Cyanotriazole compounds and uses thereof

A compound, phenyl technology, applied in the field of cyanotriazole compounds, can solve problems such as reluctance to take miltefocin

Pending Publication Date: 2021-02-02
NOVARTIS AG
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This makes affected people

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
  • Cyanotriazole compounds and uses thereof
  • Cyanotriazole compounds and uses thereof
  • Cyanotriazole compounds and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0198] In the preparation of compounds of the invention, it may be desirable to protect remote functionality of intermediates. The need for such protection will vary depending on the nature of the remote functionality and the conditions of the preparation method. The need for such protection is readily ascertainable by those skilled in the art. For a general description of protecting groups and their use, see Greene, T.W. et al., Protecting Groups in Organic Synthesis, 4th ed., Wiley (2007). Protecting groups introduced in the preparation of compounds of the present invention, such as the trityl protecting group, may appear as one regioisomer, but may also exist as a mixture of regioisomers.

[0199] General Synthetic Route 1

[0200]

[0201] Reaction conditions:

[0202] a. Coupling the amide with a coupler in a polar aprotic solvent;

[0203] b. In inorganic bases such as Na 2 CO 3 or K 3 PO 4 Suzuki couplings were performed with various Pd catalysts in the prese...

example 1

[0367] Example 1: 1-(2-(5-(2-(difluoromethyl)pyridin-3-yl)isoindoline-2-yl)-2-oxoethyl)-1H-1,2, 4-triazole-3-carbonitrile

[0368]

[0369] Preparation of 3-bromo-2-(difluoromethyl)pyridine

[0370]

[0371] To a solution of 3-bromopicolinaldehyde (0.50 g, 2.68 mmol) in dichloromethane (10 mL) was added diethylamidosulfur trifluoride (DAST, 0.86 g, 5.37 mmol) dropwise at 0°C. The reaction mixture was stirred at 0 °C for 3 hours. It was then very carefully quenched with saturated sodium bicarbonate solution at 0 °C and extracted with dichloromethane (10 mL X 3). The combined organic layers were dried over sodium sulfate and concentrated under vacuum. The crude compound was purified by column chromatography using 0-30% EtOAc in n-Hexane to give the title compound (0.25 g, 44.84%) as a colorless liquid, Rf = 0.9 (30% EtOAc in n-Hexane); Rf = 0.90 (30% EtOAc in n-Hexane); 1 H NMR (300MHz, chloroform-d) δ8.65 (dd, J = 4.7, 1.4Hz, 1H), 7.98 (dd, J = 8.1, 1.2Hz, 1H), 7.32 ...

example 2

[0380] Example 2: 1-(2-(5-(3-Chloro-5-(trifluoromethyl)pyridin-4-yl)isoindoline-2-yl)-2-oxoethyl)-1H- 1,2,4-triazole-3-carbonitrile

[0381]

[0382] Preparation of 3-chloro-5-(trifluoromethyl)pyridin-2-amine

[0383]

[0384] Stir 2,3-dichloro-5-(trifluoromethyl)pyridine (1.0 g, 4.65 mmol) in aqueous NH in a sealed tube at 100 °C 3 (0.5 mL) for 12 h. The reaction mixture was concentrated to dryness and purified by combi flash column chromatography using 70% EtOAc in n-Hexane to give the title compound 0.8 g (90.0%), Rf = 0.1 (70% EtOAc in n-Hexane); 1 HNMR (300MHz, chloroform-d) δ8.23(d, J=1.8Hz, 1H), 7.70(d, J=1.8Hz, 1H); LC-MS m / z 196.9[M+H] + , retention time = 0.98 min (method D); HPLC: 95.32%, retention time = 6.53 min (method E).

[0385] Preparation of N-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)pivalamide

[0386]

[0387] To a stirred solution of the precursor (400 mg, 2.04 mmol) in DCM (10 mL) was added pyridine (480 mg, 6.12 mmol) at 0 °C, followed by...

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
Ec50aaaaaaaaaa
Login to view more

Abstract

The present invention provides a compound of Formula (I), or a pharmaceutically acceptable salt thereof: (I) wherein R1, R2, R3, and R4 are as defined herein. The present invention further provides therapeutic uses of these compounds, for example against human African typanosomiasis; pharmaceutical compositions comprising these compounds, and compositions comprising these compounds with a therapeutic co-agent.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of priority to U.S. Serial No. 62 / 687,045, filed June 19, 2018, the contents of which are incorporated herein by reference. technical field [0003] The present invention relates to cyanotriazole compounds, compositions comprising such compounds, and their use in the treatment of kinetoplasmic diseases, in particular human African trypanosomiasis (HAT), Chagas disease and Leishmania disease (leishmaniasis). Background technique [0004] Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic disease caused by the protozoan parasite Trypanosomabrucei (T.b) and transmitted by the bite of tsetse flies. More than 95% of reported sleeping sickness cases are caused by T. b. gambiense and <5% by T. b. rhodesiense. The disease is endemic in 36 sub-Saharan African countries, and WHO recently reported <5000 new cases of the disease in 2016, but there may st...

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): C07D401/14C07D403/06A61K31/4196A61K31/4439A61P33/02
CPCC07D401/14C07D403/06A61P33/02A61K31/4196A61K31/4439A61K45/06
Inventor J·基里塞克S·P·恩格S·P·S·拉奥
Owner NOVARTIS AG
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap