CAS: 912999-49-6; (2,4-Dihydroxy-5-Isopropylphenyl)(5-((4-Methylpiperazin-1-yl)Methyl)Isoindolin-2-yl)Methanone

该化合物是一个小分子抑制剂,主要针对热休克蛋白90(Hsp90),这是一种与各种客户蛋白适当折叠和稳定有关的保护伞蛋白,其中许多蛋白与癌症和其他疾病有关.Onalespib作为Hsp90抑制剂,扰乱了该蛋白的功能,导致其客户蛋白退化,可能导致抗肿瘤效应.该化合物已经研究其肿瘤学的潜在治疗应用,特别是在治疗各种癌症方面.Onalespib的特征是,它与Hsp90(Hsp90)与AP-约束性网站有特别的结合性,这对于其抑制行动至关重要.此外,它在临床前期研究中评估了该蛋白的功效和安全状况.与许多调查药物一样,继续研究其药性,最佳剂量疗法和可能的组合疗法,以提高其治疗效果.

英文名称(2,4-Dihydroxy-5-Isopropylphenyl)(5-((4-Methylpiperazin-1-yl)Methyl)Isoindolin-2-yl)Methanone
中文名称奥那司匹
IUPAC名称(2,4-dihydroxy-5-isopropylphenyl)(5-((4-methylpiperazin-1-yl)methyl)isoindolin-2-yl)methanone
CAS编号912999-49-6
MFCD编号:MFCD18633198
FDA UNII编号:Q7Y33N57ZZ
分子式:C24H31N3O3分子量:409.53
产品CID: 1948364
同类组份化合物CAS912999-49-6 (free base)1019889-35-0 (lactate)
产品分类生物化工 → 抑制剂 → 细胞骨架(Cytoskeletal Signaling)

相似结构搜索
InChIKey: IFRGXKKQHBVPCQ-UHFFFAOYSA-N
InChI=1S/C24H31N3O3/c1-16(2)20-11-21(23(29)12-22(20)28)24(30)27-14-18-5-4-17(10-19(18)15-27)13-26-8-6-25(3)7-9-26/h4-5,10-12,16,28-29H,6-9,13-15H2,1-3H3
计算化学: 氢键受体数5.0氢键供体数2.0可旋转键数4.0

物理性质

沸点605.7±55.0 °C at 760 mmHg
闪点320.1±31.5 °C
密度1.2±0.1 g/cm3
pKa:8.50±0.48(预测)
PSA:67.25
LogP:1.52
折射率1.633
蒸汽压0.0±1.8 mmHg at 25°C
溶解性Insoluble In H2O; ≥13.25 mg/mL In DMSO; ≥47.7 mg/mL In Etoh With Ultrasonic
外观形态白色至类白色固体
储存条件储存在 -20°C
产品应用该化合物用作该化合物用作用.

上下游产品

CAS号127168-84-7 5-溴异二氢吲哚 | CAS号6941-75-9 4-溴邻苯二甲酰亚胺 | CAS号201940-08-1 5-溴异吲哚啉-2-碳酸叔丁酯盐酸盐 | CAS号1015484-22-6 三氟((4-甲基哌嗪-1-基)... | CAS号109-01-3 N-甲基哌嗪

合成工艺路线路线简述

1415742-78-7 + 1293965-69-1 = 912999-49-6
反应条件:1.1 Reagents: Chloro(1-Methylethyl)Magnesium Solvents: Tetrahydrofuran; -20 °C; 3 H,-20 °C -> 0 °C; 12 H,0 °C -> 20 °C1.2 Reagents: Ammonium Chloride Solvents: Water1.3 Reagents: Hydrochloric Acid Solvents: Water; Ph 6 - 7
标题:Total Synthesis Of Resorcinol Amide Hsp90 Inhibitor At13387
作者:Patel,Bhavesh H.; Et Al
参考文献:Journal Of Organic Chemistry 日期:2012 卷标:77(24) 页码:11296-11301]

