US 2006/0142247 A1Published application

Tricyclic heterocycles

OwnerGuy Georges, Bernhard Goller +6inventors

InventorsGuy Georges, Bernhard Goller, Klaus-Peter Kuenkele, Anja Limberg, Ulrike Reiff, Petra Rueger, Matthias Rueth, Christine Schuell

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Abstract

The present invention relates to the compounds of formula I their pharmaceutically acceptable salts or esters, enantiomeric forms, diastereoisomers and racemates, the preparation of the above-mentioned compounds, pharmaceutical compositions containing such compounds and their manufacture, as well as the use of such compounds in the control or prevention of illnesses such as cancer.

Claims53

Dependent claims

A compound of formula I and all pharmaceutically acceptable salts or esters thereof wherein formula I is:

wherein:
(a) R1 is selected from the group consisting of:
(1) hydrogen;
(2) alkyl, which is optionally substituted one or more times with halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cycloalkyl, heterocyclyl, dialkylphosphinoyl, alkoxyalkoxy, alkyl-O—C(O)—, cyano, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, (alkyl)3Si—O—, H2N—C(S)—, HO—C(O)—, H2N—C(O)—, alkyl-S(O)2—NH—, or phenyl-S(O)2—NH—;
(3) alkenyl, which is optionally substituted one or more times with halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cycloalkyl, heterocyclyl, dialkylphosphinoyl, alkoxyalkoxy, alkyl-O—C(O)—, cyano, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, (alkyl)3Si—O—, H2N—C(S)—, HO—C(O)—, H2N—C(O)—, alkyl-S(O)2—NH—, or phenyl-S(O)2—NH—;
(4) alkynyl, which is optionally substituted one or more times with halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cycloalkyl, heterocyclyl, dialkylphosphinoyl, alkoxyalkoxy, alkyl-O—C(O)—, cyano, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, (alkyl)3Si—O—, H2N—C(S)—, HO—C(O)—, H2N—C(O)—, alkyl-S(O)2—NH—, or phenyl-S(O)2—NH—;
(5) arylalkyl, wherein the aryl is a mono- or bicyclic aromatic ring with 6 to 10 ring carbon atoms and wherein the aryl is optionally substituted one or more times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4)alkyl, halogenated (C1-C4)alkoxy or alkylsulfonyl;
(6) heteroarylalkyl,
wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms, and wherein the heteroaryl is optionally substituted one or more times with alkyl or halogen;
(7) heterocyclyl-C(O)—(CH2)n—;
(8) R8—NH—C(O)—(CH2)n—;
and
(9) R9—C(O)—NH—(CH2)n—;
(b) R8 is selected from the group consisting of:
(1) hydroxyl;
(2) alkoxy;
(3) benzyloxy;
(4) alkyl, which is optionally substituted one to three times with halogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino;
(5) phenyl-(CH2)m—, wherein the phenyl is optionally substituted one to three times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4)alkyl, or halogenated (C1-C4)alkoxy;
and
(6) heteroaryl-(CH2)m—, wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms;
(c) R9 is selected from the group consisting of:
(1) cycloalkyl, wherein said alkyl is optionally substituted one to three times with halogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino;
(2) heterocyclyl;
(3) benzylamino;
(4) alkyl, wherein said alkyl is optionally substituted one to three times with halogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino;
(5) phenyl-(CH2)m—, wherein the phenyl is optionally substituted one to three times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4)alkyl or halogenated (C1-C4)alkoxy;
and
(6) heteroaryl-(CH2)m—, wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms;
(d) n is 1, 2 or 3;
(e) m is 0 or 1;
(f) R2 and R3 form together with the carbon atom to which they are attached a cycloalkyl ring;
or alternatively, R2 is hydrogen or alkyl and R3 is hydrogen or alkyl;
(g) R4 is hydrogen or halogen;
(h) R7 is hydrogen or halogen;
(i) R5 is selected from the group consisting of:
(1) hydrogen;
(2) halogen;
(3) cyano;
(4) nitro;
(5) amino;
(6) hydroxyl;
(7) sulfonic acid;
(8) carboxylic acid;
(9) CH3O—C(O)—;
(10) H2N—C(O)—;
(11) CH3O—N(CH3)—C(O)—;
(12) cycloalkyl-X—, wherein the alkyl is optionally substituted one or more times with halogen;
(13) heterocyclyl-X—;
(14) alkyl, which is optionally substituted one or more times with halogen;
(15) alkyl-X—, wherein the alkyl is optionally substituted one or more times with halogen;
(16) aryl-X—, wherein the aryl is optionally substituted one or more times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4) alkyl, halogenated (C1-C4)alkoxy, or alkylsulfonyl;
(17) arylalkyl-X—, wherein the aryl is optionally substituted one or more times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4)alkyl, or halogenated (C1-C4)alkoxy;
(18) heteroaryl-X—, wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms, and wherein the heteroaryl is optionally substituted one or more times with alkyl;
and
(19) heteroarylalkyl-X—, wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms;
(j) R6 is selected from group consisting of:
(1) hydrogen;
(2) halogen;
(3) cyano;
(4) nitro;
(5) amino;
(6) hydroxy;
(7) sulfonic acid;
(8) carboxylic acid;
(9) CH3O—C(O)—;
(10) H2N—C(O)—;.
(11) CH3O—N(CH3)—C(O)—;
(12) cycloalkyl-X—, wherein the alkyl is optionally substituted one or more times with halogen;
(13) heterocyclyl-X—;
(14) alkyl, which is optionally substituted one or more times with halogen;
(15) alkyl-X—, wherein the alkyl is optionally substituted one or more times with halogen;
(16) aryl-X—, wherein the aryl is optionally substituted one or more times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4)alkyl, halogenated (C1-C4)alkoxy, or alkylsulfonyl;
(17) arylalkyl-X—, wherein the aryl is optionally substituted one or more times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4)alkyl, or halogenated (C1-C4)alkoxy;
(18) heteroaryl-X—, wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms, and wherein the heteroaryl is optionally substituted one or more times with alkyl;
and
(19) heteroarylalkyl-X—, wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms;
(k) X is —NH—, —N(alkyl)-, —O—, —S(O)2NH—, —NHS(O)2—, —NHC(O)—, —N(alkyl)C(O)—, —C(O)—, —OC(O)NH—, —C(O)NH— or —C(O)N(alkyl)—;
and
(l) A is a single bond or —CH2—.

