TW202304425A - 包含瑞博西尼和安森司群（ａｍｃｅｎｅｓｔｒａｎｔ）的組合 - Google Patents
包含瑞博西尼和安森司群（ａｍｃｅｎｅｓｔｒａｎｔ）的組合 Download PDFInfo
- Publication number
- TW202304425A TW202304425A TW111113411A TW111113411A TW202304425A TW 202304425 A TW202304425 A TW 202304425A TW 111113411 A TW111113411 A TW 111113411A TW 111113411 A TW111113411 A TW 111113411A TW 202304425 A TW202304425 A TW 202304425A
- Authority
- TW
- Taiwan
- Prior art keywords
- ribociclib
- pharmaceutically acceptable
- acceptable salt
- succinate
- ansenstrant
- Prior art date
Links
- RHXHGRAEPCAFML-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N1CCNCC1 RHXHGRAEPCAFML-UHFFFAOYSA-N 0.000 title claims abstract description 86
- 229950003687 ribociclib Drugs 0.000 title claims abstract description 85
- KISZAGQTIXIVAR-VWLOTQADSA-N 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid Chemical compound ClC1=C(C=CC(=C1)Cl)C1=C(C2=C(CCC1)C=C(C=C2)C(=O)O)C1=CC=C(C=C1)O[C@@H]1CN(CC1)CCCF KISZAGQTIXIVAR-VWLOTQADSA-N 0.000 title abstract description 13
- 229940070192 amcenestrant Drugs 0.000 title abstract description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 84
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 69
- NHANOMFABJQAAH-UHFFFAOYSA-N butanedioic acid;7-cyclopentyl-n,n-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound OC(=O)CCC(O)=O.N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N1CCNCC1 NHANOMFABJQAAH-UHFFFAOYSA-N 0.000 claims abstract description 37
- 229950010518 ribociclib succinate Drugs 0.000 claims abstract description 37
- 201000011510 cancer Diseases 0.000 claims abstract description 29
- 238000011282 treatment Methods 0.000 claims abstract description 29
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 21
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 238000011260 co-administration Methods 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 4
- 238000010791 quenching Methods 0.000 claims 1
- 241001465754 Metazoa Species 0.000 description 21
- 241000699660 Mus musculus Species 0.000 description 10
- 229940125943 SAR439859 Drugs 0.000 description 10
- 238000011580 nude mouse model Methods 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 9
- 230000000259 anti-tumor effect Effects 0.000 description 9
- 108010007005 Estrogen Receptor alpha Proteins 0.000 description 8
- 102100038595 Estrogen receptor Human genes 0.000 description 8
- 238000007920 subcutaneous administration Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 230000001575 pathological effect Effects 0.000 description 7
- 208000016261 weight loss Diseases 0.000 description 7
- 230000037396 body weight Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000007619 statistical method Methods 0.000 description 4
- 230000004580 weight loss Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 230000002124 endocrine Effects 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 238000007492 two-way ANOVA Methods 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000010835 comparative analysis Methods 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 102000015694 estrogen receptors Human genes 0.000 description 2
- 108010038795 estrogen receptors Proteins 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
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- 230000007170 pathology Effects 0.000 description 2
- 229940125944 selective estrogen receptor degrader Drugs 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 229940097346 sulfobutylether-beta-cyclodextrin Drugs 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- 206010063746 Accidental death Diseases 0.000 description 1
- 238000011729 BALB/c nude mouse Methods 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 229940124297 CDK 4/6 inhibitor Drugs 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 102000013701 Cyclin-Dependent Kinase 4 Human genes 0.000 description 1
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 229940102550 Estrogen receptor antagonist Drugs 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 206010050283 Tumour ulceration Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
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- 238000000540 analysis of variance Methods 0.000 description 1
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- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
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- 239000002585 base Substances 0.000 description 1
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- 238000006243 chemical reaction Methods 0.000 description 1
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- 238000009261 endocrine therapy Methods 0.000 description 1
- 229940034984 endocrine therapy antineoplastic and immunomodulating agent Drugs 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229960002258 fulvestrant Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
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- 239000005556 hormone Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000004063 proteosomal degradation Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 150000003890 succinate salts Chemical group 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Images
Classifications
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP21315064 | 2021-04-12 | ||
| EP21315064.2 | 2021-04-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202304425A true TW202304425A (zh) | 2023-02-01 |
Family
ID=75825774
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW111113411A TW202304425A (zh) | 2021-04-12 | 2022-04-08 | 包含瑞博西尼和安森司群（ａｍｃｅｎｅｓｔｒａｎｔ）的組合 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20240197739A1 (https=) |
| EP (1) | EP4322941A1 (https=) |
| JP (1) | JP2024516363A (https=) |
| CN (1) | CN117136053A (https=) |
| AR (1) | AR125331A1 (https=) |
| TW (1) | TW202304425A (https=) |
| WO (1) | WO2022218956A1 (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112021003440A2 (pt) | 2018-09-07 | 2021-05-18 | Sanofi | sais de 6-(2,4-diclorofenil)-5-[4-[(3s)-1-(3-fluoropropil) pirrolidin-3-il]oxifenil]-8,9-di-hidro-7h-benzo[7]anuleno-2-carboxilato de metila e seu processo de preparação |
| EP4037768B1 (en) | 2019-10-01 | 2023-10-11 | Sanofi | Novel substituted 6,7-dihydro-5h-benzo[7]annulene compounds, processes for their preparation and therapeutic uses thereof |
| AU2020399168A1 (en) | 2019-12-09 | 2022-07-28 | Sanofi | Crystalline form of a 7H-benzo[7]annulene-2-carboxylic acid derivative |
| TW202146007A (zh) | 2020-02-27 | 2021-12-16 | 法商賽諾菲公司 | 包含阿培利司（ａｌｐｅｌｉｓｉｂ）與６－（２，４－二氯苯基）－５－［４－［（３ｓ）－１－（３－氟丙基）吡咯啶－３－基］氧苯基］－８，９－二氫－７ｈ－苯并［７］輪烯－２－羧酸之組合 |
| TW202233572A (zh) | 2020-10-19 | 2022-09-01 | 法商賽諾菲公司 | 新穎之經取代的6,7-二氫-5h-苯並[7]輪烯衍生物，其製備方法及其治療用途 |
| WO2022084280A1 (en) | 2020-10-19 | 2022-04-28 | Sanofi | Substituted 6,7-dihydro-5h-benzo[7]annulene compounds and their derivatives, processes for their preparation and therapeutic uses thereof |
| TW202543650A (zh) | 2024-03-08 | 2025-11-16 | 美商海爾達醫療運營公司 | 異雙官能化合物及其在治療疾病中之用途 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105828822B (zh) * | 2013-08-14 | 2019-10-18 | 诺华股份有限公司 | 用于治疗癌症的组合疗法 |
| EA034994B1 (ru) | 2016-02-15 | 2020-04-15 | Санофи | 6,7-дигидро-5h-бензо[7]аннуленовые производные в качестве модуляторов эстрогеновых рецепторов |
| EP3434272A1 (en) * | 2017-07-25 | 2019-01-30 | Sanofi | Combination comprising palbociclib and 6-(2,4-dichlorophenyl)-5-[4-[(3s)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7h-benzo[7]annulene-2-carboxylic acid |
| CA3169679A1 (en) * | 2020-03-06 | 2021-09-10 | Olema Pharmaceuticals, Inc. | Methods of treating estrogen receptor-associated diseases |
-
2022
- 2022-04-08 TW TW111113411A patent/TW202304425A/zh unknown
- 2022-04-11 AR ARP220100915A patent/AR125331A1/es not_active Application Discontinuation
- 2022-04-12 WO PCT/EP2022/059700 patent/WO2022218956A1/en not_active Ceased
- 2022-04-12 CN CN202280028202.XA patent/CN117136053A/zh active Pending
- 2022-04-12 EP EP22718731.7A patent/EP4322941A1/en active Pending
- 2022-04-12 US US18/286,510 patent/US20240197739A1/en active Pending
- 2022-04-12 JP JP2023562511A patent/JP2024516363A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20240197739A1 (en) | 2024-06-20 |
| WO2022218956A1 (en) | 2022-10-20 |
| AR125331A1 (es) | 2023-07-05 |
| JP2024516363A (ja) | 2024-04-15 |
| EP4322941A1 (en) | 2024-02-21 |
| CN117136053A (zh) | 2023-11-28 |
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