# US 9,040,261 B2 · Compounds as L-cystine crystallization inhibitors and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,261 B2 - Document ID: US9040261B2 - Status: Granted - Kind: B2 - Application number: 13/902,114 - Filed: 2013-05-24 - Published: 2013-12-19 - Granted: 2015-05-26 - Earliest claimed: 2009-11-23 - Assignees: New York University - Applicants: Michael D. Ward; Jeffrey Rimer - Inventors: Michael D. Ward; Jeffrey Rimer - Web page: https://patentgrep.com/patent/US9040261B2 ## CPC - A61K 31/223: of alpha-aminoacids - A61K 31/10: Sulfides; Sulfoxides; Sulfones - A61K 31/105: Persulfides (thiuram disulfides A61K31/145; thiosulfonic acids A61K31/185) - A61K 31/145: having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) (isothiourea A61K31/155) - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 13/12: of the kidneys - 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 ## Abstract A method of preventing or inhibiting L-cystine crystallization using the compounds of formula I is disclosed. wherein A, L, R1a, R1b, and m are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of conditions that are causally related to L-cystine crystallization, such as comprising (but not limited to) kidney stones. ## Claims ### Claim 1 A method for inhibiting, or slowing the growth of L-cystine crystallization comprising administering an effective amount of a compound of formula I or a pharmaceutically acceptable salt, solvate, cocrystal, or prodrug thereof, and stereoisomers, tautomers and isotopic variants thereof; and wherein A is L is —O—C1-C6 alkylene-O—, —O-aryl-O—, or a group —O—(CH2—CH2—O—)t—; the subscript t is 1-10; the subscript m is 0-10; each R1a and R1b is independently selected from H, alkyl, alkenyl, alkynyl, aryl, aralkyl, and cycloalkyl; each R2a, R2b, R3a, R3b, R3c, R3d, R4a, and R4b is independently selected from H, and alkyl; and each subscript n1 and n2 is independently 0, 1, or 2; provided that when each n1 and n2 is 0, then at least one of R1a and R1b is other than H. ### Claim 2 (depends on 1) A method according to claim 1 wherein the compound is of formula I; and the subscript m is 1-5. ### Claim 3 (depends on 1) A method according to claim 1 wherein the compound is of formula I; and L is —OCH2—O—. ### Claim 4 (depends on 1) A method according to claim 1 wherein the compound is of formula I; and L is ### Claim 5 (depends on 1) A method according to claim 1 wherein the compound is of formula I; L is —O—CH2—CH2—O—; and the subscript t is 1. ### Claim 6 (depends on 1) A method according to claim 1 wherein the compound is of formula I; and the subscript m is 0. ### Claim 7 (depends on 1) A method according to claim 1 wherein the compound is of formula I; the subscript m is 0; and the compound is according to formula II: and wherein A, R1a and R1b are as in claim 1. ### Claim 8 A method for inhibiting, or slowing the growth of L-cystine crystallization comprising administering an effective amount of a compound of formula III: or a pharmaceutically acceptable salt, solvate, cocrystal, or prodrug thereof, and stereoisomers, tautomers and isotopic variants thereof; and wherein each R1a and R1b is independently selected from H, alkyl, alkenyl, alkynyl, and cycloalkyl; each R2a, R2b, R3a, R3b, R3c, R3d, R4a, and R4b is independently selected from H, and alkyl; and each n1 and n2 is independently 0, 1, or 2; provided that when each n1 and n2 is 0, then at least one of R1a and R1b is other than H. ### Claim 9 (depends on 1) The method of claim 1, wherein each of R2a and R2b is H. ### Claim 10 (depends on 1) The method of claim 1, wherein one of R2a and R2b is H; and the other is alkyl. ### Claim 11 (depends on 1) The method of claim 1, wherein each of R2a and R2b is alkyl. ### Claim 12 (depends on 1) The method of claim 1, wherein each of R3a and R3b is H. ### Claim 13 (depends on 1) The method of claim 1, wherein one of R3a and R3b is H; and the other is alkyl. ### Claim 14 (depends on 1) The method of claim 1, wherein each of R3a and R3b is alkyl. ### Claim 15 (depends on 1) The method of claim 1, wherein