1019890-58-4 = 912999-49-6
反应条件:1.1 Reagents: Hydrochloric Acid Solvents: Dichloromethane; 10 Min,Rt; 4 H,Rt2.1 Reagents: 1-Hydroxybenzotriazole,1-Ethyl-3-(3′-Dimethylaminopropyl)Carbodiimide Hydrochloride Solvents: Dimethylformamide; 0.5 H,Rt2.2 Reagents: Diisopropylethylamine; 0.5 H,0 °C; 0 °C -> Rt; 10 H,Rt3.1 Reagents: Hydrogen Catalysts: Palladium Solvents: Methanol; 12 H,Rt
标题:Alternate Synthesis Of Hsp90 Inhibitor At13387
作者:Liang,Cuirong; Et Al
参考文献:Synthetic Communications 日期:2014 卷标:44(16) 页码:2416-2425]

109-94-4 + 1332372-71-0 = 912999-49-6
反应条件:1.1 Reagents: Diisopropylamine,Butyllithium Solvents: Tetrahydrofuran,Hexane; -78 °C; 20 Min,-78 °C; 50 Min,-78 °C1.2 Reagents: Diethylzinc Solvents: Tetrahydrofuran,Hexane; -78 °C; 30 Min,-78 °C1.3 Solvents: Tetrahydrofuran; -78 °C; 2 H,-78 °C1.4 Reagents: Sodium Hydroxide Solvents: Water; -78 °C; -78 °C -> Rt; 10 Min,Rt1.5 Reagents: Hydrochloric Acid Solvents: Water; Ph 1 - 22.1 Reagents: Chloro(1-Methylethyl)Magnesium Solvents: Tetrahydrofuran; -20 °C; 3 H,-20 °C -> 0 °C; 12 H,0 °C -> 20 °C2.2 Reagents: Ammonium Chloride Solvents: Water2.3 Reagents: Hydrochloric Acid Solvents: Water; Ph 6 - 7
标题:Total Synthesis Of Resorcinol Amide Hsp90 Inhibitor At13387
作者:Patel,Bhavesh H.; Et Al
参考文献:Journal Of Organic Chemistry 日期:2012 卷标:77(24) 页码:11296-11301]

1293965-69-1 + 912545-09-6 = 912999-49-6
反应条件:1.1 Reagents: 1-Hydroxybenzotriazole,1-Ethyl-3-(3′-Dimethylaminopropyl)Carbodiimide Hydrochloride Solvents: Dimethylformamide; 0.5 H,Rt1.2 Reagents: Diisopropylethylamine; 0.5 H,0 °C; 0 °C -> Rt; 10 H,Rt2.1 Reagents: Hydrogen Catalysts: Palladium Solvents: Methanol; 12 H,Rt
标题:Alternate Synthesis Of Hsp90 Inhibitor At13387
作者:Liang,Cuirong; Et Al
参考文献:Synthetic Communications 日期:2014 卷标:44(16) 页码:2416-2425]

1015484-22-6 + 201940-08-1 = 912999-49-6
反应条件:1.1 Reagents: Cesium Carbonate Catalysts: Palladium Diacetate,X-Phos Solvents: Tetrahydrofuran,Water; 24 H,80 °C2.1 Reagents: Hydrochloric Acid Solvents: Methanol; 16 H,Rt3.1 Reagents: Chloro(1-Methylethyl)Magnesium Solvents: Tetrahydrofuran; -20 °C; 3 H,-20 °C -> 0 °C; 12 H,0 °C -> 20 °C3.2 Reagents: Ammonium Chloride Solvents: Water3.3 Reagents: Hydrochloric Acid Solvents: Water; Ph 6 - 7
标题:Total Synthesis Of Resorcinol Amide Hsp90 Inhibitor At13387
作者:Patel,Bhavesh H.; Et Al
参考文献:Journal Of Organic Chemistry 日期:2012 卷标:77(24) 页码:11296-11301]

