SI2509974T1 - Pyrazoles derivatives modulators of calcium release-activated calcium channel and methods for treatment of non-small cell lung cancer - Google Patents
Pyrazoles derivatives modulators of calcium release-activated calcium channel and methods for treatment of non-small cell lung cancer Download PDFInfo
- Publication number
- SI2509974T1 SI2509974T1 SI201031711T SI201031711T SI2509974T1 SI 2509974 T1 SI2509974 T1 SI 2509974T1 SI 201031711 T SI201031711 T SI 201031711T SI 201031711 T SI201031711 T SI 201031711T SI 2509974 T1 SI2509974 T1 SI 2509974T1
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- SI
- Slovenia
- Prior art keywords
- substituted
- pyrazol
- unsubstituted
- cyclopropyl
- trifluoromethyl
- Prior art date
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- 238000011282 treatment Methods 0.000 title claims abstract 7
- 208000002154 non-small cell lung carcinoma Diseases 0.000 title claims abstract 6
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 title claims abstract 6
- 108090000312 Calcium Channels Proteins 0.000 title claims 3
- 102000003922 Calcium Channels Human genes 0.000 title claims 3
- 150000001669 calcium Chemical class 0.000 title abstract 2
- 150000003217 pyrazoles Chemical class 0.000 title 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract 2
- 206010028980 Neoplasm Diseases 0.000 claims abstract 2
- 229910052791 calcium Inorganic materials 0.000 claims abstract 2
- 239000011575 calcium Substances 0.000 claims abstract 2
- 201000011510 cancer Diseases 0.000 claims abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 2
- -1 nitro, hydroxy Chemical group 0.000 claims 26
- 150000001875 compounds Chemical class 0.000 claims 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims 6
- 229910052736 halogen Inorganic materials 0.000 claims 6
- 150000002367 halogens Chemical class 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 239000001257 hydrogen Substances 0.000 claims 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 6
- 125000000217 alkyl group Chemical group 0.000 claims 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims 5
- 125000000623 heterocyclic group Chemical group 0.000 claims 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 4
- 125000003342 alkenyl group Chemical group 0.000 claims 4
- 125000000304 alkynyl group Chemical group 0.000 claims 4
- 125000004429 atom Chemical group 0.000 claims 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 125000005842 heteroatom Chemical group 0.000 claims 4
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 229920006395 saturated elastomer Polymers 0.000 claims 4
- 125000001424 substituent group Chemical group 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- 150000001204 N-oxides Chemical class 0.000 claims 3
- 125000003118 aryl group Chemical group 0.000 claims 3
- 150000002148 esters Chemical class 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 108091006146 Channels Proteins 0.000 claims 2
- 229910003827 NRaRb Inorganic materials 0.000 claims 2
- 101150066814 Orai3 gene Proteins 0.000 claims 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims 2
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- AIEWPUPGEAKMFQ-UHFFFAOYSA-N n-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]pyrazolo[1,5-a]pyrimidine-2-carboxamide Chemical compound C=1C=C(NC(=O)C2=NN3C=CC=NC3=C2)C=CC=1N1N=C(C(F)(F)F)C=C1C1CC1 AIEWPUPGEAKMFQ-UHFFFAOYSA-N 0.000 claims 2
- PPPQPLAZICCCNM-UHFFFAOYSA-N quinoxaline-6-carboxamide Chemical compound N1=CC=NC2=CC(C(=O)N)=CC=C21 PPPQPLAZICCCNM-UHFFFAOYSA-N 0.000 claims 2
