CA2806332C - Quinoline derivatives and melk inhibitors containing the same - Google Patents
Quinoline derivatives and melk inhibitors containing the same Download PDFInfo
- Publication number
- CA2806332C CA2806332C CA2806332A CA2806332A CA2806332C CA 2806332 C CA2806332 C CA 2806332C CA 2806332 A CA2806332 A CA 2806332A CA 2806332 A CA2806332 A CA 2806332A CA 2806332 C CA2806332 C CA 2806332C
- Authority
- CA
- Canada
- Prior art keywords
- compound
- quinolin
- chloro
- methanone
- dimethylamino
- Prior art date
- 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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- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title abstract description 3
- 229940124787 MELK inhibitor Drugs 0.000 title description 3
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 2
- 101710154611 Maternal embryonic leucine zipper kinase Proteins 0.000 claims abstract description 23
- 102100024299 Maternal embryonic leucine zipper kinase Human genes 0.000 claims abstract description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 201000010099 disease Diseases 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 230000002018 overexpression Effects 0.000 claims abstract description 9
- -1 dimethylaminopropylaminocarbonyl Chemical group 0.000 claims description 926
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 319
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 294
- 150000001875 compounds Chemical class 0.000 claims description 284
- 125000001424 substituent group Chemical group 0.000 claims description 245
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 223
- 125000005466 alkylenyl group Chemical group 0.000 claims description 132
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 110
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 105
- 125000001931 aliphatic group Chemical group 0.000 claims description 100
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 74
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 69
- 125000000623 heterocyclic group Chemical group 0.000 claims description 63
- 150000003839 salts Chemical class 0.000 claims description 62
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 57
- 229910052736 halogen Chemical group 0.000 claims description 52
- 150000002367 halogens Chemical group 0.000 claims description 52
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 37
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 30
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
- 125000003107 substituted aryl group Chemical group 0.000 claims description 24
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 20
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 16
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 claims description 13
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 11
- 125000003277 amino group Chemical group 0.000 claims description 11
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 10
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 10
- 150000007945 N-acyl ureas Chemical class 0.000 claims description 9
- 229910052805 deuterium Inorganic materials 0.000 claims description 9
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 8
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 8
- 208000026310 Breast neoplasm Diseases 0.000 claims description 8
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 8
- 125000004431 deuterium atom Chemical group 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 206010005003 Bladder cancer Diseases 0.000 claims description 5
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 5
- 230000003449 preventive effect Effects 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 5
- 125000005936 piperidyl group Chemical group 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 201000011199 bladder lymphoma Diseases 0.000 claims description 2
- 206010046766 uterine cancer Diseases 0.000 claims description 2
- 102220480121 H/ACA ribonucleoprotein complex subunit DKC1_R10A_mutation Human genes 0.000 claims 2
- DLMHQUGZXIWVLQ-UHFFFAOYSA-N 1-[4-[[6-(3-aminopiperidin-1-yl)pyridin-3-yl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]propan-1-one Chemical compound CCC(=O)C1=CN=C2C=CC(C=3C=C(Cl)C(O)=C(Cl)C=3)=CC2=C1NC(C=N1)=CC=C1N1CCCC(N)C1 DLMHQUGZXIWVLQ-UHFFFAOYSA-N 0.000 claims 1
- DLMHQUGZXIWVLQ-SFHVURJKSA-N 1-[4-[[6-[(3s)-3-aminopiperidin-1-yl]pyridin-3-yl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]propan-1-one Chemical compound CCC(=O)C1=CN=C2C=CC(C=3C=C(Cl)C(O)=C(Cl)C=3)=CC2=C1NC(C=N1)=CC=C1N1CCC[C@H](N)C1 DLMHQUGZXIWVLQ-SFHVURJKSA-N 0.000 claims 1
- PEAZQTKOWOEYCZ-UKIBZPOASA-N C1C[C@@H](CN(C)C)CC[C@@H]1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 Chemical compound C1C[C@@H](CN(C)C)CC[C@@H]1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 PEAZQTKOWOEYCZ-UKIBZPOASA-N 0.000 claims 1
- YFBRRBWSRJPOIT-RUCARUNLSA-N C1C[C@@H](CN(C)C)CC[C@@H]1NC1=C(C(C)=O)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 Chemical compound C1C[C@@H](CN(C)C)CC[C@@H]1NC1=C(C(C)=O)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 YFBRRBWSRJPOIT-RUCARUNLSA-N 0.000 claims 1
- UYIMHVQEXCPIKN-RUCARUNLSA-N C1C[C@@H](CN(C)C)CC[C@@H]1NC1=C(C(C)=O)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(F)C=3)C=C12 Chemical compound C1C[C@@H](CN(C)C)CC[C@@H]1NC1=C(C(C)=O)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(F)C=3)C=C12 UYIMHVQEXCPIKN-RUCARUNLSA-N 0.000 claims 1
- LCFDWDAPNUMZKM-LJQANCHMSA-N [4-[[6-[(3r)-3-aminopiperidin-1-yl]pyridin-3-yl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]-cyclopropylmethanone Chemical compound C1[C@H](N)CCCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 LCFDWDAPNUMZKM-LJQANCHMSA-N 0.000 claims 1
- LCFDWDAPNUMZKM-IBGZPJMESA-N [4-[[6-[(3s)-3-aminopiperidin-1-yl]pyridin-3-yl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]-cyclopropylmethanone Chemical compound C1[C@@H](N)CCCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 LCFDWDAPNUMZKM-IBGZPJMESA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 2
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 306
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 191
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 174
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 126
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 93
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 90
- JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 78
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 63
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 description 58
- 241001024304 Mino Species 0.000 description 47
- ZVDDJPSHRNMSKV-UHFFFAOYSA-N acetaldehyde;hydrochloride Chemical compound Cl.CC=O ZVDDJPSHRNMSKV-UHFFFAOYSA-N 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 38
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 28
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 23
- DJXNJVFEFSWHLY-UHFFFAOYSA-M quinoline-3-carboxylate Chemical compound C1=CC=CC2=CC(C(=O)[O-])=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-M 0.000 description 22
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 20
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 19
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 18
- WTDFFADXONGQOM-UHFFFAOYSA-N formaldehyde;hydrochloride Chemical compound Cl.O=C WTDFFADXONGQOM-UHFFFAOYSA-N 0.000 description 16
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 16
