University of California

University of Missouri

USA As Represented by Secretary of the Navy

Rohm and Haas Company

Coremetals Research, Inc.

Immunomedics, Inc.

Neutron Therapies Inc.

Marion Frederick Hawthorne

Kenneth John Shelly

Toralf Peymann

George R Kracke

Gary B Dunks

Debra Arliene Feakes

Yulia Sevryugina

Alexander Valentinovich Safronov

Satish Subray Jalisatgi

Debra Arlene Feaks

Robert R Kane

Timm E Paxson

Leonidas G Bachas

Mark T Groudine

Mark S Delaney

Mark Wayne Lee

Oleg Bondarev

Ibrahim H Badr

William Kalb

Andreas Maderna

Lalit N Goswami

Axel Hans-Joachim Herzog

Satish S Jalisatgi

Disclosed herein are carborane derivatives of Formula I or Formula V, or a pharmaceutically acceptable salt thereof, for use as neuromuscular blocking agents. The carborane is substituted with two cationic functional groups selected from amines that form ammonium cations, ethers and/or alcohols that form oxonium cations, sulfides and/or thiols that form sulfonium cations, and phosphanes and/or phosphines that form phosphonium cations.

Neuromuscular blocking agents

The present invention relates to novel cluster boron compounds and their use as sodium channel blockers. The invention also provides methods for making and using the compounds.

Boron cluster compounds and uses thereof

The present invention relates in general to a method for the synthesis and purification of 1) the polyhedral borane decahydrodecaborate and dodecahydrododecaborate anions and their salts and 2) amines and amine boranes. The organoammonium halide is combined with alkali metal tetrahydroborate to form organoammonium tetrahydroborate, which upon pyrolysis provides organoammonium decahydrodecaborate and organoammonium dodecahydrododecaborate.

Synthesis of amine boranes and polyhedral boranes

The present invention is directed to a process for the synthesis of alkali metal tetrahydroborates-B and amine borane-B precursors, such as sodium tetrahydroborate-B and triethylamine borane-B.

Synthesis of borane compounds

The present invention provides methods and devices for producing polyhedral boron compounds. The process is generally an anhydrous, one-pot process that comprises a pyrolytic reaction of a tetraborohydride with a quaternary amine salt to form the polyhedral borane. In another aspect of the present invention, polyhedral boranes are produced, without isolation of the Lewis base-borane complex.

Process and device for the production of polyhedral boranes

The present invention relates to novel cluster boron compounds and their use as sodium channel blockers. In particular, the novel cluster boron compounds may be lidocaine analogs where the aromatic ring of the lidocaine molecule is replaced with a cluster boron group. The invention also provides methods for making the cluster boron compounds comprising contacting a halogenated cluster boron with an amino acetamide in the presence of a catalyst, a proton acceptor, and a ligand.

Cluster boron compounds and uses thereof

The present invention relates to a synthetic method for producing a per-hydroxylated icosahedral boron compound via catalytic hydroxylation of icosahedral boron compound using a soft electrophile.

Hydroxylation of icosahedral boron compounds

New boron icosahedral ethers and esters formed from Cs &lsqb;closo-B (OH) &rsqb;,; Cs&lsqb;closo-1-H-1-CB (OH) &rsqb;; and closo-1,12-H -1,12-C B (OH) are disclosed. Also set forth are their preparation by reacting the icosahedral boranes &lsqb;closo-B H &rsqb; , &lsqb;closo-1-CB H &rsqb; and closo-1,12-(CH OH) -1,12-C B H with an acid anhdride or acid chloride to form the ester or an alkylating agent to form the ether.

Ether and ester derivatives of the perborate icosahedron

Boron neutron capture therapy can be used to destroy tumors. This treatment modality is enhanced by delivering compounds to the tumor site where the compounds have high concentrations of boron, the boron compounds being encapsulated in the bilayer of a liposome or in the bilayer as well as the internal space of the liposomes. Preferred compounds, include carborane units with multiple boron atoms within the carborane cage structure. Liposomes with increased tumor specificity may also be used.

