Piperidine derivatives as human papilloma virus inhibitors
Inventors
Blumenfeld, Marta • Compere, Delphine • Gauthier, Jean-Michel
Assignees
Publication Number
US-9974779-B2
Publication Date
2018-05-22
Expiration Date
2027-05-18
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Abstract
The present disclosure is directed to antiviral compounds directed against the papilloma virus, to pharmaceutical compositions containing them, to their preparation method and synthesis intermediates, as well as to their use for treating or preventing an infection by the papilloma virus. The present method thus provides an efficient way of treating patients that have lesions associated with an infection by the papilloma virus.
Core Innovation
The present invention provides novel antiviral compounds, specifically piperidine derivatives, that are active against the papilloma virus. The compounds are designed to inhibit replication of human papilloma viruses (HPVs), particularly by interfering with the formation of the E1/E2 protein complex required for viral genome replication. This invention also encompasses pharmaceutical compositions containing these compounds, methods for their preparation, synthesis intermediates, and their applications for treating or preventing infections caused by papilloma viruses.
HPVs are widespread and cause various epithelial lesions, including warts and more severe diseases such as anogenital cancers. Existing treatments for HPV-related lesions rely on physical destruction or application of cytotoxic or immunomodulator agents. However, none of the existing strategies completely eliminates viral particles and current therapies are associated with high recurrence and significant side effects, highlighting the need for effective antiviral agents that specifically target HPV replication.
The invention addresses this need by introducing compounds of formula (I), and their specific derivatives and salts, which can inhibit HPV by blocking the E1/E2 interaction, thereby impeding viral DNA replication. These compounds, including preferred and more preferred derivatives detailed in the patent, have demonstrated inhibitory effects on HPV6 and HPV11 replication in cellular assays with potent activity, and thus provide a new class of targeted ant-HPV agents for clinical use.
Claims Coverage
There is one independent claim, supported by several dependent claims. The independent claim covers the inventive method of treating HPV 6 or HPV 11 infections using specific piperidine derivatives.
Method for treating infection by HPV 6 or HPV 11 with a compound of formula (I)
A method of treating an infection by HPV 6 or HPV 11 papilloma virus comprising the administration to a patient in need thereof of an efficient quantity of a compound of formula (I): - The compound of formula (I) is broadly defined in the claim and throughout the specification to cover a wide range of piperidine-based derivatives, including salts and various substitutions on core structural scaffolds as detailed in the description. - The claim is further supported by dependent claims specifying that the inventive compounds include, but are not limited to, the group consisting of 33 specific derivatives listed (including 5-bromo-2-methoxy-4-[N'-(4-methoxy-phenyl)-N'-(2-piperidin-1-yl-phenyl)-hydrazinocarbonylmethyl]-benzoic acid hydrochloride and related compounds). - The method is stated to encompass treating patients who have lesions associated with infection by the papilloma virus, including specific lesion types such as ano-genital warts, laryngeal, conjunctive or buccal papillomas, and specific epithelial lesions (including recurrent respiratory papillomatosis, intra-epithelial neoplasias, bowenoid papulosis, various warts, epidermodysplasia verruciformis, and carcinomas). - Dependent claims further clarify that 'wart' includes verruca vulgaris, verruca plantaris, myrmecia wart, surface wart, and verruca plana; and that 'carcinoma' specifically includes ano-genital carcinoma.
The main inventive feature claimed is the medical use of specific piperidine derivatives of formula (I), particularly the 33 exemplified compounds, for the treatment of HPV 6 or 11 infections and related lesions, providing a molecularly targeted anti-HPV therapy.
Stated Advantages
The invention provides an efficient way of treating patients with lesions associated with infection by the papilloma virus.
The compounds inhibit replication of papilloma viruses by inhibiting the formation of the E1/E2 protein complex.
The invention offers compounds active against a broad spectrum of HPV types, including those unable to be effectively treated by existing methods.
The invention addresses the shortcomings of existing therapeutic strategies, which fail to eliminate all viral particles and are associated with high recurrence and significant side effects.
Documented Applications
Treating or preventing infection by the papilloma virus, preferably in humans.
Inhibiting replication of the papilloma virus by inhibiting formation of the E1/E2 protein complex.
Preparing a drug intended for treating or preventing infection by low risk papilloma viruses, such as HPV6, HPV7, HPV11, HPV13, HPV32, HPV34, HPV40, HPV42, HPV43, HPV44, HPV53, HPV54, HPV55, HPV57, HPV58, HPV74, HPV91.
Preparing a drug intended for treating or preventing infection by HPV6 and/or HPV11.
Preparing a drug intended for treating or preventing lesions and diseases associated with infections by the papilloma virus (including anogenital warts such as acuminated condylomas and plane condylomas, laryngeal, conjunctive or buccal papillomas, respiratory recurrent papillomatoses, intra-epithelial neoplasias, bowenoid papuloses, warts, epidermodysplasia verruciformis, carcinomas, anogenital carcinomas, and all lesions associated with the papilloma virus).
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