CN117427079A - 含氰基取代的大环类化合物的用途 - Google Patents
含氰基取代的大环类化合物的用途 Download PDFInfo
- Publication number
- CN117427079A CN117427079A CN202310893963.8A CN202310893963A CN117427079A CN 117427079 A CN117427079 A CN 117427079A CN 202310893963 A CN202310893963 A CN 202310893963A CN 117427079 A CN117427079 A CN 117427079A
- Authority
- CN
- China
- Prior art keywords
- substance
- formula
- compound
- ros1
- intracranial tumor
- 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
- 150000002678 macrocyclic compounds Chemical class 0.000 title abstract description 5
- 239000003814 drug Substances 0.000 claims abstract description 50
- 150000001875 compounds Chemical class 0.000 claims abstract description 43
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 36
- 238000007917 intracranial administration Methods 0.000 claims abstract description 32
- 229940079593 drug Drugs 0.000 claims abstract description 27
- 239000000126 substance Substances 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 210000004556 brain Anatomy 0.000 claims description 20
- 101000686031 Homo sapiens Proto-oncogene tyrosine-protein kinase ROS Proteins 0.000 claims description 19
- 102100023347 Proto-oncogene tyrosine-protein kinase ROS Human genes 0.000 claims description 19
- 206010018338 Glioma Diseases 0.000 claims description 17
- 208000032612 Glial tumor Diseases 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 14
- 206010027476 Metastases Diseases 0.000 claims description 11
- 230000009401 metastasis Effects 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 8
- 230000004927 fusion Effects 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 238000011321 prophylaxis Methods 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 description 22
- 230000000694 effects Effects 0.000 description 18
- 230000004083 survival effect Effects 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- FIKPXCOQUIZNHB-WDEREUQCSA-N repotrectinib Chemical compound C[C@H]1CNC(=O)C2=C3N=C(N[C@H](C)C4=C(O1)C=CC(F)=C4)C=CN3N=C2 FIKPXCOQUIZNHB-WDEREUQCSA-N 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 4
- 101150035397 Ros1 gene Proteins 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 238000011081 inoculation Methods 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 3
- 238000011729 BALB/c nude mouse Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 208000010877 cognitive disease Diseases 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000002173 dizziness Diseases 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 201000005249 lung adenocarcinoma Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- -1 polyethylene Polymers 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 208000010470 Ageusia Diseases 0.000 description 2
- 208000031648 Body Weight Changes Diseases 0.000 description 2
- 208000028698 Cognitive impairment Diseases 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 101100091501 Mus musculus Ros1 gene Proteins 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 235000019666 ageusia Nutrition 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004579 body weight change Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 208000025997 central nervous system neoplasm Diseases 0.000 description 2
- 239000012050 conventional carrier Substances 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 210000001652 frontal lobe Anatomy 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000001384 succinic acid Substances 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 210000002620 vena cava superior Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 206010013886 Dysaesthesia Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 102100035108 High affinity nerve growth factor receptor Human genes 0.000 description 1
- SHBUUTHKGIVMJT-UHFFFAOYSA-N Hydroxystearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OO SHBUUTHKGIVMJT-UHFFFAOYSA-N 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010034719 Personality change Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 206010061924 Pulmonary toxicity Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 208000021017 Weight Gain Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 208000037844 advanced solid tumor Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 201000007455 central nervous system cancer Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 229940072106 hydroxystearate Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 208000037843 metastatic solid tumor Diseases 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229940124303 multikinase inhibitor Drugs 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 208000035824 paresthesia Diseases 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 231100000374 pneumotoxicity Toxicity 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000007047 pulmonary toxicity Effects 0.000 description 1
