ES2557383T3 - Carboxamidas azaheterocíclicas bicíclicas como inhibidores de la cinasa p70S6K - Google Patents

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Publication number

ES2557383T3

ES2557383T3 ES11738160.8T ES11738160T ES2557383T3 ES 2557383 T3 ES2557383 T3 ES 2557383T3 ES 11738160 T ES11738160 T ES 11738160T ES 2557383 T3 ES2557383 T3 ES 2557383T3

Authority

ES

Spain

Prior art keywords

methyl

substituted

ethyl

hal

methylamino

Prior art date

2010-07-29

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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• 125000002619 bicyclic group Chemical group 0.000 title description 4
• 150000003857 carboxamides Chemical class 0.000 title description 4
• 229940043355 kinase inhibitor Drugs 0.000 title description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 151
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 111
• 150000003839 salts Chemical class 0.000 claims abstract description 53
• 239000012453 solvate Substances 0.000 claims abstract description 49
• 125000004429 atom Chemical group 0.000 claims abstract description 29
• 229910052731 fluorine Inorganic materials 0.000 claims abstract description 24
• 229910052801 chlorine Inorganic materials 0.000 claims abstract description 23
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 9
• 229910052794 bromium Inorganic materials 0.000 claims abstract description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
• 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 8
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 7
• 125000004122 cyclic group Chemical group 0.000 claims abstract description 7
• 125000004434 sulfur atom Chemical group 0.000 claims abstract description 7
• 229910006074 SO2NH2 Inorganic materials 0.000 claims abstract description 5
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
• 125000000565 sulfonamide group Chemical group 0.000 claims abstract description 5
• 229910052786 argon Inorganic materials 0.000 claims abstract description 4
• 125000000815 N-oxide group Chemical group 0.000 claims abstract description 3
• 125000002950 monocyclic group Chemical group 0.000 claims abstract description 3
• 229920006395 saturated elastomer Polymers 0.000 claims abstract description 3
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract 36
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract 7
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims abstract 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract 2
• -1 methylamino, dimethylamino Chemical group 0.000 claims description 109
• 238000000034 method Methods 0.000 claims description 78
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 32
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
• 239000002253 acid Substances 0.000 claims description 23
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 21
• 206010028980 Neoplasm Diseases 0.000 claims description 19
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
• 201000010099 disease Diseases 0.000 claims description 16
• 201000011510 cancer Diseases 0.000 claims description 15
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• 239000004480 active ingredient Substances 0.000 claims description 7
• 230000003463 hyperproliferative effect Effects 0.000 claims description 7
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 230000008569 process Effects 0.000 claims description 5
• SWJLPMOSDVXEPJ-MRXNPFEDSA-N 4-[[(1s)-1-(4-fluorophenyl)-2-(methylamino)ethyl]amino]-2-methylquinazoline-8-carboxamide Chemical compound C1([C@H](NC=2C3=CC=CC(=C3N=C(C)N=2)C(N)=O)CNC)=CC=C(F)C=C1 SWJLPMOSDVXEPJ-MRXNPFEDSA-N 0.000 claims description 4
