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Boronic acid ester prodrugs and uses thereof

An unsubstituted, compound technology, applied in the field of boronate prodrugs and their uses, can solve the problems of tissue penetration or bursting, poor payload release, ineffective penetration and accumulation, suboptimal MM treatment, etc.

Pending Publication Date: 2022-05-27
MASSACHUSETTS INST OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

23-27 But this size range is suboptimal for MM therapy because these sizes cannot efficiently penetrate and accumulate in diseased plasma cells that are either present in the bone marrow microenvironment or nonvascularized circulating tumor cells
30 In addition, problems with liposome-based DDSs, such as poor tissue penetration or burst, uncontrolled payload release, remain unsolved.

Method used

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  • Boronic acid ester prodrugs and uses thereof
  • Boronic acid ester prodrugs and uses thereof
  • Boronic acid ester prodrugs and uses thereof

Examples

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[0382] Methods of making compounds and polymers

[0383] The present disclosure describes methods for preparing polymers from the monomers described herein. In certain embodiments, the method of making a polymer comprises polymerizing the monomers described herein.

[0384] The present disclosure also describes a method of making a polymer comprising reacting an existing polymer with a compound described herein, wherein the existing polymer includes a reaction handle capable of reacting with X, and in the reacting step, capable of reacting with The reaction handle of the X reaction reacts with the X. In certain embodiments, the existing polymer is a polymer described herein. In certain embodiments, the existing polymer is an addition polymer (eg, polyethylene, polytetrafluoroethylene, polypropylene, polyisobutylene, polystyrene, polyacrylonitrile, polyvinyl chloride, polymethyl acrylate, polymethyl methacrylate, polybutadiene, chlorambucil, poly(cis-1,4-isoprene) or poly(tr...

Embodiment

[0483] In order that the present disclosure may be more fully understood, the following examples are illustrated. The synthetic and biological examples described in this application are provided to illustrate the compounds, pharmaceutical compositions, and methods provided herein, and should not be construed in any way to limit their scope.

[0484] DETAILED DESCRIPTION OF THE EMBODIMENTS

[0485] Rational design of boronate-based Btz prodrugs.

[0486]To construct Btz-loaded BBPs, linkers were first developed that made Btz sufficiently stable and inactive in circulation in vivo, but also released Btz "on demand" once in the tumor microenvironment. The structure of the linker should be chemically modifiable, which translates to tunable release rates depending on the end application—similar to the design strategies that have been reported for several drug conjugates. 40,41 Therefore, 1,2-diol azide linker A5 ( figure 1 , full synthesis details are described in SI). A5 conta...

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Abstract

Disclosed herein are compounds of Formula (I) or (II). The compounds include an agent (e.g., a pharmaceutical agent, a cosmetic agent or a nutritional agent) via a linker that includes a borate moiety in the linker backbone. The compound may be a monomer. Also provided herein are polymers prepared by polymerizing the monomers. The polymer can be used to deliver the agent to a subject, tissue, biological sample, or cell. Also provided herein are methods of making the polymers, compositions, and kits comprising the polymers, as well as methods of use involving the polymers or compositions (e.g., for delivering agents, treating disease, preventing disease, diagnosing disease). The structure of the borate moiety may be fine tuned so that properties associated with delivery to a subject, biological sample, tissue, or cell may be fine tuned.

Description

[0001] Related applications [0002] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. U.S.S.N. 62 / 850,492, filed May 20, 2019, which is incorporated herein by reference. [0003] governmental support [0004] This invention was made with government support under Grant No. R01 CA220468 awarded by the National Institutes of Health. The government has certain rights in this invention. Background technique [0005] The delivery of formulations (eg, drugs) by nanoparticles or other delivery vehicles has been studied previously. The linker between the carrier and the drug formulation is critical for successful delivery with a balance between stability and transferability. Preferably, the linker is stable under physiological conditions until the vector reaches its intended destination, at which point the linker is cleaved to allow delivery of the agent. Linkers can also be used to modulate potency, efficacy, bioavailability, toxicity, ...

Claims

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Application Information

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IPC IPC(8): C07F5/02A61K31/69A61P35/00
CPCC07F5/025A61K31/69A61P35/00C08L85/04B01J23/462A61K47/59C07F5/02
Inventor J·A·约翰逊P·戈罗吉安Y·蒋H·V·阮I·戈布里亚尔A·德塔普
Owner MASSACHUSETTS INST OF TECH