Source: http://www.google.com/patents/US5756726?dq=5,222,134
Timestamp: 2017-06-24 22:40:04
Document Index: 773044586

Matched Legal Cases: ['art 1', 'art 1', 'art 1', 'art 1', 'art 1', 'art 1', 'art 1']

Patent US5756726 - Methods of producing singlet oxygen using compounds having improved ... - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inPatentsNovel texaphyrin compounds having improved functionalization are described. Metal complexes of these compounds are active as photosensitizers for the generation of singlet oxygen and thus are potentially useful for treatments performed with singlet oxygen. Several of the metallotexaphyrin complexes absorb...http://www.google.com/patents/US5756726?utm_source=gb-gplus-sharePatent US5756726 - Methods of producing singlet oxygen using compounds having improved functionalizationAdvanced Patent SearchTry the new Google Patents, with machine-classified Google Scholar results, and Japanese and South Korean patents.Publication numberUS5756726 APublication typeGrantApplication numberUS 08/468,935Publication dateMay 26, 1998Filing dateJun 6, 1995Priority dateJun 2, 1995Fee statusLapsedAlso published asUS5591422, US5601802Publication number08468935, 468935, US 5756726 A, US 5756726A, US-A-5756726, US5756726 A, US5756726AInventorsGregory W. Hemmi, Jonathan L. Sessler, Tarak D. ModyOriginal AssigneePharmacyclics, Inc., Board Of Regents, The University Of Texas SystemExport CitationBiBTeX, EndNote, RefManPatent Citations (32), Non-Patent Citations (248), Referenced by (63), Classifications (19), Legal Events (9) External Links: USPTO, USPTO Assignment, EspacenetMethods of producing singlet oxygen using compounds having improved functionalization
US 5756726 AAbstract
Novel texaphyrin compounds having improved functionalization are described. Metal complexes of these compounds are active as photosensitizers for the generation of singlet oxygen and thus are potentially useful for treatments performed with singlet oxygen. Several of the metallotexaphyrin complexes absorb light in the physiologically important range of 690-880 nm. The complexes form long-lived triplet states and thus may act as efficient photosensitizers for generation of singlet oxygen.
1. A method of producing light-induced singlet oxygen, the method comprising subjecting a texaphyrin to light in the presence of oxygen, wherein the texaphyrin has the structure: ##STR14## wherein M is a diamagnetic metal cation;R1 -R4, R7 and R8 are independently hydrogen, halide, hydroxyl, alkyl, aryl, haloalkyl, nitro, formyl, acyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxy, carboxyalkyl, carboxyamidealkyl, a site-directing molecule, a catalytic group, or a couple to a site-directing molecule or to a catalytic group; R6 and R9 are independently selected from the groups of R1 -R4, R7 and R8, with the proviso that the halide is other than iodide and the haloalkyl is other than iodoalkyl; R5 and R10 -R12 are independently hydrogen, alkyl, aryl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, carboxyalkyl, carboxyamidealkyl or a couple to a saccharide, to a site-directing molecule or to a catalytic group; at least one of R5, R6, R9, R10, R11 and R12 is other than hydrogen; and Z is an integer less than or equal to 5. 2. The method of claim 1 where the paramagnetic metal cation is selected from the group consisting of Cd(II), Zn(II), In(III), Y(III), La(III), and Lu(III).
3. The method of claim 1 where the light has a wavelength range from about 730 to about 770 nm.
4. The method of claim 1 where the couple is an amide, disulfide, thioether or ether covalent bond.
5. The method of claim 1 where the catalytic group is selected from the group consisting of imidazole, guanidine, substituted saccharides, amino acids, derivatives of amino acids, polymers of amino acids, and texaphyrin metal complexes.
6. The method of claim 1 where the site-directing molecule has binding specificity for localization to a treatment site.
7. The method of claim 1 where the site-directing molecule is selected from the group consisting of an oligonucleotide, an antibody, a hormone, a hormone mimic, a peptide having affinity for a biological receptor, and a sapphyrin molecule.
8. The method of claim 1 where at least one of R5 and R10 -R12 is other than hydrogen; andwhen R5 is other than hydrogen, then R6 is hydrogen, halide other than iodide, or hydroxyl; and when R10 is other than hydrogen, then R9 is hydrogen, halide other than iodide, or hydroxyl. 9. The method of claim 1 where at least one of R6 and R9 is other than hydrogen; andwhen R6 is other than hydrogen, then R5 is hydrogen or methyl; and when R9 is other than hydrogen, then R10 is hydrogen or methyl. 10. The method of claim 1 where R5 and R10 are aryl having an R13 substituent where R13 is hydrogen, nitro, carboxy, sulfonic acid, hydroxy, oxyalkyl or halide.
11. The method of claim 1 where each of R1 -R12 is any one of the substituents for R1 -R12 set out in Tables A and B.
12. The method of claim 1 where R1 is CH2 (CH2)2 OH, R2 and R3 are CH2 CH3, R4, R5 and R10 are CH3, R6 and R9 are H, and R7 and R8 are O(CH2 CH2 O)3 CH3 or R7 is H or OCH3 and R8 is a site-directing molecule or a couple to a site-directing molecule.
13. The method of claim 12 where R11 and R12 are H or CH3.
14. The method of claim 1 where the texaphyrin is selected from texaphyrins A1-A56 of Tables A and B.
This application is a continuation application of U.S. application Ser. No. 08/459,333, filed Jun. 2, 1995, now U.S. Pat. No. 5,599,929, the entire text of which is incorporated herein by reference.
In certain embodiments, the present invention provides a texaphyrin having the structure: ##STR1## M is H, a divalent metal cation, or a trivalent metal cation. R1 -R4, R7 and R8 are independently hydrogen, halide, hydroxyl, alkyl, aryl, haloalkyl, nitro, formyl, acyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxy, carboxyalkyl, carboxyamidealkyl, a site-directing molecule, a catalytic group, or a couple to a site-directing molecule or to a catalytic group.
The charge, Z is an integer value less than or equal to 5. Here, as would be apparent to one skilled in the art, the charge Z would be adjusted so as to account for the choice of metal, M, the pH under consideration, and the substituents R1 -R12. For instance, if R1 =carboxyl and R2 -R12 =alkyl and the metal M=Gd+3, and the solution is pH=7 (so that R1 =CO2 -), the charge Z would be zero. The charge would be negative when substituents have a sufficient number of negative charges, for example, when a substituent is an oligonucleotide. The charge would be +5, for example, when the M is Gd+3 and the net charge of a substituent(s) is three positive charges.
In a preferred method of synthesis, the Br.o slashed.onsted base is triethylamine or N,N,N',N'-tetramethyl-1,8-diaminonaphthalene ("proton sponge"), and the oxidant is air saturating the organic solvent, oxygen, platinum oxide, o-chloranil or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. The stirring or heating at reflux step may comprise stirring or heating at reflux the mixture for at least 24 hours. The organic solvent may comprise methanol, or methanol and chloroform, or methanol and benzene, or methanol and dimethylformamide.
For the above-described texaphyrins, oxyhydroxyalkyl may be alkyl having independently hydroxy substituents and ether branches or may be C.sub.(n-x) H.sub.((2n+1)-2x) Ox Oy or OC.sub.(n-x) H.sub.((2n+1)-2x) Ox Oy where n is a positive integer from 1 to 10, x is zero or a positive integer less than or equal to n, and y is zero or a positive integer less than or equal to ((2n+l)-2x).
Carboxyamidealkyl may be alkyl having secondary or tertiary amide linkages or (CH2)n CONHRa, O(CH2)n CONHRa, (CH2)NCON(Ra)2, or O(CH2)n CON(Ra)2 where n is a positive integer from 1 to 10, Ra is independently H, alkyl, hydroxyalkyl, saccharide, C.sub.(m-w) H.sub.((2m+1)-2w) Ow Oz, O2 CC.sub.(m-w) H.sub.((2m+1)-2w) Ow Oz or N(R)OCC.sub.(m-w) H.sub.((2m+1)-2w) Ow Oz, where m is a positive integer from 1 to 10, w is zero or a positive integer less than or equal to m, z is zero or a positive integer less than or equal to ((2m+1)-2w), R is H, alkyl, hydroxyalkyl, or Cm H.sub.((2m+1)-r) OzR b r where m is a positive integer from 1 to 10, z is zero or a positive integer less than ((2m+1)-r), r is zero or a positive integer less than or equal to 2m+1, and Rb is independently H, alkyl, hydroxyalkyl, or saccharide.
A couple may be described as a linker, i.e., a reactive group for attaching another molecule at a distance from the texaphyrin macrocycle. An exemplary linker or couple is an amide, disulfide, thioether or ether covalent bond as described in the examples for attachment of oligonucleotides and antibodies. Certain reactions utilizing the texaphyrin complexes of the present invention, such as hydrolytic cleavage of phosphate ester bonds for example, by may be enhanced by additional catalytic groups appended to the texaphyrin metal complex or to a texaphyrin complex-site directing molecule conjugate. The term "catalytic group" means a chemical functional group that assists catalysis by acting as a general acid, Br.o slashed.nsted acid, general base, Br.o slashed.nsted base, nucleophile, or any other means by which the activation barrier to reaction is lowered or the ground state energy of the substrate is increased. Exemplary catalytic groups contemplated include, but are not limited to, imidazole; guanidine; substituted saccharides such as D-glucosamine, D-mannosamine, D-galactosamine, D-glucamine, and the like; amino acids such as L-histidine and L-arginine; derivatives of amino acids such as histamine; polymers of amino acids such as poly-L-lysine, (LysAla)n or (LysLeuAla)n where n is from 1-30 or preferably 1-10 or more preferably 2-7, and the like; derivatives thereof; and texaphyrin metal complexes. The term "appended to the texaphyrin-site directing molecule conjugate means that the catalytic groups are attached either directly to the texaphyrin metal complex or to the texaphyrin complex via a linker or couple of variable length, or are attached to the ligand portion of a texaphyrin complex-ligand conjugate either with or without a linker or couple of variable length.
Further preferred embodiments of the present invention are where R2 and R3 are CH2 CH3 and R4 is CH3, where R5 and R10 are methyl, or where R5 and R10 are (CH2),CH3 where n is 0, 1, 2, 3 or 4. Furthermore, R5 and R10 may be aryl having an R13 substituent where R13 is hydrogen, nitro, carboxy, sulfonic acid, hydroxy, oxyalkyl or halide. A presently preferred aryl is phenyl. The derivatization of the R13 group may occur after the condensation of the macrocycle. Preferred substituents for R6 include carboxy, alkyl or carboxyamidealkyl having a tertiary amide linkage. Preferred substituents for R7, R8 and R9 are oxyalkyl or hydroxyalkyl.
Electron-donating substituents at the 2, 7, 12, 15, 18 and/or 21 positions of the macrocycle stabilize the molecule against decomposition processes involving hydrolysis of the imine bonds. Such substituents also stabilize the resulting complex against demetallation by contributing electrons to the aromatic π system. Such electron-donating groups include hydroxyl, alkyl, haloalkyl other than iodoalkyl, aryl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxyalkyl, carboxyamidealkyl, a site-directing molecule, or a couple to any of these molecules. Hydrolysis-resistant texaphyrin metal complexes are useful for localization, magnetic resonance imaging, radiosensitization, radiation therapy, fluorescence imaging, photodynamic therapy and applications requiring singlet oxygen production for cytotoxicity.
It is contemplated that the texaphyrins of the present invention will prove useful in a variety of applications. One example is in a method of deactivating a retrovirus or enveloped virus in an aqueous fluid. Such a method comprises the step of adding a texaphyrin metal complex having a substituent at the 2, 7, 12, 15, 18 and/or 21 position to said aqueous fluid and exposing the mixture to light to effect the formation of singlet oxygen.
The aqueous fluid may be a biological fluid, blood, plasma, edema tissue fluid, ex vivo fluid for injection into body cavities, cell culture media, or a supernatant solution from cell culture and the like.
In these methods, determining localization sites may occur by observing fluorescence from the texaphyrin. When the first agent is complexed with a metal, the metal may be a gamma-emitting metal and determining localization sites would occur by gamma body imaging, or the metal may be a paramagnetic metal and determining localization sites would occur by magnetic resonance imaging. "Exhibiting greater biolocalization in the tumor relative to non-tumor tissue" means having an inherently greater affinity for tumor tissue relative to non-tumor tissue. The second agent has essentially identical biolocalization property as the first agent and exhibits the ability to generate singlet oxygen upon exposure to light. The photodynamic effect may be derived from anaerobic electron transfer processes. A preferred diamagnetic metal texaphyrin complex is the Lu(III), La(III) or In(III) complex of a texaphyrin. "Essentially identical biolocalization property" means the second agent is a texaphyrin derivative having about the same selective targeting characteristics in tissue as demonstrated by the first agent. The first agent and the second agent may be the same texaphyrin.
1 H and 13 C NMR spectra are obtained on a General Electric QE-300 (300 MHz.) spectrometer. Electronic spectra are recorded on a Beckman DU-7 spectrophotometer in CHCl3. Infrared spectra are recorded, as KBr pellets, from 4000 to 600 cm-1 on a Nicolet 510P FT-IR spectrophotometer. Chemical ionization mass spectrometric analyses (CI MS) are made using a Finnigan MAT 4023. Low resolution and high resolution fast atom bombardment mass spectrometry (FAB MS) are performed with a Finnigan-MAT TSQ-70 and VG ZAB2E instruments, respectively. A nitrobenzyl alcohol (NBA) matrix is utilized with CHCl3 as the co-solvent. Elemental analyses are performed by Atlantic Microlab, Inc. Melting points are measured on a Mel-temp apparatus and are uncorrected. ##STR4##
Tripyrrane ketone AS: An example of the synthesis of a precursor to a tripyrrane ketone, the 2,5-bis (3-(3-hydroxypropyl)-5-carboxyl-4-methylpyrrol-2-yl)methyl!-3,4-diethylpyrrole F5, Scheme F, was presented in prior application, U.S. Ser. No. 08/135,118, incorporated by reference herein. In this example, R1 is 3-hydroxypropyl, R2 and R3 are ethyl and R4 is methyl.
