# US 10,118,910 B2 · Benzothiophene-based selective estrogen receptor downregulators > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,118,910 B2 - Document ID: US10118910B2 - Status: Granted - Kind: B2 - Application number: 15/374,966 - Filed: 2016-12-09 - Published: 2017-06-15 - Granted: 2018-11-06 - Earliest claimed: 2015-12-09 - Assignees: The Board of Trustees of the University of Illinois - Applicants: The Board of Trustees of the University of Illinois - Inventors: Gregory R. Thatcher; Rui Xiong; Jiong Zhao; Debra A. Tonetti - Web page: https://patentgrep.com/patent/US10118910B2 ## CPC - C07D 333/64: Oxygen atoms - A61P 19/10: for osteoporosis - A61P 35/00: Antineoplastic agents - C07D 409/06: linked by a carbon chain containing only aliphatic carbon atoms - C07D 409/12: linked by a chain containing hetero atoms as chain links - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract This invention is benzothiophene-based estrogen receptor downregulators and their compositions and uses to treat estrogen-related medical disorders. ## Claims ### Claim 1 A compound or a pharmaceutically acceptable salt thereof of the formula: wherein: m is 0, 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; XA is—O—; Ring B is phenyl, naphthyl, quinolinyl, 5- or 6-membered monocyclic heteroaryl or 7-, 8-, 9- or 10 membered bicyclic heterocyclyl; Ring C is phenyl, thiophenyl, 5- or 6-membered monocyclic heteroaryl or 7-, 8-, 9- or 10-membered bicyclic heterocyclyl; R1 is selected from hydroxyl, hydrogen, halogen, —O(C1-C6 alkyl), —OC(O)(C1-C6 alkyl), —OC(O)C6H5, —OC(O)O(C1-C6 alkyl), —OC(O)OC6H5 and —OSO2(C2-C6 alkyl); R2 is selected from —CH═CHCOOH, —NH(CO)COOH, —COOH, C2-C6alkenylene-COOH and C2-C6alkynylene-COOH; R3 is independently selected at each occurrence from hydrogen, halogen, —CN, —NO2, C1-C6alkyl and C1-C6fluoroalkyl; and R4 is independently selected at each occurrence from hydrogen, halogen, hydroxyl, C1-C6alkyl, C1-C6fluoroalkyl, —CN, —O(C1-C6 alkyl), and —O(C1-C6fluoroalkyl). ### Claim 2 (depends on 1) The compound of claim 1, wherein R1 is selected from hydroxyl and —O(C1-C6 alkyl). ### Claim 3 (depends on 2) The compound of claim 2, wherein R2 is selected from —COOH, —NH(CO)COOH and —CH═CHCOOH. ### Claim 4 (depends on 3) The compound of claim 3, wherein Ring B is phenyl, naphthyl or quinolinyl and Ring C is phenyl or thienyl. ### Claim 5 (depends on 1) The compound of claim 1, or a pharmaceutically acceptable salt thereof, of Formula: ### Claim 6 (depends on 5) The compound of claim 5, wherein R3 is independently selected at each occurrence from hydrogen, halogen, and C1-C6alkyl, wherein C1-C6alkyl is methyl. ### Claim 7 (depends on 1) The compound of claim 1, or a pharmaceutically acceptable salt thereof, of Formula: ### Claim 8 (depends on 7) The compound of claim 7, wherein R3 is independently selected at each occurrence from hydrogen, halogen, and C1-C6alkyl, wherein C1-C6alkyl is methyl. ### Claim 9 (depends on 1) The compound according to claim 1 selected from or a pharmaceutically acceptable salt thereof. ### Claim 10 (depends on 1) The compound according to claim 1 selected from or a pharmaceutically acceptable salt thereof. ### Claim 11 (depends on 1) The compound according to claim 1 selected from or a pharmaceutically acceptable salt thereof. ### Claim 12 (depends on 1) A pharmaceutical composition comprising an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient. ### Claim 13 (depends on 12) The pharmaceutical composition of claim 12 wherein the compound is of structure: ### Claim 14 (depends on 12) The pharmaceutical composition of claim 12 wherein the compound is of structure: ### Claim 15 (depends on 12) The pharmaceutical composition of claim 12 wherein the compound is of structure: ### Claim 16 (depends on 1) The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is: ### Claim 17 (depends on 1) The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is: ### Claim 18 (depends on 1) The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is: ### Claim 19 (depends on 1) The compound according to claim 1 selected from or a pharmaceutically acceptable salt thereof. ### Claim 20 (depends on 1) The compound according to claim 1 selected from or a pharmaceutically acceptable salt thereof. ### Claim 21 (depends on 5) The compound according to claim 5, wherein R3 is hydrogen. ### Claim 22 (depends on 21) The compound according to claim 21, wherein n is 1. ### Claim 23 (depends on 21) The compound according to claim 21, wherein n is 