10364-92-8 + 5394-63-8 = 912999-49-6
反应条件:1.1 Reagents: Butyllithium,Hexamethyldisilazane Solvents: Tetrahydrofuran,Hexane; -78 °C; 20 Min,-78 °C; 1 H,-78 °C1.2 Reagents: Diethylzinc Solvents: Tetrahydrofuran,Hexane; -78 °C; 20 Min,-78 °C; -78 °C -> -20 °C1.3 Solvents: Tetrahydrofuran; -20 °C -> -10 °C; 3.5 H,-10 °C1.4 Reagents: Hydrochloric Acid Solvents: Water; Ph 1 - 22.1 Reagents: Diisopropylamine,Butyllithium Solvents: Tetrahydrofuran,Hexane; -78 °C; 20 Min,-78 °C; 50 Min,-78 °C2.2 Reagents: Diethylzinc Solvents: Tetrahydrofuran,Hexane; -78 °C; 30 Min,-78 °C2.3 Solvents: Tetrahydrofuran; -78 °C; 2 H,-78 °C2.4 Reagents: Sodium Hydroxide Solvents: Water; -78 °C; -78 °C -> Rt; 10 Min,Rt2.5 Reagents: Hydrochloric Acid Solvents: Water; Ph 1 - 23.1 Reagents: Chloro(1-Methylethyl)Magnesium Solvents: Tetrahydrofuran; -20 °C; 3 H,-20 °C -> 0 °C; 12 H,0 °C -> 20 °C3.2 Reagents: Ammonium Chloride Solvents: Water3.3 Reagents: Hydrochloric Acid Solvents: Water; Ph 6 - 7
标题:Total Synthesis Of Resorcinol Amide Hsp90 Inhibitor At13387
作者:Patel,Bhavesh H.; Et Al
参考文献:Journal Of Organic Chemistry 日期:2012 卷标:77(24) 页码:11296-11301]

1019890-18-6 = 912999-49-6
反应条件:1.1 Reagents: Hydrogen Catalysts: Palladium Solvents: Methanol; 12 H,Rt
标题:The Succinct Synthesis Of At13387,A Clinically Relevant Hsp90 Inhibitor
作者:Kaur,Jatinder; Et Al
参考文献:Synthetic Communications 日期:2019 卷标:49(11) 页码:1436-1443]

109-01-3 = 912999-49-6
反应条件:1.1 Reagents: Lithium Aluminum Hydride Solvents: Tetrahydrofuran; 1.5 H,0 °C1.2 Reagents: Potassium Bisulfate Solvents: Water1.3 Reagents: Acetic Acid,Sodium Triacetoxyborohydride Solvents: Dichloromethane; 5 H,Rt1.4 Reagents: Water1.5 Reagents: Potassium Carbonate,Hydrogen Catalysts: Palladium Solvents: Methanol,Water; 16 H,Rt1.6 Reagents: Hydrochloric Acid Solvents: Water; Neutralized
标题:Discovery Of (2,4-Dihydroxy-5-Isopropylphenyl)-[5-(4-Methylpiperazin-1-Ylmethyl)-1,3-Dihydroisoindol-2-Yl]Methanone (At13387),A Novel Inhibitor Of The Molecular Chaperone Hsp90 By Fragment Based Drug Design
作者:Woodhead,Andrew J.; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2010 卷标:53(16) 页码:5956-5969]

1015484-22-6 = 912999-49-6
反应条件:1.1 Reagents: Cesium Carbonate Catalysts: Palladium Diacetate,Tri-Tert-Butylphosphonium Tetrafluoroborate Solvents: Toluene,Water; 14 H,100 °C2.1 Reagents: Hydrogen Catalysts: Palladium Solvents: Methanol; 12 H,Rt
标题:The Succinct Synthesis Of At13387,A Clinically Relevant Hsp90 Inhibitor
作者:Kaur,Jatinder; Et Al
参考文献:Synthetic Communications 日期:2019 卷标:49(11) 页码:1436-1443]

1019890-58-4 = 912999-49-6
反应条件:1.1 Reagents: Hydrochloric Acid Solvents: Methanol; 16 H,Rt2.1 Reagents: Chloro(1-Methylethyl)Magnesium Solvents: Tetrahydrofuran; -20 °C; 3 H,-20 °C -> 0 °C; 12 H,0 °C -> 20 °C2.2 Reagents: Ammonium Chloride Solvents: Water2.3 Reagents: Hydrochloric Acid Solvents: Water; Ph 6 - 7
标题:Total Synthesis Of Resorcinol Amide Hsp90 Inhibitor At13387
作者:Patel,Bhavesh H.; Et Al
参考文献:Journal Of Organic Chemistry 日期:2012 卷标:77(24) 页码:11296-11301]

