CA2985161A1 - Novel amidoheteroaryl aroyl hydrazide ethynes - Google Patents
Novel amidoheteroaryl aroyl hydrazide ethynes Download PDFInfo
- Publication number
- CA2985161A1 CA2985161A1 CA2985161A CA2985161A CA2985161A1 CA 2985161 A1 CA2985161 A1 CA 2985161A1 CA 2985161 A CA2985161 A CA 2985161A CA 2985161 A CA2985161 A CA 2985161A CA 2985161 A1 CA2985161 A1 CA 2985161A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- pyridin
- formula
- alkyl
- hydrazinocarbonyl
- 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.)
- Abandoned
Links
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 title abstract description 8
- 125000003435 aroyl group Chemical group 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 150000001408 amides Chemical class 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- YDNKKVBURJSGKM-UHFFFAOYSA-N N-[5-[2-[2-methyl-5-[[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]carbamoyl]phenyl]ethynyl]pyridin-2-yl]cyclopropanecarboxamide Chemical compound CC1=C(C=C(C=C1)C(=O)NNC(C1=CC(=CC(=C1)C(F)(F)F)N1C=NC(=C1)C)=O)C#CC=1C=CC(=NC=1)NC(=O)C1CC1 YDNKKVBURJSGKM-UHFFFAOYSA-N 0.000 claims 2
- PSWVXKCLQUYTCY-UHFFFAOYSA-N N-[5-[2-[2-methyl-5-[[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]carbamoyl]phenyl]ethynyl]pyridin-2-yl]cyclopropanecarboxamide Chemical compound CC1=C(C=C(C=C1)C(=O)NNC(C1=CC=C(C=C1)CN1CCN(CC1)C)=O)C#CC=1C=CC(=NC=1)NC(=O)C1CC1 PSWVXKCLQUYTCY-UHFFFAOYSA-N 0.000 claims 2
- NZXDVMRNUSTTGO-UHFFFAOYSA-N N-[5-[2-[5-[[(2-chloro-6-methylbenzoyl)amino]carbamoyl]-2-methylphenyl]ethynyl]pyridin-2-yl]cyclopropanecarboxamide Chemical compound ClC1=C(C(=O)NNC(=O)C=2C=CC(=C(C=2)C#CC=2C=CC(=NC=2)NC(=O)C2CC2)C)C(=CC=C1)C NZXDVMRNUSTTGO-UHFFFAOYSA-N 0.000 claims 2
- AUIIWQULVSVOFU-UHFFFAOYSA-N 1-[5-[2-[5-[[(2-chloro-6-methylbenzoyl)amino]carbamoyl]-2-methylphenyl]ethynyl]pyridin-2-yl]-3-cyclopropylurea Chemical compound ClC1=C(C(=O)NNC(=O)C=2C=CC(=C(C=2)C#CC=2C=CC(=NC=2)NC(=O)NC2CC2)C)C(=CC=C1)C AUIIWQULVSVOFU-UHFFFAOYSA-N 0.000 claims 1
- XKGODAYHQIZONO-UHFFFAOYSA-N N-[5-[2-[5-[[(2-chloro-6-methylbenzoyl)amino]carbamoyl]-2-methylphenyl]ethynyl]pyridin-2-yl]-2-[3-(dimethylamino)pyrrolidin-1-yl]acetamide Chemical compound ClC1=C(C(=O)NNC(=O)C=2C=CC(=C(C=2)C#CC=2C=CC(=NC=2)NC(CN2CC(CC2)N(C)C)=O)C)C(=CC=C1)C XKGODAYHQIZONO-UHFFFAOYSA-N 0.000 claims 1
- BSQVFLAGPYVFBJ-UHFFFAOYSA-N N-[5-[2-[5-[[(2-chloro-6-methylbenzoyl)amino]carbamoyl]-2-methylphenyl]ethynyl]pyridin-2-yl]-2-[4-(dimethylamino)piperidin-1-yl]acetamide Chemical compound ClC1=C(C(=O)NNC(=O)C=2C=CC(=C(C=2)C#CC=2C=CC(=NC=2)NC(CN2CCC(CC2)N(C)C)=O)C)C(=CC=C1)C BSQVFLAGPYVFBJ-UHFFFAOYSA-N 0.000 claims 1
- IFLOEAVTCNHYAU-UHFFFAOYSA-N N-[5-[2-[5-[[(2-chloro-6-methylbenzoyl)amino]carbamoyl]-2-methylphenyl]ethynyl]pyridin-2-yl]acetamide Chemical compound ClC1=C(C(=O)NNC(=O)C=2C=CC(=C(C=2)C#CC=2C=CC(=NC=2)NC(C)=O)C)C(=CC=C1)C IFLOEAVTCNHYAU-UHFFFAOYSA-N 0.000 claims 1
- MISDRDJVYWKPTI-UHFFFAOYSA-N N-[5-[2-[5-[amino-(2-chloro-6-methylbenzoyl)carbamoyl]-2-methylphenyl]ethynyl]pyridin-2-yl]-3-(4-methylpiperazin-1-yl)propanamide Chemical compound ClC1=C(C(=O)N(N)C(=O)C=2C=CC(=C(C=2)C#CC=2C=CC(=NC=2)NC(CCN2CCN(CC2)C)=O)C)C(=CC=C1)C MISDRDJVYWKPTI-UHFFFAOYSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 16
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 abstract description 9
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 abstract description 9
- 230000008569 process Effects 0.000 abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 238000002360 preparation method Methods 0.000 abstract description 7
- 208000035475 disorder Diseases 0.000 abstract description 5
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 abstract description 4
- 239000005483 tyrosine kinase inhibitor Substances 0.000 abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- -1 Kit Proteins 0.000 description 31
- 239000002253 acid Substances 0.000 description 20
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
- 150000008064 anhydrides Chemical class 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 238000009833 condensation Methods 0.000 description 6
- 230000005494 condensation Effects 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 5
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229960002448 dasatinib Drugs 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 3
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 150000001718 carbodiimides Chemical class 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 3
- 229960002411 imatinib Drugs 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 3
- 229940080818 propionamide Drugs 0.000 description 3
- 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 description 3
- 229940086542 triethylamine Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 229960001346 nilotinib Drugs 0.000 description 2
- BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000001301 oxygen Chemical group 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
- 229960001131 ponatinib Drugs 0.000 description 2
- PHXJVRSECIGDHY-UHFFFAOYSA-N ponatinib Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2N3N=CC=CC3=NC=2)=C1 PHXJVRSECIGDHY-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- LHJGJYXLEPZJPM-UHFFFAOYSA-N 2,4,5-trichlorophenol Chemical compound OC1=CC(Cl)=C(Cl)C=C1Cl LHJGJYXLEPZJPM-UHFFFAOYSA-N 0.000 description 1
- UKPHSBYFUYSAIM-UHFFFAOYSA-N 2-chloro-6-methylbenzohydrazide Chemical compound CC1=CC=CC(Cl)=C1C(=O)NN UKPHSBYFUYSAIM-UHFFFAOYSA-N 0.000 description 1
- CEFMMQYDPGCYMG-UHFFFAOYSA-N 2-chloro-6-methylbenzoic acid Chemical compound CC1=CC=CC(Cl)=C1C(O)=O CEFMMQYDPGCYMG-UHFFFAOYSA-N 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B43/00—Formation or introduction of functional groups containing nitrogen
- C07B43/06—Formation or introduction of functional groups containing nitrogen of amide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1953MU2015 | 2015-05-18 | ||
| IN1953/MUM/2015 | 2015-05-18 | ||
| PCT/IN2016/050142 WO2016185490A1 (en) | 2015-05-18 | 2016-05-18 | Novel amidoheteroaryl aroyl hydrazide ethynes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2985161A1 true CA2985161A1 (en) | 2016-11-24 |
Family
ID=57319598
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2985161A Abandoned CA2985161A1 (en) | 2015-05-18 | 2016-05-18 | Novel amidoheteroaryl aroyl hydrazide ethynes |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US10150733B2 (enExample) |
| EP (1) | EP3297991B1 (enExample) |
| JP (1) | JP6689887B2 (enExample) |
| KR (1) | KR20180011772A (enExample) |
| CN (1) | CN107709300A (enExample) |
| AU (1) | AU2016263311A1 (enExample) |
| BR (1) | BR112017024633A2 (enExample) |
| CA (1) | CA2985161A1 (enExample) |
| EA (1) | EA032697B1 (enExample) |
| ES (1) | ES2774501T3 (enExample) |
| MX (1) | MX2017014752A (enExample) |
| WO (1) | WO2016185490A1 (enExample) |
| ZA (1) | ZA201707664B (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RS63243B1 (sr) | 2016-06-02 | 2022-06-30 | Sun Pharma Advanced Res Co Ltd | Lečenje parkinsonove bolesti |
| EA037697B1 (ru) * | 2016-06-02 | 2021-05-12 | Сан Фарма Адвансед Ресёрч Компани Лимитед | Лечение болезни паркинсона |
| WO2018167803A1 (en) * | 2017-03-15 | 2018-09-20 | Sun Pharma Advanced Research Company Limited | Novel amorphous dispersion of cyclopropanecarboxylic acid (5-{5-[ n'-(2-chloro-6-methylbenzoyl) hydrazinocarbonyl] -2-methyl-phenylethynyl}-pyridin-2-yl) amide |
| TWI831259B (zh) | 2018-06-15 | 2024-02-01 | 漢達生技醫藥股份有限公司 | 包含達沙替尼十二烷基硫酸鹽組合物的膠囊 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103435595A (zh) * | 2006-05-08 | 2013-12-11 | 阿里亚德医药股份有限公司 | 炔类杂芳基化合物 |
| WO2012089106A1 (zh) * | 2010-12-27 | 2012-07-05 | Sun Shuping | 作为蛋白激酶抑制剂的芳炔类衍生物及其医疗用途 |
| US9024021B2 (en) * | 2011-01-21 | 2015-05-05 | Sun Pharma Advanced Research Company Ltd. | Diarylacetylene hydrazide containing tyrosine kinase inhibitors |
| US8859541B2 (en) * | 2012-02-27 | 2014-10-14 | Boehringer Ingelheim International Gmbh | 6-alkynylpyridines |
-
2016
- 2016-05-18 EP EP16796030.1A patent/EP3297991B1/en active Active
- 2016-05-18 CN CN201680028615.2A patent/CN107709300A/zh not_active Withdrawn
- 2016-05-18 CA CA2985161A patent/CA2985161A1/en not_active Abandoned
- 2016-05-18 KR KR1020177033739A patent/KR20180011772A/ko not_active Withdrawn
- 2016-05-18 ES ES16796030T patent/ES2774501T3/es active Active
- 2016-05-18 MX MX2017014752A patent/MX2017014752A/es unknown
- 2016-05-18 EA EA201792445A patent/EA032697B1/ru not_active IP Right Cessation
- 2016-05-18 US US15/574,967 patent/US10150733B2/en active Active
- 2016-05-18 JP JP2017560135A patent/JP6689887B2/ja not_active Expired - Fee Related
- 2016-05-18 WO PCT/IN2016/050142 patent/WO2016185490A1/en not_active Ceased
- 2016-05-18 BR BR112017024633A patent/BR112017024633A2/pt not_active Application Discontinuation
- 2016-05-18 AU AU2016263311A patent/AU2016263311A1/en not_active Abandoned
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2017
- 2017-11-13 ZA ZA2017/07664A patent/ZA201707664B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MX2017014752A (es) | 2018-03-23 |
| AU2016263311A1 (en) | 2017-11-30 |
| KR20180011772A (ko) | 2018-02-02 |
| EA032697B1 (ru) | 2019-07-31 |
| JP6689887B2 (ja) | 2020-04-28 |
| EA201792445A1 (ru) | 2018-04-30 |
| EP3297991A1 (en) | 2018-03-28 |
| BR112017024633A2 (pt) | 2018-07-31 |
| EP3297991B1 (en) | 2020-01-29 |
| JP2018515550A (ja) | 2018-06-14 |
| ES2774501T3 (es) | 2020-07-21 |
| CN107709300A (zh) | 2018-02-16 |
| US10150733B2 (en) | 2018-12-11 |
| EP3297991A4 (en) | 2018-11-21 |
| WO2016185490A1 (en) | 2016-11-24 |
| US20180127372A1 (en) | 2018-05-10 |
| ZA201707664B (en) | 2019-08-28 |
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| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20220301 |