JP2018501261A5 - - Google Patents
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- Publication number
- JP2018501261A5 JP2018501261A5 JP2017533503A JP2017533503A JP2018501261A5 JP 2018501261 A5 JP2018501261 A5 JP 2018501261A5 JP 2017533503 A JP2017533503 A JP 2017533503A JP 2017533503 A JP2017533503 A JP 2017533503A JP 2018501261 A5 JP2018501261 A5 JP 2018501261A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- acetamide
- inden
- hydroxy
- dimethoxybenzylidene
- 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.)
- Pending
Links
- -1 nitro, hydroxyl Chemical group 0.000 claims description 154
- 150000001875 compounds Chemical class 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 37
- 229940002612 prodrug Drugs 0.000 claims description 36
- 239000000651 prodrug Substances 0.000 claims description 36
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 102000016914 ras Proteins Human genes 0.000 claims description 26
- 108010014186 ras Proteins Proteins 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 230000031018 biological processes and functions Effects 0.000 claims description 16
- 230000001404 mediated effect Effects 0.000 claims description 16
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 15
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 14
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 14
- 206010028980 Neoplasm Diseases 0.000 claims description 14
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 14
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 14
- 239000004202 carbamide Substances 0.000 claims description 14
- 235000013877 carbamide Nutrition 0.000 claims description 14
- 230000002401 inhibitory effect Effects 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 12
- 150000001540 azides Chemical class 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 12
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 12
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 12
- 125000001188 haloalkyl group Chemical group 0.000 claims description 12
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 11
- 229940124530 sulfonamide Drugs 0.000 claims description 11
- 150000003456 sulfonamides Chemical class 0.000 claims description 11
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 11
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 10
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 10
- 229940124597 therapeutic agent Drugs 0.000 claims description 10
- 230000002159 abnormal effect Effects 0.000 claims description 8
- KFJCFMUEEDXYBN-FMCGGJTJSA-N [4-[(Z)-[5-fluoro-2-methyl-3-[2-(3-methylanilino)-2-oxoethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl] methanesulfonate Chemical compound CS(=O)(=O)OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(NC=1C=C(C=CC=1)C)=O)C)OC KFJCFMUEEDXYBN-FMCGGJTJSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 4
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 101150040459 RAS gene Proteins 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 230000005855 radiation Effects 0.000 claims description 4
- 108700042226 ras Genes Proteins 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 210000001519 tissue Anatomy 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 238000001727 in vivo Methods 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 206010059866 Drug resistance Diseases 0.000 claims description 2
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 206010027476 Metastases Diseases 0.000 claims description 2
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 238000003556 assay Methods 0.000 claims description 2
- 239000004305 biphenyl Chemical group 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 2
- 201000007455 central nervous system cancer Diseases 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 201000003115 germ cell cancer Diseases 0.000 claims description 2
- 201000010536 head and neck cancer Diseases 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 208000029559 malignant endocrine neoplasm Diseases 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 230000009401 metastasis Effects 0.000 claims description 2
- 230000035755 proliferation Effects 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 150000003457 sulfones Chemical class 0.000 claims description 2
- 230000004083 survival effect Effects 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 230000004565 tumor cell growth Effects 0.000 claims description 2
- 206010046766 uterine cancer Diseases 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 19
- 238000011321 prophylaxis Methods 0.000 claims 2
- 230000001225 therapeutic effect Effects 0.000 claims 2
- IAVUPMFITXYVAF-HTRCEHHLSA-N (4r,6r)-4-(ethylamino)-6-methyl-7,7-dioxo-5,6-dihydro-4h-thieno[2,3-b]thiopyran-2-sulfonamide Chemical compound CCN[C@@H]1C[C@@H](C)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 IAVUPMFITXYVAF-HTRCEHHLSA-N 0.000 claims 1
- 229940078123 Ras inhibitor Drugs 0.000 claims 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- 238000000034 method Methods 0.000 description 15
- 150000002431 hydrogen Chemical class 0.000 description 2
- 241000790917 Dioxys <bee> Species 0.000 description 1
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2014/070511 WO2016099452A1 (en) | 2014-12-16 | 2014-12-16 | Ras-inhibiting indenyl acetamide compounds, compositions, and uses |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2018501261A JP2018501261A (ja) | 2018-01-18 |
| JP2018501261A5 true JP2018501261A5 (enExample) | 2018-03-01 |
Family
ID=56127110
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017533503A Pending JP2018501261A (ja) | 2014-12-16 | 2014-12-16 | Ｒａｓ阻害インデニルアセトアミド化合物、組成物、およびその使用 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20170342021A1 (enExample) |
| EP (1) | EP3233070A4 (enExample) |
| JP (1) | JP2018501261A (enExample) |
| CN (1) | CN107530303A (enExample) |
| WO (1) | WO2016099452A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20160168108A1 (en) | 2014-12-16 | 2016-06-16 | Adt Pharmaceuticals, Inc. | Method of treating or preventing ras-mediated diseases |
| US9862698B2 (en) * | 2014-12-16 | 2018-01-09 | Adt Pharmaceuticals, Inc. | Indenyl compounds, pharmaceutical compositions, and medical uses thereof |
| WO2018218087A1 (en) * | 2017-05-24 | 2018-11-29 | K-Gen, Inc. | Methods of cancer treatment |
| JP7348906B2 (ja) | 2018-02-28 | 2023-09-21 | フェロ セラピューティクス， インコーポレイテッド | フェロトーシス誘導活性を有する化合物およびそれらの使用方法 |
| US11186596B2 (en) | 2018-04-26 | 2021-11-30 | Adt Pharmaceuticals, Llc | Anticancer indenes, indanes, azaindenes, azaindanes, pharmaceutical compositions and uses |
| US11040964B2 (en) | 2019-02-27 | 2021-06-22 | Ferro Therapeutics, Inc. | Compounds and methods of use |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6063818A (en) * | 1996-06-13 | 2000-05-16 | Cell Pathways Inc. | Substituted benzylidene indenyl formamides, acetamides and propionamides |
| CN101031289A (zh) * | 2004-04-26 | 2007-09-05 | 范德比尔特大学 | 作为具有降低胃肠毒性的治疗剂的吲哚乙酸和茚乙酸衍生物 |
| JP5337491B2 (ja) * | 2006-01-04 | 2013-11-06 | サザン リサーチ インスティテュート | スリンダクの誘導体類、その使用及びその調製 |
-
2014
- 2014-12-16 WO PCT/US2014/070511 patent/WO2016099452A1/en not_active Ceased
- 2014-12-16 CN CN201480084636.7A patent/CN107530303A/zh active Pending
- 2014-12-16 US US15/537,222 patent/US20170342021A1/en not_active Abandoned
- 2014-12-16 EP EP14908546.6A patent/EP3233070A4/en not_active Withdrawn
- 2014-12-16 JP JP2017533503A patent/JP2018501261A/ja active Pending
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