109-01-3 + 1351815-45-6 = 912999-49-6
反应条件:1.1 Reagents: Acetic Acid,Sodium Triacetoxyborohydride Solvents: 1,2-Dimethoxyethane2.1 Reagents: Hydrogen Catalysts: Palladium Solvents: Methanol; 12 H,Rt
标题:The Succinct Synthesis Of At13387,A Clinically Relevant Hsp90 Inhibitor
作者:Kaur,Jatinder; Et Al
参考文献:Synthetic Communications 日期:2019 卷标:49(11) 页码:1436-1443]

109-01-3 = 912999-49-6
反应条件:1.1 Reagents: Potassium Carbonate Solvents: Dimethylformamide; 12 H,Rt2.1 Reagents: Hydrogen Catalysts: Palladium Solvents: Methanol; 12 H,Rt
标题:Alternate Synthesis Of Hsp90 Inhibitor At13387
作者:Liang,Cuirong; Et Al
参考文献:Synthetic Communications 日期:2014 卷标:44(16) 页码:2416-2425]

6638-79-5 = 912999-49-6
反应条件:1.1 Reagents: Sodium Hydroxide Solvents: Methanol,Water; 48 H,50 °C1.2 Reagents: Hydrochloric Acid Solvents: Water; Acidified1.3 Reagents: Triethylamine,1-Hydroxybenzotriazole,1-Ethyl-3-(3′-Dimethylaminopropyl)Carbodiimide Hydrochloride Solvents: Dimethylformamide; 48 H,Rt2.1 Reagents: Lithium Aluminum Hydride Solvents: Tetrahydrofuran; 1.5 H,0 °C2.2 Reagents: Potassium Bisulfate Solvents: Water2.3 Reagents: Acetic Acid,Sodium Triacetoxyborohydride Solvents: Dichloromethane; 5 H,Rt2.4 Reagents: Water2.5 Reagents: Potassium Carbonate,Hydrogen Catalysts: Palladium Solvents: Methanol,Water; 16 H,Rt2.6 Reagents: Hydrochloric Acid Solvents: Water; Neutralized
标题:Discovery Of (2,4-Dihydroxy-5-Isopropylphenyl)-[5-(4-Methylpiperazin-1-Ylmethyl)-1,3-Dihydroisoindol-2-Yl]Methanone (At13387),A Novel Inhibitor Of The Molecular Chaperone Hsp90 By Fragment Based Drug Design
作者:Woodhead,Andrew J.; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2010 卷标:53(16) 页码:5956-5969

📜2,4-二羟基苯甲酸置于4-二甲氨基吡啶,N-溴代丁二酰亚胺(Nbs),Palladium 10% On Activated Carbon,水,氢气,Palladium Diacetate,Potassium Carbonate,1-羟基苯并三唑,Caesium Carbonate,盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺,Lithium Hydroxide,Tri Tert-Butylphosphoniumtetrafluoroborate,2-二环己基磷-2,4,6-三异丙基联苯体系中,用四氢呋喃,甲醇,二氯甲烷,水,甲苯,乙腈作为反应溶剂,化学反应 61.0H,反应生成 [1,3-二氢-5-[(4-甲基-1-哌嗪基)甲基]-2H-异吲哚-2-基][2,4-二羟基-5-(1-甲基乙基)苯基]甲酮
参考文献:The Succinct Synthesis Of At13387,A Clinically Relevant Hsp90 Inhibitor
标题:The Succinct Synthesis Of At13387,A Clinically Relevant Hsp90 Inhibitor
摘要:At13387 Is An Orally Bioavailable Clinical Candidate Developed To Inhibit Heat Shock Protein 90 (Hsp90). This Article Describes A Modified Synthetic Route For The Multi-Gram Production Of At13387 In 46% Overall Yield. The Modified Synthetic Route Is Short,Avoids Stringent Reaction Conditions And Difficult Purifications,Which Led To An Increase In Overall Yield.
DOI:10.1080/00397911.2019.1602654

海关参考信息

2902600000-乙苯
2902700000-异丙基苯
2907221000-对苯二酚
2912110000-甲醛
💡 提示：海关信息按照顺序优先匹配，如需确认的海关信息，请参考相关资料。
详情请参考：📖 海关编码查询和海关进出口税则

专利信息

专利号:WO-2014018862-A1
优先权日:2012-07-27
标题 :Pharmaceutical compositions comprising a heat shock protein inhibitor and a; purine de novo synthesis inhibitor for treating rheumatoid arthritis or cancer
发明人：FANG YE
权利人:CORNING INC; FANG YE
摘要:A pharmaceutical composition including an effective amount of the combination of: an heat shock protein (HSP) inhibitor, and a purine de novo biosynthesis inhibitor, or a pharmaceutically acceptable salt thereof. Also disclosed is a method of treating rheumatoid arthritis or cancer including administering an effective amount of the above mentioned pharmaceutical composition to a patient in need of such treatment, as defined herein.

专利号:US-11312722-B2
优先权日:2019-05-08
标题:Hsp90 inhibitors and uses thereof
发明人：BROWN LAUREN ELAINE; HUANG DAVID S; COWEN LEAH E; WHITESELL LUKE; MARCYK PAUL
权利人:UNIV BOSTON; GOVERNING COUNCIL UNIV TORONTO
摘要:Herein is described the design and synthesis of resorcylate aminopyrazole compounds. These compounds show broad, potent and fungal-selective Hsp90 inhibitory activity. These compounds also find use in treating Hsp90 related diseases.

专利号:CN-118812489-A
优先权日:2024-06-03
标题:Synthesis method and application of 2, 2-dimethyl-6- (2-oxo-5-hexene-1-yl) -4H-1, 3-dioxane-4-one

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主要参考文献

1: Williams NO, Quiroga D, Johnson C, Brufsky A, Chambers M, Bhattacharya S, Patterson M, Sardesai SD, Stover D, Lustberg M, Noonan AM, Cherian M, Bystry DM, Hill KL, Chen M, Phelps MA, Grever M, Stephens JA, Ramaswamy B, Carson WE 3rd, Wesolowski R. Phase Ib study of HSP90 inhibitor, onalespib (AT13387), in combination with paclitaxel in patients with advanced triple-negative breast cancer. Ther Adv Med Oncol. 2023 Dec 25;15:17588359231217976. doi: 10.1177/17588359231217976.
2: Mortensen ACL, Berglund H, Hariri M, Papalanis E, Malmberg C, Spiegelberg D. Combination therapy of tyrosine kinase inhibitor sorafenib with the HSP90 inhibitor onalespib as a novel treatment regimen for thyroid cancer. Sci Rep. 2023 Oct 6;13(1):16844. doi: 10.1038/s41598-023-43486-z.
3: Mohajershojai T, Spangler D, Chopra S, Frejd FY, Yazaki PJ, Nestor M. Enhanced Therapeutic Effects of 177Lu-DOTA-M5A in Combination with Heat Shock Protein 90 Inhibitor Onalespib in Colorectal Cancer Xenografts. Cancers (Basel). 2023 Aug 24;15(17):4239. doi: 10.3390/cancers15174239.

合成参考文献

参考文献:10.18632/oncotarget.5363
摘要:Spiegelberg D, Dascalu A, Mortensen AC, Abramenkovs A, Kuku G, Nestor M, Stenerlöw B. The novel HSP90 inhibitor AT13387 potentiates radiation effects in squamous cell carcinoma and adenocarcinoma cells. Oncotarget. 2015 Nov 03;6(34):35652–66.
参考文献:10.1186/s43556-022-00070-7
摘要:Ruan H, Leibowitz BJ, Peng Y, Shen L, Chen L, Kuang C, Schoen RE, Lu X, Zhang L, Yu J. Targeting Myc-driven stress vulnerability in mutant KRAS colorectal cancer. Molecular Biomedicine. 2022 Mar 21;3(1):10. doi: 10.1186/s43556-022-00070-7.