JPWO2021156180A5 - - Google Patents
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- JPWO2021156180A5 JPWO2021156180A5 JP2022542952A JP2022542952A JPWO2021156180A5 JP WO2021156180 A5 JPWO2021156180 A5 JP WO2021156180A5 JP 2022542952 A JP2022542952 A JP 2022542952A JP 2022542952 A JP2022542952 A JP 2022542952A JP WO2021156180 A5 JPWO2021156180 A5 JP WO2021156180A5
- Authority
- JP
- Japan
- Prior art keywords
- compound
- salt
- cancer
- hydrogen
- pharmaceutically acceptable
- 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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- 150000003839 salts Chemical class 0.000 claims description 33
- 150000001875 compounds Chemical class 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000013543 active substance Substances 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 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
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 208000022072 Gallbladder Neoplasms Diseases 0.000 claims description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant 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
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 201000009036 biliary tract cancer Diseases 0.000 claims description 2
- 208000020790 biliary tract neoplasm Diseases 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 239000003814 drug Substances 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
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000025402 neoplasm of esophagus Diseases 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
Description
活性物質を粉砕し、ラクトース及び一部のトウモロコシデンプンと一緒に混合する。混合物を篩過してから、ポリビニルピロリドン溶液を用いて湿式造粒する。これらの顆粒、残りのトウモロコシデンプン及びステアリン酸マグネシウムを一緒に混合する。混合物を圧縮して適切な形状及びサイズの錠剤を作製する。
本発明の好ましい態様は、下記の通りである。
〔１〕式(I)
（式中、
R
1
は、水素、-CH
3
、-CCH、-OCH
3
及びハロゲンから成る群より選択され、
R
2
は、水素又はハロゲンであり、
R
3
は、水素又はハロゲンであり、
R
4
は、水素又は-CH
3
であり、
かつR
1
、R
2
及びR
3
の少なくとも1つは水素でない）
の化合物又はその塩。
〔２〕R
1
が、-CH
3
及びハロゲンから成る群より選択される、前記〔1〕に記載の化合物又はその塩。
〔３〕R
1
が、-CH
3
、塩素及びフッ素から成る群より選択される、前記〔1〕に記載の化合物又はその塩。
〔４〕R
2
が、水素である、前記〔1〕に記載の化合物又はその塩。
〔５〕R
2
が、塩素である、前記〔1〕に記載の化合物又はその塩。
〔６〕R
2
が、フッ素である、前記〔1〕に記載の化合物又はその塩。
〔７〕R
3
が、水素である、前記〔1〕に記載の化合物又はその塩。
〔８〕R
4
が、水素である、前記〔1〕に記載の化合物又はその塩。
〔９〕R
4
が、-CH
3
である、前記〔1〕に記載の化合物又はその塩。
〔１０〕下記化合物：
の中から選択される、前記〔1〕に記載の化合物又はその塩。
〔１１〕治療有効量の前記〔1〕～〔10〕のいずれか1項に記載の式(I)の少なくとも1種の化合物又はその医薬的に許容される塩と、1種以上の医薬的に許容される賦形剤とを含む、医薬組成物。
〔１２〕薬物として使用するための、前記〔1〕～〔10〕の1項以上に記載の化合物、又はその医薬的に許容される塩。
〔１３〕脳癌、乳癌、胆道癌、膀胱癌、子宮頚癌、結腸直腸癌、子宮内膜癌、皮膚癌、食道腫瘍、頭頚部腫瘍、胃腸癌、胆嚢腫瘍、腎臓癌、肝臓癌、肺癌又は前立腺癌を患っている患者を治療するための、前記〔1〕～〔10〕の1項以上に記載の化合物の使用。
〔１４〕式(I)の化合物に加えて、細胞分裂阻害活性物質及び細胞傷害活性物質から成る群より選択される医薬的に活性な化合物を含む、医薬組成物。
The active substance is ground and mixed together with lactose and some corn starch. The mixture is sieved and then wet granulated using polyvinylpyrrolidone solution. Mix these granules, remaining corn starch and magnesium stearate together. The mixture is compressed to make tablets of the appropriate shape and size.
Preferred embodiments of the present invention are as follows.
[1] Formula (I)
(In the formula,
R 1 is selected from the group consisting of hydrogen, -CH 3 , -CCH, -OCH 3 and halogen;
R 2 is hydrogen or halogen;
R 3 is hydrogen or halogen;
R4 is hydrogen or -CH3 ,
and at least one of R 1 , R 2 and R 3 is not hydrogen)
or its salt.
[2] The compound or salt thereof according to [1] above, wherein R 1 is selected from the group consisting of -CH 3 and halogen.
[3] The compound or salt thereof according to [1] above, wherein R 1 is selected from the group consisting of -CH 3 , chlorine, and fluorine.
[4] The compound or a salt thereof according to [1] above, wherein R 2 is hydrogen.
[5] The compound or a salt thereof according to [1] above, wherein R 2 is chlorine.
[6] The compound or a salt thereof according to [1] above, wherein R 2 is fluorine.
[7] The compound or a salt thereof according to [1] above, wherein R 3 is hydrogen.
[8] The compound or salt thereof according to [1] above, wherein R 4 is hydrogen.
[9] The compound or a salt thereof according to [1] above, wherein R 4 is -CH 3 .
[10] The following compound:
The compound according to [1] above or a salt thereof selected from these.
[11] A therapeutically effective amount of at least one compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of [1] to [10] above, and one or more pharmaceutically acceptable salts thereof; A pharmaceutical composition comprising an excipient that is acceptable to .
[12] A compound according to one or more of items [1] to [10] above, or a pharmaceutically acceptable salt thereof, for use as a drug.
