-C6)heteroalkyl;
- R4 is a member selected from the group consisting of hydrogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, —OR10, —SR10 and —NR10R11, wherein R10 and R11 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl and (C1-C6)heteroalkyl;
- and optionally, R1 is linked to R2 to form a fused ring, R2 is linked to R3 to form a fused ring, or R2 is linked to both of R1 and R3 to form two additional fused rings;
- X is a member selected from the group consisting of —S(O)p— and —C(O)—, wherein subscript p is 1 or 2;
- Y is a member selected from the group consisting of a single bond, —CH2— and —N(R12)—, wherein R12 is selected from the group consisting of hydrogen, (C1-C6)alkyl, (C1-C6)heteroalkyl and arylalkyl;
- and
- Z is a member selected from the group consisting of aryl and arylalkyl, optionally having from 1 to 5 substituents independently selected from the group consisting of halogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, —CN, —NO2, —OR′, —SR′, —OC(O)NR′R″, NR″C(O)R′, —NR″C(O)2R′, —NH—C(NH2)═NH, —NR′C(NH2)═NH, —NH—C(NH2)═NR′, —NR′R″, perfluoro(C1-C8)alkoxy, and perfluoro(C1-C8)alkyl, wherein R′ and R″ are independently selected from the group consisting of hydrogen, (C1-C8)alkyl, and (C1-C8)heteroalkyl.
10 more elements
A method for 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 containing a compound having the formula:
- wherein,
- A is C—R1;
- B is N;
- wherein R1 is selected from the group consisting of hydrogen, halogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, —OR6, —NR6R7, —S(O)mR6, —CN, —NO2, —S(O)nN6R7, and —N3, wherein R6 and R7 are independently selected from hydrogen, (C1-C8)alkyl, and (C1-C8)heteroalkyl;
- subscript m is an integer of from 0 to 3;
- and subscript n is an integer of from 1 to 2;
- R2 and R3 are members independently selected from the group consisting of —OR8, —SR8 and —NR8R9, wherein R8 and R9 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl and (C1-C6)heteroalkyl;
- R4 is a member selected from the group consisting of hydrogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, —OR10, —SR10 and —NR10R11, wherein R10 and R11 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl and (C1-C6)heteroalkyl;
- and optionally, R1 is linked to R2 to form a fused ring, R2 is linked to R3 to form a fused ring, or R2 is linked to both of R1 and R3 to form two additional fused rings;
- X is a member selected from the group consisting of —S(O)p— and —C(O)—, wherein subscript p is 1 or 2;
- Y is a member selected from the group consisting of a single bond, —CH2— and —N(R12)—, wherein R12 is selected from the group consisting of hydrogen, (C1-C6)alkyl, (C1-C6)heteroalkyl and arylalkyl;
- and
- Z is a member selected from the group consisting of aryl and arylalkyl, optionally having from 1 to 5 substituents independently selected from the group consisting of halogen, (C1-C8)alkyl, (C1-C8)heteroalkyl, —CN, —NO2, —OR′, —SR′, —OC(O)NR′R″, NR″C(O)R′, —NR″C(O)2R′, —NH—C(NH2)═NH, —NR′C(NH2)═NH, —NH—C(NH2)═NR′, —NR′R″, perfluoro(C1-C8)alkoxy, and perfluoro(C1-C8)alkyl, wherein R′ and R″ are independently selected from the group consisting of hydrogen, (C1-C8)alkyl, and (C1-C8)heteroalkyl.
10 more elements
Dependencies are inferred from the claim text.