2,5-Bis (5-benzyloxycarbonyl-4-methyl-3-methoxycarbonylethylpyrrol-2-yl)methyl!-3,4-diethylpyrrole. F3, Scheme F. In a 500 mL round bottom flask was placed 250 mL of ethanol from an unopened bottle which is purged with dry nitrogen for ten minutes. 3,4-Diethylpyrrole F2 (1.29 g, 0.01 mol) and 2-acetoxymethyl-5-benzyloxycarbonyl-4-methyl-3-methoxycarbonylethylpyrrole F1 (7.83 g, 0.02 mol) were added and the mixture heated until all of the pyrroles dissolved. p-Toluenesulfonic acid (65 mg) was added and the reaction temperature maintained at 60° C. The reaction slowly changed color from a clear yellow to a dark red with the product precipitating out of the solution as the reaction progressed. After ten hours the reaction was cooled to room temperature, the volume reduced to one half on a rotary evaporator, and then placed in the freezer for several hours. The product was collected by filtration, washed with a small amount of cold ethanol to afford 4.61 g of an off-white fine powder (61%): 1 H NMR (CDCl3, 250 MHz): δ 1.14 (6H, t, CH2 CH3), 2.23 (6H, s, pyrrole--CH3), 2.31 (4H, t, CH2 CH2 CO2 CH3), 2.50 (4H, q, CH2 CH3), 2.64 (4H, t, CH2 CH2 CO2 CH3), 3.60 (10H, br s, CH3 CO2 -- and (pyrrole)2 --CH2), 4.44 (4H, br s, C6 H5 CH2), 6.99-7.02 (4H, m, aromatic), 7.22-7.26 (6H, m, aromatic), 8.72 (1H, s, NH), 10.88 (2H, br s, NH); 13 C NMR (CDCl3, 250 MHz): δ 10.97, 16.78, 17.71, 19.40, 22.07, 35.09, 51.46, 65.32, 117.37, 119.34, 122.14, 126.58, 126.79, 127.36, 128.19, 133.55, 136.62, 162.35, 173.49; CI MS (M+H)+750; HRMS 749.3676 (calc. for C44 H51 N3 O8 : 749.3676).
2,5-Bis (5-benzyloxycarbonyl-3-(3-hydroxypropyl)-4-methylpyrrol-2-yl)methyl!-3,4-diethylpyrrole. F4, Scheme F. 2,5-Bis (5-benzyloxycarbonyl-4-methyl-3-methoxycarbonylethylpyrrol-2-yl)methyl!-3,4-diethylpyrrole F3 (5.00 g, 0.007 mol) was placed in a three necked 100 mL round bottom flask and vacuum dried for at least 30 minutes. The flask was equipped with a thermometer, an addition funnel, a nitrogen inlet tube, and a magnetic stir bar. After the tripyrrane was partially dissolved into 10 mL of dry THF, 29 mL of borane (1M BH3 in THF) was added dropwise with stirring. The reaction became mildly exothermic and was cooled with a cool water bath. The tripyrrane slowly dissolved to form a homogeneous orange solution which turned to a bright fluorescent orange color as the reaction went to completion. After stirring the reaction for one hour at room temperature, the reaction was quenched by adding methanol dropwise until the vigorous effervescence ceased. The solvents were removed under reduced pressure and the resulting white solid redissolved into CH2 Cl2. The tripyrrane was washed three times with 0.5M HCl (200 mL total), dried over anhydrous K2 CO3, filtered, and the CH2 Cl2 removed under reduced pressure until crystals of the tripyrrane just started to form. Hexanes (50 Ml) was added and the tripyrrane allowed to crystallize in the freezer for several hours. The product was filtered and again recrystallized from CH2 Cl2 /ethanol. The product was collected by filtration and vacuum dried to yield 3.69 g of an orangish white solid (76%): mp 172°-173° C.; 1 H NMR (CDCl3, 300 MHz): δ 1.11 (6H, t, CH2 CH3), 1.57 (4H, p, CH2 CH2 CH2 OH), 2.23 (6H, s, pyrrole--CH3), 2.39-2.49 (8H, m, CH2 CH3 and CH2 CH2 CH2 OH), 3.50 (4H, t, CH2 CH2 CH2 OH), 3.66 (4H; s, (pyrrole)2 --CH2), 4.83 (4H, s, C6 H5 --CH2), 7.17-7.20 (4H, m, aromatic), 7.25-7.30 (6H, m, aromatic), 8.64 (1H, s, NH), 9.92 (2H, s, NH); 13 C NMR (CDCl3, 300 MHz): δ 10.97, 16.72, 17.68, 20.00, 22.38, 33.22, 62.01, 65.43, 117.20, 119.75, 120.72, 122.24, 127.23, 127.62, 128.30, 132.95, 136.60, 162.13; FAB MS (M+) 693.
2,5-Bis (3-(3-hydroxypropyl)-5-carboxyl-4-methyl pyrrol-2-yl) methyl!-3,4-diethylpyrrole F5, Scheme F. 2,5-Bis (3-(3-hydroxypropyl)-5-benzyloxycarbonyl-4-methylpyrrol-2-yl)methyl!-3,4-diethylpyrrole F4 (15.0 g, 0.02 mol) was placed in a 1 L round bottom flask and dried in vacuo for ca. 30 min. The tripyrrane was dissolved in dry THF (600 mL) with triethylamine (10 drops) and 10% Pd on carbon (600 mg) and the reaction was stirred at room temperature under one atmosphere of H2. After 15 h, the suspension was filtered through celite to remove the catalyst and the resulting clear solution was concentrated under reduced pressure to yield a light pink solid. This material, obtained in near quantitative yield, was taken on to the next step without further purification.
A carboxyl tripyrrane A4 (a specific example presented as F5 in Scheme F) (0.02 mol) is placed in a 250 mL round bottom flask and dried in vacuo for ca. 1 h. At room temperature under nitrogen, trifluoroacetic acid (31 mL, 0.40 mol) is added dropwise via syringe. The tripyrrane dissolves with visible evolution of CO2 to form a homogeneous yellow solution. The reaction is stirred at room temperature for ca. 15 min, then cooled to 0° C. using a water/ice bath. A triethyl-ortho-ester (or trimethyl-ortho-ester, ca. 18 eq) is added to the reaction mixture dropwise with stirring after which the reaction is stirred for an additional 15 minutes at 0° C. If the ester is acetate, then a methyl group would be attached, propionate would attach an ethyl group, for example. The reaction is warmed to room temperature and 100 mL of water added dropwise. After stirring the resulting two phase mixture for ca. 30 minutes, the reaction mixture is extracted three times with CH2 Cl2. The CH2 Cl2 extracts are combined and washed three times with 1M aq. NaHCO3, once with water, dried over anhydrous sodium sulfate, filtered, and the solvent removed under reduced pressure. The resulting solid is recrystallized from CH2 Cl2 /hexanes.
General procedure for the synthesis of a metal complex of texaphyrin (A7, Scheme A). One equivalent of the hydrochloride salt of the macrocycle A6, 1.5 equivalents of the M(OAc3)3 ·XH2 O metal salt (where M=metal ion),and triethylamine (ca. 1 mL) are mixed together in methanol and heated to reflux under air. After completion of the reaction (as judged by the UV/vis spectrum of the reaction mixture), the solution is cooled to room temperature, the solvent is removed under reduced pressure and the crude complex dried in vacuo for several hours. A solution of dichloromethane/methanol (99:1 v/v) is added to the crude complex and the suspension is sonicated a few min. The suspension is filtered in order to remove impurities in the filtrate (incomplete oxidation products and excess triethylamine). The resulting solid is dissolved in methanol and then chloroform is added to reduce the polarity of the mixture (1:2 v/v). This solution is filtered through celite and loaded on a (pre-treated/pre-washed 1M NaNO3) neutral alumina column (10 cm). The column is first eluted with a 1:10 (v/v) methanol/chloroform solution by gravity to remove any impurity. The metal complex is then obtained by eluting the column with chloroform containing increasing amounts of methanol (20-50%). The purified lanthanide(III) texaphyrin complex is recrystallized by dissolving the complex in methanol/chloroform and carefully layering the solution with a small amount of methanol, then with diethylether. The layered solution is kept at room temperature in the dark for a few days. The texaphyrin metal complex is recrystallized twice for analytically pure measurements and characterizations.
Lanthanum(III), Cerium(III), Praseodymium(III), Neodymium(III), Samarium(III), Europium(III), Gadolinium (III), Terbium(III), Dysprosium(III), Holmium(III), Erbium(III), Thulium(III), Ytterbium(III), Lutetium(III) complexes of texaphyrin: The hydrochloride salt of macrocycle A6 (0.407 mmol), and one of the following lanthanide salts: La(OAc3)3 ·6H2 O (0.814 mmol), Ce(OAc3)3 ·6H2 O (0.611 mmol), Pr(OAc3)3 ·5H2 O (0.611 mmol), Nd(OAc3)3 ·6H2 O(0.611 mmol), Sm(OAc3)3 ·5H2 O (0.611 mmol), Eu(OAc3)3 ·5H2 O (0.65 mmol), Gd(OAc3)3 ·5H2 O (1.5 mmol), Tb(OAc3)3 ·6H2 O (0.611 mmol), Dy(OAc3)3 ·5H2 O (0.611 mmol), Ho(OAC3)3 ·5H2 O (0.611 mmol), Er(OAc3)3 ·5H2 O (0.611 mmol), Tm(OAc3)3 ·5H2 O (0.611 mmol), Yb(OAc3)3 ·5H2 O (0.611 mmol), or Lu(OAc3)3 ·H2 O (0.611 mmol), together with TBANO3 (1.0 mmol) and triethylamine (ca. 0.5 mL) in 350 mL methanol are heated to reflux under air for 5-24 h. The workup uses the general procedure outlined above. The thulium and lutetium complexes may be more difficult to purify due to their lower solubility in methanol/chloroform solutions, which leads to a lower yield.
2,3,4-Trihydroxybenzoic acid B1, is reacted with an alkyl 5 halide where the halide is chloride, bromide, or iodide in the presence of potassium carbonate and acetonitrile to form a trialkoxy derivative B2. The alkyl group of the halide may be a primary or secondary alkyl having one or more hydroxy, alkoxy, carboxy, ester, amine, amide or protected amine substituents at positions at least one carbon removed from the site of halide attachment. These alkyl groups may be unsubstituted, singly or multiply functionalized. They may be branched or unbranched. Preferred alkyl groups are methyl, hydroxypropyl or methoxy(ethoxy)nethoxy (n=1-100; a polyethylene glycol substituent). Compound B2 is reacted with 90% nitric acid to form the dinitro derivative B3 which is then reacted with either hydrazine hydrate or ammonium formate and 10% palladium on carbon in methanol to form compound B4.
Scheme D shows the formation of a tertiary amine at the R6 position. The starting material is 2,3,4-trihydroxybenzoic acid (D1). Compound D3 (B3) is treated with an amine component in 1,3-dicyclohexylcarbodiimide and dimethylformamide to form D4 having an amide linkage. Alternative coupling reagents include 1,1-carbonyldiimidazole (CDI) or ECC. Reduction as described above yields the diamine for condensation with a tripyrrane ketone. ##STR8##
Synthesis of I3, Scheme I, part 1: Pyrrole I1(readily available from Aldrich Chemical Co., Milwaukee, Wis.) of Scheme I is reacted with sulfuryl chloride in dichloromethane, followed by hydrolysis with sodium acetate, and acidification to afford the acid pyrrole, 12 (see A. R. Battersby et al., J. C. S. Perkin I, 1976, 1008). Decarboxylation via trifluoroacetic acid yields 13 (see M. J. Cyr, Ph.D. Dissertation, University of Texas at Austin, 1992). ##STR10##
Synthesis of the diformyl tripyrrane I9. With compound I7 in hand, the tripyrrane is transformed to the desired diformyl tripyrrane I9 (R5 =H) by standard organic synthesis reported earlier (U.S. Pat. No. 5,252,720). Compound I7 is reduced by borane/THF, followed by acetylation via acetic anhydride or acetyl chloride to afford tripyrrane I8. At this point, debenzylation of I8, followed by subsequent Clezy formylation of the intermediate, and basic hydrolysis with lithium hydroxide, provides tripyrrane I9.
