Unlock instant, AI-driven research and patent intelligence for your innovation.

Application of IGF-1R small-molecule inhibitor in preparation of combined medicine for treating and/or preventing cancer

A small molecule inhibitor, 1. The technology of IGF-1R, applied in the field of medicine, can solve the problems of wasting drugs, irrationality, and delaying the timing of treatment, etc., to prolong the half-life, prolong the median survival period, improve effectiveness and long-term Effect

Active Publication Date: 2022-04-05
NAIN BIOTECH (HANGZHOU) CO LTD
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unreasonable combination of drugs can not only increase the occurrence of adverse reactions, but also waste drugs and delay the timing of correct treatment

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of IGF-1R small-molecule inhibitor in preparation of combined medicine for treating and/or preventing cancer
  • Application of IGF-1R small-molecule inhibitor in preparation of combined medicine for treating and/or preventing cancer
  • Application of IGF-1R small-molecule inhibitor in preparation of combined medicine for treating and/or preventing cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Example 1, relative-(5R,5aS,8aR,9R)-2,2-difluoro-9-hydroxyl-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9 -Tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]-dioxan-6(5aH)-one (Compound 1, PB-001)

[0067]

[0068] Such as figure 1 Shown, the synthetic process of compound 1 comprises:

[0069] Step 1), synthesis of 4-vinyldihydrofuran-2(3H)-one (intermediate 1.1):

[0070] To a mixture of 2-butene-1,4-diol (206.4g, 2.34mol, 1.0eq) and triethylorthoacetate (546.7g, 3.4mol, 1.4eq) was added catalytic hydroquinone (54.00g , 0.49mol, 0.2eq), the mixture was heated to 120°C. Ethanol was continued to be distilled off until no more ethanol was produced, the reaction temperature was raised to 150°C and the reaction mixture was stirred for 48 hours. Intermediate 1.1 was collected by vacuum distillation (70-75 °C, 2-3 mmHg) as a colorless oil (170.0 g, 65% yield). 1 HNMR (400MHz, CDCl 3)δ (ppm) 2.36 (dd, J = 17.4Hz, 8.7Hz, 1H), 2.69 (dd, J = 17.7Hz, 8.4Hz, 1H), 3.19-3.29 (m, 1H), 4.01-4...

Embodiment 2

[0083] Example 2, relative-(5R,5aS,8aR,9R)-2,2-difluoro-8-oxa-9-(3,4,5-trimethoxyphenyl)-5,5a,6, 8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]-dioxan-5-yl acetate (compound 2, PB-002)

[0084]

[0085] Compound 1 (1.15g, 2.55mmol, 1.0eq) and dichloromethane (30ml) were continuously stirred and mixed, and Et 3 N (770mg, 7.6mmol, 3.0eq) and DMAP (310mg, 2.55mmol, 1.0eq), then AcCl (400mg, 5.1mmol, 2.0eq) was added under ice bath, and the mixture was stirred at ambient temperature for 12 hours. Add LiAl(OtBu) dropwise 3 (200ml, 197mmol, 2.0eq), then gradually warmed to ambient temperature overnight. React with saturated NH 4Quenched with Cl, the aqueous phase was further extracted with dichloromethane. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The residue was recrystallized from petroleum ether / ethyl acetate to obtain compound 2 (810 mg, yield 65%) as a white solid. 1 HNMR (400MHz, CDCl 3 )δ(ppm)7.02(s,1H...

Embodiment 3

[0086] Example 3, relative-(5R,5aS,8aR,9R)-2,2,9-trifluoro-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9-tetrahydrofuran And[3',4':6,7]naphtho[2,3-d][1,3]-dioxan-6(5aH)-one (compound 3, PB-006)

[0087]

[0088] Compound 1 (700mg, 1.60mmol, 1.0eq) and dichloromethane (20ml) were continuously stirred and mixed, diethylaminosulfur trifluoride (520mg, 3.20mmol, 2.0eq) was added dropwise, and the mixture was stirred at ambient temperature for 12 Hour. React with saturated NaHCO 3 Quenched and stirring was continued for 30 minutes. After separation of the organic phase, the aqueous phase was further extracted with dichloromethane. The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The residue was purified by silica gel column chromatography (200-300 silica gel, dichloromethane:methanol=100 / 1-50 / 1) to obtain compound 3 (130 mg, yield 18%) as a white solid. 1 HNMR (400MHz, CDCl 3 )δ(ppm)7.27(s,1H),6.66(s,1H),6.44(s,2H),5.49-5.34(d,J=5...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
wavelengthaaaaaaaaaa
Login to View More

Abstract

The invention discloses an application of an IGF-1R small-molecule inhibitor in preparation of a combined medicine for treating and / or preventing cancers. The IGF-1R small-molecule inhibitor used in the invention is a compound as shown in a formula I, an optical isomer or a pharmaceutically acceptable salt thereof, and a fluorine atom is used for replacing a hydrogen atom at a position 2 on picropodophyllotoxin, so that the ability of molecules to penetrate through a blood-brain barrier can be improved. Furthermore, deuterium atoms are used for replacing multiple hydrogen atoms on the picropodophyllotoxin, so that the half-life period of molecules in an organism can be prolonged. The small-molecule inhibitor used in the invention can be used for preparing combined medicines for treating and / or preventing various types of cancers when being combined with other medicines. The combined application of the medicines can improve the treatment effectiveness, thereby prolonging the median lifetime.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to the use of a small molecule inhibitor of IGF-1R in the preparation of combined drugs for treating and / or preventing cancer. Background technique [0002] In 1956, someone discovered in serum a substance that can promote osteogenesis, called insulin-like growth factors (insulin-like growth factors, IGFs), which can promote cell proliferation, differentiation, and inhibit apoptosis. Insulin-like growth factor receptors include insulin-like growth factor-1 receptor (insulin-like growth factor-1 receptor, IGF-1R) and the like. IGF-1R plays an important role in the occurrence and development of various types of tumors, and has the prospect of becoming a targeted therapy drug for various types of tumors. [0003] Picropodophyllin (PPP) is a cyclolignan compound with the following structure: [0004] [0005] Picropodophyllotoxin is considered to be a specific IGF-1R t...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D493/04A61K31/365A61P35/00
CPCC07D493/04A61P35/00
Inventor 王英杰康博
Owner NAIN BIOTECH (HANGZHOU) CO LTD
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com