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US 8,710,044 B2Granted
Bicyclic azaheterocyclic carboxamides
AssigneeMerck Patent GmbH
InventorsBayard R. Huck, Constantin Neagu, Reinaldo Jones, Lizbeth Celeste DeSelm, Yufang Xiao, Srinivasa R. Karra, Ruoxi Lan, Igor Mochalkin, Amanda E. Sutton, Thomas E. Richardson
Life of this patent
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Abstract
The invention provides novel bicyclic azaheterocyclic carboxamide compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.
Claims9
A compound of Formula (I)
- and pharmaceutically acceptable salts, thereof, wherein:
- X is N,
- Y is NH, O or absent,
- R1 is L1-R4-L2-R5 or L1-R4,
- R2 is A, Hal, OH, OA, SH, CN, NH2, NO2, NHA, NH-L1-Ar, NHCOA, NHCO-L-1-Ar, NHSO2A, NHSO2-L1-Ar, NHCONHA, NHCONH-L1-Ar, L1-Ar, O-L1-Ar, L1-R4,
- L1 is a single bond, methylene, or methyl substituted methylene, wherein the methylene, or the methyl group of the methyl substituted methylene may be unsubstituted or mono- or disubstituted with Hal, OH, CN, NH2, NH(LA), N(LA)2, NO2, COOH, N3, ethenyl or ethynyl, and/or monosubstituted with R4, and in which one or two CH2 groups may be replaced by an O or S atom or by an —NH—, —N(LA)-, —CONH—, —N(LA)COO—, —SO2— or —NHCO— group,
- R3 is H, A, Hal, OH, COOH, SH, NH2, NO2 or CN,
- R4, R5 each, independently of one another, are Ar, or cyclic A which may be mono- or disubstituted by Hal or LA,
- L2 is —NHCO—, —NHCOO—, —NHCONH—, —NHCONA-, —NHCOA—, —O—, —S—, —NH—, —NHSO2—, —SO2NH—, —CONH—, —CONHCONH—, —NHCONHCO—, or -A-,
- Ar is a mono- or bicyclic aromatic homo- or heterocycle having 0, 1, 2, 3 or 4 N, O and/or S atoms and 5, 6, 7, 8, 9, or 10 skeleton atoms, which may be unsubstituted or, independently of one another, mono-, di- or trisubstituted by Hal, A, OH, SH, OA, NH2, NHA, NA2, NO2, CN, OCN, SCN, COOH, COOA, CONH2, CONHA, CONA2, NHCOA, NHCONHA, NHCONH2, NHSO2A, CHO, COA, SO2NH2, SO2A and/or SO2Hal, and in which a ring N-atom may be substituted by an O-atom to form an N-oxide group, and in which in the case of a bicyclic aromatic cycle on of the two rings may be partly saturated,
- A is unbranched or branched linear or cyclic alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, in which one or two CH2 groups may be replaced by an O or S atom and/or by an —NH—, —CO—, —NHCOO—, —NHCONH—, —N(LA)-, —CONH—, —NHCO— or —CH═CH— group, and in which 1-3 H atoms may be replaced by Hal, and in which one or two CH3 groups may be replaced by OH, SH, NH2, NH(LA), N(LA)2, NHCOOH, NHCONH2 or CN,
- LA is unbranched or branched, linear alkyl having 1, 2, 3 or 4 C atoms, wherein 1, 2 or 3 H atoms may be replaced by Hal,
- Hal is F, Cl, Br or I.
10 more elements
Dependencies are inferred from the claim text.