77 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound of formula I and all pharmaceutically acceptable salts or esters thereof wherein formula I is:

wherein:
(a) R1 is selected from the group consisting of:
(1) hydrogen;
(2) alkyl, which is optionally substituted one or more times with halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cycloalkyl, heterocyclyl, dialkylphosphinoyl, alkoxyalkoxy, alkyl-O—C(O)—, cyano, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, (alkyl)3Si—O—, H2N—C(S)—, HO—C(O)—, H2N—C(O)—, alkyl-S(O)2—NH—, or phenyl-S(O)2—NH—;
(3) alkenyl, which is optionally substituted one or more times with halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cycloalkyl, heterocyclyl, dialkylphosphinoyl, alkoxyalkoxy, alkyl-O—C(O)—, cyano, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, (alkyl)3Si—O—, H2N—C(S)—, HO—C(O)—, H2N—C(O)—, alkyl-S(O)2—NH—, or phenyl-S(O)2—NH—;
(4) alkynyl, which is optionally substituted one or more times with halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cycloalkyl, heterocyclyl, dialkylphosphinoyl, alkoxyalkoxy, alkyl-O—C(O)—, cyano, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, (alkyl)3Si—O—, H2N—C(S)—, HO—C(O)—, H2N—C(O)—, alkyl-S(O)2—NH—, or phenyl-S(O)2—NH—;
(5) arylalkyl, wherein the aryl is a mono- or bicyclic aromatic ring with 6 to 10 ring carbon atoms and wherein the aryl is optionally substituted one or more times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4)alkyl, halogenated (C1-C4)alkoxy or alkylsulfonyl;
(6) heteroarylalkyl,
wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms, and wherein the heteroaryl is optionally substituted one or more times with alkyl or halogen;
(7) heterocyclyl-C(O)—(CH2)n—;
(8) R8—NH—C(O)—(CH2)n—;
and
(9) R9—C(O)—NH—(CH2)n—;
(b) R8 is selected from the group consisting of:
(1) hydroxyl;
(2) alkoxy;
(3) benzyloxy;
(4) alkyl, which is optionally substituted one to three times with halogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino;
(5) phenyl-(CH2)m—, wherein the phenyl is optionally substituted one to three times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4)alkyl, or halogenated (C1-C4)alkoxy;
and
(6) heteroaryl-(CH2)m—, wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms;
(c) R9 is selected from the group consisting of:
(1) cycloalkyl, wherein said alkyl is optionally substituted one to three times with halogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino;
(2) heterocyclyl;
(3) benzylamino;
(4) alkyl, wherein said alkyl is optionally substituted one to three times with halogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino;
(5) phenyl-(CH2)m—, wherein the phenyl is optionally substituted one to three times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4)alkyl or halogenated (C1-C4)alkoxy;
and
(6) heteroaryl-(CH2)m—, wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms;
(d) n is 1, 2 or 3;
(e) m is 0 or 1;
(f) R2 and R3 form together with the carbon atom to which they are attached a cycloalkyl ring;
or alternatively, R2 is hydrogen or alkyl and R3 is hydrogen or alkyl;
(g) R4 is hydrogen or halogen;
(h) R7 is hydrogen or halogen;
(i) R5 is selected from the group consisting of:
(1) hydrogen;
(2) halogen;
(3) cyano;
(4) nitro;
(5) amino;
(6) hydroxyl;
(7) sulfonic acid;
(8) carboxylic acid;
(9) CH3O—C(O)—;
(10) H2N—C(O)—;
(11) CH3O—N(CH3)—C(O)—;
(12) cycloalkyl-X—, wherein the alkyl is optionally substituted one or more times with halogen;
(13) heterocyclyl-X—;
(14) alkyl, which is optionally substituted one or more times with halogen;
(15) alkyl-X—, wherein the alkyl is optionally substituted one or more times with halogen;
(16) aryl-X—, wherein the aryl is optionally substituted one or more times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4) alkyl, halogenated (C1-C4)alkoxy, or alkylsulfonyl;
(17) arylalkyl-X—, wherein the aryl is optionally substituted one or more times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4)alkyl, or halogenated (C1-C4)alkoxy;
(18) heteroaryl-X—, wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms, and wherein the heteroaryl is optionally substituted one or more times with alkyl;
and
(19) heteroarylalkyl-X—, wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms;
(j) R6 is selected from group consisting of:
(1) hydrogen;
(2) halogen;
(3) cyano;
(4) nitro;
(5) amino;
(6) hydroxy;
(7) sulfonic acid;
(8) carboxylic acid;
(9) CH3O—C(O)—;
(10) H2N—C(O)—;.
(11) CH3O—N(CH3)—C(O)—;
(12) cycloalkyl-X—, wherein the alkyl is optionally substituted one or more times with halogen;
(13) heterocyclyl-X—;
(14) alkyl, which is optionally substituted one or more times with halogen;
(15) alkyl-X—, wherein the alkyl is optionally substituted one or more times with halogen;
(16) aryl-X—, wherein the aryl is optionally substituted one or more times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4)alkyl, halogenated (C1-C4)alkoxy, or alkylsulfonyl;
(17) arylalkyl-X—, wherein the aryl is optionally substituted one or more times with halogen, cyano, nitro, amino, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, halogenated (C1-C4)alkyl, or halogenated (C1-C4)alkoxy;
(18) heteroaryl-X—, wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms, and wherein the heteroaryl is optionally substituted one or more times with alkyl;
and
(19) heteroarylalkyl-X—, wherein the heteroaryl is a mono- or bicyclic aromatic ring with 5 to 10 ring atoms, which contains up to 4 heteroatoms selected independently from the group consisting of N, O and S with the remaining ring atoms being carbon atoms;
(k) X is —NH—, —N(alkyl)-, —O—, —S(O)2NH—, —NHS(O)2—, —NHC(O)—, —N(alkyl)C(O)—, —C(O)—, —OC(O)NH—, —C(O)NH— or —C(O)N(alkyl)—;
and
(l) A is a single bond or —CH2—.

77 more elements