2,5-Bis (3-acetoxypropyl-5-benzoyl-4-methylpyrrol-2-yl)methyl!-3,4-diethylpyrrole (J2). 2,5-Bis (3-acetoxypropyl-5-carboxyl-4-methylpyrrol-2-yl)methyl!-3,4-diethylpyrrole J1(1.00 g, 1.67 mmol) was placed in a 100 mL three-neck round-bottom flask and dried under high vacuum for ca. 1 hr. The round-bottom flask was equipped with an argon inlet line and for magnetic stirring. At room temperature under argon, CH2 Cl2 (10 mL) was added to the flask and the resulting mixture stirred to form a suspension. Trifluoroacetic acid (2.7 mL) was then added all at once to the suspension. The tripyrrane dissolved to form a light orange solution. The reaction was stirred at room temperature under argon for ca. 45 min, after which it was cooled to 0° C. using an ice/water bath. Triethylorthobenzoate (3.8 mL) was added dropwise to the reaction with stirring over a two minute period under a flow of argon. The reaction was stirred for 40 min at 0° C. then allowed to warm to room temperature over 20 min. Water (20 mL) was added to the reaction and stirring continued for another 2 hr. Transferred reaction to a separatory funnel, separated and discarded the upper aqueous phase, and basified the lower organic layer with sat. aqueous NaHCO3 (Caution: gas evolution and frothing occurs). Separated the two layers and washed the organic phase once with sat. aqueous NaHCO3 and once with water. Dried organic phase over anhydrous MgSO4, filtered off the drying agent, removed the solvent under reduced pressure, and dried the resulting orange-red oil under high vacuum overnight. The oil was dissolved into a minimum amount of CH2 Cl2 (5-10 mL), the solution layered with hexanes (ca. 50 mL), and the tripyrrane allowed to crystallize at -20° C. The product was collected by filtration and dried under high vacuum to yield 1.06 grams of a tan solid (J2) (88%). 1 H NMR (CDCl3, 300 MHz): δ 1.06 (6H, t, CH2 CH3), 1.67 (4H, p, CH2 CH2 CH2 OAc), 1.81 (6H, s, CH3 CO2 --), 2.02 (6H, s, pyrr--CH3), 2.37-2.44 (8H, m, CH2 CH3 and CH2 CH2 CH2 OAc), 3.71 (4H, s, (pyrr)2 --CH2), 3.99 (4H, t, CH2 CH2 CH2 OAc), 7.29-7.48 (10H, m, aromatic), 9.16 (1H, s, NH), 9.66 (2H, s, NH); 13 C NMR (CDCl3): δ 11.8, 16.4, 17.7, 20.1, 20.9, 22.7, 29.1, 63.9, 120.9, 121.5, 127.3, 128.1, 128.2, 129.1, 130.8, 135.6, 140.1, 171.3, 185.7; FAB MS, M+ : m/e 717.
4,5-Diethyl-9,24-bis(3-hydroxypropyl)-16,17-dimethoxy-10,23-dimethyl-1 2,21-diphenyl-13,20,25,26,27-pentaazapentacyclo- 20.2.1.13,6.18,11.014, 19 !heptacosa-3,5,8,10,12,14,16,18,20,22,24-undecaene (J6).
2,5-Bis (3-acetoxypropyl-5-benzoyl-4-methylpyrrol-2-yl)methyl!-3,4-diethylpyrrole J2 (100 mg, 0.14 mmol) and 4,5-dimethoxy-1,2-phenylenediamine J5 (23 mg, 0.14 mmol) were dissolved into 100 mL of absolute methanol under argon. Concentrated HCl (5 drops) was added and the reaction heated at reflux under argon. After heating for 2 days, the reaction was cooled to room temperature and the solvent removed under reduced pressure. The resulting red solid was dissolved into CH2 Cl2 (5 mL), filtered, and the CH2 Cl2 solution layered with hexanes (20 mL). The product was allowed to slowly precipitate out of solution at room temperature overnight. The mother liquor was decanted off and the remaining solid washed with hexanes. After drying the solid under high vacuum, 39 mg of dark red product (J6) was obtained. FAB MS, (M+H)+ : m/e 766.
Cadmium(II) complex of 4,5-diethyl-9,24-bis(3-hydroxypropyl)-16,17-dimethoxy-10,23-dimethyl-1 2,21-diphenyl-13,20,25,26,27-pentaazapentacyclo 20.2.1.13,6.18,11.014,19 !-heptacosa-1,3,5,7,9,11(27),12,14(19),15, 17,20,22(25),23-tridecaene (J8). The protonated form of the macrocycle J6 (11 mg, 0.014 mmol), cadmium(II) chloride (11 mg, 0.06 mmol) and triethylamine (20 mL) in 20 mL of methanol were heated at reflux under air for 2 days. The reaction was cooled to room temperature, the solvent removed under reduced pressure, and the complex dried in vacuo overnight to give the final texaphyrin-Cd(II) metal complex (J8). UV/vis (CH3 OH) λmax, nm!: 472.0, 756.0; FAB MS, (M+H)+ : m/e 875. ##STR11##
2,5-bis (5-benzoyl-3-ethyl-4-methylpyrrol-2-yl)meth-yl!-3,4-diethylpyrrole (J4). 2,5-Bis (5-carboxyl-3-ethyl-4-methylpyrrol-2-yl)methyl!-3,4-diethylpyrrole J3 (1.00 g, 2.20 mmol) was placed in a 100 mL three-neck round-bottom flask and dried under high vacuum for 1 hr. The round-bottom flask was equipped with an argon inlet line and for magnetic stirring. At room temperature under argon, CH2 Cl2 (10 mL) was added to the reaction flask and the resulting mixture stirred to form a suspension. Trifluoroacetic acid (3.5 mL) was then added all at once to the suspension. The tripyrrane dissolved to form a yellowish orange solution. The reaction was stirred at room temperature under argon for ca. 35 min, after which it was cooled to 0° C. using an ice/water bath. Triethylorthobenzoate (5.0 mL) was added dropwise to the reaction with stirring over a two minute period under a flow of argon. The reaction was stirred for 40 min at 0° C. then allowed to warm to room temperature over 20 min. Water (20 mL) was added to the reaction and stirring continued for another 1 hr. Transferred reaction to a separatory funnel, separated and discarded the upper aqueous phase, and basified the lower organic layer with sat. aqueous NaHCO3 (30 mL) (Caution: gas evolution and frothing occurs). Separated the two layers and washed the organic phase once with sat. aqueous NaHCO3 and once with water. Dried organic phase over anhydrous MgSO4, filtered off the drying agent, and removed the solvent under reduced pressure to yield a dark oil with some precipitate. The oil and solid were dissolved into a minimum amount of CH2 Cl2 (5 mL), the solution layered with hexanes (ca. 50 mL), and the product allowed to crystallize at -20° C. The product was collected by filtration, washed with a small amount of hexanes, and dried under high vacuum to yield 0.88 grams of a tan solid (J4) (70%). 1 H NMR (CDCl3, 300 MHz): δ 0.95 (6H, t, CH2 CH3), 1.05 (6H, t, CH2 CH3), 1.80 (6H, s, pyrr--CH3), 2.32-2.40 (8H, m, CH2 CH3), 3.67 (4H, s, (pyrr)2 --CH2), 7.27-7.48 (10H, m, aromatic), 9.27 (1H, s, NH), 9.66 (2H, S, NH); 13 C NMR (CDCl3): δ 11.7, 15.1, 16.3, 17.1, 17.7, 22.8, 120.8, 121.4, 124.8, 127.0, 128.0(6), 128.1(4), 129.2, 130.6, 135.5, 140.2, 185.7; FAB MS, (M+H)+ : m/e 574.
4,5,9,24-Tetraethyl-16,17-dimethoxy-10,23-dimethyl-12,21-diphenyl-13,2 0,25,26,27-pentaazapentacyclo- 20.2.1.13,6.18,11.014,19 !heptacosa-3,5,8,10,12,14,16,18,20,22,24-undecaene (J7). 2,5-Bis (5-benzoyl-3-ethyl-4-methylpyrrol-2-yl)methyl!-3,4-diethylpyrrole J4 (101 mg, 0.18 mmol) and 4,5-dimethoxy-1,2-phenylenediamine J5 (30 mg, 0.18 mmol) were dissolved into 200 mL of toluene and 100 mL of absolute methanol. The solvents were sparged with argon for approximately 5 min before the reaction was started. Concentrated HCl (3 drops) was then added and the reaction heated at reflux under an atmosphere of argon. After heating for ca. 2.75 days, the reaction was cooled to room temperature, the solvent removed under reduced pressure and the remaining solid dried in vacuo. The macrocycle was dissolved into CH2 Cl2 (10 mL), filtered, and the CH2 Cl2 solution layered with hexanes (80 mL). The product was allowed to slowly precipitate out of solution at -20° C. overnight. The macrocycle was collected by filtration, dissolved into a minimum amount of ethanol, and the solution layered with hexanes. The macrocycle was allowed to slowly precipitate out of solution at -20° C. for several days. The macrocycle was collected by filtration, washed with a small amount of hexanes, and dried under high vacuum to yield 28 mg of dark red product (J7). FAB MS, (M+H)+ : m/e 707.
R5, R6, R9, and/or R10 Substituents
TABLE A__________________________________________________________________________Representative Substituents for Texaphyrin Macrocycles A1-A50 of thePresent Invention.Substituents for R1 -R6 are provided in TABLE A and for R7-R12 in TABLE B.TXP   R1      R2                  R3                         R4                             R5                                    R8__________________________________________________________________________A1 CH2 (CH2)2 OH           CH2 CH3                  CH2 CH3                         CH3                             H      COOHA2 "            "      "      "   "      COOHA3 "            "      "      "   "      CONHCH--(CH2 OH)2A4 "            "      "      "   "      "A5 "            "      "      "   "      HA6 "            "      "      "   "      OCH3A7 "            "      "      "   "      "AB "            "      "      "   "      "A9 "            "      "      "   "      "A10   "            "      "      "   "      "A11   "            "      "      "   "      "A12   "            "      "      "   "      "A13   "            "      "      "   "      CH3A14   "            "      "      "   "      "A15   "            "      "      "   "      "A16   "            "      "      "   "      "A17   "            "      "      "   CH3                                    HA18   "            "      "      "   "      "A19   "            "      "      "   "      "A20   CH2 (CH2)2 OH           CH2 CH3                  CH2 CH3                         CH3                             CH3                                    HA21   "            "      "      "   "      "A22   "            "      "      "   "      "A23   "            "      "      "   "      "A24   "            "      "      "   "      "A25   "            "      "      "   "      "A26   "            "      "      "   "      OHA27   "            "      "      "   "      FA28   "            "      "      "   CH2 (CH2)6 OH                                    HA29   "            "      "      "   H      BrA30   "            "      "      "   "      NO2A31   "            "      "      "   "      COOHA32   "            "      "      "   "      CH3A33   "            "      "      "   C6 H5                                    HA34   "            COOH   COOH   "   CH2 CH3                                    "A35   "            COOCH2 CH3                  COOCH2 CH3                         "   CH3                                    "A36   CH2 CH2 CON(CH2 CH2 OH)2           CH2 CH3                  CH2 CH3                         "   CH3                                    "A37   CH2 CH2 ON(CH3)CH2.           "      "      "   "      "   (CHOH)4 CH2 OHA38   CH2 CH3           "      "      "   CH2 (CH2)6 OH                                    "A39   CH2 (CH2)2 OH           CH2 CH3                  CH2 CH3                         CH3                             CH3                                    H                             or CH2 CH3A40   "            "      "      "   "      "A41   "            "      "      "   "      "A42   "            "      "      "   "      "A43   "            "      "      "   "      "A44   "            "      "      "   "      "A45   "            "      "      "   "      "A46   "            "      "      "   "      "A47   "            "      "      "   "      "A48   "            "      "      "   "      "A49   "            "      "      "   "      "A50   "            "      "      "   "      "A51   "            "      "      "   H      "A52   "            "      "      "   "      "A53   "            "      "      "   "      "A54   "            "      "      "   "      "A55   "            "      "      "   CH3 or                                    "                             CH2 CH3A56   "            "      "      "   "      "__________________________________________________________________________
