# US 7,608,613 B2 · Analogs of benzoquinone-containing ansamycins and methods of use thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,608,613 B2 - Document ID: US7608613B2 - Status: Granted - Kind: B2 - Application number: 12/199,211 - Filed: 2008-08-27 - Published: 2009-03-05 - Granted: 2009-10-27 - Earliest claimed: 2003-12-23 - Assignees: Infinity Pharmaceuticals, Inc. - Inventors: Julian Adams; Yun Gao; Asimina T. Georges Evangelinos; Louis Grenier; Roger H. Pak; James R. Porter; James L. Wright - Web page: https://patentgrep.com/patent/US7608613B2 ## CPC - A61K 31/395: having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - A61P 35/04: specific for metastasis - C07D 211/60: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals - C07D 225/06: condensed with one six-membered ring - C07F 9/6561: containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22) ## Abstract The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog. ## Claims ### Claim 1 A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the formula: ### Claim 2 A compound of the formula: ### Claim 3 (depends on 1) The composition of claim 1, wherein the pharmaceutically acceptable excipient comprises an antioxidant. ### Claim 4 (depends on 3) The composition of claim 3, wherein the antioxidant is selected from the group consisting of ascorbic acid, cysteine hydrochloride, sodium bisulfite, sodium metabisulfite, sodium sulfite, thioglycerol, sodium mercaptoacetate, sodium formaldehyde sulfoxylate, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, lecithin, propyl gallate, and alpha-tocopherol. ### Claim 5 (depends on 3) The composition of claim 3, wherein the antioxidant comprises ascorbic acid. ### Claim 6 (depends on 5) The composition of claim 5, wherein the antioxidant comprises L-ascorbic acid. ### Claim 7 (depends on 1) The composition of claim 1, wherein the pharmaceutically acceptable excipient comprises a metal chelator. ### Claim 8 (depends on 7) The composition of claim 7, wherein the metal chelator is selected from the group consisting of ethylenediamine tetraacetic acid (EDTA), diethylenetriamine pentaacetlc acid (DTPA), ethylene glycol tetraacetic acid (EGTA), nitriloacetic acid (NTA), sorbitol, tartaric acid, N-hydroxy iminodiacetate, hydroxyethyl-ethylene diamine-tetraacetic acid, 1-propanediamine tetra acetic acid, 3-propanediamine tetra acetic acid, 1-diamino-2-hydroxy propane tetra-acetic acid, 3-diamino-2-hydroxy propane tetra-acetic acid, sodium gluconate, hydroxy ethane diphosphonic acid, phosphoric acid and salts thereof. ### Claim 9 (depends on 7) The composition of claim 7, wherein the metal chelator comprises ethylenediamine tetraacetic acid (EDTA). ### Claim 10 (depends on 7) The composition of claim 7, wherein the metal chelator comprises ethylenediamine tetraacetic acid (EDTA) disodium calcium salt dihydrate. ### Claim 11 (depends on 1) The composition of claim 1, wherein the pharmaceutically acceptable excipient comprises a buffering agent. ### Claim 12 (depends on 11) The composition of claim 11, wherein the buffering agent is selected from the group consisting of citrate, ascorbate, phosphate, bicarbonate, carbonate, fumarate, acetate, tartarate, malate, succinate, lactate, maleate, and glycine. ### Claim 13 (depends on 11) The composition of claim 11, wherein the buffering agent comprises citrate. ### Claim 14 (depends on 11) The composition of claim 11, wherein the buffering agent comprises citric acid monohydrate. ### Claim 15 (depends on 1) The composition of claim 1, wherein the pharmaceutically acceptable excipient comprises an antioxidant, and the composition further comprises a metal chelator. ### Claim 16 (depends on 1) The composition of claim 1, wherein the pharmaceutically acceptable excipient comprises an antioxidant, and the composition further comprises a buffering agent. ### Claim 17 (depends on 1) The composition of claim 1, wherein the pharmaceutically acceptable excipient comprises a metal chelator, and the composition further comprises a buffering agent. ### Claim 18 A pharmaceutical composition comprising an antioxidant, a metal chelator, a buffering agent, and a compound of the formula: ### Claim 19 (depends on 18) The composition of claim 18, wherein the antioxidant comprises ascorbic acid. ### Claim 20 (depends on 19) The composition of claim 19, wherein the antioxidant comprises L-ascorbic acid. ### Claim 21 (depends on 18) The composition of claim 18, wherein the metal chelator comprises ethylenediamine tetraacetic acid (EDTA). ### Claim 22 (depends on 18) The composition of claim 18, wherein the metal chelator comprises ethylenediamine tetraacetic acid (EDTA) disodium calcium dihydrate. ### Claim 23 (depends on 18) The composition of claim 18, wherein the buffering agent comprises citrate. ### Claim 24 (depends on 18) The composition of claim 18, wherein the buffering agent comprises citric acid monohydrate. ### Claim 25 A pharmaceutical composition comprising L-ascorbic acid, ethylenediamine tetraacetic acid (EDTA) disodium calcium dihydrate, citric acid monohydrate, and a compound of the formula: