2,4,6-trisubstituted s-triazine compound, preparation method therefor, and use thereof
Inventors
Yao, Qizheng • Wu, Jianping • Chen, Ruihuan • Zhang, Lei • Yao, Shining • Mo, Lian • Zhang, QingQing
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Assignees
Nanjing Shiqi Pharmaceutical Co Ltd • Aluda Pharmaceuticals Inc
Member
Aluda Pharmaceuticals, Inc.Aluda Pharmaceuticals develops novel small molecule therapeutics for severe immune and fibrotic diseases, utilizing a systems biology approach targeting under-recognized and complex disease mechanisms. The company focuses on discovery and development of new molecular entities aimed at key regulatory proteins such as vimentin and STAT3, leveraging expertise in phenotypic screening, network-driven biology, and translational science. Aluda's pipeline addresses unmet needs in autoimmune, fibrotic, and refractory cancer conditions, with a scientific foundation in deep cell biology and state-of-the-art discovery methods.
Aluda Pharmaceuticals develops novel small molecule therapeutics for severe immune and fibrotic diseases, utilizing a systems biology approach targeting under-recognized and complex disease mechanisms. The company focuses on discovery and development of new molecular entities aimed at key regulatory proteins such as vimentin and STAT3, leveraging expertise in phenotypic screening, network-driven biology, and translational science. Aluda's pipeline addresses unmet needs in autoimmune, fibrotic, and refractory cancer conditions, with a scientific foundation in deep cell biology and state-of-the-art discovery methods.
Publication Number
US-10611736-B2
Publication Date
2020-04-07
Expiration Date
Abstract
The present invention provides a 2,4,6-trisubstituted s-triazine compound represented by general formula (I) or pharmaceutically acceptable salts, prodrugs or solvates thereof, a preparation method therefor, and use of these compounds in preparing drugs for preventing or treating diseases associated with protein kinase and vimentin dysregulation, and cell vacuolization, and in particular, drugs for treating or preventing cancer growth and metastasis, tissue fibrosis and atherosclerosis.
Core Innovation
The invention provides a class of compounds represented by Formula I, or pharmaceutically acceptable salts, prodrugs, and solvates thereof. The compounds are defined with broad substituent options using R1, R2, R3, and Ra, together with a para- or meta-phenyl linkage parameter X, where X is NH or O linked to the phenyl group on a para- or meta-position. Multiple formula variants and exemplary substituted structures are described within the disclosed structure definitions.
The compounds are proposed for regulating protein kinase and vimentin dysregulation to induce methuosis, described as vacuolization. The disclosure links methuosis to vimentin dysregulation and to EMT, and states that the compounds are indicated for preventing and/or treating cancer involving growth and metastasis, as well as tissue fibrosis and atherosclerosis.
The disclosure includes experimental and computational evidence directed to the proposed target and phenotypic effects. A probe fishing workflow is described using probe isolation with click/streptavidin pull-down to identify target proteins, and vimentin is identified as a target, together with docking interactions between a lead compound and vimentin and in vitro evidence showing tumor-cell growth inhibition across cell lines and vacuolization phenotypes.
Claims Coverage
The independent claims define the invention as a compound represented by Formula I, or a pharmaceutically acceptable salt or solvate thereof, with extensive structural variability. The main inventive features are the structural limitations on Formula I and the associated composition and therapeutic-use contexts.
Formula I compound with defined substituent classes
A compound represented by Formula I, or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, and Ra are constrained by detailed substituent definitions including allowed functional groups and heterocyclic ring-forming patterns, with X being NH or O linked to the phenyl group on a para- or meta-position.
Pharmaceutical composition with pharmaceutically acceptable carrier
A pharmaceutical composition containing the compound, or its pharmaceutically acceptable salt or solvate, together with a pharmaceutically acceptable carrier.
Therapeutic use for treating tissue fibrosis
Treating tissue fibrosis by administering to a subject in need thereof the compound, a pharmaceutically acceptable salt, or a solvate.
Overall claim coverage focuses on Formula I compounds constrained by detailed substituent and heterocycle definitions, including para/meta phenyl linkage for X, with additional coverage for pharmaceutical compositions containing a carrier and for using the compounds to treat tissue fibrosis.
Stated Advantages
Induce methuosis (vacuolization) through regulating protein kinase and vimentin dysregulation.
Prevent and/or treat cancer, including growth and metastasis.
Prevent and/or treat tissue fibrosis.
Prevent and/or treat atherosclerosis.
Documented Applications
Preventing or treating cancer, including growth and metastasis.
Preventing or treating tissue fibrosis.
Preventing or treating atherosclerosis.
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