ES2548768T3 - Imidazolotiadiazoles para su uso como inhibidores de proteína quinasa - Google Patents

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Publication number

ES2548768T3

ES2548768T3 ES08806437.3T ES08806437T ES2548768T3 ES 2548768 T3 ES2548768 T3 ES 2548768T3 ES 08806437 T ES08806437 T ES 08806437T ES 2548768 T3 ES2548768 T3 ES 2548768T3

Authority

ES

Spain

Prior art keywords

represent

imidazo

thiadiazol

formula

compound

Prior art date

2007-09-27

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

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• BOXRDDIXJOUZLV-UHFFFAOYSA-N 2h-imidazo[4,5-d]thiadiazole Chemical class N1SC2=NC=NC2=N1 BOXRDDIXJOUZLV-UHFFFAOYSA-N 0.000 title description 11
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title description 8
• 239000003909 protein kinase inhibitor Substances 0.000 title description 8
• 150000001875 compounds Chemical class 0.000 claims abstract description 327
• -1 4-fluoro-1-naphthyl Chemical group 0.000 claims abstract description 140
• 125000001424 substituent group Chemical group 0.000 claims abstract description 84
• 125000005843 halogen group Chemical group 0.000 claims abstract description 69
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 67
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 63
• 239000001257 hydrogen Substances 0.000 claims abstract description 59
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 49
• 125000003118 aryl group Chemical group 0.000 claims abstract description 47
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 46
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 42
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 32
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 30
• 150000003839 salts Chemical class 0.000 claims abstract description 30
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 29
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 28
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 26
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 25
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
• 239000012453 solvate Substances 0.000 claims abstract description 20
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 19
• 150000001408 amides Chemical group 0.000 claims abstract description 19
• 229910052731 fluorine Inorganic materials 0.000 claims abstract description 13
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims abstract description 13
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 12
• 239000011737 fluorine Substances 0.000 claims abstract description 12
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 11
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 10
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims abstract description 10
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims abstract description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 9
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract description 7
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 7
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 6
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 3
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract 25
• 150000002431 hydrogen Chemical group 0.000 claims abstract 10
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• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
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• 229910052757 nitrogen Inorganic materials 0.000 claims description 10
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• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
• 229910052740 iodine Inorganic materials 0.000 claims description 9
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 7
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• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
