Application examples of 1-(pyridin-4-yl)cyclopropylamine dihydrochloride_Industrial additives

Background and overview of application examples of 1-(pyridin-4-yl)cyclopropylamine dihydrochloride

1-(pyridin-4-yl)cyclopropylamine dihydrochloride is a pharmaceutical intermediate that can be used to prepare N-(3,4-difluorophenyl)-2-fluoro-5-dimethyl Sulfoxide (N-(1-(pyridin-4-yl)cyclopropyl)sulfamoyl)benzamide. N-(3,4-difluorophenyl)-2-fluoro-5-(N-(1-(pyridin-4-yl)cyclopropyl)sulfamoyl)benzamide as a nucleocapsid assembly inhibitor Agents, particularly but not exclusively, include for the treatment of hepatitis B virus (HBV) infection and related conditions.

HBV is a non-cytopathic, hepatotropic DNA virus belonging to the Hepadnaviridae family. Pregenomic (pg) RNA is the template for reverse transcription replication of HBV DNA, and it is encapsidated into nucleocapsid together with viral DNA polymerase, which is necessary for subsequent viral DNA synthesis. Inhibiting progenomic RNA (pg) encapsidation blocks HBV replication and provides a novel therapeutic approach to treat HBV. Similar approaches will lead to novel treatments for other viruses.

Clinically, inhibition of pregenomic RNA (pg) encapsidation, or more generally, inhibition of nucleocapsid assembly, offers the following therapeutic advantages: First, inhibition of pregenomic RNA (pg) encapsidation will inhibit pregenomic RNA (pg) encapsidation by Subpopulations of patients who do not tolerate or benefit from current medications provide another option to supplement current medications. Second, based on their different antiviral mechanisms, inhibition of pregenomic RNA (pg) encapsidation would effectively target HBV variants that are resistant to currently available DNA polymerase inhibitors (Zoulim and Locarnini, 2009). Third, similar to highly active antiretroviral therapy (HAART) used for human immunodeficiency virus (HIV) infection (Este and Cihlar), a combination of pregenomic RNA (pg) encapsidation inhibitors and DNA polymerase inhibitors Therapies should synergistically suppress HBV replication and prevent the emergence of drug resistance, and thus provide safer and more effective treatment of chronic hepatitis B infection.

Application examples of 1-(pyridin-4-yl)cyclopropylamine dihydrochlorideApplication examples

Use 3-(3,4-difluorophenyl-carbamoyl)-4-fluorobenzene-1-sulfonyl chloride (50 mg, 0.14 mmol), NEt3 (56 mg, 0.56 mmol) and 1-(pyridine- 4-yl)cyclopropylamine dihydrochloride can be used as raw material to prepare N-(3,4-difluorophenyl)-2-fluoro-5-(N-(1-(pyridine-4- cyclopropyl)sulfamoyl)benzamide (15 mg, 24%).

References

[1][Invented in China] CN201380072796.5 New antiviral agent for HBV infection