- 125000000217 alkyl group Chemical group 0.000 description 15
- 239000000460 chlorine Substances 0.000 description 15
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 14
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 14
- BLTDCIWCFCUQCB-UHFFFAOYSA-N quinoline-3-carboxamide Chemical compound C1=CC=CC2=CC(C(=O)N)=CN=C21 BLTDCIWCFCUQCB-UHFFFAOYSA-N 0.000 description 14
- 125000003118 aryl group Chemical group 0.000 description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 13
- 125000006308 propyl amino group Chemical group 0.000 description 13
- PCDHSSHKDZYLLI-UHFFFAOYSA-N butan-1-one Chemical compound CCC[C]=O PCDHSSHKDZYLLI-UHFFFAOYSA-N 0.000 description 12
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 11
- IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 description 11
- 125000001245 hexylamino group Chemical group [H]N([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 10
- NDYMQOUYJJXCKJ-UHFFFAOYSA-N (4-fluorophenyl)-morpholin-4-ylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CCOCC1 NDYMQOUYJJXCKJ-UHFFFAOYSA-N 0.000 description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 9
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 9
- 125000004076 pyridyl group Chemical group 0.000 description 9
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 8
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 8
- 125000004430 oxygen atom Chemical group O* 0.000 description 8
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 8
- 125000004434 sulfur atom Chemical group 0.000 description 8
- 125000001544 thienyl group Chemical group 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 7
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 6
- FQYRLEXKXQRZDH-UHFFFAOYSA-N 4-aminoquinoline Chemical compound C1=CC=C2C(N)=CC=NC2=C1 FQYRLEXKXQRZDH-UHFFFAOYSA-N 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 6
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 6
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 6
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 6
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 6
- 125000004193 piperazinyl group Chemical group 0.000 description 6
- 125000003226 pyrazolyl group Chemical group 0.000 description 6
- 241000009298 Trigla lyra Species 0.000 description 5
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 5
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 5
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
- 125000003282 alkyl amino group Chemical group 0.000 description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 4
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 150000007942 carboxylates Chemical class 0.000 description 4
- MFYHAZBNBNFBHF-UHFFFAOYSA-N cyclopropyl-(2,5-dihydroxyphenyl)methanone Chemical compound OC1=CC=C(O)C(C(=O)C2CC2)=C1 MFYHAZBNBNFBHF-UHFFFAOYSA-N 0.000 description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 description 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 3
- 125000005955 1H-indazolyl group Chemical group 0.000 description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 3
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- BGFKXNIBFGAUER-QAQDUYKDSA-N C1C[C@@H](N)CC[C@@H]1NC1=CC=NC2=CC=C(C=3C=CC(O)=CC=3)C=C12 Chemical compound C1C[C@@H](N)CC[C@@H]1NC1=CC=NC2=CC=C(C=3C=CC(O)=CC=3)C=C12 BGFKXNIBFGAUER-QAQDUYKDSA-N 0.000 description 3
- 206010008342 Cervix carcinoma Diseases 0.000 description 3
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 3
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 3
- 101150006573 PAN1 gene Proteins 0.000 description 3
- 206010041067 Small cell lung cancer Diseases 0.000 description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 description 3
- 201000010881 cervical cancer Diseases 0.000 description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 description 3
- VELDYOPRLMJFIK-UHFFFAOYSA-N cyclopentanecarbaldehyde Chemical compound O=CC1CCCC1 VELDYOPRLMJFIK-UHFFFAOYSA-N 0.000 description 3
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 229960001867 guaiacol Drugs 0.000 description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
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- RILSCBLGXDGPRT-UHFFFAOYSA-N ethyl 4-(4-acetamidoanilino)-6-fluoroquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(F)=CC2=C1NC1=CC=C(NC(C)=O)C=C1 RILSCBLGXDGPRT-UHFFFAOYSA-N 0.000 description 1
- NAZMBTHXECFPGP-UHFFFAOYSA-N ethyl 4-(4-aminoanilino)-6-chloroquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Cl)=CC2=C1NC1=CC=C(N)C=C1 NAZMBTHXECFPGP-UHFFFAOYSA-N 0.000 description 1
- GDNVPLHZYNZCSG-UHFFFAOYSA-N ethyl 4-[(3-aminocyclohexyl)amino]-6-bromoquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1NC1CCCC(N)C1 GDNVPLHZYNZCSG-UHFFFAOYSA-N 0.000 description 1
- XOUDNJZLQCPTMS-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-(3-hydroxyphenyl)quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=CC(O)=C1 XOUDNJZLQCPTMS-UHFFFAOYSA-N 0.000 description 1
- UOPGUFUVRUJYBU-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-(4-hydroxy-3-methoxyphenyl)quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(O)C(OC)=C1 UOPGUFUVRUJYBU-UHFFFAOYSA-N 0.000 description 1
- YGSZDFHEWKHNAF-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-(4-hydroxyphenyl)quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(O)C=C1 YGSZDFHEWKHNAF-UHFFFAOYSA-N 0.000 description 1
- LGWOQYCBBXBJSH-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-(4-methoxyphenyl)quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(OC)C=C1 LGWOQYCBBXBJSH-UHFFFAOYSA-N 0.000 description 1
- USAZUNDHJPBZQQ-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-(4-sulfamoylphenyl)quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(S(N)(=O)=O)C=C1 USAZUNDHJPBZQQ-UHFFFAOYSA-N 0.000 description 1
- OABFDBDSRJQHQT-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-methylquinoline-3-carboxylate Chemical compound C1=CC(C)=CC2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C21 OABFDBDSRJQHQT-UHFFFAOYSA-N 0.000 description 1
- QZBNGVMWXLQUQW-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-pyridin-4-ylquinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=NC=C1 QZBNGVMWXLQUQW-UHFFFAOYSA-N 0.000 description 1
- VMTGQJIMLUYLLC-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-thiophen-2-ylquinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=CS1 VMTGQJIMLUYLLC-UHFFFAOYSA-N 0.000 description 1
- ITZRBOCLNMKQQP-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]quinoline-3-carboxylate Chemical compound C1=CC=CC2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C21 ITZRBOCLNMKQQP-UHFFFAOYSA-N 0.000 description 1
- SSMWAAZPTJIPOJ-UHFFFAOYSA-N ethyl 4-[[3-(aminomethyl)cyclohexyl]methylamino]-6-bromoquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1NCC1CCCC(CN)C1 SSMWAAZPTJIPOJ-UHFFFAOYSA-N 0.000 description 1
- AWNWSRDLFOECAK-UHFFFAOYSA-N ethyl 6-bromo-4-(3-carbamoylpiperidin-1-yl)quinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1N1CCCC(C(N)=O)C1 AWNWSRDLFOECAK-UHFFFAOYSA-N 0.000 description 1
- BFNXREBOONZFTR-UHFFFAOYSA-N ethyl 6-bromo-4-(piperidin-4-ylmethylamino)quinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1NCC1CCNCC1 BFNXREBOONZFTR-UHFFFAOYSA-N 0.000 description 1
- OQGHFXOAFBNLLA-UHFFFAOYSA-N ethyl 6-bromo-4-(pyridin-4-ylmethylamino)quinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1NCC1=CC=NC=C1 OQGHFXOAFBNLLA-UHFFFAOYSA-N 0.000 description 1
- GCXYTARBKLKKKQ-UHFFFAOYSA-N ethyl 6-bromo-4-[3-(2-hydroxyethylamino)propylamino]quinoline-3-carboxylate Chemical compound C1=CC(Br)=CC2=C(NCCCNCCO)C(C(=O)OCC)=CN=C21 GCXYTARBKLKKKQ-UHFFFAOYSA-N 0.000 description 1
- NPMCACCUGBYQNL-UHFFFAOYSA-N ethyl 6-bromo-4-[3-(diethylamino)propylamino]quinoline-3-carboxylate Chemical compound C1=CC(Br)=CC2=C(NCCCN(CC)CC)C(C(=O)OCC)=CN=C21 NPMCACCUGBYQNL-UHFFFAOYSA-N 0.000 description 1
- KPZFUROUFCADHP-UHFFFAOYSA-N ethyl 6-bromo-4-[3-(dimethylamino)propylamino]quinoline-3-carboxylate Chemical compound C1=CC(Br)=CC2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C21 KPZFUROUFCADHP-UHFFFAOYSA-N 0.000 description 1
- CVBAGPILGWGLKT-UHFFFAOYSA-N ethyl 6-bromo-4-[4-[(dimethylamino)methyl]piperidin-1-yl]quinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1N1CCC(CN(C)C)CC1 CVBAGPILGWGLKT-UHFFFAOYSA-N 0.000 description 1
- IVZIOBTVAJBBAS-UHFFFAOYSA-N ethyl 6-bromo-4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=C(Br)C=C2C(=O)C(C(=O)OCC)=CNC2=C1 IVZIOBTVAJBBAS-UHFFFAOYSA-N 0.000 description 1
- KMUSVINZSCTMHQ-UHFFFAOYSA-N ethyl 6-chloro-4-[3-(dimethylamino)propylamino]quinoline-3-carboxylate Chemical compound C1=CC(Cl)=CC2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C21 KMUSVINZSCTMHQ-UHFFFAOYSA-N 0.000 description 1
- MYXXMMCDGYPHRN-UHFFFAOYSA-N ethyl 6-chloro-4-[4-(dimethylamino)anilino]quinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Cl)=CC2=C1NC1=CC=C(N(C)C)C=C1 MYXXMMCDGYPHRN-UHFFFAOYSA-N 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- NMUZMGPHYASFRU-UHFFFAOYSA-N formaldehyde;dihydrochloride Chemical compound Cl.Cl.O=C NMUZMGPHYASFRU-UHFFFAOYSA-N 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- XCLRCCIRGKHUEX-UHFFFAOYSA-N heptanamide;hydrochloride Chemical compound Cl.CCCCCCC(N)=O XCLRCCIRGKHUEX-UHFFFAOYSA-N 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- QBYJBZPUGVGKQQ-DIFDVCDBSA-N isodrin Chemical compound C1[C@@H]2C=C[C@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-DIFDVCDBSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- ZBELDPMWYXDLNY-UHFFFAOYSA-N methyl 9-(4-bromo-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate Chemical compound C12=C3SC(C(=N)OC)=NC3=CC=C2N=CN=C1NC1=CC=C(Br)C=C1F ZBELDPMWYXDLNY-UHFFFAOYSA-N 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
- QCCWVNLOJADEAV-UHFFFAOYSA-N n,n-dimethyl-1h-pyrrol-3-amine Chemical compound CN(C)C=1C=CNC=1 QCCWVNLOJADEAV-UHFFFAOYSA-N 0.000 description 1
- YCJZWBZJSYLMPB-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-2,5-dimethyl-1-phenylimidazole-4-carboxamide Chemical compound CC=1N(C=2C=CC=CC=2)C(C)=NC=1C(=O)NC1=CC=NC(Cl)=N1 YCJZWBZJSYLMPB-UHFFFAOYSA-N 0.000 description 1
- APVPOHHVBBYQAV-UHFFFAOYSA-N n-(4-aminophenyl)sulfonyloctadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 APVPOHHVBBYQAV-UHFFFAOYSA-N 0.000 description 1
- GAMIJGSNOYVKJP-UHFFFAOYSA-N n-(4-chlorophenyl)-4-(piperidin-3-ylmethylamino)quinoline-3-carboxamide Chemical compound C1=CC(Cl)=CC=C1NC(=O)C1=CN=C(C=CC=C2)C2=C1NCC1CNCCC1 GAMIJGSNOYVKJP-UHFFFAOYSA-N 0.000 description 1
- ZHXBNPPHMUJAKW-UHFFFAOYSA-N n-(4-chlorophenyl)quinolin-2-amine Chemical compound C1=CC(Cl)=CC=C1NC1=CC=C(C=CC=C2)C2=N1 ZHXBNPPHMUJAKW-UHFFFAOYSA-N 0.000 description 1
- HRWBZSWGUITKPH-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-3-thiophen-2-ylquinolin-4-amine Chemical compound CCN1CCCC1CNC1=C(C=2SC=CC=2)C=NC2=CC=CC=C12 HRWBZSWGUITKPH-UHFFFAOYSA-N 0.000 description 1
- IHCHOVVAJBADAH-UHFFFAOYSA-N n-[2-hydroxy-4-(1h-pyrazol-4-yl)phenyl]-6-methoxy-3,4-dihydro-2h-chromene-3-carboxamide Chemical compound C1C2=CC(OC)=CC=C2OCC1C(=O)NC(C(=C1)O)=CC=C1C=1C=NNC=1 IHCHOVVAJBADAH-UHFFFAOYSA-N 0.000 description 1
