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Assignees
Duquesne University of the Holy Spirit
Member
Nanomedicine Manufacturing Lab, Duquesne UniversityNANOMEDICINE MANUFACTURING LABORATORY
Nanomedicine Manufacturing Laboratory (NML) is a research and development laboratory specializing in nanomaterials and biomaterials for imaging, oxygen delivery, and drug delivery, with a core emphasis on scalable manufacturing and Quality-by-Design (QbD).
More informaiton about NML: https://www.duq.edu/research/faculty-research/nanomedicine-lab/nanomed-lab-research.php
Led by Dr. Jelena M. Janjic, the Nanomedicine Manufacturing Laboratory develops colloidal nanosystems and implantable biomaterials that support molecular imaging modalities, including magnetic resonance imaging (MRI) and near-infrared fluorescence; biosensing, drug delivery; oxygen delivery; and theranostic nanomaterials, used for local and parenteral administration or as implantable biomaterials.
A major barrier to the advancement of nanotechnology-based therapeutics is not conceptual innovation but manufacturability, cost, and quality control. The Nanomedicine Manufacturing Laboratory addresses these challenges by incorporating manufacturing process design, scalability, and quality control at the earliest stages of material design. Over the past decade, the laboratory has established robust, reproducible, and cost-effective nanomedicine manufacturing methods by applying QbD frameworks, enabling reliable scale-up and controlled performance.
The laboratory’s work is supported by the U.S. Air Force, the Congressionally Directed Medical Research Programs (CDMRP), and ARPA-H through collaborative programs spanning academia, industry, and government. The Nanomedicine Manufacturing Laboratory operates at the intersection of materials science, manufacturing, and translational medicine, with a focus on developing innovative nanomedicines and biomaterials that translate into accessible, cost-effective future treatments for civilian and military medical needs.
NANOMEDICINE MANUFACTURING LABORATORY Nanomedicine Manufacturing Laboratory (NML) is a research and development laboratory specializing in nanomaterials and biomaterials for imaging, oxygen delivery, and drug delivery, with a core emphasis on scalable manufacturing and Quality-by-Design (QbD). More informaiton about NML: https://www.duq.edu/research/faculty-research/nanomedicine-lab/nanomed-lab-research.php Led by Dr. Jelena M. Janjic, the Nanomedicine Manufacturing Laboratory develops colloidal nanosystems and implantable biomaterials that support molecular imaging modalities, including magnetic resonance imaging (MRI) and near-infrared fluorescence; biosensing, drug delivery; oxygen delivery; and theranostic nanomaterials, used for local and parenteral administration or as implantable biomaterials. A major barrier to the advancement of nanotechnology-based therapeutics is not conceptual innovation but manufacturability, cost, and quality control. The Nanomedicine Manufacturing Laboratory addresses these challenges by incorporating manufacturing process design, scalability, and quality control at the earliest stages of material design. Over the past decade, the laboratory has established robust, reproducible, and cost-effective nanomedicine manufacturing methods by applying QbD frameworks, enabling reliable scale-up and controlled performance. The laboratory’s work is supported by the U.S. Air Force, the Congressionally Directed Medical Research Programs (CDMRP), and ARPA-H through collaborative programs spanning academia, industry, and government. The Nanomedicine Manufacturing Laboratory operates at the intersection of materials science, manufacturing, and translational medicine, with a focus on developing innovative nanomedicines and biomaterials that translate into accessible, cost-effective future treatments for civilian and military medical needs.
Publication Number
US-11897886-B2
Publication Date
2024-02-13
Expiration Date
2039-03-06
Abstract
A compound of Formula II, or optionally a salt or a hydrate of the compound of Formula II is provided: wherein R1 is selected from the group consisting of a hydrogen, an alkyl group having from one to six carbon atoms, an aryl group, and a heteroaryl group; R2 is selected from the group consisting of an alkyl group having from one to six carbon atoms, a hydrogen, a NRaRb group wherein Ra is either a hydrogen or an alkyl group having from one to six carbon atoms and Rb is either a hydrogen or an alkyl group having from one to six carbon atoms, an aryl group, a heteroaryl group, and a halogen; R is an alkyl group having from one to six carbon atoms; and Ar is selected from the group consisting of an alkyl group having from one to six carbon atoms, a substituted aryl, and a substituted heteroaryl.
Core Innovation
The invention provides pyrazolo[4,3-d]pyrimidine compounds represented by Formula II, as well as their pharmaceutically acceptable salts and hydrates. These compounds are further extended to pharmaceutical compositions containing the same and methods of their use in medicine. The compounds of the invention are structurally defined by various substituents at key positions, offering a diverse class of molecules targeted for specific biological activity.
The problem being addressed is the need for new microtubule targeting agents, specifically those that bind to the colchicine site of tubulin, for effective control of cell proliferation in cancer. No colchicine site binding agents have been approved despite their recognized importance in overcoming resistance mechanisms, such as P-glycoprotein-mediated drug efflux and β-III tubulin expression, which limit the efficacy of many current antitumor drugs.
The core innovation comprises the design, synthesis, and use of pyrazolo[4,3-d]pyrimidine derivatives that act as antitumor agents by inhibiting tubulin assembly and binding at the colchicine site. The compounds are shown to exhibit strong inhibition of [3H]colchicine binding, with certain substitutions resulting in enhanced activity compared to known lead compounds. The invention also details methods of synthesis and pharmaceutical formulation to address solubility challenges and enable diverse routes of administration.
Claims Coverage
There is one main independent claim covering the inventive features of the compound of Formula II and its related embodiments.
Pyrazolo[4,3-d]pyrimidine compounds of Formula II
A compound of Formula II, or a salt or hydrate thereof, wherein: - R1 is selected from hydrogen, an alkyl group having from one to six carbon atoms, an aryl group, and a heteroaryl group; - R2 is selected from an alkyl group having from one to six carbon atoms, a hydrogen, a NRaRb group (where Ra and Rb are either hydrogen or an alkyl group having from one to six carbon atoms), an aryl group, a heteroaryl group, and a halogen; - R is an alkyl group having from one to six carbon atoms; - Ar is selected from an alkyl group having from one to six carbon atoms, a substituted aryl, and a substituted heteroaryl.
The inventive features of the claim center on the specific chemical structure of pyrazolo[4,3-d]pyrimidine derivatives with defined substituents, encompassing both the compound itself and its pharmaceutically acceptable forms.
Stated Advantages
The compounds of the invention overcome water solubility problems associated with previous antitumor agents, allowing for formulation as water soluble salts suitable for oral dosage forms.
The compounds inhibit tubulin assembly and colchicine binding with enhanced or comparable activity to known lead compounds, showing effectiveness against cell lines exhibiting drug resistance mechanisms.
Pharmaceutical compositions of the invention can be administered via various routes, including parenteral and oral, providing flexibility in clinical administration.
Documented Applications
Treatment of a patient having cancer by administering a therapeutically effective amount of a compound of Formula I or II, or their salts or hydrates.
Pharmaceutical compositions containing the compounds are intended for use in the treatment of various human cancers, including leukemia, non-small cell lung cancer, colon cancer, central nervous system cancer, melanoma, ovarian cancer, breast cancer, renal cancer, prostate cancer, and pancreatic cancer.
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