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims 1
- BNYCHCAYYYRJSH-UHFFFAOYSA-N 1h-pyrazole-5-carboxamide Chemical compound NC(=O)C1=CC=NN1 BNYCHCAYYYRJSH-UHFFFAOYSA-N 0.000 claims 1
- GFEXQYDXDNDRNL-UHFFFAOYSA-N 4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-fluoro-n-(quinolin-6-ylmethyl)benzamide;hydrochloride Chemical compound Cl.FC1=CC(C(=O)NCC=2C=C3C=CC=NC3=CC=2)=CC=C1N1N=C(C(F)(F)F)C=C1C1CC1 GFEXQYDXDNDRNL-UHFFFAOYSA-N 0.000 claims 1
- LSBDFXRDZJMBSC-UHFFFAOYSA-N Amide-Phenylacetic acid Natural products NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 claims 1
- 108091022898 Calcium release-activated calcium channel Proteins 0.000 claims 1
- 102000020167 Calcium release-activated calcium channel Human genes 0.000 claims 1
- 102100039319 Calcium release-activated calcium channel protein 1 Human genes 0.000 claims 1
- 101000745520 Homo sapiens Calcium release-activated calcium channel protein 1 Proteins 0.000 claims 1
- DXJCJYLYRFJKSE-UHFFFAOYSA-N N-[6-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]pyridin-3-yl]acetamide Chemical compound C(C)(=O)NC=1C=NC(=CC=1)N1N=C(C=C1C1CC1)C(F)(F)F DXJCJYLYRFJKSE-UHFFFAOYSA-N 0.000 claims 1
- 101710137312 Protein orai Proteins 0.000 claims 1
- 125000000848 adenin-9-yl group Chemical group [H]N([H])C1=C2N=C([H])N(*)C2=NC([H])=N1 0.000 claims 1
- 125000002619 bicyclic group Chemical group 0.000 claims 1
- 238000009395 breeding Methods 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- ARVDNOLJGIWRPY-UHFFFAOYSA-N n-[4-(3,5-dicyclopropylpyrazol-1-yl)-3-fluorophenyl]-2-quinolin-6-ylacetamide;hydrochloride Chemical compound Cl.FC1=CC(NC(=O)CC=2C=C3C=CC=NC3=CC=2)=CC=C1N1N=C(C2CC2)C=C1C1CC1 ARVDNOLJGIWRPY-UHFFFAOYSA-N 0.000 claims 1
- RVVCOHUMRKGYOQ-UHFFFAOYSA-N n-[4-(3,5-dicyclopropylpyrazol-1-yl)phenyl]-2-imidazo[1,2-a]pyridin-2-ylacetamide;hydrochloride Chemical compound Cl.C=1N2C=CC=CC2=NC=1CC(=O)NC(C=C1)=CC=C1N1N=C(C2CC2)C=C1C1CC1 RVVCOHUMRKGYOQ-UHFFFAOYSA-N 0.000 claims 1
- DSDZJXDZFHZFCS-UHFFFAOYSA-N n-[4-(3,5-dicyclopropylpyrazol-1-yl)phenyl]quinoline-6-carboxamide Chemical compound C=1C=C2N=CC=CC2=CC=1C(=O)NC(C=C1)=CC=C1N1N=C(C2CC2)C=C1C1CC1 DSDZJXDZFHZFCS-UHFFFAOYSA-N 0.000 claims 1
- CNKXCBXGFXKCLU-UHFFFAOYSA-N n-[4-(3,5-dicyclopropylpyrazol-1-yl)phenyl]quinoline-6-carboxamide;hydrochloride Chemical compound Cl.C=1C=C2N=CC=CC2=CC=1C(=O)NC(C=C1)=CC=C1N1N=C(C2CC2)C=C1C1CC1 CNKXCBXGFXKCLU-UHFFFAOYSA-N 0.000 claims 1
- VTHOULHKCFBBGL-UHFFFAOYSA-N n-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-1-methyl-3-(trifluoromethyl)thieno[2,3-c]pyrazole-5-carboxamide Chemical compound S1C=2N(C)N=C(C(F)(F)F)C=2C=C1C(=O)NC(C=C1)=CC=C1N1N=C(C(F)(F)F)C=C1C1CC1 VTHOULHKCFBBGL-UHFFFAOYSA-N 0.000 claims 1
- NJFPDHIQNGAWOR-UHFFFAOYSA-N n-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-2-quinolin-6-ylpropanamide Chemical compound C=1C=C2N=CC=CC2=CC=1C(C)C(=O)NC(C=C1)=CC=C1N1N=C(C(F)(F)F)C=C1C1CC1 NJFPDHIQNGAWOR-UHFFFAOYSA-N 0.000 claims 1
- KJHRSKBLZWQIII-UHFFFAOYSA-N n-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]quinoline-6-carboxamide;hydrochloride Chemical compound Cl.C=1C=C(NC(=O)C=2C=C3C=CC=NC3=CC=2)C=CC=1N1N=C(C(F)(F)F)C=C1C1CC1 KJHRSKBLZWQIII-UHFFFAOYSA-N 0.000 claims 1
- RWAAUILDZAEDCU-UHFFFAOYSA-N n-[6-(3,5-dicyclopropylpyrazol-1-yl)pyridin-3-yl]-2-quinolin-6-ylacetamide Chemical compound C=1C=C2N=CC=CC2=CC=1CC(=O)NC(C=N1)=CC=C1N1N=C(C2CC2)C=C1C1CC1 RWAAUILDZAEDCU-UHFFFAOYSA-N 0.000 claims 1
- DIKLBJAGDNPCAR-UHFFFAOYSA-N n-[6-(3,5-dicyclopropylpyrazol-1-yl)pyridin-3-yl]-2-quinolin-6-ylacetamide;dihydrochloride Chemical compound Cl.Cl.C=1C=C2N=CC=CC2=CC=1CC(=O)NC(C=N1)=CC=C1N1N=C(C2CC2)C=C1C1CC1 DIKLBJAGDNPCAR-UHFFFAOYSA-N 0.000 claims 1
- MSQODCVDYGUJNP-UHFFFAOYSA-N n-[6-(3,5-dicyclopropylpyrazol-1-yl)pyridin-3-yl]quinoline-6-carboxamide;dihydrochloride Chemical compound Cl.Cl.C=1C=C2N=CC=CC2=CC=1C(=O)NC(C=N1)=CC=C1N1N=C(C2CC2)C=C1C1CC1 MSQODCVDYGUJNP-UHFFFAOYSA-N 0.000 claims 1
- ZWPBCJNFUABMDA-UHFFFAOYSA-N n-[6-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]pyridin-3-yl]-2-quinolin-6-ylacetamide;hydrochloride Chemical compound Cl.C=1C=C(NC(=O)CC=2C=C3C=CC=NC3=CC=2)C=NC=1N1N=C(C(F)(F)F)C=C1C1CC1 ZWPBCJNFUABMDA-UHFFFAOYSA-N 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 101150060735 orai1 gene Proteins 0.000 claims 1
- YMNAJWHTELQUJU-UHFFFAOYSA-N quinoline-6-carboxamide Chemical compound N1=CC=CC2=CC(C(=O)N)=CC=C21 YMNAJWHTELQUJU-UHFFFAOYSA-N 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract 2
- 239000003814 drug Substances 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
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- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
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- A61K31/4192—1,2,3-Triazoles
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-
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- 2010-10-06 US US12/899,410 patent/US8993612B2/en not_active Expired - Fee Related
- 2010-10-07 WO PCT/IB2010/002539 patent/WO2011042798A1/en not_active Ceased
- 2010-10-07 JP JP2012532676A patent/JP5909312B2/ja not_active Expired - Fee Related
- 2010-10-07 ES ES10776149.6T patent/ES2676317T3/es active Active
- 2010-10-07 DK DK10776149.6T patent/DK2509974T3/en active
- 2010-10-07 EP EP10776149.6A patent/EP2509974B1/en active Active
- 2010-10-07 LT LTEP10776149.6T patent/LT2509974T/lt unknown
- 2010-10-07 CN CN201080055388.5A patent/CN102958925B/zh not_active Expired - Fee Related
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- 2010-10-07 CN CN201910890829.6A patent/CN110627724A/zh active Pending
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- 2010-10-07 CN CN201510114126.6A patent/CN104788430B/zh not_active Expired - Fee Related
- 2010-10-07 TR TR2018/09711T patent/TR201809711T4/tr unknown
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- 2010-10-07 HU HUE10776149A patent/HUE039261T2/hu unknown
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| Publication number | Publication date |
|---|---|
| CA2784277A1 (en) | 2011-04-14 |
| JP2018080176A (ja) | 2018-05-24 |
| CN104788430B (zh) | 2019-10-22 |
| CN102958925B (zh) | 2015-04-15 |
| US10174034B2 (en) | 2019-01-08 |
| US20110112058A1 (en) | 2011-05-12 |
| LT2509974T (lt) | 2018-07-10 |
| EA201290139A1 (ru) | 2012-11-30 |
| EA025302B1 (ru) | 2016-12-30 |
| EA025302B8 (ru) | 2017-07-31 |
| EP2509974B1 (en) | 2018-04-11 |
| TR201809711T4 (tr) | 2018-07-23 |
| JP5909312B2 (ja) | 2016-04-26 |
| JP2016028037A (ja) | 2016-02-25 |
| US20150291588A1 (en) | 2015-10-15 |
| CA2784277C (en) | 2019-09-24 |
| PL2509974T3 (pl) | 2018-11-30 |
| WO2011042798A1 (en) | 2011-04-14 |
| CN110627724A (zh) | 2019-12-31 |
| JP6266568B2 (ja) | 2018-01-24 |
| HRP20181014T1 (hr) | 2018-08-24 |
| US8993612B2 (en) | 2015-03-31 |
| ES2676317T3 (es) | 2018-07-18 |
| RS57441B1 (sr) | 2018-09-28 |
| DK2509974T3 (en) | 2018-07-30 |
| HUE039261T2 (hu) | 2018-12-28 |
| CN102958925A (zh) | 2013-03-06 |
| EP2509974A1 (en) | 2012-10-17 |
| US20190248791A1 (en) | 2019-08-15 |
| SMT201800361T1 (it) | 2018-09-13 |
| CN104788430A (zh) | 2015-07-22 |
| JP2013507351A (ja) | 2013-03-04 |
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