TABLE B__________________________________________________________________________Representative Substituents for Texaphyrin Macrocycles A1-A50 of thePresent Invention.Substituents for R1 -R6 Are Provided in TABLE A and for R7-R12 in TABLE B.TXP   R7  R8     R9  R10                                   R11                                          R12__________________________________________________________________________A1 O(CH2)3 OH       O(CH2)3 OH                   O(CH2)3 OH                            H      H      HA2 O(CH2 CH2 O)3 CH3       O(CH2 CH2 O)3 CH3                   COOH     "      "      "A3 O(CH2 CH2 O)3 CH3       O(CH2 CH2 O)3 CH3                   O-saccharide                            "      "      "A4 "        "           O(CH2 CH2 O)3 CH3                            "      "      "A5 "        O(CH2)3 CON-linker-oligo                   "        "      "      "A6 H        OCH2 CON-linker-oligo                   OCH3                            "      "      "A7 "        OCH2 CO-poly-L-lysine                   "        "      "      "A8 "        OCH2 CO-estradiol                   "        "      "      "A9 "        O(CH2 CH2 O)3 CH3                   "        "      "      "A10   O(CH2 CH2 O)3 CH3       "           "        "      "A11   "        OCH2 CON-linker-oligo                   "        "      "      "A12   "        OCH2 CO-estradiol                   "        "      "      "A13   "        O(CH2 CH2 O)3 CH3                   O(CH2 CH2 O)3 CH3                            "      "      "A14   "        OCH2 CO-estradiol                   "        "      "      "A15   O(CH2 CH2 O)3 CH3       O(CH2 CH2 O)120 CH3                   OCH3                            "      "      "A16   H        saccharide  "        "      "      "A17   O(CH2)3 OH       O(CH2)3 OH                   H        CH3                                   "      "A18   H        O(CH2 CH2 O)3 CH3                   "        "      "      "A19   O(CH2 CH2 O)3 CH3       "           "        "      "      "A20   H        OCH2 CON-linker-oligo                   H        CH3                                   "      "A21   "        OCH2 CO-estradiol                   "        "      "      "A22   "        OCH2 CON(CH2 CH2 OH)2                   "        "      "      "A23   O(CH2 CH2 O)3 CH3       O(CH2 CH2 O)120 CH3                   "        "      "      "A24   "        OCH2 CON-linker-oligo                   "        "      "      "A25   H        CH2 CON(CH3)CH2.                   "        "      "      "       (CHOH)4 CH2 OH                   "        "      "      "A26   O(CH2 CH2 O)3 CH3       O(CH2 CH2 O)3 CH3                   OH       "      "      "A27   "        "           F        "      "      "A28   "        "           H        CH2 (CH2)6 OH                                   "      "A29   "        "           Br       H      "      "A30   "        "           NO2 "      "      "A31   "        "           COOH     "      "      "A32   "        "           CH3 "      "      "A33   "        "           H        C6 H5                                   "      "A34   "        "           "        CH2 CH3                                   "      "A35   "        "           "        CH3                                   "      "A36   "        "           "        "      "      "A37   OCH3       OCH3   "        "      "      "A38   H        OCH2 CO2 -glucosamine                   "        CH2 (CH2)6 OH                                   "      "A39   O(CH2)3 OH       O(CH2)3 OH                   H        CH3                                   CH3                                          CH3                            or     or     or                            CH2 CH3                                   CH2 CH3                                          CH2 CH3A40   O(CH2 CH2 O)3 CH3       O(CH2 CH2 O)3 CH3                   "        "      "      "A41   O(CH2)3 OH       O(CH2 CH2 O)3 CH3                   "        "      "      "A42   H        O(CH2)n CON-linker-oligo,                   "        "      "      "       n = 1,2,3A43   H        O(CH2)n CO-estradiol,                   "        "      "      "       n = 1,2,3A44   H        saccharide  "        "      "      "A45   O(CH2)3 OH       O(CH2)n CON-linker-oligo,                   "        "      "      "       n = 1,2,3   "        "      "      "A46   "        O(CH2)n CO-estradiol,                   "        "      "      "       n = 1,2,3A47   "        saccharide  "        "      "      "A48   O(CH2 CH2 O)3 CH3       O(CH2)n CON-linker-oligo,                   "        "      "      "       n = 1,2,3A49   "        O(CH2)n CO-estradiol,                   "        "      "      "       n = 1,2,3A50   "        saccharide  "        "      "      "A51   "        O(CH2)n CON-linker-oligo                   "        H      "      "       n = 1,2,3A52   "        O(CH2 CH2 O)3 CH3                   "        "      "      "A53   "        "           "        "      CH2 (CH2)2                                          CH2 (CH2)2                                          OHA54   "        O(CH2)n CON-linker-oligo                   "        "      "      "       n = 1,2,3A55   "        "           "        CH3 or                                   "      "                            CH2 CH3A56   "        O(CH2 CH2 O.sub.)3 CH3                   "        "      "      "__________________________________________________________________________
Patent CitationsCited PatentFiling datePublication dateApplicantTitleUS4318825 *Aug 18, 1980Mar 9, 1982Frame Robert RCatalytic composite, and method of manufactureUS4647447 *Jan 23, 1984Mar 3, 1987Schering AktiengesellschaftDiagnostic mediaUS4835263 *Dec 18, 1986May 30, 1989Centre National De La Recherche ScientifiqueNovel compounds containing an oligonucleotide sequence bonded to an intercalating agent, a process for their synthesis and their useUS4878891 *Jun 25, 1987Nov 7, 1989Baylor Research FoundationMethod for eradicating infectious biological contaminants in body tissuesUS4880008 *May 7, 1986Nov 14, 1989The General Hospital CorporationVivo enhancement of NMR relaxivityUS4883790 *Apr 23, 1987Nov 28, 1989University Of British ColumbiaWavelength-specific cytotoxic agentsUS4899755 *May 8, 1985Feb 13, 1990The General Hospital CorporationHepatobiliary NMR contrast agentsUS4915683 *Mar 10, 1987Apr 10, 1990The Medical College Of Wisconsin, Inc.Antiviral method, agents and apparatusUS4935498 *Mar 6, 1989Jun 19, 1990Board Of Regents, The University Of Texas SystemExpanded porphyrins: large porphyrin-like tripyrroledimethine-derived macrocyclesUS4959363 *Jun 23, 1989Sep 25, 1990Sterling Drug Inc.Quinolonecarboxamide compounds, their preparation and use as antivirals.US4977177 *Apr 30, 1985Dec 11, 1990Nippon Petrochemicals Company, Ltd.Tetrapyrrole polyaminomonocarboxylic acid therapeutic agentsUS5021236 *Mar 2, 1987Jun 4, 1991Schering AktiengesellschaftMethod of enhancing NMR imaging using chelated paramagnetic ions bound to biomoleculesUS5030200 *Nov 6, 1989Jul 9, 1991Baylor Research FoundationMethod for eradicating infectious biological contaminants in body tissuesUS5041078 *Dec 21, 1989Aug 20, 1991Baylor Research Foundation, A Nonprofit Corporation Of The State Of TexasPhotodynamic viral deactivation with sapphyrinsUS5141911 *Aug 7, 1990Aug 25, 1992Societe Nationale Elf AquitaineOxidation catalysts based on supported metalloporphyrinUS5162509 *Jun 18, 1990Nov 10, 1992Board Of Regents, The University Of Texas SystemProcess for preparing expanded porphyrins: large porphyrin-like tripyrroledimethine-derived macrocyclesUS5242797 *Jan 2, 1992Sep 7, 1993Myron J. BlockNucleic acid assay methodUS5252720 *Jan 21, 1992Oct 12, 1993Board Of Regents, The University Of Texas SystemMetal complexes of water soluble texaphyrinsUS5256399 *May 7, 1992Oct 26, 1993Board Of Regents, The University Of Texas SystemAromatic pentadentate expanded porphyrins in magnetic resonance imagingUS5272056 *Jan 3, 1991Dec 21, 1993The Research Foundation Of State University Of New YorkModification of DNA and oligonucleotides using metal complexes of polyaza ligandsUS5272142 *May 7, 1992Dec 21, 1993Board Of Regents, The University Of Texas SystemExpanded porphyrins: large porphyrin-like tripyrroledimethine-derived macrocycles and methods for treating tumorsUS5292414 *Apr 20, 1992Mar 8, 1994Board Of Regents, The University Of Texas SystemExpanded porphyrins: large porphyrin-like tripyrroledimethine-derived macrocycles for singlet oxygen productionUS5302714 *Oct 26, 1992Apr 12, 1994Board Of Regents, The University Of Texas SystemSapphyrins, derivatives and synthesesUS5369101 *Dec 16, 1993Nov 29, 1994Board Of Regents, The University Of Texas SystemExpanded porphyrins: large porphyrin-like tripyrroledimethine-derived macrocyclesUS5371199 *Aug 14, 1992Dec 6, 1994The Trustees Of The University Of PennsylvaniaSubstituted porphyrins, porphyrin-containing polymers, and synthetic methods thereforUS5432171 *Jul 28, 1993Jul 11, 1995Board Of Regents, The University Of Texas SystemWater soluble texaphyrin metal complexes for viral deactivationUS5439570 *Aug 25, 1993Aug 8, 1995Board Of Regents, The University Of Texas SystemWater soluble texaphyrin metal complexes for singlet oxygen productionEP0196515A1 *Mar 13, 1986Oct 8, 1986Baxter Travenol Laboratories, Inc.Photodynamic inactivation of virus in therapeutic protein compositionsEP0233701A2 *Jan 16, 1987Aug 26, 1987HAMARI YAKUHIN KOGYO KABUSHIKI KAISHA also known as HAMARI CHEMICALS, LTD.Porphyrin derivativesWO1990001208A1 *Jul 28, 1989Feb 8, 1990Best Industries, Inc.Device and method for encapsulating radioactive materialsWO1994009003A1 *Oct 18, 1993Apr 28, 1994Board Of Regents, The University Of Texas SystemSapphyrin derivatives, conjugates and polymers thereof and expanded porphyrin chromatographic supportsWO1994029316A2 *Jun 9, 1994Dec 22, 1994Board Of Regents, The University Of Texas SystemTexaphyrin metal complex mediated ester hydrolysis* Cited by examinerNon-Patent CitationsReference1"2-Athylamino-2-methyl-propanol-(1)", Beilstein's Handbuch, 4:785, 1950.2"Tentative Rules for Carbohydrate Nomenclature Part 1 (1969)," Handbook of Biochemistry and Molecular Biology, 3rd ed., Fasman, Ed., CRC Press, Cleveland, Ohio, pp. 100-102.3 *2 A thylamino 2 methyl propanol (1) , Beilstein s Handbuch , 4:785, 1950.4Abid et al., "Lanthanide Complexes of Some Macrocyclic Schiff Bases Derived from Pyridine-2, 6-dicarboxaldehyde and α,ω-Primary Diamines", Inorg. Chim. Acta, 95:119-125, 1984.5 *Abid et al., Lanthanide Complexes of Some Macrocyclic Schiff Bases Derived from Pyridine 2, 6 dicarboxaldehyde and , Primary Diamines , Inorg. Chim. Acta , 95:119 125, 1984.6Acholla et al., "A Binucleating Accordian Tetrapyrrole Macrocycle", Tetrahedron Lett., 25:3269-3270, 1984.7Acholla et al., "Binucleating Tetrapyrrole Macrocycles", J. Am. Chem. Soc., 107:6902-690, 1985.8 *Acholla et al., A Binucleating Accordian Tetrapyrrole Macrocycle , Tetrahedron Lett., 25:3269 3270, 1984.9 *Acholla et al., Binucleating Tetrapyrrole Macrocycles , J. Am. Chem. Soc. , 107:6902 690, 1985.10Agrawal and Tang, "Efficient Synthesis of Oligoribonucleotide and Its Phosphorothioate Analogue Using H-Phosphonate Approach," Tetrahedron Letters, 31(52) :7541-7544, 1990.11Agrawal et al., "Cellular Uptake and Anti-HIV Activity of Oligonucleotides and Their Analogs," Gene Regulation: biology of Antisense RNA and DNA, 273-283, 1992.12Akhtar et al., "Pharmaceutical Aspects of the Biological