• 229910052740 iodine Inorganic materials 0.000 claims description 4
• 125000001424 substituent group Chemical group 0.000 claims description 4
• 239000008186 active pharmaceutical agent Substances 0.000 claims description 3
• 150000001408 amides Chemical class 0.000 claims description 3
• 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 3
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• ASFAFOSQXBRFMV-LJQANCHMSA-N 3-n-(2-benzyl-1,3-dihydroxypropan-2-yl)-1-n-[(1r)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzene-1,3-dicarboxamide Chemical compound N([C@H](C)C=1C=CC(F)=CC=1)C(=O)C(C=1)=CC(N(C)S(C)(=O)=O)=CC=1C(=O)NC(CO)(CO)CC1=CC=CC=C1 ASFAFOSQXBRFMV-LJQANCHMSA-N 0.000 claims 3
• GZSKSABPMQXDBI-MRXNPFEDSA-N 4-[[(1s)-1-(3-chlorophenyl)-2-(methylamino)ethyl]amino]-2-ethylquinazoline-8-carboxamide Chemical compound C1([C@@H](CNC)NC=2N=C(N=C3C(C(N)=O)=CC=CC3=2)CC)=CC=CC(Cl)=C1 GZSKSABPMQXDBI-MRXNPFEDSA-N 0.000 claims 1
• TUGQXVDVBAIMQT-MRXNPFEDSA-N 4-[[(1s)-1-(3-chlorophenyl)-2-(methylamino)ethyl]amino]-2-methylquinazoline-8-carboxamide Chemical compound C1([C@H](NC=2C3=CC=CC(=C3N=C(C)N=2)C(N)=O)CNC)=CC=CC(Cl)=C1 TUGQXVDVBAIMQT-MRXNPFEDSA-N 0.000 claims 1
• GDZSUVPAQIUIGI-CQSZACIVSA-N 4-[[(1s)-1-(3-fluorophenyl)-2-(methylamino)ethyl]amino]-2-(trifluoromethyl)quinazoline-8-carboxamide Chemical compound C1([C@H](NC=2C3=CC=CC(=C3N=C(N=2)C(F)(F)F)C(N)=O)CNC)=CC=CC(F)=C1 GDZSUVPAQIUIGI-CQSZACIVSA-N 0.000 claims 1
• DSLKQMBMFBKGRK-MRXNPFEDSA-N 4-[[(1s)-1-(3-fluorophenyl)-2-(methylamino)ethyl]amino]-2-methylquinazoline-8-carboxamide Chemical compound C1([C@H](NC=2C3=CC=CC(=C3N=C(C)N=2)C(N)=O)CNC)=CC=CC(F)=C1 DSLKQMBMFBKGRK-MRXNPFEDSA-N 0.000 claims 1
• NMCWJLCHHFXWFC-MRXNPFEDSA-N 4-[[(1s)-1-(4-chlorophenyl)-2-(methylamino)ethyl]amino]-2-ethylquinazoline-8-carboxamide Chemical compound C1([C@@H](CNC)NC=2N=C(N=C3C(C(N)=O)=CC=CC3=2)CC)=CC=C(Cl)C=C1 NMCWJLCHHFXWFC-MRXNPFEDSA-N 0.000 claims 1
• NDQZVNOJBBXGOJ-MRXNPFEDSA-N 4-[[(1s)-1-(4-chlorophenyl)-2-(methylamino)ethyl]amino]-2-methylquinazoline-8-carboxamide Chemical compound C1([C@H](NC=2C3=CC=CC(=C3N=C(C)N=2)C(N)=O)CNC)=CC=C(Cl)C=C1 NDQZVNOJBBXGOJ-MRXNPFEDSA-N 0.000 claims 1
• PYWWWUCMNVNQOM-QGZVFWFLSA-N 4-[[(1s)-1-(4-chlorophenyl)-2-(methylamino)ethyl]amino]-2-propan-2-ylquinazoline-8-carboxamide Chemical compound C1([C@H](NC=2C3=CC=CC(=C3N=C(N=2)C(C)C)C(N)=O)CNC)=CC=C(Cl)C=C1 PYWWWUCMNVNQOM-QGZVFWFLSA-N 0.000 claims 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
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• 239000002699 waste material Substances 0.000 claims 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 abstract description 40
• 125000004432 carbon atom Chemical group C* 0.000 abstract 2
• 125000004433 nitrogen atom Chemical group N* 0.000 abstract 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 57
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
• 239000000460 chlorine Substances 0.000 description 29
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 28
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• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
• 150000001414 amino alcohols Chemical class 0.000 description 22
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 22
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
• 238000006243 chemical reaction Methods 0.000 description 20
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• 108091000080 Phosphotransferase Proteins 0.000 description 7
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