[13] Brain cancer, breast cancer, biliary tract cancer, bladder cancer, cervix cancer, colorectal cancer, endometrial cancer, skin cancer, esophageal tumor, head and neck tumor, gastrointestinal cancer, gallbladder tumor, kidney cancer, liver cancer, lung cancer or the use of a compound according to one or more of items [1] to [10] above for treating a patient suffering from prostate cancer.
[14] A pharmaceutical composition comprising, in addition to the compound of formula (I), a pharmaceutically active compound selected from the group consisting of cytostatically active substances and cytotoxically active substances.
Claims (16)
R1は、水素、-CH3、-CCH、-OCH3及びハロゲンから成る群より選択され、
R2は、水素又はハロゲンであり、
R3は、水素又はハロゲンであり、
R4は、水素又は-CH3であり、
かつR1、R2及びR3の少なくとも1つは水素でない）
の化合物又はその塩。 Formula (I)
R 1 is selected from the group consisting of hydrogen, -CH 3 , -CCH, -OCH 3 and halogen;
R 2 is hydrogen or halogen;
R 3 is hydrogen or halogen;
R4 is hydrogen or -CH3 ,
and at least one of R 1 , R 2 and R 3 is not hydrogen)
or its salt.
の中から選択される、請求項1に記載の化合物又はその塩。 The following compounds:
2. The compound or salt thereof according to claim 1, selected from the group consisting of:
A compound with the following structure.
A pharmaceutically acceptable salt of a compound having the structure:
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP20155161.1 | 2020-02-03 | ||
| EP20155161 | 2020-02-03 | ||
| PCT/EP2021/052263 WO2021156180A1 (en) | 2020-02-03 | 2021-02-01 | [1,3]diazino[5,4-d]pyrimidines as her2 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2023512175A JP2023512175A (en) | 2023-03-24 |
| JPWO2021156180A5 true JPWO2021156180A5 (en) | 2024-02-08 |
Family
ID=69467427
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022542952A Pending JP2023512175A (en) | 2020-02-03 | 2021-02-01 | [1,3]diazino[5,4-d]pyrimidines as HER2 inhibitors |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20230131720A1 (en) |
| EP (1) | EP4100412A1 (en) |
| JP (1) | JP2023512175A (en) |
| CN (1) | CN115052881A (en) |
| WO (1) | WO2021156180A1 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11608343B2 (en) | 2020-04-24 | 2023-03-21 | Boehringer Ingelheim International Gmbh | Substituted pyrimido[5,4-d]pyrimidines as HER2 inhibitors |
| TW202214641A (en) | 2020-06-30 | 2022-04-16 | 美商艾瑞生藥股份有限公司 | Her2 mutation inhibitors |
| WO2023081637A1 (en) * | 2021-11-02 | 2023-05-11 | Enliven Therapeutics, Inc. | Fused tetracyclic quinazoline derivatives as inhibitors of erbb2 |
| CN114031619A (en) * | 2021-12-17 | 2022-02-11 | 山东汇海医药化工有限公司 | Preparation method of intermediate of Tecatinib |
| CN114621221B (en) * | 2022-03-12 | 2022-10-11 | 陕西海辰风扬医药科技有限公司 | Tourtinib key intermediate and preparation method thereof |
| CN117384162A (en) * | 2022-05-17 | 2024-01-12 | 浙江文达医药科技有限公司 | Selective HER2 inhibitors |
| WO2024027695A1 (en) * | 2022-08-04 | 2024-02-08 | 微境生物医药科技(上海)有限公司 | Compounds as her2 inhibitors |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19608588A1 (en) | 1996-03-06 | 1997-09-11 | Thomae Gmbh Dr K | Pyrimido [5,4-d] pyrimidines, medicaments containing these compounds, their use and processes for their preparation |
| CN1602195A (en) * | 2001-12-12 | 2005-03-30 | 辉瑞产品公司 | Quinazoline derivatives for the treatment of abnormal cell growth |
| MXPA06005024A (en) * | 2003-11-06 | 2006-07-06 | Pfizer Prod Inc | Selective erbb2 inhibitor/anti-erbb antibody combinations in the treatment of cancer. |
| US8648087B2 (en) * | 2005-11-15 | 2014-02-11 | Array Biopharma, Inc. | N4-phenyl-quinazoline-4-amine derivatives and related compounds as ErbB type I receptor tyrosine kinase inhibitors for the treatment of hyperproliferative diseases |
| CN106687457B (en) * | 2014-05-13 | 2020-01-10 | 阿里亚德医药股份有限公司 | Heteroaryl compounds for kinase inhibition |
| CA2949793C (en) | 2014-06-19 | 2024-02-27 | Ariad Pharmaceuticals, Inc. | Heteroaryl compounds for kinase inhibition |
| WO2016183278A1 (en) * | 2015-05-13 | 2016-11-17 | Ariad Pharmaceuticals, Inc. | Heteroaryl compounds for kinase inhibition |
| CN115322193A (en) | 2017-08-31 | 2022-11-11 | 达纳-法伯癌症研究所股份有限公司 | EGFR and/or HER2 inhibitors and methods of use |
| WO2019042409A1 (en) * | 2017-09-01 | 2019-03-07 | 上海医药集团股份有限公司 | Nitrogenous heterocyclic compound, preparation method, intermediate, composition, and application |
-
2021
- 2021-02-01 JP JP2022542952A patent/JP2023512175A/en active Pending
- 2021-02-01 CN CN202180012676.0A patent/CN115052881A/en active Pending
- 2021-02-01 WO PCT/EP2021/052263 patent/WO2021156180A1/en unknown
- 2021-02-01 US US17/759,890 patent/US20230131720A1/en active Pending
- 2021-02-01 EP EP21703191.3A patent/EP4100412A1/en active Pending
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