Stability and Membrane Transport Characteristics of Antisense Oligonucleotides," Gene Regulation: Biology of Antisense RNA and DNA, 133-145, 1992.13Ansell, "X-Ray Crystal Structure of the Pentagonal Bipyramidal Nickel (11) Complex Ni11 (L) (H2 O)2 ! (BF4)2 and the Selective Stabilization of the Nickel (1) Oxidation State by a Quinquedentate Macrocyclic Ligand", J. Chem. Soc., Chem. Commun. pp. 546-547, 1982.14 *Ansell, X Ray Crystal Structure of the Pentagonal Bipyramidal Nickel (11) Complex Ni 11 (L) (H 2 O) 2 (BF 4 ) 2 and the Selective Stabilization of the Nickel (1) Oxidation State by a Quinquedentate Macrocyclic Ligand , J. Chem. Soc., Chem. Commun. pp. 546 547, 1982.15Aoyama et al., "Multi-Point Interaction of Phosphates with Protonated Pyridylporphyrin. Discrimination of Monoalkyl and Dialkyl Phosphates,"Chemistry Letters, 1241-1244 (1991).16 *Aoyama et al., Multi Point Interaction of Phosphates with Protonated Pyridylporphyrin. Discrimination of Monoalkyl and Dialkyl Phosphates, Chemistry Letters , 1241 1244 (1991).17Basile et al., "Metal-Activated Hydrolytic Cleavage of DNA," J. Am. Chem. Soc.109:7550-7551, 1987.18Bauer et al., "Sapphyrins: Novel Aromatic Pentapyrrolic Macrocycles", J. Am. Chem. Soc., 105:6429-6436, 1983.19 *Bauer et al., Sapphyrins: Novel Aromatic Pentapyrrolic Macrocycles , J. Am. Chem. Soc. , 105:6429 6436, 1983.20Bhan and Miller, "Photo-Cross Linking of Psoralen-Derivatized Oligonucleoside Methylphosphonates to Single-Stranded DNA," Bioconjugate Chem., 1:82-88, 1990.21 *Bhan and Miller, Photo Cross Linking of Psoralen Derivatized Oligonucleoside Methylphosphonates to Single Stranded DNA, Bioconjugate Chem. , 1:82 88, 1990.22Boutorine et al., "Fullerene-Oligonucleotides Conjugates: Photo-Induced Sequence Specific DNA Cleavage", Agnew. Chem. Int. Ed. Engl., 33(23/24) :2462-2465, 1994.23 *Boutorine et al., Fullerene Oligonucleotides Conjugates: Photo Induced Sequence Specific DNA Cleavage , Agnew. Chem. Int. Ed. Engl. , 33(23/24) :2462 2465, 1994.24Bradley et al., "Antisense Therapeutics," Gene Regulation: Biology of Antisense RNA and DNA, 285-293, 1992.25Breslow et al., "Effects of Metal Ions, Including Mg2× and Lanthanides, on the Cleavage of Ribonucleotides and RNA Model Compounds," Proc. Natl. Acad. Sci. USA, 88:4080-4083, 1991.26Broadhurst et al., "18-and 22-π-Electron Macrocycles Containing Furan, Pyrrole, and Thiophen Rings", J. Chem. Soc., Chem. Commun. pp. 1480-1482, 1969.27Broadhurst et al., "New Macrocyclic Aromatic Systems Related to Porphins", J. Chem. Soc., Chem. Commun. pp. 23-24, 1969.28Broadhurst et al., "Preparation of Some Sulphur-containing Polypyrrolic Macrocycles. Sulphur Extrusion from a meso-Thiaphlorin", J. Chem. Soc., Chem. Commun. pp. 807-809, 1970.29Broadhurst et al., "The Synthesis of 22 π-Electron Macrocycles. Sapphyrins and Related Compounds", J. Chem. Soc. Perkin Trans., 1:2111-2116, 1972.30 *Broadhurst et al., 18 and 22 Electron Macrocycles Containing Furan, Pyrrole, and Thiophen Rings , J. Chem. Soc., Chem. Commun. pp. 1480 1482, 1969.31 *Broadhurst et al., New Macrocyclic Aromatic Systems Related to Porphins , J. Chem. Soc., Chem. Commun. pp. 23 24, 1969.32 *Broadhurst et al., Preparation of Some Sulphur containing Polypyrrolic Macrocycles. Sulphur Extrusion from a meso Thiaphlorin , J. Chem. Soc., Chem. Commun. pp. 807 809, 1970.33 *Broadhurst et al., The Synthesis of 22 Electron Macrocycles. Sapphyrins and Related Compounds , J. Chem. Soc. Perkin Trans. , 1:2111 2116, 1972.34Brown and Truscott, "New Light on Cancer Therapy," Chemistry in Britain, 955-958, 1993.35 *Brown and Truscott, New Light on Cancer Therapy, Chemistry in Britain , 955 958, 1993.36Browne and Bruice, "Chemistry of Phosphodiesters, DNA and Models. 2. The Hydrolysis of Bis(8-hydroxyquinoline) Phosphate in the Absence and Presence of Metal Ions," Journal of the American Chemical Society, 114(13) :4951-4958, 1992.37Chin and Banaszczyk, "Highly Efficient Hydrolytic Cleavage of Adenosine Monophosphate Resulting in a Binuclear Co(III) Complex with a Novel Doubly Bidentate μ4 -Phosphato Bridge," J. Am. Chem. Soc., 111:4103-4105, 1989.38Chin and Banaszczyk, "Rate-Determining Complexation in Catalytic Hydrolysis of Unactivated Esters in Neutral Water," J. Am. Chem. Soc., 111:2724-2726, 1989.39Chin and Zou, "Catalytic Hydrolysis of cAMP," Can. J. Chem., 65:1882-1884, 1987.40Chin et al., "Co(III) Complex Promoted Hydrolysis of Phosphate Diesters: Comparison in Reactivity of Rigid cis-Diaquotetraazacobalt(III) Complexes, " J. Am. Chem. Soc., 111:186-190, 1989.41Chung et al., "Synthesis ad Characterization of a Reactive Binuclear Co(III) Complex. Cooperative Promotion of Phosphodiester Hydrolysis," Tetrahedron Letters, 31(38) :5413-5416, 1990.42Claude et al., "Binding of Nucleosides, Nucleotides and Anionic Planar Substrates by Bis-Intercaland Receptor Molecules," J. Chem. Soc. Chem. Commun., 1991, 17:1182-1185.43 *Claude et al., Binding of Nucleosides, Nucleotides and Anionic Planar Substrates by Bis Intercaland Receptor Molecules, J. Chem. Soc. Chem. Commun. , 1991, 17:1182 1185.44Cohen, Jack S., "Chemically Modified Oligodeoxynucleotide Analogs as Regulators of Viral and Cellular Gene Expression," Gene Regulation: Biology of Antisense RNA and DNA, 247-259, 1992.45Cramer et al., "Sythesis and Structure of the Chloride and Nitrate Inclusion Complexes of 16-Pyrimidinium crown-4!," J. Am. Chem. Soc., 1991, 113:7033-7034.46 *Cramer et al., Sythesis and Structure of the Chloride and Nitrate Inclusion Complexes of 16 Pyrimidinium crown 4 , J. Am. Chem. Soc. , 1991, 113:7033 7034.47Cuellar et al., "Synthesis and Characterization of Metallo and Metal-Free Octaalkyphthalocyanines and Uranyl Decaalkylsuperphthalocyanines", Inorg. Chem., 20:3766-3770, 1981.48 *Cuellar et al., Synthesis and Characterization of Metallo and Metal Free Octaalkyphthalocyanines and Uranyl Decaalkylsuperphthalocyanines , Inorg. Chem. , 20:3766 3770, 1981.49Day et al., "Large Metal Ion-Centered Template Reactions. A Uranyl Complex of Cyclopentakis (2-iminoisoindoline)", J. Am. Chem. Soc., 97 :4519-4527, 1975.50 *Day et al., Large Metal Ion Centered Template Reactions. A Uranyl Complex of Cyclopentakis (2 iminoisoindoline) , J. Am. Chem. Soc. , 97 :4519 4527, 1975.51De Cola et al., "Hexaaza Macrocyclic Complexes of the Lanthanides", Inorg. Chem., 25:1729-1732, 1986.52 *De Cola et al., Hexaaza Macrocyclic Complexes of the Lanthanides , Inorg. Chem. , 25:1729 1732, 1986.53Dervan Peter B., "Design of Sequence-Specific DNA-Binding Molecules," Science, 232:464-471, 1986.54 *Dervan Peter B., Design of Sequence Specific DNA Binding Molecules, Science , 232:464 471, 1986.55Dietrich et al., "Proton Coupled Membrane Transport of Anions Mediated by Cryptate Carriers," J. Chem. Soc. Chem. Comm., 1988, 11:691-692.56 *Dietrich et al., Proton Coupled Membrane Transport of Anions Mediated by Cryptate Carriers, J. Chem. Soc. Chem. Comm. , 1988, 11:691 692.57Dixon et al., "Molecular Recognition: Bis-Acylguanidiniums Provide a Simple Family of Receptors for Phosphodiesters," J. Am. Chem. Soc., 1992, 114:365-366.58 *Dixon et al., Molecular Recognition: Bis Acylguanidiniums Provide a Simple Family of Receptors for Phosphodiesters, J. Am. Chem. Soc. , 1992, 114:365 366.59Doan et al., "Sequence-targeted Chemical Modifications of Nucleic Acids by Complemetary Oligonucleotides Covalently Linked to Porphyrins," Nucleic Acids Research, 15(21) :8643-8659, 1987.60Doan et al., "Targeted Cleavage of Polynucleotides by Complementary Oligonucleotides Covalently Linked to Iron-Prophyrins," Biochemistry, 26:6736-6739, 1986.61 *Doan et al., Sequence targeted Chemical Modifications of Nucleic Acids by Complemetary Oligonucleotides Covalently Linked to Porphyrins, Nucleic Acids Research , 15(21) :8643 8659, 1987.62 *Doan et al., Targeted Cleavage of Polynucleotides by Complementary Oligonucleotides Covalently Linked to Iron Prophyrins, Biochemistry , 26:6736 6739, 1986.63Dolphin et al., "Porphocyanine: An Expanded Tetrapyrrolic Macrocycle," J. Am. Chem. Soc., 115:9301-9302, 1993.64 *Dolphin et al., Porphocyanine: An Expanded Tetrapyrrolic Macrocycle, J. Am. Chem. Soc. , 115:9301 9302, 1993.65Dougherty, "Photosensitizers: Therapy and Detection of Malignant Tumors", Photochem. Photobiol., 45:879-889, (1987).66 *Dougherty, Photosensitizers: Therapy and Detection of Malignant Tumors , Photochem. Photobiol. , 45:879 889, (1987).67Dreyer and Dervan, "Sequence-specific Cleavage of Single-Stranded DNA: Oligodeoxynucleotide-EDTA•Fe(II)," Proc. Natl. Acad. Sci. USA, 82:968-972, 1985.68 *Dreyer and Dervan, Sequence specific Cleavage of Single Stranded DNA: Oligodeoxynucleotide EDTA Fe(II), Proc. Natl. Acad. Sci. USA , 82:968 972, 1985.69Ehrenberg et al., "Spectroscopy, Photokinetics and Cellular Effect of Far-Red and Near Infrared Absorbing Photosensitizers," Proc. SPIE-Int. Soc. opt. Eng. 1992, 1645 (Proc. Opt. Methods Tumor Treat. Dect.: Mech. Tech. Photodyn. Ther. . , 259-263, 1992.70Ehrenberg et al., "The Binding and Photosensitization Effects of Tetrabenzoporphyrins and Texaphyrin in Bacterial Cells," Lasers in Medical Science, 8:197-203, 1993.71 *Ehrenberg et al., Spectroscopy, Photokinetics and Cellular Effect of Far Red and Near Infrared Absorbing Photosensitizers, Proc. SPIE Int. Soc. opt. Eng. 1992, 1645 ( Proc. Opt. Methods Tumor Treat. Dect.: Mech. Tech. Photodyn. Ther. . , 259 263, 1992.72 *Ehrenberg et al., The Binding and Photosensitization Effects of Tetrabenzoporphyrins and Texaphyrin in Bacterial Cells, Lasers in Medical Science , 8:197 203, 1993.73Fedorova et al., "Palladium (II)-Coprophyrin I as a Photoactivable Group in Sequence-Specific Modification of Nucleic Acids by Oligonucleotide Derivatives," FEBS Lett., 259(2) 335-337, 1990.74Fiel, Robert J., "Porphyrin-Nucleic Acid Interactions: A Review," Journal of Biomolecular Structure & Dynamics, 6(6) :1259-1275, 1989.75 *Fiel, Robert J., Porphyrin Nucleic Acid Interactions: A Review, Journal of Biomolecular Structure & Dynamics , 6(6) :1259 1275, 1989.76Furuta et al., "Enhanced Transport of Nucleosides and Nucleoside Analogues with Complementary Base-Pairing Agents," Journal of the American Chemical Society, 1991, 113:4706-4707.77Furuta et al., "Phosphate Anion Binding: Enhanced Transport of Nucleotide Monophosphates Using a Sapphyrin Carrier," J. Am. Chem. Soc., 113:6677-6678, 1991.78 *Furuta et al., Enhanced Transport of Nucleosides and Nucleoside Analogues with Complementary Base Pairing Agents, Journal of the American Chemical Society , 1991, 113:4706 4707.79 *Gal a n et al., A Synthetic Receptor for Dinucleotides, J. Am. Chem. Soc. , 1991, 113:9424 9425.80 *Gal a n et al., Selective Complexation of Adenosine Monophosphate Nucleotides By Rigid Bicyclic Guanidinium Abiotic Receptors, Tetrahedron Letters , 32(15) :1827 1830, 1991.81Galan et al., "A Synthetic Receptor for Dinucleotides," J. Am. Chem. Soc., 1991, 113:9424-9425.82Galan et al., "Selective Complexation of Adenosine Monophosphate Nucleotides By Rigid Bicyclic Guanidinium Abiotic Receptors," Tetrahedron Letters, 32(15) :1827-1830, 1991.83Goodchild, John, "Conjugates of Oligonucleotides and Modified Oligonucleotides: A Review of Their Synthesis and Properties," Bioconjugate Chemistry, 1(3) :165-187, 1990.84 *Goodchild, John, Conjugates of Oligonucleotides and Modified Oligonucleotides: A Review of Their Synthesis and Properties, Bioconjugate Chemistry , 1(3) :165 187, 1990.85Gosmann et al., "Synthesis of a Fourfold Enlarged Porphyrin with an Extremely Large, Diamagnetic Ring-Current Effect", Angew. Chem., Int. Ed Engl., 25:1100-1101, (1986).86 *Gosmann et al., Synthesis of a Fourfold Enlarged Porphyrin with an Extremely Large, Diamagnetic Ring Current Effect , Angew. Chem., Int. Ed Engl. , 25:1100 1101, (1986).87Gossauer, "Syntheses of Some Unusual Polypyrrole Macrocycles", Bull. Soc. Chim. Belg., 92:793-795, (1983).88 *Gossauer, Syntheses of Some Unusual Polypyrrole Macrocycles , Bull. Soc. Chim. Belg. , 92:793 795, (1983).89Groves and Farrell, "DNA Cleavage by a Metal Chelating Tricationic Porphyrin," J. Am. Chem. Soc., 111:4998-5000, 1989.90 *Groves and Farrell, DNA Cleavage by a Metal Chelating Tricationic Porphyrin, J. Am. Chem. Soc. , 111:4998 5000, 1989.91Hanvey et al., "Antisense and Antigene Properties of Peptide Nucleic Acids," Science, 258:1481-1485, 1992.92Harriman et al., "Metallotexaphyrins: A New Family of Photosensitisers for Efficient Generation of Singlet Oxygen", J. Chem. Soc., Chem. Commun., 314-316, 1989. Submitted as A32 in 1449 for UTSB:458.93 *Harriman et al., Metallotexaphyrins: A New Family of Photosensitisers for Efficient Generation of Singlet Oxygen , J. Chem. Soc., Chem. Commun. , 314 316, 1989. Submitted as A32 in 1449 for UTSB:458.94Hayashi et al., "Site-Selective Hydrolysis of tRNA by Lanthanide Metal Complexes," Inorg. Chem., 32:5899-5900, 1993.95Hendry and Sargeson, "Metal Ion Promoted Phosphate Ester Hydrolysis Intramolecular Attack of Coordinated Hydroxide Ion," J. Am. Chem. Soc., 111:2521-2527, 1989.96Hisatome et al., "Porphyrins Coupled with Nucleoside Bases. Synthesis and Characterization of Adenine-and Thymine-Porphyrin Derivatives," Chemistry Letters, 1990, 2251-2254.97 *Hisatome et al., Porphyrins Coupled with Nucleoside Bases. Synthesis and Characterization of Adenine and Thymine Porphyrin Derivatives, Chemistry Letters , 1990, 2251 2254.98Hosseini et al., "Multiple Molecular Recognition and Catalysis. A Multifunctional Anion Receptor Bearing an Anion Bindings Site, an Intercalating Group, and a Catalytic Site for Nucleotide Binding and Hydrolysis," J. Am. Chem. Soc., 1990, 112:3896-3904.99Hosseini et al., "Multiple Molecular Recognition and Catalysis. Nucleotide Binding and ATP Hydrolysis by a Receptor Molecule Bearing an Anion Binding Site, an Intercalcator Group, and a Catalytic Site," J. Chem. Soc. Chem. Comm., 1988, 9:596-598.100 *Hosseini et al., Multiple Molecular Recognition and Catalysis. A Multifunctional Anion Receptor Bearing an Anion Bindings Site, an Intercalating Group, and a Catalytic Site for Nucleotide Binding and Hydrolysis, J. Am. Chem. Soc. , 1990, 112:3896 3904.101 *Hosseini et al., Multiple Molecular Recognition and Catalysis. Nucleotide Binding and ATP Hydrolysis by a Receptor Molecule Bearing an Anion Binding Site, an Intercalcator Group, and a Catalytic Site, J. Chem. Soc. Chem. Comm. , 1988, 9:596 598.102International Search Report mailed Dec. 6, 1994.103International Search Report mailed Feb. 22, 1994.104International Search Report mailed Feb. 3, 1994.105Iverson et al., "Interactions Between Expanded Porphyrins and Nucleic Acids," Pure Applied Chemistry, 66(4) :845-850, 1994.106 *Iverson et al., Interactions Between Expanded Porphyrins and Nucleic Acids, Pure Applied Chemistry , 66(4) :845 850, 1994.107Kim and Chin, "Dimethyl Phospahte Hydrolysis at Neutral pH," J. Am. Chem. Soc., 114:9792-9795, 1992.108Kimura et al., "A Study of New Bis (macrocyclic polyamine) Ligands as Inorganic and Organic Anion Receptors," J. Org. Chem., 1990, 55(1) :46-48.109 *Kimura et al., A Study of New Bis (macrocyclic polyamine) Ligands as Inorganic and Organic Anion Receptors, J. Org. Chem. , 1990, 55(1) :46 48.110Kimura, "Macrocyclic Polyamines as Biological Cation and Anion Complexones--An Application to Calculi Dissolution," 113-141.111 *Kimura, Macrocyclic Polyamines as Biological Cation and Anion Complexones An Application to Calculi Dissolution, 113 141.112Knubel et al., "Biomimetic Synthesis of an Octavinylogous Porphyrin with an Aromatic 34! Annulene System", Angew. Chem., Int. Ed. Engl., 27:1170-1172, 1988.113 *Knubel et al., Biomimetic Synthesis of an Octavinylogous Porphyrin with an Aromatic 34 Annulene System , Angew. Chem., Int. Ed. Engl. , 27:1170 1172, 1988.114Kobayashi et al., "Uptake of Chlorophyll-Derivatives by Cellular Nuclei and Mitochondria," Photomed. Photobiol., 15:75-84, 1993.115 *Kobayashi et al., Uptake of Chlorophyll Derivatives by Cellular Nuclei and Mitochondria, Photomed. Photobiol. , 15:75 84, 1993.116Koenig et al., "PDT of Tumor-Bearing Mice Using Liposome Delivered Texaphyrins," International Conference, Milan, Italy, Biosis citation only, Jun. 24-27, 1992.117 *Koenig et al., PDT of Tumor Bearing Mice Using Liposome Delivered Texaphyrins, International Conference, Milan, Italy, Biosis citation only, Jun. 24 27, 1992.118Kolasa et al., "Trivalent Lanthanide Ions Do Not Cleave RNA in DNA-RNA Hybrids," Inorg. Chem., 32:3983-3984, 1993.119Komiyama et al., "Unprecedentedly Fast Hydrolysis of the RNA Dinucleoside Monophosphates ApA and UpU by Rare Earth Metal Ions," J. Chem. Soc. Chem. Commun., 640-641, 1992.120Lauffer, "Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging: Theory and Design", Chem. Rev., 87: 901-927, 1987.121 *Lauffer, Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging: Theory and Design , Chem. Rev. , 87: 901 927, 1987.122Le Doan et al., "Sequence-Specific Recognition, Photocrosslinking and Cleavage of the DNA Double Helix by an Oligo- α!-Thymidylate Covalently Attached to an Azidoproflavine," Nucleic Acids Res., 15:7749-7760, 1987.123Le Doan et al., "Sequence-Taregeted Photochemical Modifications of Nucleic Acids by Complementary Oligonucleotides Covalently Linked to Porphyrins," Bioconjugate Chem., 1:108-113, 1990.124 *Le Doan et al., Sequence Specific Recognition, Photocrosslinking and Cleavage of the DNA Double Helix by an Oligo Thymidylate Covalently Attached to an Azidoproflavine, Nucleic Acids Res. , 15:7749 7760, 1987.125 *Le Doan et al., Sequence Taregeted Photochemical Modifications of Nucleic Acids by Complementary Oligonucleotides Covalently Linked to Porphyrins, Bioconjugate Chem. , 1:108 113, 1990.126Lee et al., "Interaction of Psoralen-Derivatized Oligodeoxyribonucleoside Methylphosphonates with Single-Stranded DNA," Biochemistry, 27:3197-3203, 1988.127 *Lee et al., Interaction of Psoralen Derivatized Oligodeoxyribonucleoside Methylphosphonates with Single Stranded DNA, Biochemistry , 27:3197 3203, 1988.128Leff, "Texas `Son-of-Porphyrin` Molecule Lassos Europium to Kill Drug Resistance Gene," BioWorld Today, 5(156):1, 1994.129 *Leff, Texas Son of Porphyrin Molecule Lassos Europium to Kill Drug Resistance Gene, BioWorld Today , 5(156):1, 1994.130LeGoff et al., "Synthesis of a 1, 5, 1, 5! Platyrin, a 26 π-Electron Tetrapyrrolic Annulene", J. Org. Chem., 52:710-711, 1987.131 *LeGoff et al., Synthesis of a 1, 5, 1, 5 Platyrin, a 26 Electron Tetrapyrrolic Annulene , J. Org. Chem. , 52:710 711, 1987.132Levina et al., "Photomodification of RNA and DNA Fragments by Oligonucleotide Reagents Bearing Arylazide Groups," Biochimie, 75:25-27, 1993.133 *Levina et al., Photomodification of RNA and DNA Fragments by Oligonucleotide Reagents Bearing Arylazide Groups, Biochimie , 75:25 27, 1993.134Li and Diederich, "Carriers for Liquid Membrane Transport of Nucleotide 5'-Triphosphates," J. Org. Chem., 1992, 47:3449-3454.135 *Li and Diederich, Carriers for Liquid Membrane Transport of Nucleotide 5 Triphosphates, J. Org. Chem. , 1992, 47:3449 3454.136Lin et al., "Use of EDTA Derivatization to Characterize Interactions between Oligodeoxyribonucleoside Methylphosphonates and Nucleic Acids," Biochemistry, 28:1054-1061, 1989.137 *Lin et al., Use of EDTA Derivatization to Characterize Interactions between Oligodeoxyribonucleoside Methylphosphonates and Nucleic Acids, Biochemistry , 28:1054 1061, 1989.138Magda et al., "Sequence-Specific Photocleavage of DNA by an Expanded Porphyrin with Irradiation Above 700 nm," J. Am. Chem. Soc., 117:3629-3630, 1995.139Magda et al., "Site-Specific Hydrolysis of RNA by Emporium (III) Texaphyrin Conjugated to a Synthetic Oligodeoxyribonucleotide," Journal of the American Chemical Society, 116(16) :7439-7440, 1994.140 *Magda et al., Site Specific Hydrolysis of RNA by Emporium (III) Texaphyrin Conjugated to a Synthetic Oligodeoxyribonucleotide, Journal of the American Chemical Society , 116(16) :7439 7440, 1994.141Maiya et al., "Ground-and Excited-State Spectral and Redox Properties of Cadmium (II) Texaphyrin," Journal of Physical Chemistry, 93(24):8111-8115, 1989.142 *Maiya et al., Ground and Excited State Spectral and Redox Properties of Cadmium (II) Texaphyrin, Journal of Physical Chemistry , 93(24):8111 8115, 1989.143Marks and Stojakowvic, "Large Metal Ion-Centered Template Reactions. Chemical and Spectral Studies of the Superphthalocyanine Dioxocyclopentakis (1-iminoisoindolinato) uranium (VI) and Its Derivatives," J. Am. Chem. Soc., 1978, 1695-1705.144 *Marks and Stojakowvic, Large Metal Ion Centered Template Reactions. Chemical and Spectral Studies of the Superphthalocyanine Dioxocyclopentakis (1 iminoisoindolinato) uranium (VI) and Its Derivatives, J. Am. Chem. Soc. , 1978, 1695 1705.145Marks et al., "Large Metal Ion-Centered Template Reactions. Chemical and Spectral Studies of the Superphthalocyanine Dioxocyclopentakis (1-iminoisoindolinato) uranium (VI) and Its Derivatives", J. Am. Chem. Soc., 100:1695-1705, 1978.146 *Marks et al., Large Metal Ion Centered Template Reactions. Chemical and Spectral Studies of the Superphthalocyanine Dioxocyclopentakis (1 iminoisoindolinato) uranium (VI) and Its Derivatives , J. Am. Chem. Soc. , 100:1695 1705, 1978.147Mastruzzo et al., "Targeted Photochemical Modification of HIV-Derived Oligoribonucleotides by Antisense Oligonucleotides Linked to Porphyrins," Photochem. Photobiol.60(4):316-322, 1994.148 *Mastruzzo et al., Targeted Photochemical Modification of HIV Derived Oligoribonucleotides by Antisense Oligonucleotides Linked to Porphyrins, Photochem. Photobiol. 60(4):316 322, 1994.149Matthews et al., "Inactivation of Viruses with Photoactive Compounds," Blood Cells, 18(1) :75-89, 1992.150 *Matthews et al., Inactivation of Viruses with Photoactive Compounds, Blood Cells , 18(1) :75 89, 1992.151Menger et al., "Phosphate Ester Hydrolysis Catalyzed by Metallomicelles," J. Am. Chem. Soc., 109:2800-2803, 1987.152Modak et al., "Toward Chemical Ribonucleases. 2. Synthesis and Characterization of Nucleoside-Bipyridine Conjugates. Hydrolytic Cleavage of RNA by Their Copper (II) Complexes," J. Am. Chem. Soc., 113:283-291.153Morgan and Skalkos, "Second Generation Sensitizers: Where are We and Where Should We Be Going?" Proc. SPIE Int. Soc. Opt. Eng. Ser., 6:87-106, 1990.154Morrow et al., "Efficient Catalytic Cleavage of RNA by Lanthanide (III) Macrocyclic Complexes: Toward Synthetic Nucleases for in Vivo Applications," J. Am. Chem. Soc., 114:1903-1905, 1992.155Nam -Chiang Wang et al., "Pyrrole chemistry. XVII. Alkylation of the pyrrolyl ambident anion," Can. J. Chem., 55:4112-4116, 1977.156 *Nam Chiang Wang et al., Pyrrole chemistry. XVII. Alkylation of the pyrrolyl ambident anion, Can. J. Chem. , 55:4112 4116, 1977.157PCT Search Report mailed Feb. 23, 1995.158Perrouault et al., "Sequence-Specific Artifical Photo-Induced Endonucleases Based on Triple Helix-Forming Oligonucleotides," Nature, 344:358-360, 1990.159Phillips and Wasserman, "Promise of Radiosensitizers and Radioprotectors in the Treatment of Human Cancer," Cancer Treatment Reports, 68(1) :291-301, 1984.160Pieles and Englisch, "Psoralen Covalently Linked to Oligodeoxyribonucleotides: Synthesis, Sequence Specific Recognition of DNA and Photo-Cross-Linking to Pyrimidine Residues of DNA," Nucleic Acids Res., 17(1) :285-299, 1989.161Praseuth et al., "Sequence-Specific Binding and Photocrosslinking of α and β Oligodeoxynucleotides to the Major Groove of DNA via Triple-Helix Formation," Proc. Natl. Acad. Sci. USA, 85:1349-1353, 1988.162Praseuth et al., "Sequence-Targeted Photosensitized Reactions in Nucleic Acids by Oligo-α-Deoxynucleotides and Oligo-β-Deoxynucleotides Covalently Linked to Proflavin," Biochemistry, 27:3031-3038, 1988.163Ranganathan et al., "Design of a Chemical Nuclease Model with (Lys)2 Cu as the Core Motif," Journal of the Chemical Society, 4:337-339, 1993.164Rexhausen et al., "The Synthesis of a New 22 π-Electron Macrocycle: Pentaphyrin", J. Chem. Soc., Chem. Commun. p. 275, 1983.165 *Rexhausen et al., The Synthesis of a New 22 Electron Macrocycle: Pentaphyrin , J. Chem. Soc., Chem. Commun. p. 275, 1983.166Schmidtchen, "A Non-Macrocyclic Host for Binding Organic Phosphates in Protic Solvents," Tetrahedron Letters, 1989, 30(34) :4493-4496.167 *Schmidtchen, A Non Macrocyclic Host for Binding Organic Phosphates in Protic Solvents, Tetrahedron Letters , 1989, 30(34) :4493 4496.168Schneider et al., "Catalysis of the Hydrolysis of Phosphoric Acid Diesters by Lanthanide Ions and the Influence of Ligands," Angew. Chem. Int. Ed. Engl., 32(12):1716-1719, 1993.169Seel and Vogtle, "Molecular Recognition and Transport of Nucleobases--Superiority of Macrobicyclid Host Molecules," Angew, Chem. Int. Ed. Engl., 1991, 30(4) :442-444.170 *Seel and Vogtle, Molecular Recognition and Transport of Nucleobases Superiority of Macrobicyclid Host Molecules, Angew, Chem. Int. Ed. Engl. , 1991, 30(4) :442 444.171Sessler and Burrell, "Expanded Porphyrins," Topics in Current Chemistry, 161:180-273, 1991.172 *Sessler and Burrell, Expanded Porphyrins, Topics in Current Chemistry , 161:180 273, 1991.173Sessler et al., "`Texaphyrin`: A Novel 22 π-Electron Aromatic Pentadentate Macrocyclic Ligand", ACS meeting, Los Angeles, Sep. 1988.174Sessler et al., "A Water-Stable Gadolinium (III) Complex Derived from a New Pentadentate Expanded Porphyrin Ligand", Inorg. Chem., 28:3390-3393, 1989.175Sessler et al., "A Water-Stable Gadolinium (III) Complex Derived from a New Pentadentate", Chem. Absts., 111:720, abstract no. 125716e, Oct. 2, 1989.176Sessler et al., "An Expanded Porphyrin: The Synthesis and Structure of a New Aromatic Pentadentate Ligand", J. Am. Chem. Soc., 110:5586-5588, 1988.177Sessler et al., "Anion Binding: A New Direction in Porphyrin-Related Research, " Pure & Applied Chem., 65(3) :393-398, 1993.178Sessler et al., "Binding of Pyridine and Benzimidazole to a Cadmium Expanded Porphyrin: Solution and X-ray Structural Studies", Inorg. Chem., 28:1333-1341, 1989.179Sessler et al., "Cytosine Amine Derivatives," J. Org. Chem., 1992, 47:826-834.180Sessler et al., "Expanded Porphyrins. Receptors for Cationic, Anionic, And Neutral Substrates," in Transition Metals in Supermolecular Chemistry, L. Fabbrizzi and A. Poggi, Editors, NATO ASI Series, Kluwer, Amsterdam, pp. 391-408, 1994.181Sessler et al., "Expanded Porpyhrins: The synthesis and Metal Binding Properties of Novel Triphyrranine-Containing Macrocycles", J. Coord. Chem., 18:99-104, 1988.182Sessler et al., "Gadolinium (III) Texaphyrin: A Novel MRI Contrast Agent," Journal of the American Chemical Society, 115(22):10, 368-10, 369, 1993.183Sessler et al., "Photodynamic Inactivation of Enveloped Viruses Using Sapphyrin, α 22 π-Electron Expanded Porphyrin: Possible Approaches to Prophylactic Blood Purification Protocols," SPIE Photodynamic Therapy: Mechanisms II. 1203:233-245, 1990.184Sessler et al., "Preparation of Lanthanide (III) Texaphyrin Complexes and Their Applications to Magnetic Resonance Imaging and Photodynamic Therapy," Abstracts of Papers, Part 1, 204th ACS National Meeting, Aug. 23-28, 1992, Washington, DC.185Sessler et al., "Sapphyrins and Heterosapphyrins," Tetrahedron, 48(44) :9661-9672, 1992.186Sessler et al., "Sapphyrins: New Life for an Old Expanded Porphyrin," Synlett, 127-134, 1991.187Sessler et al., "Synthesis and Applications of Schiff-Base Derived Expanded Porphyrins," Abstracts of Papers, Part 1, 204th ACS National Meeting, Aug. 23-28, 1992, Washington, DC.188Sessler et al., "Synthesis and Crystal Structure of a Novel Tripyrrane-Containing Porphyrinogen-like Macrocycle", J. Org. Chem., 52:4394-4397, 1987.189Sessler et al., "Synthesis and Structural Characterization of Lanthanide (III) Texaphyrins," Inorganic Chemistry, 32(14):3175-3187, 1993.190Sessler et al., "Texaphyrins: Synthesis and Applications," Accounts of Chemical Research, 27(2):43-50, 1994.191Sessler et al., "The Coordination Chemistry of Planar Pentadentate Porphyrin-Like Ligands", Comm. Inorg. Chem., 7:333-350, 1988.192Sessler et al., "The Synthesis and Structure of A Novel 22 π-Electron Aromatic Pentadentate Macrocyclic Ligand: An Expanded Porphyrin", Toronto ACS Meeting, Jun. 1988. USA.193Sessler et al., "Tripyrroledimethine-derived (Texaphyrin-type) Macrocycles: Potential Photosensitizers Which Absorb in the Far-red Spectral Region", SPIE, Optical Methods for Tumor Treatment and Early Diagnosis: Mechanism and Technique, 1426:318-329, 1991.194 *Sessler et al., A Water Stable Gadolinium (III) Complex Derived from a New Pentadentate , Chem. Absts. , 111:720, abstract no. 125716e, Oct. 2, 1989.195 *Sessler et al., A Water Stable Gadolinium (III) Complex Derived from a New Pentadentate Expanded Porphyrin Ligand , Inorg. Chem. , 28:3390 3393, 1989.196 *Sessler et al., An Expanded Porphyrin: The Synthesis and Structure of a New Aromatic Pentadentate Ligand , J. Am. Chem. Soc. , 110:5586 5588, 1988.197 *Sessler et al., Anion Binding: A New Direction in Porphyrin Related Research, Pure & Applied Chem. , 65(3) :393 398, 1993.198 *Sessler et al., Binding of Pyridine and Benzimidazole to a Cadmium Expanded Porphyrin: Solution and X ray Structural Studies , Inorg. Chem. , 28:1333 1341, 1989.199 *Sessler et al., Cytosine Amine Derivatives, J. Org. Chem. , 1992, 47:826 834.200 *Sessler et al., Expanded Porpyhrins: The synthesis and Metal Binding Properties of Novel Triphyrranine Containing Macrocycles , J. Coord. Chem. , 18:99 104, 1988.201 *Sessler et al., Gadolinium (III) Texaphyrin: A Novel MRI Contrast Agent, Journal of the American Chemical Society , 115(22):10, 368 10, 369, 1993.202 *Sessler et al., Photodynamic Inactivation of Enveloped Viruses Using Sapphyrin, 22 Electron Expanded Porphyrin: Possible Approaches to Prophylactic Blood Purification Protocols, SPIE Photodynamic Therapy: Mechanisms II . 1203:233 245, 1990.203 *Sessler et al., Preparation of Lanthanide (III) Texaphyrin Complexes and Their Applications to Magnetic Resonance Imaging and Photodynamic Therapy, Abstracts of Papers , Part 1, 204th ACS National Meeting, Aug. 23 28, 1992, Washington, DC.204 *Sessler et al., Synthesis and Applications of Schiff Base Derived Expanded Porphyrins, Abstracts of Papers , Part 1, 204th ACS National Meeting, Aug. 23 28, 1992, Washington, DC.205 *Sessler et al., Synthesis and Crystal Structure of a Novel Tripyrrane Containing Porphyrinogen like Macrocycle , J. Org. Chem. , 52:4394 4397, 1987.206 *Sessler et al., Synthesis and Structural Characterization of Lanthanide (III) Texaphyrins, Inorganic Chemistry , 32(14):3175 3187, 1993.207 *Sessler et al., Texaphyrin : A Novel 22 Electron Aromatic Pentadentate Macrocyclic Ligand , ACS meeting , Los Angeles, Sep. 1988.208 *Sessler et al., Texaphyrins: Synthesis and Applications, Accounts of Chemical Research , 27(2):43 50, 1994.209 *Sessler et al., The Coordination Chemistry of Planar Pentadentate Porphyrin Like Ligands , Comm. Inorg. Chem. , 7:333 350, 1988.210 *Sessler et al., The Synthesis and Structure of A Novel 22 Electron Aromatic Pentadentate Macrocyclic Ligand: An Expanded Porphyrin , Toronto ACS Meeting, Jun. 1988. USA.211 *Sessler et al., Tripyrroledimethine derived (Texaphyrin type) Macrocycles: Potential Photosensitizers Which Absorb in the Far red Spectral Region , SPIE, Optical Methods for Tumor Treatment and Early Diagnosis: Mechanism and Technique , 1426:318 329, 1991.212Sessler, Jonathan L., "Texas-Sized Molecule," Discovery, 13(1):44-49, 1993.213 *Sessler, Jonathan L., Texas Sized Molecule, Discovery , 13(1):44 49, 1993.214Shelton and Morrow, "Catalytic Transesterification and Hydrolysis of RNA by Zinc(II) Complexes," Inorg. Chem., 30:4295-4299, 1991.215Shelton and Morrow, "Catalytic Transesterification and Hydrolysis of RNA by Zinc(II) Complexes," Inorganic Chemistry, 30:4295-4299, 1991.216Stern et al., "Hydrolysis of RNA by Transitional-Metal Complexes," J. Am. Chem. Soc., 112:5357-5359, 1990.217Stinson, "Unusual Porphyrin Analog Promises Many Applications", Chemical and Engineering News, pp. 26-27, Aug. 8, 1988.218 *Stinson, Unusual Porphyrin Analog Promises Many Applications , Chemical and Engineering News , pp. 26 27, Aug. 8, 1988.219Strobel and Dervan, "Cooperative Site Specific Binding of Oligonucleotides to Duplex DNA," Journal of the American Chemical Society, 111(18) :7286-7287, 1989.220 *Strobel and Dervan, Cooperative Site Specific Binding of Oligonucleotides to Duplex DNA, Journal of the American Chemical Society , 111(18) :7286 7287, 1989.221Sumaoka et al., "Remarkably Fast Hydrolysis of 3', 5'-=Cyclic Adenosine Monophosphate by Cerium(III) Hydroxide Cluster," J. Chem. Soc. Chem. Comm., 2 pages, 1992.222T.D. Mody et al., "Lutetium (III) Texaphyrin: A Novel Photodynamic Therapy Agent," Abstract, 22nd Annual American Society for Photobiology, Scottsdale, AZ, Jun. 25-29, 1994.223 *T.D. Mody et al., Lutetium (III) Texaphyrin: A Novel Photodynamic Therapy Agent, Abstract, 22nd Annual American Society for Photobiology , Scottsdale, AZ, Jun. 25 29, 1994.224Tabushi et al., "Lilophilic Diammonium Cation Having a Rigid Structure Complementary to Pyrophosphate Dianions of Nucleotides. Selective Extraction and Transport of Nucleotides," J. Am. Chem. Soc., 1981, 103:6152-6157.225 *Tabushi et al., Lilophilic Diammonium Cation Having a Rigid Structure Complementary to Pyrophosphate Dianions of Nucleotides. Selective Extraction and Transport of Nucleotides, J. Am. Chem. Soc. , 1981, 103:6152 6157.226Takasugi et al., "Sequence-Specific Photo-Induced Cross-Linking of the Two Strands of Double-Helical DNA by a Psoralen Covalently Linked to a Triple Helix-Forming Oligonucleotide," Proc. Natl. Acad. Sci. USA, 88:5602-5606, 1991.227Teare and Wollenzien, "Specificity of Site Directed Psoralen Addition to RNA," Nucleic Acids Res. , 17(9) :3359-3372, 1989.228 *Tentative Rules for Carbohydrate Nomenclature Part 1 (1969), Handbook of Biochemistry and Molecular Biology , 3rd ed., Fasman, Ed., CRC Press, Cleveland, Ohio, pp. 100 102.229Thaller et al., "Potential Use of Radiolabelled Porphyrins for Tumor Scanning," Porphyrin Photosensitization, Kessel and Dougherty, Eds., Plenum Press, New York and London, Publisher, pp. 265-278, 1981.230 *Thaller et al., Potential Use of Radiolabelled Porphyrins for Tumor Scanning, Porphyrin Photosensitization , Kessel and Dougherty, Eds., Plenum Press, New York and London, Publisher, pp. 265 278, 1981.231To and Neiman, "The Potential For Effective Antisense Inhibition of Retroviral Replication Mediated Vectors," Gene Regulation: Biology of Antisense RNA and DNA, 261-271, 1992.232Tohda et al., "Liquid Membrane Electrode for Guanosine Nucleotides Using a Cytosine-Pendant Triamine Host as the Sensory Element," Analytical Chemistry, 1992, 64(8):960-964.233 *Tohda et al., Liquid Membrane Electrode for Guanosine Nucleotides Using a Cytosine Pendant Triamine Host as the Sensory Element, Analytical Chemistry , 1992, 64(8):960 964.234Tweedle et al., "Principles of Contrast-Enhanced MRI", in Magnetic Resonance Imaging, 2nd ed. Partain, et al, Eds., W. B. Saunders: Philadelphia, vol. I (1988) 793-809.235 *Tweedle et al., Principles of Contrast Enhanced MRI , in Magnetic Resonance Imaging, 2nd ed. Partain, et al, Eds., W. B. Saunders: Philadelphia, vol. I (1988) 793 809.236Vlassov et al., "Photoactivatable Porphyrin Oligonucleotide Derivatives for Sequence Specific Chemical Modification and Cleavage of DNA," Nucleosides & Nucleotides, 10(1-3) :641-643, 1991.237 *Vlassov et al., Photoactivatable Porphyrin Oligonucleotide Derivatives for Sequence Specific Chemical Modification and Cleavage of DNA, Nucleosides & Nucleotides , 10(1 3) :641 643, 1991.238Vogel et al., "2, 7, 12, 17-Tetrapropylporphycene--Counterpart of Octaethylporphyrin in the Porphycene Series", Angew. Chem. Int. Ed. Engl., 26:928-931, 1987.239Vogel et al., "New Porphycene Ligands: Octaethyl-and Etioporphycene (OEPc and EtioPc)-Tetra-and Pentacoordinated Zinc Complexes of OEPc," Angew. Chem. Int. Ed. Engl., 32(11) :1600-1604, 1993.240Vogel et al., "Porphycene--a Novel Porphin Isomer", Angew. Chem., Int. Ed. Engl., 25:257-259, 1986.241 *Vogel et al., 2, 7, 12, 17 Tetrapropylporphycene Counterpart of Octaethylporphyrin in the Porphycene Series , Angew. Chem. Int. Ed. Engl. , 26:928 931, 1987.242 *Vogel et al., Porphycene a Novel Porphin Isomer , Angew. Chem., Int. Ed. Engl. , 25:257 259, 1986.243Wagener and Beyrich, "Radiosensitizer-Biochemie und Tumortherapeutische Erfahrungen," Pharmazie, 47:815-824, 1992.244Wessel et al., "Porphyrins with Aromatic 26π-Electron Systems," Agnew. Chem. Int. Ed. Eng., 32(8) :1148-1151, 1993.245Young et al., "Preclinical Evaluation of Gadolinium (III) Texaphyrin Complex. A New Paramagnetic Contrast Agent for Magnetic Resonance Imaging," Investigative Radiology, 29(3):330-338, 1994.246 *Young et al., Preclinical Evaluation of Gadolinium (III) Texaphyrin Complex. A New Paramagnetic Contrast Agent for Magnetic Resonance Imaging, Investigative Radiology , 29(3):330 338, 1994.247Zuk et al., "Pharmacokinetic and Tissue Distribution Studies of the Photosensitizer bis(Di-Isobutyl Octadecysiloxy) Silicon 2, 3-Naphthalocyanine (isoBosinc) in Normal and Tumor-Bearing Rats," Photochemistry and Photobiology, 59(1) :66-72, 1994.248 *Zuk et al., Pharmacokinetic and Tissue Distribution Studies of the Photosensitizer bis (Di Isobutyl Octadecysiloxy) Silicon 2, 3 Naphthalocyanine ( iso Bosinc) in Normal and Tumor Bearing Rats, Photochemistry and Photobiology , 59(1) :66 72, 1994.* Cited by examinerReferenced byCiting PatentFiling datePublication dateApplicantTitleUS5919923 *May 19, 1998Jul 6, 1999Brueckner; ChristianMeso-substituted tripyrrane compounds, compositions, and methods for making and using the sameUS5969111 *Feb 4, 1997Oct 19, 1999Board Of Regents, The University Of Texas SystemTexaphyrins substituted with imidazole are providedUS6069140 *Nov 14, 1997May 30, 2000The Board Of Regents University Of Texas SystemPharmaceutical compositions comprising texaphyrinsUS6627400Oct 27, 2000Sep 30, 2003Aclara Biosciences, Inc.Multiplexed measurement of membrane protein populationsUS6649351Nov 9, 2001Nov 18, 2003Aclara Biosciences, Inc.Methods for detecting a plurality of analytes by mass spectrometryUS6673550Nov 9, 2001Jan 6, 2004Aclara Biosciences, Inc.Electrophoretic tag reagents comprising fluorescent compoundsUS6686152Apr 2, 2001Feb 3, 2004Aclara Biosciences, Inc.Methods employing oligonucleotide-binding e-tag probesUS6774249 *Sep 27, 2001Aug 10, 2004Lumigen, Inc.Uses of improved polymer-supported photosensitizers in the generation of singlet oxygenUS6818399Apr 2, 2001Nov 16, 2004Aclara Biosciences, Inc.Methods employing generalized target-binding e-tag probesUS6916612Apr 2, 2001Jul 12, 2005Aclara Biosciences, Inc.Sets of oligonucleotide-binding e-tag probesUS6949347Mar 4, 2003Sep 27, 2005Aclara Biosciences, Inc.Multiplex analysis using membrane-bound sensitizersUS6955874Apr 2, 2001Oct 18, 2005Aclara Biosciences, Inc.Kits employing oligonucleotide-binding e-tag probesUS7001725Apr 2, 2001Feb 21, 2006Aclara Biosciences, Inc.Kits employing generalized target-binding e-tag probesUS7025840Jul 15, 2003Apr 11, 2006Lockheed Martin CorporationExplosive/energetic fullerenesUS7037654Nov 9, 2001May 2, 2006Aclara Biosciences, Inc.Methods and compositions for enhancing detection in determinations employing cleavable electrophoretic tag reagentsUS7041459May 21, 2002May 9, 2006Monogram Biosciences, Inc.Analyzing phosphorylated proteinsUS7045311Oct 25, 2002May 16, 2006Monogram Biosciences, Inc.Whole cell assay systems for cell surface proteasesUS7160735Nov 8, 2002Jan 9, 2007Monogram Biosciences, Inc.Tagged microparticle compositions and methodsUS7217531Aug 27, 2005May 15, 2007Monogram BiosciencesMultiplex analysis using membrane-bound sensitizersUS7255999May 21, 2002Aug 14, 2007Monogram Biosciences, Inc.Methods and compositions for analyzing proteinsUS7358052May 24, 2002Apr 15, 2008Monogram Biosciences, Inc.Catalytic amplification of multiplexed assay signalsUS7402397Aug 10, 2004Jul 22, 2008Monogram Biosciences, Inc.Detecting and profiling molecular complexesUS7537938Jan 26, 2004May 26, 2009Monogram Biosciences, Inc.Biomarker detection in circulating cellsUS7635571Dec 7, 2000Dec 22, 2009Siemens Healthcare Diagnostics Products GmbhAmplified signal in binding assaysUS7648828Jan 21, 2005Jan 19, 2010Monogram Biosciences, Inc.Methods for detecting receptor complexes comprising PI3KUS7771929Apr 18, 2003Aug 10, 2010Monogram Biosciences, Inc.Tag library compounds, compositions, kits and methods of useUS8133474Sep 14, 2007Mar 13, 2012Massachusetts Institute Of TechnologySensors for fluorescence and magnetic resonance imagingUS8198031Mar 12, 2007Jun 12, 2012Monogram Biosciences, Inc.Detecting and profiling molecular complexesUS8247180Jul 18, 2008Aug 21, 2012Monogram Biosciences, Inc.Measuring receptor homodimerizationUS9110075Oct 4, 2011Aug 18, 2015Monogram Biosciences, Inc.Compositions for analyzing proteinsUS20020009737 *Apr 2, 2001Jan 24, 2002Sharat SinghKits employing oligonucleotide-binding e-tag probesUS20020015954 *Apr 2, 2001Feb 7, 2002Sharat SinghSets of oligonucleotide-binding e-tag probesUS20020197649 *May 24, 2002Dec 26, 2002Sharat SinghCatalytic amplification of multiplexed assay signalsUS20030013126 *May 21, 2002Jan 16, 2003Sharat SinghMethods and compositions for analyzing proteinsUS20030108978 *Oct 25, 2002Jun 12, 2003Ciambrone Gary J.Whole cell assay systems for cell surface proteasesUS20030134333 *Nov 8, 2002Jul 17, 2003Peter DehlingerTagged microparticle compositions and methodsUS20030170915 *Mar 4, 2003Sep 11, 2003Sharat SinghMultiplex analysis using membrane-bound sensitizersUS20030207300 *Jan 7, 2003Nov 6, 2003Matray Tracy J.Multiplex analytical platform using molecular tagsUS20030235832 *Nov 8, 2002Dec 25, 2003Ahmed ChennaMultiplexed analysis by chromatographic separation of molecular tagsUS20040063114 *Apr 18, 2003Apr 1, 2004Sharat SinghTag library compounds, compositions, kits and methods of useUS20040157271 *Jan 26, 2004Aug 12, 2004Hrair KirakossianBiomarker detection in circulating cellsUS20040175696 *Dec 7, 2000Sep 9, 2004Ullman Edwin F.Amplified luminescent homogeneous immunoassayUS20040175765 *Dec 18, 2003Sep 9, 2004Sharat SinghCell-screening assay and compositionUS20040197815 *Apr 22, 2004Oct 7, 2004Sharat SinghMethods for detecting aggregations of proteinsUS20040229293 *Mar 30, 2004Nov 18, 2004Po-Ying Chan-HuiSurface receptor complexes as biomarkersUS20040229299 *Mar 30, 2004Nov 18, 2004Badal M. YoussoufIntracellular complexes as biomarkersUS20040248150 *Dec 2, 2003Dec 9, 2004Sharat SinghMethods employing oligonucleotide-binding e-tag probesUS20040265858 *Feb 13, 2004Dec 30, 2004Sharat SinghSets of generalized target-binding e-tag probesUS20050079565 *Aug 10, 2004Apr 14, 2005Po-Ying Chan-HuiDetecting and profiling molecular complexesUS20050130238 *Jan 21, 2005Jun 16, 2005Po-Ying Chan-HuiErbB surface receptor complexes as biomarkersUS20050130246 *Oct 25, 2004Jun 16, 2005Hossein Salimi-MoosaviDetecting human anti-therapeutic antibodiesUS20050170438 *Jan 21, 2005Aug 4, 2005Po-Ying Chan-HuiMethods for Detecting Receptor Complexes Comprising PDGFRUS20050170439 *Jan 21, 2005Aug 4, 2005Po-Ying Chan-HuiMethods for Detecting Receptor Complexes Comprising PI3KUS20060024846 *Aug 27, 2005Feb 2, 2006Sharat SinghMultiplex analysis using membrane-bound sensitizersUS20060181579 *Feb 14, 2006Aug 17, 2006Brother Kogyo Kabushiki KaishaInkjet Recording ApparatusUS20080138292 *Sep 14, 2007Jun 12, 2008Massachusetts Institute Of TechnologySensors for fluorescence and magnetic resonance imagingUS20080187948 *Dec 27, 2007Aug 7, 2008Monogram Biosciences Inc.Erbb heterodimers as biomarkersUS20080233602 *Mar 12, 2007Sep 25, 2008Po-Ying Chan-YuiDetecting and profiling molecular complexesUS20090155818 *Jul 18, 2008Jun 18, 2009Monogram Biosciences, Inc.Measuring Receptor HomodimerizationUS20090173631 *Aug 7, 2006Jul 9, 2009Travis BooneSingle Cell Analysis of Membrane MoleculesUS20110272273 *May 9, 2011Nov 10, 2011Molycorp Minerals, LlcLanthanide-mediated photochemical water splitting process for hydrogen and oxygen generationUSRE44437Jan 18, 2012Aug 13, 2013Monogram Biosciences, Inc.Methods for detecting receptor complexes comprising PI3KWO2003027007A1 *Aug 23, 2002Apr 3, 2003Lumigen, Inc.Uses of improved polymer-supported photosensitizers in the generation of singlet oxygen* Cited by examinerClassifications U.S. Classification540/474, 204/157.15, 604/222, 540/472, 534/14, 204/157.5, 534/15, 534/10International ClassificationC07D487/18, A61K41/00, C07D487/22Cooperative ClassificationA61K41/0076, C07D487/18, A61K41/0038, C07D487/22European ClassificationA61K41/00P, A61K41/00W10, C07D487/22, C07D487/18Legal EventsDateCodeEventDescriptionNov 21, 2001FPAYFee paymentYear of fee payment: 4Dec 9, 2005SULPSurcharge for late paymentYear of fee payment: 7Dec 9, 2005FPAYFee paymentYear of fee payment: 8Dec 14, 2005REMIMaintenance fee reminder mailedDec 28, 2009REMIMaintenance fee reminder mailedMay 26, 2010LAPSLapse for failure to pay maintenance feesJul 13, 2010FPExpired due to failure to pay maintenance feeEffective date: 20100526Jul 18, 2015ASAssignmentOwner name: PHARMACYCLICS, INC., CALIFORNIAFree format text: MERGER;ASSIGNOR:OXFORD AMHERST CORPORATION;REEL/FRAME:036130/0254Effective date: 20150526Owner name: PHARMACYCLICS LLC, CALIFORNIAFree format text: MERGER AND CHANGE OF NAME;ASSIGNORS:PHARMACYCLICS, INC.;OXFORD AMHERST LLC;REEL/FRAME:036130/0285Effective date: 20150526May 18, 2016ASAssignmentOwner name: PHARMACYCLICS LLC, CALIFORNIAFree format text: CORRECTIVE ASSIGNMENT TO CORRECT THE CONVEYING PARTY DATA PREVIOUSLY RECORDED ON REEL 036130 FRAME 0285. ASSIGNOR(S) HEREBY CONFIRMS THE MERGER AND CHANGE OF NAME;ASSIGNORS:PHARMACYCLICS, INC.;OXFORD AMHERST LLC;REEL/FRAME:038742/0673Effective date: 20150526Owner name: PHARMACYCLICS, INC., CALIFORNIAFree format text: CORRECTIVE ASSIGNMENT TO CORRECT THE CONVEYING PARTY DATA PREVIOUSLY RECORDED ON REEL 036130 FRAME 0254. ASSIGNOR(S) HEREBY CONFIRMS THE MERGER;ASSIGNORS:OXFORD AMHERST CORPORATION;PHARMACYCLICS, INC.;REEL/FRAME:038742/0624Effective date: 20150526RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services