2. ### Claim 24 (depends on 21) The compound according to claim 21, wherein n is 3. ### Claim 25 (depends on 24) The compound according to claim 24, wherein at least one R4 is halogen. ### Claim 26 (depends on 24) The compound according to claim 24, wherein at least one R4 is C1-C6alkyl. ### Claim 27 (depends on 24) The compound according to claim 24, wherein at least one R4 is C1-C6fluoroalkyl. ### Claim 28 (depends on 24) The compound according to claim 24, wherein each R4 is independently selected from halogen, C1-C6alkyl, and C1-C6fluoroalkyl. ### Claim 29 (depends on 28) The compound according to claim 28, wherein one R4 is halogen. ### Claim 30 (depends on 29) The compound according to claim 29, wherein the remaining two R4s are C1-C6alkyl. ### Claim 31 (depends on 7) The compound according to claim 7, wherein R3 is hydrogen. ### Claim 32 (depends on 31) The compound according to claim 31, wherein n is 1. ### Claim 33 (depends on 31) The compound according to claim 31, wherein n is 2. ### Claim 34 (depends on 31) The compound according to claim 31, wherein n is 3. ### Claim 35 (depends on 34) The compound according to claim 34, wherein at least one R4 is halogen. ### Claim 36 (depends on 34) The compound according to claim 34, wherein at least one R4 is C1-C6alkyl. ### Claim 37 (depends on 34) The compound according to claim 34, wherein at least one R4 is C1-C6fluoroalkyl. ### Claim 38 (depends on 34) The compound according to claim 34, wherein each R4 is independently selected from halogen, C1-C6alkyl, and C1-C6fluoroalkyl. ### Claim 39 (depends on 38) The compound according to claim 38, wherein one R4 is halogen. ### Claim 40 (depends on 39) The compound according to claim 39, wherein the remaining two R4s are C1-C6alkyl. ### Claim 41 (depends on 1) The compound according to claim 1, wherein n is 1. ### Claim 42 (depends on 1) The compound according to claim 1, wherein n is 2. ### Claim 43 (depends on 1) The compound according to claim 1, wherein n is 3. ### Claim 44 (depends on 1) The compound according to claim 1, wherein at least one R4 is halogen. ### Claim 45 (depends on 1) The compound according to claim 1, wherein at least one R4 is C1-C6alkyl. ### Claim 46 (depends on 1) The compound according to claim 1, wherein at least one R4 is C1-C6fluoroalkyl. ### Claim 47 (depends on 1) The compound according to claim 1, wherein each R4 is independently selected from halogen, C1-C6alkyl, and C1-C6fluoroalkyl. ### Claim 48 (depends on 1) The compound according to claim 1, wherein one R4 is halogen. ### Claim 49 (depends on 1) The compound according to claim 1, wherein two R4s are C1-C6alkyl. ### Claim 50 (depends on 1) The compound according to claim 1, wherein m is 0. ### Claim 51 (depends on 1) The compound according to claim 1, wherein Ring B is phenyl. ### Claim 52 (depends on 1) The compound according to claim 1, wherein Ring C is phenyl. ### Claim 53 (depends on 1) The compound according to claim 1, wherein R1 is hydroxyl. ### Claim 54 (depends on 1) The compound according to claim 1, wherein R2 is —CH═CHCOOH. ### Claim 55 (depends on 1) The compound according to claim 1, wherein R2 is —CH═CHCOOH or —NH(CO)COOH. ### Claim 56 (depends on 54) The compound according to claim 54, wherein Ring B is phenyl. ### Claim 57 (depends on 56) The compound according to claim 56, wherein Ring C is phenyl. ### Claim 58 (depends on 57) The compound according to claim 57, wherein R1 is hydroxyl. ### Claim 59 (depends on 58) The compound according to claim 58, wherein m is 0. ### Claim 60 (depends on 59) The compound according to claim 59, wherein n is 1. ### Claim 61 (depends on 59) The compound according to claim 59, wherein n is 2. ### Claim 62 (depends on 59) The compound according to claim 59, wherein n is 3. ### Claim 63 (depends on 62) The compound according to claim 62, wherein at least one R4 is halogen. ### Claim 64 (depends on 62) The compound according to claim 62, wherein at least one R4 is C1-C6alkyl. ### Claim 65 (depends on 62) The compound according to claim 62, wherein at least one R4 is C1-C6fluoroalkyl. ### Claim 66 (depends on 62) The compound according to claim 62, wherein each R4 is independently selected from halogen, C1-C6alkyl, and C1-C6fluoroalkyl. ### Claim 67 (depends on 66) The compound according to claim 66, wherein one R4 is halogen. ### Claim 68 (depends on 67) The compound according to claim 67, wherein the remaining two R4s are C1-C6alkyl. ### Claim 69 (depends on 68) The compound according to claim 68, wherein C1-C6alkyl is methyl.