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US 2009/0264653 A1Published application
Useful indole compounds
AssigneeIronwood Pharmaceuticals, Inc.
InventorsWilmin Bartolini, Brian M Cali, Barbara Chen, Yueh-Tyng Chien, Mark G. Currie, G. Todd Milne, James Philip Pearson, John Jeffrey Talley, Jane Yang, Craig Zimmerman, Charles Kim, Kevin Sprott, Timothy Barden, Regina Lundigran, Ara Mermerian
Life of this patent
Estimating the term…
Abstract
Indoles that have activity as inhibitors of FAAH are described as are indoles and indole derivatives that have activity as inhibitors of DAO.
Claims7
A compound having Formula I
- Wherein:
- A is O:
- each R1a and R1b is independently:
- H, halogen, hydroxyl, —CN, an optionally substituted C1-C5 alkyl, an optionally substituted C2-C5 alkenyl, an optionally substituted C2-C5 alkynyl, an optionally substituted C1-C5 alkoxy, —NO2;
- or an R1a and R1b attached to the same carbon, taken together with the carbon, form an optionally substituted C3-C6 cycloalkyl or carbocycle or an optionally substituted heterocycle;
- or an R1a attached to a carbon directly bonded to the ring bearing R8, taken with R8 and the carbon to which R1a is attached, form an optionally, substituted C3-C6 cycloalkyl or carbocycle or an optionally substituted heterocycle;
- or an R1a attached to a carbon directly bonded to the ring bearing R12, taken with R12 and the carbon to which R1a is attached form an optionally substituted C3-C6 cycloalkyl or carbocycle or an optionally substituted heterocycle;
- m=1, 2 or 3;
- R2 is H, hydroxyl, —NO2, an optionally substituted C1-C5, alkoxy, —CN, an optionally substituted C1-C5 alkyl, an optionally substituted C2-C5 alkenyl, an optionally substituted C2-C5 alkynyl or halogen;
- R3 is an optionally substituted heteroaryl;
- each of R4, R5, R6 and R7 are independently:
- H, a halogen, an optionally substituted C1-C5 alkyl, an optionally substituted C2-C5 alkenyl, an optionally substituted C2-C5 alkynyl, hydroxyl, NO2, an optionally substituted C1-C5 alkoxy, —CN, —C(O)OH, an optionally substituted —SO2CH3, and optionally substituted —SO2NH2, an optionally substituted —SO2OH, —C(O)H, an optionally substituted —C(O)CH3, an optionally substituted —C(O)N(CH3)2, an optionally substituted —C(O)NH2, an optionally substituted —SCH3, an optionally substituted heterocycle or heteroaromatic, or —N(R2a)(R2B);
- wherein each R2a and R2b is independently:
- H, hydroxy, an optionally substituted C1-C5 alkyl, an optionally substituted C2-C5 alkenyl;
- an optionally substituted C2-C5 alkynyl;
- an optionally substituted C1-C5 alkoxy or an R2a and R2b attached to the same nitrogen, taken together with that nitrogen form an optionally substituted heterocycle or heteroaromatic;
- and
- each of R8, R9, R10, R11 and R12 is independently H;
- —CN, hydroxyl, a halogen, an optionally substituted C1-C5 alkyl, an optionally substituted C2-C5 alkenyl, an optionally substituted C2-C5alkynyl, hydroxy, NO2, an optionally substituted C1-C5 alkoxy, —N(R2a)(R2B), —C(O)OH, an optionally substituted —SO2CH3, an optionally substituted —SO2NH2, an optionally substituted —SO2OH, —C(O)H, an optionally substituted —C(O)CH3, an optionally substituted —C(O)N(CH3)2, an optionally substituted —C(O)NH2, an optionally substituted —SCH3, an optionally substituted heterocycle or heteroaromatic, or R8 taken with an R1a attached to a carbon directly bonded to the ring bearing R8 and the carbon to which the R1a is attached form an optionally substituted C3-C6 cycloalkyl or carbocycle or an optionally substituted heterocycle, or R12 taken with an R1a attached to a carbon directly bonded to the ring bearing R12 and the carbon to which the R1a is attached, form an optionally substituted C3-C6 cycloalkyl or carbocycle or an optionally substituted heterocycle and pharmaceutically acceptable salts thereof.
