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Amide compounds and methods for the production and use thereof

A technology for compounds and medicinal salts, applied in chemical instruments and methods, active ingredients of heterocyclic compounds, drug combinations, etc.

Pending Publication Date: 2017-02-22
OBSCHESTVO S OGRANICHENNOI OTVETABTVENNOSTIYU PHARMENTERPRISES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are no effective drugs for the treatment of adenovirus infection

Method used

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  • Amide compounds and methods for the production and use thereof
  • Amide compounds and methods for the production and use thereof
  • Amide compounds and methods for the production and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0429] Antiviral activity of compounds of formula I against Coxsackie virus in vitro

[0430] The trypsin-dependent strain HCXV A2, which was pre-adapted and caused the death of coxsackievirus-infected mice, was used in this study.

[0431] The experiment was carried out in mice weighing 6 to 7 g. Animals were infected intramuscularly at a dose of 0.1 mL / mouse. The infectious dose used which resulted in the mortality of mice was 10 LD 50 .

[0432] The ability of a compound to provide a therapeutic effect is determined by the mortality of HCXV A2 virus infected mice in the experimental group relative to the group of untreated animals.

[0433] Study compounds and placebo were administered orally according to the treatment regimen. A saline solution was administered to the mice as a placebo. Untreated animals served as negative controls and were kept in separate rooms under the same conditions as the experimental animals.

[0434] For this experiment, groups were formed...

Embodiment 2

[0442] Antiviral activity of compounds of general formula I against mouse-adapted RS virus

[0443] The antiviral effectiveness of chemical compounds against RSV in an in vitro mouse model was determined against the human virus hRSV, which was previously adapted to grow in mouse lungs. Mice were briefly anesthetized with ether at a volume of 0.05 mL / mouse and treated with 0.5 logTCID 50 doses to infect the virus intranasally. The compound under study was administered orally once daily for 5 days at a dose of 30 mg / kg according to the treatment regimen. The first administration was performed 24 hours after infection. A saline solution was administered to the mice as a placebo. Untreated animals served as negative controls and were kept in separate rooms under the same conditions as the experimental animals. Each experimental group contained 12 animals. Ribavirin was used as reference drug at a dose of 40 mg / kg.

[0444] The antiviral activity of the investigated compoun...

Embodiment 3

[0456] Antiviral activity of compounds of general formula I against RS virus in an immune system suppressed mouse model

[0457] Compounds against human respiratory syncytial virus (strain A2, infection titer is 5×10 6 TCID 50 / mL) was evaluated in the Balb / c mouse model of viral pneumonia. Animals were inoculated intranasally with virus in a volume of 50 μL under brief ether anesthesia. The animals' immune response to RS virus was suppressed by intraperitoneal administration of cyclophosphamide at a dose of 100 mg / kg 5 days before infection. Starting 24 hours after infection, the compound under study was administered once daily for 5 days according to the treatment protocol at a dose of 30 mg / kg. Compound activity was determined by the reduction of pulmonary edema in respiratory syncytial virus-infected lungs relative to controls at 5 days post-infection.

[0458] The results shown in Table 6 for some specific compounds of general formula I (without any limitation to th...

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Abstract

This invention relates to the field of medicine and concerns a method for the prophylaxis or treatment of diseases caused by RNA- and DNA-containing viruses, and concomitant diseases, which envisages the use of an effective amount of a compound of general formula I or a pharmaceutically acceptable salt thereof. The invention also relates to methods for producing the aforesaid compounds, and to pharmaceutical compositions for the prophylaxis or treatment of diseases caused by RNA- and DNA-containing viruses, which contain an effective amount of a compound of general formula I or a pharmaceutically acceptable salt thereof. The invention solves the problem of providing a novel agent effective in the treatment of diseases caused by RNA-containing viruses belonging to the enterovirus genus, the metapneumovirus genus, the pneumovirus genus, the respirovirus genus or the alphacoronavirus genus, and DNA-containing viruses belonging to the adenovirus family and the herpesvirus family, and also effective in the prophylaxis and treatment of asthma exacerbations, chronic obstructive pulmonary disease, cystic fibrosis, conjunctivitis, gastroenteritis, hepatitis and myocarditis, and in the prophylaxis and treatment of rhinorrhea, acute and infectious rhinitis, pharyngitis, nasopharyngitis, tonsillitis, laryngitis, laryngotracheitis, laryngotracheobronchitis, bronchitis, bronchiolitis, pneumonia or obstructive airways syndrome.

Description

technical field [0001] The present invention relates to medicine, in particular to the use of the compound of general formula I or its possible salts for preventing and / or treating diseases caused by RNA-containing viruses and DNA-containing viruses, as well as accompanying diseases. Background technique [0002] Viral infections are serious health problems. Antiviral drugs for the most critical and dangerous viral infections have yet to be developed, and existing drugs are often toxic or insufficiently effective in humans. Most existing or developing drugs work by specifically interacting with certain viral proteins. Such drugs have a limited spectrum of activity and facilitate the rapid emergence of resistant virus variants. According to the Baltimore virus classification system, class I includes viruses whose genomes consist of double-stranded DNA, and classes IV and V include viruses containing single-stranded (+) or (-) RNA. One family belonging to class I is the Ade...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/06C07K5/037A61K38/05A61P31/12A61P31/14A61P31/20A61P31/04A61P27/02A61P11/00A61P11/06A61P1/04A61P1/16
CPCA61K38/05A61P1/04A61P1/16A61P11/00A61P11/06A61P27/02A61P31/04A61P31/12A61P31/14A61P31/20C07K5/06A61K38/00C07C279/12C07D207/09C07D207/22C07D207/32C07D209/14C07D209/16C07D211/26C07D213/36C07D231/12C07D233/24C07D233/56C07D233/64C07D233/66C07D235/14C07D237/08C07D239/26C07D241/04C07D241/12C07D249/04C07D249/08C07D249/18C07D257/04C07D261/08C07D261/10C07D263/32C07D265/30C07D271/06C07D271/08C07D275/02C07D277/28C07D277/64C07D285/10C07D285/22C07D295/067C07D307/52C07D333/20C07D401/12C07D403/12C07D417/12C07D471/04C07D487/04C07D513/04C07K5/02C07K5/06104C07K5/06147A61K31/40A61K31/41
Inventor 弗拉迪米尔·叶夫根尼耶维奇·涅博利辛塔季亚纳·亚历山德罗芙娜·克罗莫瓦
Owner OBSCHESTVO S OGRANICHENNOI OTVETABTVENNOSTIYU PHARMENTERPRISES
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