JP2018517752A5 - - Google Patents
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- JP2018517752A5 JP2018517752A5 JP2017565777A JP2017565777A JP2018517752A5 JP 2018517752 A5 JP2018517752 A5 JP 2018517752A5 JP 2017565777 A JP2017565777 A JP 2017565777A JP 2017565777 A JP2017565777 A JP 2017565777A JP 2018517752 A5 JP2018517752 A5 JP 2018517752A5
- Authority
- JP
- Japan
- Prior art keywords
- hydrogen
- amino
- methyl
- fluoro
- alkyl
- 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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- 229910052739 hydrogen Inorganic materials 0.000 claims description 112
- 239000001257 hydrogen Substances 0.000 claims description 112
- 150000002431 hydrogen Chemical class 0.000 claims description 94
- 125000000217 alkyl group Chemical group 0.000 claims description 78
- 125000005843 halogen group Chemical group 0.000 claims description 70
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 70
- 125000001153 fluoro group Chemical group F* 0.000 claims description 66
- -1 cyclopropyl-carbonyl-amino Chemical group 0.000 claims description 54
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
- 150000003839 salts Chemical class 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 30
- 150000001875 compounds Chemical class 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 16
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 14
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 claims description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 10
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 6
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 6
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 6
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 4
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 206010029260 Neuroblastoma Diseases 0.000 claims description 4
- 102100033019 Tyrosine-protein phosphatase non-receptor type 11 Human genes 0.000 claims description 4
- 101710116241 Tyrosine-protein phosphatase non-receptor type 11 Proteins 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- MYTHQSLASJNVRG-MRXNPFEDSA-N (4R)-8-[5-(2-aminophenyl)sulfanylpyrazin-2-yl]-8-azaspiro[4.5]decan-4-amine Chemical compound NC1=C(C=CC=C1)SC=1N=CC(=NC=1)N1CCC2(CCC[C@H]2N)CC1 MYTHQSLASJNVRG-MRXNPFEDSA-N 0.000 claims description 2
- KOUHTVINHNKPPC-LJQANCHMSA-N (4R)-8-[5-(2-tert-butylphenyl)sulfanylpyrazin-2-yl]-8-azaspiro[4.5]decan-4-amine Chemical compound C(C)(C)(C)C1=C(C=CC=C1)SC=1N=CC(=NC=1)N1CCC2(CCC[C@H]2N)CC1 KOUHTVINHNKPPC-LJQANCHMSA-N 0.000 claims description 2
- OBSORTGEYVDFIG-MRXNPFEDSA-N (4R)-8-[5-[2-(trifluoromethyl)phenyl]sulfanylpyrazin-2-yl]-8-azaspiro[4.5]decan-4-amine Chemical compound FC(C1=C(C=CC=C1)SC=1N=CC(=NC=1)N1CCC2(CCC[C@H]2N)CC1)(F)F OBSORTGEYVDFIG-MRXNPFEDSA-N 0.000 claims description 2
- PCDXJTLHNWHOPH-MRXNPFEDSA-N (4R)-8-[5-[3-(trifluoromethoxy)phenyl]sulfanylpyrazin-2-yl]-8-azaspiro[4.5]decan-4-amine Chemical compound FC(OC=1C=C(C=CC=1)SC=1N=CC(=NC=1)N1CCC2(CCC[C@H]2N)CC1)(F)F PCDXJTLHNWHOPH-MRXNPFEDSA-N 0.000 claims description 2
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 claims description 2
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 claims description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 2
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- 208000005101 LEOPARD Syndrome Diseases 0.000 claims description 2
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 206010062901 Multiple lentigines syndrome Diseases 0.000 claims description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 2
- 208000037538 Myelomonocytic Juvenile Leukemia Diseases 0.000 claims description 2
- 206010029748 Noonan syndrome Diseases 0.000 claims description 2
- 208000010708 Noonan syndrome with multiple lentigines Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- CWJSHJJYOPWUGX-UHFFFAOYSA-N chlorpropham Chemical compound CC(C)OC(=O)NC1=CC=CC(Cl)=C1 CWJSHJJYOPWUGX-UHFFFAOYSA-N 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 208000005017 glioblastoma Diseases 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 201000005992 juvenile myelomonocytic leukemia Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 2
- VXPLXMJHHKHSOA-UHFFFAOYSA-N propham Chemical compound CC(C)OC(=O)NC1=CC=CC=C1 VXPLXMJHHKHSOA-UHFFFAOYSA-N 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 description 2
- 230000004075 alteration Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562181893P | 2015-06-19 | 2015-06-19 | |
| US62/181,893 | 2015-06-19 | ||
| PCT/IB2016/053550 WO2016203406A1 (en) | 2015-06-19 | 2016-06-15 | Compounds and compositions for inhibiting the activity of shp2 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018517752A JP2018517752A (ja) | 2018-07-05 |
| JP2018517752A5 true JP2018517752A5 (enExample) | 2019-07-18 |
| JP6718889B2 JP6718889B2 (ja) | 2020-07-08 |
Family
ID=56194530
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017565777A Active JP6718889B2 (ja) | 2015-06-19 | 2016-06-15 | Ｓｈｐ２の活性を阻害するための化合物および組成物 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US10287266B2 (enExample) |
| EP (1) | EP3310774B1 (enExample) |
| JP (1) | JP6718889B2 (enExample) |
| CN (2) | CN107922388B (enExample) |
| ES (1) | ES2805232T3 (enExample) |
| WO (1) | WO2016203406A1 (enExample) |
Families Citing this family (124)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11466017B2 (en) | 2011-03-10 | 2022-10-11 | Board Of Regents, The University Of Texas System | Heterocyclic inhibitors of PTPN11 |
| EP3094627B1 (en) | 2014-01-17 | 2018-08-22 | Novartis AG | 1-pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and and compositions thereof for inhibiting the activity of shp2 |
| JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
| EP3094629B1 (en) | 2014-01-17 | 2018-08-22 | Novartis AG | 1-(triazin-3-yl/pyridazin-3-yl)-piper(-azine)idine derivatives and compositions thereof for inhibiting the activity of shp2 |
| US10287266B2 (en) * | 2015-06-19 | 2019-05-14 | Novartis Ag | Compounds and compositions for inhibiting the activity of SHP2 |
| JP6878316B2 (ja) * | 2015-06-19 | 2021-05-26 | ノバルティス アーゲー | Ｓｈｐ２の活性を阻害するための化合物および組成物 |
| ES2741746T3 (es) | 2015-06-19 | 2020-02-12 | Novartis Ag | Compuestos y composiciones para inhibir la actividad de SHP2 |
| JP7044375B2 (ja) | 2016-05-31 | 2022-03-30 | ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | Ｐｔｐｎ１１の複素環式阻害剤 |
| EA202092442A3 (ru) * | 2016-06-07 | 2021-08-31 | Джакобио Фармасьютикалс Ко., Лтд. | Новые гетероциклические производные, применимые в качестве ингибиторов shp2 |
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