each of R3c and R3d is H. ### Claim 16 (depends on 1) The method of claim 1, wherein one of R3c and R3d is H; and the other is alkyl. ### Claim 17 (depends on 1) The method of claim 1, wherein each of R3c and R3d is alkyl. ### Claim 18 (depends on 1) The method of claim 1, wherein each of R4a and R4b is H. ### Claim 19 (depends on 1) The method of claim 1, wherein one of R4a and R4b is H; and the other is alkyl. ### Claim 20 (depends on 1) The method of claim 1, wherein each of R4a and R4b is alkyl. ### Claim 21 (depends on 1) The method of claim 1, wherein the compound is according to formula IVa, IVb, or IVc: and wherein R1a and R1b are as in claim 1. ### Claim 22 (depends on 1) The method of claim 1, wherein the compound is according to formula Va, Vb, Vc, or Vd: and wherein R1a and R1b are as in claim 1. ### Claim 23 (depends on 1) The method of claim 1, wherein one of R1a and R1b is H; and the other is alkyl. ### Claim 24 (depends on 1) The method of claim 1, wherein one of R1a and R1b is H; and the other is alkenyl. ### Claim 25 (depends on 1) The method of claim 1, wherein one of R1a and R1b is H; and the other is alkynyl. ### Claim 26 (depends on 1) The method of claim 1, wherein one of R1a and R1b is H; and the other is cycloalkyl. ### Claim 27 (depends on 1) The method of claim 1, wherein each of R1a and R1b is alkyl. ### Claim 28 (depends on 1) The method of claim 1, wherein each of R1a and R1b is alkenyl. ### Claim 29 (depends on 1) The method of claim 1, wherein each of R1a and R1b is alkynyl. ### Claim 30 (depends on 1) The method of claim 1, wherein each of R1a and R1b is cycloalkyl. ### Claim 31 (depends on 1) The method of claim 1, wherein the compound is according to formula VIa, VIb, VIc, VId, VIe, VIf, or VIg: or a pharmaceutically acceptable salt, solvate, cocrystal, or prodrug thereof, and stereoisomers, tautomers and isotopic variants thereof. ### Claim 32 (depends on 1) The method of claim 1, wherein the compound is according to formula IXa, IXb, IXc, IXd, IXe, IXf, or Ixg: or a pharmaceutically acceptable salt, solvate, cocrystal, or prodrug thereof, and stereoisomers, tautomers and isotopic variants thereof. ### Claim 33 (depends on 1) The method of claim 1, wherein the compound is according to formula VIIId, VIIIg, IXd, or IXg: or a pharmaceutically acceptable salt, solvate, cocrystal, or prodrug thereof, and stereoisomers, tautomers and isotopic variants thereof. ### Claim 34 (depends on 1) A method for preventing, inhibiting or slowing growth of L-cystine kidney-stone formation in a subject in need thereof, the method comprising administering a pharmaceutically effective amount of a compound as defined in claim 1 to the subject. ### Claim 35 (depends on 1) A method of treating a subject in need thereof, having chronic kidney disease, comprising administering a pharmaceutically effective amount of a compound as defined in claim 1. ### Claim 36 (depends on 35) The method according to claim 35, wherein the subject is human. ### Claim 37 (depends on 1) A method for reducing a L-cystine crystal concentration in a human or animal in need thereof, comprising administering to a human or animal a pharmaceutically effective amount of a compound as defined in claim 1. ### Claim 38 (depends on 1) A method for treating a L-cystine crystal related condition in a human or animal in need thereof, comprising administering to a human or animal a pharmaceutically effective amount of a compound as defined in claim 1. ### Claim 39 (depends on 1) A combination method to treat L-cystine crystal related condition in a subject in need thereof, consisting of a compound as defined in claim 1, and another treatment for said condition. ### Claim 40 (depends on 39) The combination according to claim 39, wherein the L-cystine related condition is cystinuria. ### Claim 41 (depends on 39) The combination according to claim 39, wherein the L-cystine related condition is kidney stone disease. ### Claim 42 (depends on 39) The combination of claim 39, wherein said another treatment includes alkalinizing sodium and/or potassium salts.