- JYLZZCBDMCZAIE-UHFFFAOYSA-N n-[4-[(3-thiophen-2-ylquinolin-4-yl)amino]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1NC1=C(C=2SC=CC=2)C=NC2=CC=CC=C12 JYLZZCBDMCZAIE-UHFFFAOYSA-N 0.000 description 1
- FLDAQAUMQJXNCW-UHFFFAOYSA-N n-[4-[[6-bromo-3-(thiophene-2-carbonyl)quinolin-4-yl]amino]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1NC1=C(C(=O)C=2SC=CC=2)C=NC2=CC=C(Br)C=C12 FLDAQAUMQJXNCW-UHFFFAOYSA-N 0.000 description 1
- UDGCTTFBOQJODH-UHFFFAOYSA-N n-[4-[[6-chloro-3-(4-chlorobenzoyl)quinolin-4-yl]amino]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1NC1=C(C(=O)C=2C=CC(Cl)=CC=2)C=NC2=CC=C(Cl)C=C12 UDGCTTFBOQJODH-UHFFFAOYSA-N 0.000 description 1
- PHQRISXOCBUKII-UHFFFAOYSA-N n-[4-[[6-chloro-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Cl)C=C12 PHQRISXOCBUKII-UHFFFAOYSA-N 0.000 description 1
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
- FVLVBVSILSHUAF-UHFFFAOYSA-N n-benzyl-3,5-dimethyl-n-propan-2-ylbenzamide Chemical compound C=1C(C)=CC(C)=CC=1C(=O)N(C(C)C)CC1=CC=CC=C1 FVLVBVSILSHUAF-UHFFFAOYSA-N 0.000 description 1
- LPOIGVZLNWEGJG-UHFFFAOYSA-N n-benzyl-5-(4-methylpiperazin-1-yl)-2-nitroaniline Chemical compound C1CN(C)CCN1C1=CC=C([N+]([O-])=O)C(NCC=2C=CC=CC=2)=C1 LPOIGVZLNWEGJG-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- JOCYRIINDHNKNL-UHFFFAOYSA-N propanal;dihydrochloride Chemical compound Cl.Cl.CCC=O JOCYRIINDHNKNL-UHFFFAOYSA-N 0.000 description 1
- UUMZDXBZTGNJDF-UHFFFAOYSA-N propanamide;dihydrochloride Chemical compound Cl.Cl.CCC(N)=O UUMZDXBZTGNJDF-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- NGXSWUFDCSEIOO-UHFFFAOYSA-N pyrrolidin-3-amine Chemical compound NC1CCNC1 NGXSWUFDCSEIOO-UHFFFAOYSA-N 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- QZZYYBQGTSGDPP-UHFFFAOYSA-N quinoline-3-carbonitrile Chemical compound C1=CC=CC2=CC(C#N)=CN=C21 QZZYYBQGTSGDPP-UHFFFAOYSA-N 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000024642 stem cell division Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- LAWUZBKFMNSOGG-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=[C]S1 LAWUZBKFMNSOGG-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- CNHDIAIOKMXOLK-UHFFFAOYSA-N toluquinol Chemical compound CC1=CC(O)=CC=C1O CNHDIAIOKMXOLK-UHFFFAOYSA-N 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- Chemical & Material Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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- 2011-07-28 JP JP2013523213A patent/JP5849303B2/ja active Active
- 2011-07-28 BR BR112013002182A patent/BR112013002182B8/pt active IP Right Grant
- 2011-07-28 US US13/813,134 patent/US9120749B2/en active Active
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|---|---|
| SG10201505951VA (en) | 2015-08-28 |
| DK2597955T3 (en) | 2016-03-14 |
| TW201208686A (en) | 2012-03-01 |
| AU2011282588B2 (en) | 2016-01-07 |
| CA2806332A1 (en) | 2012-02-02 |
| SG187633A1 (en) | 2013-03-28 |
| CN103153063B (zh) | 2016-02-17 |
| TWI532483B (zh) | 2016-05-11 |
| CN103153063A (zh) | 2013-06-12 |
| US20130217671A1 (en) | 2013-08-22 |
| EP2597955A1 (en) | 2013-06-05 |
| US9120749B2 (en) | 2015-09-01 |
| KR20130094312A (ko) | 2013-08-23 |
| JP5849303B2 (ja) | 2016-01-27 |
| BR112013002182A2 (pt) | 2016-05-31 |
| EP2597955B1 (en) | 2016-01-20 |
| KR101826382B1 (ko) | 2018-02-06 |
| HK1184331A1 (zh) | 2014-01-24 |
| AU2011282588A1 (en) | 2013-03-21 |
| JP2013532727A (ja) | 2013-08-19 |
| EP2597955A4 (en) | 2014-02-19 |
| BR112013002182B1 (pt) | 2022-05-03 |
| MX2013001201A (es) | 2013-04-03 |
| ES2565627T3 (es) | 2016-04-06 |
| RU2013108865A (ru) | 2014-09-10 |
| RU2582610C2 (ru) | 2016-04-27 |
| WO2012016082A1 (en) | 2012-02-02 |
| MX342879B (es) | 2016-10-14 |
| BR112013002182B8 (pt) | 2023-02-28 |
| IL223871A (en) | 2016-11-30 |
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