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• YKGMCRDGQBHBRZ-UHFFFAOYSA-N 3-[2-(4-fluorophenoxy)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC(C=2N3N=C(OC=4C=CC(F)=CC=4)SC3=NC=2)=C1 YKGMCRDGQBHBRZ-UHFFFAOYSA-N 0.000 claims description 3
• BCAKJJZKSLTUOK-UHFFFAOYSA-N 4-[2-(4-fluoroanilino)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]phenol Chemical compound C1=CC(O)=CC=C1C1=CN=C2N1N=C(NC=1C=CC(F)=CC=1)S2 BCAKJJZKSLTUOK-UHFFFAOYSA-N 0.000 claims description 3
• RBKDSSSWSMXHNY-UHFFFAOYSA-N 4-[2-(4-fluorophenoxy)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]phenol Chemical compound C1=CC(O)=CC=C1C1=CN=C2N1N=C(OC=1C=CC(F)=CC=1)S2 RBKDSSSWSMXHNY-UHFFFAOYSA-N 0.000 claims description 3
• WCMVGMVOYZYSQE-UHFFFAOYSA-N 4-[2-[(4-fluorophenyl)methylamino]imidazo[2,1-b][1,3,4]thiadiazol-5-yl]phenol Chemical compound C1=CC(O)=CC=C1C1=CN=C2N1N=C(NCC=1C=CC(F)=CC=1)S2 WCMVGMVOYZYSQE-UHFFFAOYSA-N 0.000 claims description 3
• CARXPXGXWCKBJL-UHFFFAOYSA-N 5-[(3-chloro-4-fluoroanilino)methyl]-n-(2-methylpropyl)-7,7a-dihydroimidazo[2,1-b][1,3,4]thiadiazol-2-amine Chemical compound S1C(NCC(C)C)=NN2C1NC=C2CNC1=CC=C(F)C(Cl)=C1 CARXPXGXWCKBJL-UHFFFAOYSA-N 0.000 claims description 3
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• DDDUOINJEICOML-UHFFFAOYSA-N n-(cyclopropylmethyl)-5-(morpholin-4-ylmethyl)imidazo[2,1-b][1,3,4]thiadiazol-2-amine Chemical compound C1CC1CNC(SC1=NC=2)=NN1C=2CN1CCOCC1 DDDUOINJEICOML-UHFFFAOYSA-N 0.000 claims description 3
• JAMJUPRNDQABOV-UHFFFAOYSA-N n-[4-[2-(4-fluoroanilino)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1C1=CN=C2N1N=C(NC=1C=CC(F)=CC=1)S2 JAMJUPRNDQABOV-UHFFFAOYSA-N 0.000 claims description 3
• SFOYFWHJOQHZRH-UHFFFAOYSA-N n-[4-[2-(4-fluorophenoxy)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1C1=CN=C2N1N=C(OC=1C=CC(F)=CC=1)S2 SFOYFWHJOQHZRH-UHFFFAOYSA-N 0.000 claims description 3
• CVFQBICVTJEPDF-UHFFFAOYSA-N n-ethyl-2-(ethylamino)imidazo[2,1-b][1,3,4]thiadiazole-5-sulfonamide Chemical compound CCNS(=O)(=O)C1=CN=C2SC(NCC)=NN21 CVFQBICVTJEPDF-UHFFFAOYSA-N 0.000 claims description 3
• 230000003071 parasitic effect Effects 0.000 claims description 3
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• PJGLCBCBNJMVCD-UHFFFAOYSA-N 1-[3-[2-(cyclopropylmethylamino)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]phenyl]ethanone Chemical compound CC(=O)C1=CC=CC(C=2N3N=C(NCC4CC4)SC3=NC=2)=C1 PJGLCBCBNJMVCD-UHFFFAOYSA-N 0.000 claims description 2
• NYRUEMXFVPUIIS-UHFFFAOYSA-N 1-[3-[2-[(3,4-dichlorophenyl)methylamino]imidazo[2,1-b][1,3,4]thiadiazol-5-yl]phenyl]ethanone Chemical compound CC(=O)C1=CC=CC(C=2N3N=C(NCC=4C=C(Cl)C(Cl)=CC=4)SC3=NC=2)=C1 NYRUEMXFVPUIIS-UHFFFAOYSA-N 0.000 claims description 2
• ISRPTTSIDVGQRW-UHFFFAOYSA-N 1-[3-[6-chloro-2-(2-methylpropylamino)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]phenyl]ethanone Chemical compound ClC=1N=C2SC(NCC(C)C)=NN2C=1C1=CC=CC(C(C)=O)=C1 ISRPTTSIDVGQRW-UHFFFAOYSA-N 0.000 claims description 2
• QORVTJMUYZLSGU-UHFFFAOYSA-N 1-[3-[[2-(2-methoxyethylamino)-7,7a-dihydroimidazo[2,1-b][1,3,4]thiadiazol-5-yl]methylamino]phenyl]ethanone Chemical compound S1C(NCCOC)=NN2C1NC=C2CNC1=CC=CC(C(C)=O)=C1 QORVTJMUYZLSGU-UHFFFAOYSA-N 0.000 claims description 2
• WRTXUFKSQJFCCH-UHFFFAOYSA-N 1-[3-[[2-(2-methylpropylamino)-7,7a-dihydroimidazo[2,1-b][1,3,4]thiadiazol-5-yl]methylamino]phenyl]ethanone Chemical compound S1C(NCC(C)C)=NN2C1NC=C2CNC1=CC=CC(C(C)=O)=C1 WRTXUFKSQJFCCH-UHFFFAOYSA-N 0.000 claims description 2
• AISKMOQBOFWLFR-UHFFFAOYSA-N 2-(2-methylpropylamino)-n-phenylimidazo[2,1-b][1,3,4]thiadiazole-5-sulfonamide Chemical compound C=1N=C2SC(NCC(C)C)=NN2C=1S(=O)(=O)NC1=CC=CC=C1 AISKMOQBOFWLFR-UHFFFAOYSA-N 0.000 claims description 2
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