16 more elements
3-66. (canceled)
A compound having Formula II:
- wherein R2, R3, R4, and R7 are independently selected from:
- H, CO2H, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycle, carbocycle-(C(O)R8, —(CH2)nC(O)NO, —(CH2)nN(H)-aryl, —C(O)N(H)-aryl, —OR8, —C(O)N(OH)(C1-C6 alkyl), —C(O)N(H)NH2), —NR8, —N(H)OR8, —(CH2)nC(O)OR8, —S(CH2)nCO2H, —N(CH2)nCO2H, —ON(H)(CH2)nCO2H, —SO3H, —PO3H2—(CH2)naryl, —(CH2)nNH2, —(CH2)nN(OH)(C1-C6 aryl), —NO2, —SR8, —SOR8, —SO2R8, —(CH2)nCN, —(CH2)nO-carbocycle, —(CH2)nS-carbocycle, —(CH2)nS-cycloalkyl, —(CH2)nS(O)2-carbocycle, —(CH2)nS(O)2-carbocycle, —(CH2)nN(H)carbocycle, (CH2)nNCOCH3, —(CH2)n-carbocycle, —O(CH2)nCO2H, CN5H, (CH2)nCN5H, —B(OH)2, —(CH2)nN(OH),
- R5 is selected from H, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycle, carbocycle —C(O)R8, CO2H, —NR8, —NOR8, —SR8, —SOR8, —SO2R8;
- R6 is selected from:
- H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycle, carbocycle, OH, —OR8, —NR8, —NOR8, —NO2, —SR8, —SOR8, —SO2R8;
- R1 is selected from:
- H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycle, carbocycle, (CH2)ncarbocycle, (CH2)nphenyl;
- wherein R8 is selected from H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycle, carbocycle;
- n=0, 1, 2, 3, 4 or 5;
- and
- any C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycle, carbocycle can be optionally substituted and pharmaceutically acceptable salts thereof.
8 more elements
68-82. (canceled)
A compound having Formula III:
- wherein R2, R3, R4, R5, and R8 are independently selected from:
- H, —OR8, CO2H, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycle, carbocycle —C(O)R8, —(CH2)nC(O)NO, —(CH2)nN(H)aryl, —C(O)N(H)aryl, —C(O)N(OH)(C1-C6 alkyl), —(O)N(H)(NH2), —NR8, —N(H)OR8, —(CH2)nC(O)OR8—S(CH2)nCO2H, —N(CH2)nCO2H, —ON(H)(CH2)nCO2H, —SO3H, —PO3H2—(CH2)naryl, —(CH2)nNH2, —(CH2)nN(OH)(C1-C6 aryl), —NO2, —SR8, —SOR8, —SO2R8, —(CH2)nCN, —(CH2)nOcarbocycle, —(CH2)nScarbocycle, —(CH2)nScycloalkyl, —(CH2)nS(O)2carbocycle, —(CH2)nS(O)2carbocycle, —(CH2)nN(H)carbocycle, (CH2)nNCOCH3—(CH2)ncarbocycle, —O(CH2)nCO2H, CN5H, (CH2)nCN5H, B(OH)2, (CH2)nN(OH),
- R6 is selected from H, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycle, carbocycle-C(O)R8, CO2H, —NR8, —NOR8, —NO2, —SR8, —SOR8, —SO2R8;
- R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycle, carbocycle, OH, —OR8, —NR8, —NOR8, —NO2, —SR8, —SOR8, —SO2R8;
- R1 is H;
- n=0, 1, 2, 3, 4, or 5;
- and
- wherein R8 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycle, carbocycle;
- and
- wherein any C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, heterocycle, carbocycle can be optionally substituted and pharmaceutically acceptable salts thereof.
7 more elements
84-103. (canceled)
Dependencies are inferred from the claim text.