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US 7,732,481 B2Granted
Prolinylarylacetamides
AssigneeMerck Patent GmbH
InventorsWerner Mederski, Christos Tsaklakidis, Dieter Dorsch, Bertram Cezanne, Johannes Gleitz
Life of this patent
Estimating the term…
Abstract
Novel compounds of the formula (I), in which R, R1, R2, R3, X, X′ and Y have the meaning indicated in Patent Claim 1, are inhibitors of coagulation factor Xa and can be employed for the prophylaxis and/or therapy of thromboembolic diseases and for the treatment of tumors.
Claims23
A compound of formula I
- in which
- R denotes Hal, —C≡C—H, —C≡C-A or OA,
- R1 denotes H, ═O, Hal, A, OH, OA, A-COO—, Ph-(CH2)n—COO—, cycloalkyl-(CH2)n—COO—, A-CONH—, A-CONA-, Ph-CONA-, N3, NH2, NO2, CN, COOH, COOA, CONH2, CONHA, CON(A)2, O-allyl, O-propargyl, O-benzyl, ═N—OH, ═N—OA or ═CF2,
- X, X′ denote CH,
- Y denotes R4 or Hal,
- Ph denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by A, OA, OH or Hal,
- R2 denotes H, Hal or A,
- R3 denotes H or A,
- R4 denotes OH, OA, A-COO—, NHA, NHAr, NAA′, Het or —NH—CHR5—COOR3,
- R5 denotes H, A, —CHR3—OH, (CH2)n-Ph, (CH2)n—COOH, (CH2)n—CONH2, (CH2)p—NH2, (CH2)n—NH(═NH)NH2, (CH2)n-Het1 or (CH2)n—SR3,
- Het denotes a mono- or bicyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by A, OH, OA, CN, COOH, COOA and/or carbonyl oxygen (═O),
- Het1 denotes a mono- or bicyclic aromatic heterocycle having 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by A, OH, OA and/or CN,
- A, A′ each, independently of one another, denote unbranched, branched or cyclic alkyl having 1-12 C atoms, in which, in addition, 1-7 H atoms may be replaced by F and/or chlorine,
- Ar denotes naphthyl, biphenyl, or phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OR3, N(R3)2, NO2, CN, COOR3, CON(R3)2, NR3COA, NR3CON(R3)2, NR3SO2A, COR3, SO2N(R3)2, S(O)nA, —[C(R3)2]n—COOR3 or —O—[C(R3)2]p—COOR3,
- Hal denotes F, Cl, Br or I,
- n denotes 0, 1, 2 or 3, and
- p denotes 1, 2, 3, 4 or 5,
- including a stereoisomer thereof,
- or a pharmaceutically acceptable salt thereof.
16 more elements
A compound of the formula Ia
- in which
- R denotes Hal or —C≡C—H,
- R1 denotes OH,
- X denotes CH,
- X′ denotes CH,
- Y denotes R4 or Hal,
- R2 denotes H or Hal,
- R3 denotes alkyl having 1, 2, 3, 4, 5 or 6 C atoms,
- R4 denotes OH, OA, A-COO—, NHA, NAA′, Het, —NH—CHR5—COOR3 or —NH—CHR5—COOH,
- R5 denotes H or A,
- Het denotes a monocyclic saturated, unsaturated or aromatic heterocycle having 1 to 2 N and/or O atoms, which may be unsubstituted or mono-, di- or trisubstituted by A, OH and/or OA,
- A, A′ each, independently of one another, denote unbranched, branched or cyclic alkyl having 1-12 C atoms, in which, in addition, 1-7 H atoms may be replaced by F and/or chlorine,
- Hal denotes F, Cl, Br or I,
- n denotes 0, 1, 2 or 3,
- p denotes 1, 2, 3, 4 or 5,
- including a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.
13 more elements
Dependencies are inferred from the claim text.