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

Novel tricyclic aromatic heterocyclic compound as well as preparation method thereof, pharmaceutical composition and application thereof

A compound and hydrate technology, applied in the field of small molecule drugs, can solve problems such as difficult purification, injection-only administration, instability, etc.

Pending Publication Date: 2021-03-09
SHANGHAI LONGWOOD PHARMA
View PDF9 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the currently marketed and researched PD-1 monoclonal antibodies have their own defects, including injection, not oral, unstable in vivo, easy to be decomposed by protease, prone to immune cross-reaction, difficult to purify and difficult to produce. high cost

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
  • Novel tricyclic aromatic heterocyclic compound as well as preparation method thereof, pharmaceutical composition and application thereof
  • Novel tricyclic aromatic heterocyclic compound as well as preparation method thereof, pharmaceutical composition and application thereof
  • Novel tricyclic aromatic heterocyclic compound as well as preparation method thereof, pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0114]Preparation of compounds of formula I

[0115]In order to prepare the compound of the formula I, according to the structure of the formula I, the compound of the present invention can be obtained by the following synthesis route.

[0116]Equation 1:

[0117]

[0118](a) The target product I-1 is obtained by a suitable palladium catalyst catalyst by an intermediate body 1 and 2.

[0119]The preparation method of intermediate 1 is as follows:

[0120]

[0121](a) A coupling reaction formation intermediate 1-2 is formed by the compound 1-1 as the raw material (X is CL, Br OR I), under the condition of a suitable palladium catalyst and ligand.

[0122](b) Under the suitable Lewis acid catalysis, a suitable reducing agent is added to the primary and secondary amines, and the appropriate reducing agent is added to the first and secondary amines, and the formation of intermediates 1-3 is further reduced; or in a suitable reducing agent Direct reducing amination reaction in the presence, forming intermediate...

Embodiment 1

[0166]Example 1 Synthesis of Compound 001

[0167]Step 1-1:

[0168]

[0169]1.3 grams 1-1 is dissolved in DCM-3M H2SO4(1: 1) 200ml, ice bath, 0.71 g of sodium nitrate at 5 degrees, and sodium nitrate was added to the reaction system, nitrogen protection, room temperature reacted overnight. TLC Point Plate Display 1-1 disappears, LCMS analysis knows the product production. Column chromatography purified product 1-2 600mg, MS-APCI: 208 [M + H]+And 1-3 300mg, MS-APCI: 208 [M + H]+.

[0170]Step 1-2:

[0171]

[0172]4.5 g of compound 1-2 was dissolved in 200 ml DCM (in a single mouth flask in 500 ml), 6.3 g of NIS, argon protection was added. Room temperature reacted overnight. TLC Point 1-2 Reaction is complete. The reaction solution was added 2M HCl 100 mL, separation, and dried. The carnation column (Hep-DCM 1: 1, THEN DCM) was purified to give 6 g of product, pale yellow solid. MS-APCI: 334 [M + H]+.

[0173]Step 1-3:

[0174]

[0175]Add 945 mg of compound 1-4,636 mg of compound 1-5,25 mg Cui and 25 mg PD ...

Embodiment 2

[0201]Example 2 Synthesis of Compound 002

[0202]Step 2-1:

[0203]

[0204]4.5 grams of compound 1-3 were dissolved in 200 ml DCM (in a 500 ml single-mouth flask), 6.3 g of NIS, argon protection was added. Room temperature reacted overnight. TLC Point 1-3 The reaction is complete. The reaction solution was added 2M HCl 100 mL, separation, and dried. The carnation column (Hep-DCM 1: 1, THEN DCM) was purified to give 2 g of a product, pale yellow solid. MS-APCI: 334 [M + H]+.

[0205]Step 2-2:

[0206]

[0207]2 grams of compound 2-1,1 gsin cyanide and 60 mg of tetrazophenylphosphine palladium were dissolved in 50 ml dry DMF, argon protection, 140 degrees reactions. The TLC Point 2-1 is complete. The reaction solution was poured into 150 ml of water, DCM (100 ml) was extracted twice, dried. The carnation column (DCM-MeOH 100, 50: 1, 30: 1, 20: 1, 10: 1, 5: 1) was purified to give 800 mg of product, pale yellow solid. MS-APCI: 233 [M + H]+.

[0208]Step 2-3:

[0209]

[0210]500 mg of compound 2-2 was dissolve...

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

No PUM Login to View More

Abstract

The invention provides a novel tricyclic aromatic heterocyclic compound as well as a preparation method thereof, a pharmaceutical composition and an application thereof, and particularly provides a compound as shown in a formula I which is described in the specification, or an optical isomer, a hydrate, a solvate or a pharmaceutically acceptable salt thereof. Wherein the definition of each group is as shown in the specification. The compounds of formula I can be used to treat diseases associated with PD-1 / PD-L1 signaling pathways.

Description

Technical field[0001]The present invention relates to the field of small molecular drugs, and in particular, the present invention provides a small molecule compound which can be used to treat a disease associated with the PD-1 / PD-L1 signaling pathway.[0002]Inventory background[0003]The immune system plays a crucial role in control and root conformation, like diseases caused by various cancers, viruses. However, cancer cells can often develop or inhibit the immune system through some ways to rapidly breed. One way is to change activation and inhibitors of immunocytes expression. Blocking inhibiting the immunological examination point, like PD-1, proves to be a very effective method of inhibiting cancer cells.[0004]PD-1 is a procedural cytoprotein-1, also known as CD279. It is primarily expressed in activated T cells and B cells, functionality is to inhibit cell activation, which is a normal self-stability mechanism of the immune system, because excessive T / B cell activation caus...

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
IPC IPC(8): C07D471/04C07D405/14C07D413/14C07D519/00A61K31/4375A61K31/497A61K31/4709A61K31/4025A61P35/00
CPCC07D471/04C07D405/14C07D413/14C07D519/00A61P35/00C07B2200/07A61K45/06A61P31/00A61P37/00A61K31/4375A61K31/4439A61K31/519C07D487/10C07D413/10C07D487/04
Inventor 王喆白海云李德亮潜安然
Owner SHANGHAI LONGWOOD PHARMA
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