83908-06-9

Upstream product

• 50-85-1 2-hydroxy-p-toluic acid 
• 4670-56-8 methyl 2-hydroxy-4-methylbenzoate 

Downstream Products

• 153953-53-8 C₂₁H₂₂N₂O₃⁽²⁺⁾ 
• 80235-10-5 2-hydroxy-4-(hydroxymethyl)benzoic acid methyl ester 
• 311343-83-6 Methyl 2-Hydroxy-4-[({[3-hydroxy-4-(methoxycarbonyl)-phenyl]methyl}amino)methyl]benzoate Hydrochloride 
• 1613293-06-3 N-((S)-1-(((R)-1-(7-((hexadecylamino)methyl)-4-oxo-4H-benzo-[d][1,3,2]dioxaborinin-2-yl)-3-methylbutyl)amino)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxamide 
• 1613293-05-2 4-((hexadecylamino)methyl)-2-hydroxybenzoic acid 

Relevant academic research and scientific papers

Liposomal bortezomib nanoparticles via boronic ester prodrug formulation for improved therapeutic efficacy in vivo

In this study, we describe the development of liposomal bortezomib nanoparticles, which was accomplished by synthesizing bortezomib prodrugs with reversible boronic ester bonds and then incorporating the resulting prodrugs into the nanoparticles via surface conjugation. Initially, several prodrug candidates were screened based upon boronic ester stability using isobutylboronic acid as a model boronic acid compound. The two most stable candidates were then selected to create surface conjugated bortezomib prodrugs on the liposomes. Our strategy yielded stable liposomal bortezomib nanoparticles with a narrow size range of 100 nm and with high reproducibility. These liposomal bortezomib nanoparticles demonstrated significant proteasome inhibition and cytotoxicity against multiple myeloma cell lines in vitro and remarkable tumor growth inhibition with reduced systemic toxicity compared to free bortezomib in vivo. Taken together, this study demonstrates the incorporation of bortezomib into liposomal nanoparticles via reversible boronic ester bond formation to enhance the therapeutic index for improved patient outcome.

NANOPARTICLE DRUG DELIVERY SYSTEMS

The invention provides pharmaceutical compositions and method of using the compositions, wherein the compositions comprise liposomes or micelles that contain one or more targeting peptides and/or anticancer drugs. In various embodiments, the components of the liposomes can include a) a phospholipid and optionally a lipid that is not a phospholipid; b) a pegylated lipid; c) a peptide-ethylene glycol (EG)-lipid conjugate wherein the peptide is a targeting ligand, and d) one or more drug-conjugated lipid, encapsulated drugs, or a combination thereof. The peptide- EG-lipid conjugate can be, for example, a compound of Formula (I) or Formula (II). The ethylene glycol (EG) segments of the peptide-EG-lipid conjugate can be, for example, EG6 to about EG36; and the EG segment can be conjugated to one or more lysine moieties.

TRICYCLIC DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, THEIR PREPARATIONS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

The present invention relates to tricyclic derivatives or pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. More precisely, the present invention relates to tricyclic derivatives as colchicine derivatives, pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. Tricyclic derivatives of the present invention show very powerful cytotoxicity to cancer cell lines but were much less toxic than colchicine or taxol, confirmed through animal toxicity test. Tricyclic derivatives of the invention also decrease the volume and weight of a tumor and have a strong angiogenesis inhibiting activity in HUVEC cells. Thus, tricyclic derivatives of the present invention can effectively be used as an anticancer agent, anti-proliferation agent and an angiogenesis inhibitor.

Bifunctional boronic compound complexing reagents and complexes

Reagents suitable for the modification of a bioactive species for the purpose of incorporating a bifunctional boronic compound complexing moiety for subsequent conjugation to a different (or the same) bioactive species having pendant phenylboronic acid moieties of General Formula 1, wherein group R is an electrophilic or nucleophilic moiety suitable for reaction of the putative bifunctional boronic compound complexing reagent with a bioactive species, wherein group R2 is selected from one of H and OH moieties, and wherein group R3 is selected from one of an alkyl and a methylene bearing an electronegative substituent. Group Z is a spacer selected from (CH2)n and CH2O(CH2CH2O)n2, wherein n is an integer of from 1 to 5, and wherein n2 is an integer of from 1 to 4. Each of group Z2 and Z3 is a spacer selected from CH2Ar, CH2CONHCH2Ar, CH2CONH(CH2)n3CO-NHCH2Ar, and (CH2)n4NHCO(CH2)n5CONHCH2Ar, wherein the group Ar represents the aromatic ring in the reagent of General Formula I to which the spacer Z2 or Z3 is appended, wherein n3 is an integer of from 1 to 5, wherein n4 is an integer selected from one of 2 and 3, and wherein n5 is an integer of from 1 to 4. Reaction of a reagent of General Formula I with a bioactive species affords a conjugate having pendant putative bifunctional boronic compound complexing moieties. (one or more) The conjugate may be further reacted with hydroxylamine (NH2OH) by amidation of the benzoic acid ester moiety to afford a class of bifunctional boronic compound complexing conjugate, e.g., conjugate with one or more pendant bifunctional boronic compound complexing moieties.

Boronic compound complexing reagents and complexes

Boron compound complexing reagents, boron compound complexes, and methods of synthesizing these reagents and complexes are disclosed. These reagents and complexes include those shown in General Formula III, General Formula IV, and General Formula VI. In one embodiment, the reagents of General Formula III may be used to produce, after condensation with a bioactive species (BAS), the reagent of General Formula IV. The reagent of General Formula IV may be used to form a complex with a boron compound, such as a complex shown in General Formula VI. STR1

Boronic compound complexing reagents and complexes

Boron compound complexing reagents and methods of synthesizing these reagents are disclosed. These reagents, including those shown as General Formula I and General Formula II may be used, after further reactions described herein, to complex with boronic compounds, such as phenylboronic acid or derivatives thereof. STR1

Boronic compound complexing reagents and highly stable complexes

Boron compound complexing reagents, boron compound complexes, and methods of synthesizing these reagents and complexes are disclosed. These reagents and complexes include those shown in General Formula CIII, General Formula CIV, and General Formula CVI. In one embodiment, the reagents of General Formula CIII may be used to produce, after condensation with a bioactive species (BAS), the reagent of General Formula CIV. The reagent of General Formula CIV may be used to form a complex with a boron compound, such as a complex shown in General Formula CVI. STR1

Boronic compound complexing reagents and highly stable complexes

Boron compound complexing reagents, intermediate reagents of those reagents and methods of synthesizing these reagents are disclosed. These reagents, including those shown as General Formula I and General Formula II may be used, after further reactions described herein, to complex with boronic compounds, such as phenylboronic acid or derivatives thereof. STR1