Cyclopentathiophene carboxamide derivatives as platelet activating factor receptor antagonists

A compound of formula (I)

• wherein
• R1 is selected from the group consisting of C1-4-alkyl and C3-4-cycloalkyl,
• wherein the C1-4-alkyl group of R1 is optionally substituted with 1 to 3 F;
• n is selected from the group consisting of 0, 1, 2, and 3;
• R2 is independently selected from the group consisting of F, Cl, Br, I, C1-4-alkyl, C3-4-cycloalkyl, —CN, —CONH2, —CONH(C1-4-alkyl), —CON(C1-4-alkyl)2, —COOH, —COO—C1-4-alkyl, NH2, OH, —O—C1-4-alkyl, and —S(O)r-C1-4-alkyl with r=0, 1, or 2;
• wherein the C1-4-alkyl group of R2 is optionally substituted with 1 to 3 F or with 1 —CN, with 1 OH, or with 1 O—C1-4-alkyl, and
• wherein the —O—C1-4-alkyl group of R2 is optionally substituted with 1 to 3 F;
• R3 is selected from the group consisting of H and C1-4-alkyl optionally substituted with 1 to 5 F;
• and
• R4 is selected from the group consisting of C1-6-alkyl
• optionally substituted with 1 to 3 F or optionally substituted with 1 to 2 substituents independently selected from
• —CN, —CONH2, —CONH(C1-4-alkyl), —CON(C1-4-alkyl)2, —COOH, —COO—C1-4-alkyl, C1-3-alkyl-CO—NH—, C1-3-alkyl-S(═O)2—NH—, OH, and —O—C1-3-alkyl optionally substituted with 1 to 3 F;
• or
• R4 is selected from the group consisting of —C0-3-alkylene-C3-10-cycloalkyl and —C0-3-alkylene-C3-10-heterocyclyl,
• wherein said alkylene moiety of the —C0-3-alkylene-C3-10-cycloalkyl and —C0-3-alkylene-C3-10-heterocyclyl groups of R4 is optionally substituted with 1 to 2 substituents selected from F and CH3,
• wherein 1 CH2 group of said alkylene moiety of the —C0-3-alkylene-C3-10-cycloalkyl and —C0-3-alkylene-C3-10-heterocyclyl groups of R4 is optionally replaced by a
• moiety,
• wherein said cycloalkyl moiety of the —C0-3-alkylene-C3-10-cycloalkyl group of R4 and said heterocyclyl moiety of the —C0-3-alkylene-C3-10-heterocyclyl group of R4 are saturated mono- or bicyclic ring systems,
• wherein said heterocyclyl moiety of the —C0-3-alkylene-C3-10-heterocyclyl group of R4 contains 1 to 2 ring members independently selected from N, NH, N(C1-4-alkyl), NCO(C1-4-alkyl), NCOO(C1-4-alkyl), NS(═O)2(C1-4-alkyl), N-phenyl, N-pyridinyl, N-pyrimidinyl, and O, and optionally 1 ring member selected from C═O, and S(═O)r, with r=0, 1, or 2,
• provided that said heterocyclyl moiety of the —C0-3-alkylene-C3-10-heterocyclyl group of R4 does not contain any heteroatom-heteroatom bonds other than N—N, N—O, and N—S(═O)r=1,2 between ring members, and
• wherein said cycloalkyl moiety of the —C0-3-alkylene-C3-10-cycloalkyl group of R4 and said heterocyclyl moiety of the —C0-3-alkylene-C3-10-heterocyclyl group of R4 are optionally substituted with 1 to 2 F and optionally substituted with 1 to 2 substituents independently selected from
• a) Cl,
• b) —CN,
• c) —CONH2,
• d) —CONH(C1-4-alkyl),
• e) —CON(C1-4-alkyl)2,
• f) —COOH,
• g) —COO—C1-4-alkyl,
• h) OH,
• i) —O—C1-3-alkyl optionally substituted with 1 to 3 F,
• j) S(═O)2—C1-4-alkyl and
• k) C1-4-alkyl optionally substituted with 1 to 3 F or with 1 substituent selected from —CN, OH, —O—C1-4-alkyl;
• or
• R4 is selected from the group consisting of —C0-3-alkylene-phenyl and —C0-3-alkylene-heteroaryl,
• wherein said alkylene moiety of the —C0-3-alkylene-phenyl and —C0-3-alkylene-heteroaryl groups of R4 is optionally substituted with 1 to 2 substituents selected from F and CH3,
• wherein 1 CH2 group of said alkylene moiety of the —C0-3-alkylene-phenyl and —C0-3-alkylene-heteroaryl groups of R4 is optionally replaced by a
• moiety or by a
• moiety, or
• wherein 1 —CH2—CH2— group of said alkylene moiety of the —C0-3-alkylene-phenyl and —C0-3-alkylene-heteroaryl groups of R4 is optionally replaced by a
• moiety or by a
• moiety,
• wherein said heteroaryl moiety of the —C0-3-alkylene-heteroaryl group of R4 is a 5-membered monocycle containing 1 ring member selected from N, NH, O, and S and optionally further containing 1 to 2 ring members N, or a 6-membered monocycle containing 1 to 2 ring members N, and
• wherein said phenyl moiety of the —C0-3-alkylene-phenyl group of R4 and said heteroaryl moiety of the —C0-3-alkylene-heteroaryl group of R4 are optionally substituted with 1 to 3 substituents independently selected from
• a) F, Cl, Br,
• b) C3-4-cycloalkyl,
• c) —CN,
• d) —CONH2,
• e) —CONH(C1-4-alkyl),
• f) —CON(C1-4-alkyl)2,
• g) —COOH,
• h) —COO—C1-4-alkyl,
• i) —NHCO—C1-4-alkyl,
• j) —NHS(═O)2—C1-4-alkyl,
• k) —S(═O)r-C1-4-alkyl with r=0, 1, or 2,
• l) —O—C1-4-alkyl optionally substituted with 1 to 3 F, and
• m) C1-4-alkyl optionally substituted with 1 to 3 F or with 1 substituent selected from —CN, OH, and —O—C1-4-alkyl,
• or
• R4 is selected from the group consisting of 7- to 12-membered fused bicyclic aryl, heteroaryl, or heterocyclyl
• wherein said bicyclic aryl, heteroaryl, or heterocyclyl of R4 consists of one non-aromatic ring that is attached to the amide N atom in formula (I) and optionally contains 1 to 2 ring members independently selected from N—, NH, N(C1-4-alkyl), N(CO—C1-3-alkyl), N(S(═O)2-C1-3-alkyl), and O, and
• optionally contains 1 ring member selected from C═O and S(═O)r, with r=0, 1, or 2, and of
• one aromatic ring selected from phenyl, pyrrole, furan, and thiophene in each of which 1 to 2 CH ring members are optionally replaced with N,
• wherein said bicyclic aryl, heteroaryl, or heterocyclyl of R4 is optionally substituted with 1 to 4 F,
• is optionally substituted with 1 to 4 C1-3-alkyl optionally substituted with 1 to 4 F, and
• is optionally substituted with 1 to 2 substituents selected from the group consisting of Cl, —CN, —CONH2, —CONH(C1-4-alkyl), —CON(C1-4-alkyl)2, —COOH, —COO—C1-4-alkyl, HO—C1-3-alkylene-, C1-3-alkyl-O—C1-3-alkylene-, NH2, C1-3-alkyl-CO—NH—, C1-3-alkyl-S(═O)2-NH—, OH, and C1-3-alkyl-O— optionally substituted with 1 to 3 F;
• or
• R3 and R4 are selected from the group in which R3 and R4, together with the amide N atom they are attached to, form a saturated 3- to 8-membered monocyclic heterocyclyl optionally further containing 1 to 2 ring members independently selected from NH, N(C1-4-alkyl), N(CO—C1-3-alkyl), N(S(═O)2-C1-3-alkyl), and O, and
• optionally containing 1 ring member selected from C═O and S(═O)r, with r=0, 1, or 2, provided that said saturated 3- to 8-membered monocyclic heterocyclyl formed by R3 and R4 together with the amide N atom they are attached to does not contain any heteroatom-heteroatom bonds other than N—N, N—O, and N—S(═O)r=1,2 between ring members,
• wherein said heterocyclyl formed by R3 and R4 together with the amide N atom they are attached to is optionally substituted with 1 to 4 F,
• is optionally substituted with 1 to 4 C1-3-alkyl optionally substituted with 1 to 3 F, and
• is optionally substituted with 1 to 2 substituents selected from Cl, —CN, —CONH2, —CONH(C1-4-alkyl), —CON(C1-4-alkyl)2, —COOH, —COO—C1-4-alkyl, HO—C1-3-alkylene-, C1-3-alkyl-O—C1-3-alkylene-, C1-3-alkyl-CO—NH—, C1-3-alkyl-S(═O)2—NH—, OH, and C1-3-alkyl-O— optionally substituted with 1 to 3 F;
• or
• R3 and R4 are selected from the group in which R3 and R4, together with the amide N atom they are attached to, form a saturated 5- to 12-membered bicyclic heterocyclyl optionally further containing 1 to 3 ring members independently selected from N—, NH, N(C1-4-alkyl), N(CO—C1-3-alkyl), N(S(═O)2—C1-3-alkyl), and O, and
• optionally containing 1 ring member selected from C═O and S(═O)r, with r=0, 1, or 2, provided that said saturated 5- to 12-membered bicyclic heterocyclyl formed by R3 and R4 together with the amide N atom they are attached to does not contain any heteroatom-heteroatom bonds other than N—N, N—O, and N—S(═O)r=1,2 between ring members
• wherein said saturated 5- to 12-membered bicyclic heterocyclyl formed by R3 and R4 together with the amide N atom they are attached to is optionally substituted with 1 to 6 F,
• is optionally substituted with 1 to 4 C1-3-alkyl optionally substituted with 1 to 3 F, or is optionally substituted with 1 to 2 substituents selected from Cl, —CN, —CONH2, —CONH(C1-4-alkyl), —CON(C1-4-alkyl)2, —COOH, —COO—C1-4-alkyl, HO—C1-3-alkylene-, C1-3-alkyl-O—C1-3-alkylene-, C1-3-alkyl-CO—NH—, C1-3-alkyl-S(═O)2-NH—, OH, and C1-3-alkyl-O—;
• or a salt thereof.