- 229940121602 repotrectinib Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000020685 sleep-wake disease Diseases 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical 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
- 210000004881 tumor cell Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
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
- A61K31/495—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)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210861773 | 2022-07-20 | ||
CN2022108617733 | 2022-07-20 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN117427079A true CN117427079A (zh) | 2024-01-23 |
Family
ID=89554261
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310893963.8A Pending CN117427079A (zh) | 2022-07-20 | 2023-07-19 | 含氰基取代的大环类化合物的用途 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN117427079A (fr) |
WO (1) | WO2024017305A1 (fr) |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017075107A1 (fr) * | 2015-10-26 | 2017-05-04 | Nanda Nisha | Mutations ponctuelles dans le cancer résistant aux inhibiteurs de trk et méthodes associées |
WO2019144885A1 (fr) * | 2018-01-23 | 2019-08-01 | 深圳市塔吉瑞生物医药有限公司 | Composé macrocyclique de pyrazolo [1,5-a]pyrimidine substitué |
JP7323748B2 (ja) * | 2018-02-28 | 2023-08-09 | ナンジン ザイミン ファーマシューティカル カンパニー リミテッド | ピラゾロピリミジン誘導体及びその使用 |
CN110577549A (zh) * | 2018-06-08 | 2019-12-17 | 焦玉奇 | 大环化合物 |
CN113773335A (zh) * | 2019-06-21 | 2021-12-10 | 成都海博为药业有限公司 | 一种作为蛋白质激酶抑制剂的化合物及其制备方法和用途 |
US20230002410A1 (en) * | 2019-11-18 | 2023-01-05 | Guangzhou Joyo Pharmatech Co., Ltd. | Compound as highly selective ros1 inhibitor and use thereof |
-
2023
- 2023-07-19 CN CN202310893963.8A patent/CN117427079A/zh active Pending
- 2023-07-19 WO PCT/CN2023/108205 patent/WO2024017305A1/fr unknown
Also Published As
Publication number | Publication date |
---|---|
WO2024017305A1 (fr) | 2024-01-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20240041864A1 (en) | Methods for treating soft tissue sarcoma | |
Da Fonseca et al. | Preliminary results from a phase I/II study of perillyl alcohol intranasal administration in adults with recurrent malignant gliomas | |
ES2586843T3 (es) | Tratamiento de trastornos relacionados con BDNF usando laquinimod | |
EP2991637B1 (fr) | Fenfluramine pour son utilisation dans le traitement du syndrome de dravet | |
JP6837486B2 (ja) | 加齢に関連する認知障害及び神経炎症を予防及び/又は治療する方法 | |
TW201343164A (zh) | 以拉喹莫德及富馬酸二甲酯之組合治療多發性硬化症 | |
US20080214569A1 (en) | Use of phosphatases to treat tumors overexpressing N-CoR | |
WO2007092414A2 (fr) | Utilisation de phosphatase pour traiter des tumeurs surexprimant n-cor | |
EA032345B1 (ru) | Способ лечения рака с использованием кофермента q10 | |
JP2004515453A (ja) | 癌を化学療法および放射線療法に付する間に細胞を保護するための組成物および方法 | |
WO2023016519A1 (fr) | Utilisation d'honokiol dans la préparation d'un médicament pour le traitement d'un méningiome | |
Ling et al. | Preparation, characterization, and pharmacokinetics of tilmicosin‐and florfenicol‐loaded hydrogenated castor oil‐solid lipid nanoparticles | |
CN110934879B (zh) | 靶向组织微环境中衰老细胞的抗衰老药物d/a及其应用 | |
ES2702578T3 (es) | Tratamiento de la inflamación dérmica crónica con norketotifeno | |
He et al. | Toxicities and therapeutic effect of 5-fluorouracil controlled release implant on tumor-bearing rats | |
EA001325B1 (ru) | Способы лечения и профилактики интерстициального цистита | |
CN117427079A (zh) | 含氰基取代的大环类化合物的用途 | |
CN113329749A (zh) | 用于治疗葡萄膜黑色素瘤的联合疗法 | |
US20110182973A1 (en) | Polymerase inhibitors and the use thereof for the treatment of tumors | |
US20190029951A1 (en) | Extended release formulations of veliparib for the treatment of cancer | |
US20150209303A1 (en) | Zeaxanthin for tumor treatment | |
CN112274509A (zh) | 西达本胺联合bcl2抑制剂在双表达型b细胞淋巴瘤中的应用 | |
JP2008501785A (ja) | 子宮腫瘍の治療用医薬の調製のための7−t−ブトキシイミノメチルカンプトテシンの使用 | |
EP4132469B1 (fr) | Administration d'inhibiteurs de mtor dans le système nerveux central | |
CN115381818A (zh) | 一种促进细胞自噬降解功能的方法及应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |