# US 9,434,759 B1 · Cationic steroidal antimicrobial compounds and methods of manufacturing such compounds > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,434,759 B1 - Document ID: US9434759B1 - Status: Granted - Kind: B1 - Application number: 14/866,213 - Filed: 2015-09-25 - Granted: 2016-09-06 - Earliest claimed: 2015-05-18 - Assignees: Brigham Young University - Applicants: Paul B. Savage - Inventors: Paul B. Savage - Web page: https://patentgrep.com/patent/US9434759B1 ## CPC - C07J 41/0088: {containing unsubstituted amino radicals} - A61K 31/575: substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol - A61P 31/04: Antibacterial agents - C07C 225/00: Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones - C07J 41/0061: {one of the carbon atoms being part of an amide group} - C07C 211/00: Compounds containing amino groups bound to a carbon skeleton - C07J 41/0055: {the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives} - C07J: STEROIDS (seco-steroids C07C) - 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 - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS ## Abstract Cationic steroidal antimicrobial (CSA) compounds having amide functionality and methods of manufacturing such CSA compounds. The CSA compound can be a compound of Formula (I), Formula (II), Formula (III), or a salt thereof: where R18 has the following structure: —R20—(C═O)—N—R21R22 R20 is omitted or substituted or unsubstituted alkyl, alkenyl, alkynyl, or aryl, and R21 and R22 are independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted aryl, provided that at least one of R21 and R22 is not hydrogen. ## Claims ### Claim 1 A cationic steroidal antimicrobial (CSA) compound of Formula (III), or salt thereof: wherein, R3, R7, and R12 are independently selected from the group consisting of aminoalkyloxy, aminoalkylcarboxy, alkylaminoalkyl, alkoxycarbonylalkyl, alkylcarbonylalkyl, di(alkyl)aminoalkyl, alkylcarboxyalkyl, aminoalkylaminocarbonyl, aminoalkylcarboxamido, guanidinoalkyloxy, guanidinoalkylcarboxy, quaternary ammonium alkylcarboxy, and hydroxyalkyl, R18 has the following structure: —R20—(C═O)—N—R21R22 R20 is a substituted or unsubstituted C1-C10 alkyl, a substituted or unsubstituted C1-C10 alkenyl, a substituted or unsubstituted C1-C10 alkynyl, or a substituted or unsubstituted C6 or C10 aryl, and R21 and R22 are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-C24 alkyl, substituted or unsubstituted C2-C24 alkenyl, substituted or unsubstituted C2-C24 alkynyl, substituted or unsubstituted C6 or C10 aryl, substituted or unsubstituted 5 to 10 membered heteroaryl, substituted or unsubstituted 5 to 10 membered heterocyclyl, substituted or unsubstituted C7-C13 aralkyl, substituted or unsubstituted (5 to 10 membered heteroaryl)-C1-C6 alkyl, substituted or unsubstituted C3-C10 carbocyclyl, substituted or unsubstituted C4-C10 (carbocyclyl)alkyl, substituted or unsubstituted (5 to 10 membered heterocyclyl)-C1-C6 alkyl, substituted or unsubstituted substituted amido, and amine protecting group, provided that at least one of R21 and R22 is not hydrogen. ### Claim 2 (depends on 1) The CSA compound of claim 1, wherein R3, R7, and R12 are independently selected from the group consisting of unsubstituted (C1-C6) hydroxyalkyl, unsubstituted (C1-C16) alkylamino-(C1-C5)alkyl, unsubstituted (C1-C5) aminoalkyloxy, unsubstituted (C1-C5) aminoalkylcarboxy, unsubstituted (C1-C5) aminoalkylaminocarbonyl, unsubstituted (C1-C5) aminoalkylcarboxamido, unsubstituted di(C1-C5 alkyl)amino-(C1-C5) alkyl, unsubstituted (C1-C5) guanidinoalkyloxy, unsubstituted (C1-C16) quaternary ammonium alkylcarboxy, and unsubstituted (C1-C16) guanidinoalkylcarboxy. ### Claim 3 (depends on 1) The CSA compound of claim 1, wherein R3, R7, and R12 are independently selected from the group consisting of aminoalkyloxy, aminoalkylcarboxy, alkoxycarbonylalkyl, aminoalkylaminocarbonyl, aminoalkylcarboxamido, guanidinoalkyloxy, guanidinoalkylcarboxy, and quaternary ammonium alkylcarboxy. ### Claim 4 (depends on 1) The CSA compound of claim 1, wherein R3, R7, and R12 are each one of aminoalkyloxy or aminoalkylcarboxy. ### Claim 5 (depends on 1) The CSA compound of claim 1, wherein R3, R7, and R12 are independently selected from the group consisting of amino-C3-alkyloxy; amino-C3-alkyl-carboxy; C8-alkylamino-C5-alkyl; C8-alkoxy-carbonyl-C4-alkyl; C8-alkyl-carbonyl-C4-alkyl; di-(C5-alkyl)amino-C5-alkyl; C13-alkylamino-C5-alkyl; C6-alkoxy-carbonyl-C4-alkyl; C6-alkyl-carboxy-C4-alkyl; and C16-alkylamino-C5-alkyl. ### Claim 6 (depends on 1) A pharmaceutical composition comprising the CSA compound of claim 1 and a pharmaceutically acceptable excipient. ### Claim 7 A cationic steroidal antimicrobial (CSA) compound selected from the group consisting of: and salts thereof. ### Claim 8 (depends on 7) The CSA compound of claim 7, wherein the CSA compound is or salt thereof. ### Claim 9 (depends on 7) The CSA compound of claim 7, wherein the CSA compound comprises a salt selected from the group consisting of: (1) salts obtained by reacting a CSA compound with an inorganic acid, a hydrohalic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and/or phosphoric acid; (2) salts obtained by reacting a CSA compound with an organic acid, an aliphatic or aromatic carboxylic or sulfonic acid, formic acid, acetic acid, propionic acid, glycolic acid, pyruvic acid, malonic acid, maleic acid, fumaric acid, trifluoroacetic acid, benzoic acid, cinnamic acid, mandelic acid, succinic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, nicotinic acid, methanesulfonic acid, ethanesulfonic acid, p-toluensulfonic acid, salicylic acid, stearic acid, muconic acid, butyric acid, phenylacetic acid, phenylbutyric acid, valproic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, and/or naphthalenesulfonic acid; (3) salts obtained by reacting a CSA compound with a base to form an ammonium salt, an alkali metal salt, a lithium, sodium or a potassium salt, an alkaline earth metal salt, a calcium, magnesium and/or aluminum salt; (4) salts of organic bases, dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, C1-C7 alkylamine, cyclohexylamine, dicyclohexylamine, triethanolamine, ethylenediamine, ethanolamine, diethanolamine, triethanolamine, and/or tromethamine, and salts with amino acids such as arginine and lysine; and (5) salts of an inorganic base, aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, and/or sodium hydroxide. ### Claim 10 (depends on 7) The CSA compound of claim 7, wherein the CSA compound comprises a salt selected from the group consisting of hydrochloride salts, mono-hydrochloride salts, di-hydrochloride salts, tri-hydrochloride salts, tetra-hydrochloride salts, sulfuric acid addition salts, sulfonic acid addition salts, disulfonic acid addition salts, 1,5-naphthalenedisulfonic acid addition salts, sulfate salts, and bisulfate salts. ### Claim 11 (depends on 1) The CSA compound of claim 1, wherein one of R21 or R22 is hydrogen and one is not hydrogen. ### Claim 12 (depends on 1) An antimicrobial composition comprising the CSA compound of claim 1 and a carrier. ### Claim 13 (depends on 6) The pharmaceutical composition of claim 6, wherein the pharmaceutically acceptable excipient comprises at least one member selected from the group consisting of carriers, solvents, stabilizers, adjuvants, diluents, and combinations thereof. ### Claim 14 (depends on 6) The pharmaceutical composition of claim 6, wherein the pharmaceutical composition is in a dosage form selected from the group consisting of tablets, capsules, solids, emulsions, suspensions, solutions, liquids, powders, syrups, creams, ointments, troches, lozenges, granules, and elixirs. ### Claim 15 (depends on 7) The CSA compound of claim 7, wherein the CSA compound is ### Claim 16 (depends on 7) A pharmaceutical composition comprising the CSA compound of claim 7 and a pharmaceutically acceptable excipient. ### Claim 17 (depends on 7) An antimicrobial composition comprising the CSA compound of claim 7 and a carrier. ### Claim 18 A cationic steroidal antimicrobial (CSA) compound of Formula (III), or salt thereof: wherein, R3, R7, and R12 are independently selected from the group consisting of aminoalkyloxy, aminoalkylcarboxy, aminoalkylaminocarbonyl, aminoalkylcarboxamido, and quaternary ammonium alkylcarboxy, R18 has the following structure: —R20—(C═O)—N—R21R22 R20 is a C4 alkyl, and R21 and R22 are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-C24 alkyl, substituted or unsubstituted C2-C24 alkenyl, substituted or unsubstituted C2-C24 alkynyl, substituted or unsubstituted C6 or C10 aryl, substituted or unsubstituted 5 to 10 membered heteroaryl, substituted or unsubstituted 5 to 10 membered heterocyclyl, substituted or unsubstituted C7-C13 aralkyl, substituted or unsubstituted (5 to 10 membered heteroaryl)-C1-C6 alkyl, substituted or unsubstituted C3-C10 carbocyclyl, substituted or unsubstituted C4-C10 (carbocyclyl)alkyl, substituted or unsubstituted (5 to 10 membered heterocyclyl)-C1-C6 alkyl, provided that at least one of R21 and R22 is not hydrogen. ### Claim 19 (depends on 18) The CSA compound of claim 18, wherein R3, R7, and R12 are each one of aminoalkyloxy or aminoalkylcarboxy. ### Claim 20 (depends on 18) The CSA compound of claim 18, wherein R3, R7, and R12 are each one of amino-C3-alkyloxy or amino-C3-alkyl-carboxy.