Methods for boron delivery to mammalian tissue

The dodecamethyl closo-borane dianion &lsqb;closo-B (CH ) &rsqb; and anion &lsqb;closo-B (CH ) &rsqb; were synthesized and characterized. Dodecamethyl-closo dodecaborate (2&minus;) was produced from &lsqb;closo-B H &rsqb; , using trimethylaluminum, and methyl iodide and modified Friedel-Crafts reaction conditions. The anion was produced from the dianion by chemical oxidation using ceric (4) ammonium nitrate in acetonitrile. The anion and dianion were both characterized by H and B NMR spectroscopy, high-resolution fast atom bombardment (FAB) mass spectrometry, cyclic voltammetry, and single-crystal X-ray diffraction. The &ldquo;camouflaged&rdquo; polyhedral borane anion &lsqb;closo-B (CH ) &rsqb; , can be used as a precursor to materials that offer a broad spectrum of novel applications ranging from drug applications and supramolecular chemistry to use as a weakly-coordinating dianion.

Synthesis of permethyldodecaborate and paramagnetic dodecaborate salt

New icosahedral borohydrates Cs,&lsqb;closo-B,(OH),&rsqb;; Cs&lsqb;closo-1-H-1-CB,(OH),&rsqb;; and closo-1,12-H,-1,12-C,B,(OH),are disclosed. Also set forth are their preparation by refluxing the icosahedral boranes &lsqb;closo-B,H,&rsqb;,, &lsqb;closo-1-CB,H,&rsqb;,and closo-1,12-(CH,OH),-1,12-C,B,H,with a hydroxylating agent, preferably 30%,hydrogen peroxide.

Synthesis of perhydroxydodecaborate salts and related species

Boron neutron capture therapy can utilize X,B,H,L where X is an alkali metal, y is 1 to 4, and L is a two electron donor such as NH,, and Na,B,H,NCO, among others. These borane salts may be used free or encapsulated in liposomes. Liposomes may also have embedded within their bilayers carboranes to increase the amount of delivered,B and/or to increase the tumor specificity of the liposome.

Compositions for boron delivery to mammalian tissue

A general synthetic method has been developed for the rapid and efficient production of a variety of boron-rich macromolecules suitable for conjugation with inclusion in receptor-mediated delivery systems as well as other delivery systems. Preparation techniques have been developed to yield precisely ordered oligophosphates which are soluble, hydrophilic, may be homogeneous, and may be prepared with a variety of functional groups.

Macromolecular structures for boron neutron-capture therapy

Boron containing compounds are targeted to hormonally responsive cells by contacting the cells with a conjugate of a boron containing moiety conjugated to a ligand having binding specificity for an intracellular receptor of the cell. The conjugates are useful for imaging or killing hormonally responsive cells, such as hormonally responsive tumor cells. For target cell killing, the cells are contacted with a .sup.10 B containing moiety conjugated to a ligand having binding specificity for an intracellular hormone receptor of the cells. The .sup.10 B containing moiety becomes associated with the hormone receptor of the cells, which may then be irradiated with neutrons to kill the cells by boron neutron capture. For target cell imaging, the cells are contacted with a .sup.11 B containing moiety conjugated to a ligand having binding specificity for an intracellular hormone receptor of the cells, and the boron that becomes associated with the hormone receptor of the cells may then be imaged using magnetic resonance imaging techniques.

Boron-containing hormone analogs and methods of their use in imaging or

Ion-selective membranes are disclosed which are suitable for use in ion-selective sensors. The membranes include a mercuracarborand ionophore. Exemplary ion-selective membranes include Mercuracarborand-3 as the ionophore which is incorporated within a polymer matrix. The ion-selective membranes may be used in a wide variety of ion sensors including ion-selective membrane electrodes.

Growing community of inventors

Columbia, MO, United States of America

Marion Frederick Hawthorne