# US 5,703,116 A · Telomerase Inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,703,116 A - Document ID: US5703116A - Status: Granted - Kind: A - Application number: 08/424,813 - Filed: 1995-04-18 - Granted: 1997-12-30 - Earliest claimed: 1995-04-18 - Assignees: Geron Corporation - Inventors: Federico C. A. Gaeta; Adam Antoni Galan; Elaine C. Stracker - Web page: https://patentgrep.com/patent/US5703116A ## CPC - C07D 495/04: Ortho-condensed systems - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract Methods and compositions for treating cancer and other diseases in which inhibition of telomerase activity can ameliorate disease symptoms or prevent or treat the disease relate to compounds that are derivatives of benzo›b!thiophenes. Such compounds are characterized by the following structure: ##STR1## In this compound, R.sub.1 is selected from the group consisting of --OR.sub.7, --NR.sub.8 R.sub.9, --NHNR.sub.10 R.sub.11, --NHNHC(X.sub.2)NHR.sub.12, --NHSO.sub.2 NR.sub.8 R.sub.9, --NHNHC(O)R.sub.12, --NHNHSO.sub.2 R.sub.12 and --NHC(O)NR.sub.8 R.sub.9. R.sub.7 -R.sub.12 are selected independently from the group consisting of hydrogen, alkyl, aryl, aralkyl, heteroaryl and heteroaralkyl. X.sub.1 and X.sub.2 are selected independently from the group consisting of oxygen and sulfur. R.sub.2 is hydrogen or halogen. R.sub.3 -R.sub.6 are selected independently from the group consisting of hydrogen, halogen, hydroxyl, --NR.sub.8 R.sub.9, nitro, cyano, alkoxyl, lower alkyl, aryl and aryloxyl. ## Claims ### Claim 1 A telomerase inhibiting compound having the structure: ##STR28## wherein R.sub.2 is hydrogen or halogen; R.sub.3 -R.sub.6 are selected independently from the group consisting of hydrogen, halogen, hydroxyl, --NR.sub.8 R.sub.9, nitro, cyano, alkoxyl, lower alkyl, aryl and aryloxyl, where R.sub.8 and R.sub.9 are selected independently from the group consisting of hydrogen, alkyl, aryl, aralkyl, heteroaryl, and heteroaralkyl; R.sub.12 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, heteroaryl, and heteroaralkyl; and X.sub.1 and X.sub.2 are selected independently from the group consisting of oxygen and sulfur; provided that when X.sub.1 is oxygen, X.sub.2 is sulfur, and R.sub.2 is chloro: R.sub.12 is not methyl, phenyl, 4-methoxyphenyl or 4-chlorophenyl when R.sub.3, R.sub.4, and R.sub.6, are hydrogen and R.sub.5 is methoxy; and R.sub.12 is not methyl, phenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-methylphenyl, 2,5-dichlorophenyl, phenylmethyl, or unsubstituted allyl when R.sub.3 -R.sub.6 are hydrogen. ### Claim 2 (depends on 1) The compound of claim 1 wherein R.sub.12 is aryl. ### Claim 3 (depends on 2) The compound of claim 2 having the structure ##STR29## wherein R.sub.13 -R.sub.17 are selected independently from the group consisting of hydrogen, halogen, hydroxyl, alkylthio, arylthio, nitro, cyano, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, alkoxyl, alkyl, aryl, aralkoxyl, aralkylthio, arylcarbonyloxy, and aryloxyl. ### Claim 4 (depends on 3) The compound of claim 3 wherein R.sub.3 -R.sub.6 are selected independently from the group consisting of hydrogen, chloro, bromo, fluoro, trifluoromethyl, dimethylamino, nitro, methyl, methoxy, phenyl, and aryloxyl. ### Claim 5 (depends on 4) The compound of claim 4, wherein X.sub.1 is oxygen, X.sub.2 is sulfur, and R.sub.2 is chloro. ### Claim 6 The compound of 5, wherein R.sub.13 -R.sub.17 are selected independently from the group consisting of hydrogen, chloro, bromo, fluoro, methyl, trifluoromethyl, dimethylamino, 4-methylphenylthio, 4-nitrophenylthio and methylthio. ### Claim 7 (depends on 6) The compound of claim 6, wherein R.sub.3 -R.sub.6 are selected independently from the group consisting of hydrogen, chloro, bromo, fluoro, and trifluoromethyl. ### Claim 8 (depends on 7) The compound of claim 7, wherein R.sub.13 -R.sub.17 are selected independently from the group consisting of hydrogen, chloro, bromo, fluoro, and trifluoromethyl. ### Claim 9 (depends on 8) The compound of claim 8, wherein R.sub.3 -R.sub.6 are selected independently from the group consisting of hydrogen and chloro. ### Claim 10 (depends on 9) The compound of claim 9, wherein R.sub.13 -R.sub.17 are selected independently from the group consisting of hydrogen and chloro. ### Claim 11 (depends on 4) The compound of claim 4, wherein X.sub.1 is oxygen, X.sub.2 is sulfur, and R.sub.2 is hydrogen. ### Claim 12 The compound of 11, wherein R.sub.13 -R.sub.17 are selected independently from the group consisting of hydrogen, chloro, bromo, fluoro, methyl, trifluoromethyl, dimethylamino, 4-methylphenylthio, 4-nitrophenylthio and methylthio. ### Claim 13 (depends on 12) The compound of claim 12, wherein R.sub.3 -R.sub.6 are selected independently from the group consisting of hydrogen, chloro, bromo, fluoro, and trifluoromethyl. ### Claim 14 (depends on 13) The compound of claim 13, wherein R.sub.13 -R.sub.17 are selected independently from the group consisting of hydrogen, chloro, bromo, fluoro, and trifluoromethyl. ### Claim 15 (depends on 14) The compound of claim 14, wherein R.sub.3 -R.sub.6 are selected independently from the group consisting of hydrogen and chloro. ### Claim 16 (depends on 15) The compound of claim 15, wherein R.sub.13 -R.sub.17 are selected independently from the group consisting of hydrogen and chloro. ### Claim 17 (depends on 10) The compound of claim 10 which is: ##STR30## ### Claim 18 (depends on 10) The compound of claim 10 which is: ##STR31## ### Claim 19 (depends on 10) The compound of claim 10 which is: ##STR32## ### Claim 20 (depends on 10) The compound of claim 10 which is: ##STR33## ### Claim 21 A composition for treating cancer, comprising a therapeutically effective amount of a compound having the structure shown below in a pharmaceutically acceptable carrier: ##STR34## wherein R.sub.2 is hydrogen or halogen; R.sub.3 -R.sub.6 are selected independently from the group consisting of hydrogen, halogen, hydroxyl, --NR.sub.8 R.sub.9, nitro, cyano, alkoxyl, lower alkyl, aryl and aryloxyl, where R.sub.8 and R.sub.9 are selected independently from the group consisting of hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroalkyl, alkylsulfonyl, arylsulfonyl, arylcarbonyl, and alkylcarbonyl; R.sub.12 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, heteroaryl, and heteroaralkyl; and X.sub.1 and X.sub.2 are selected independently from the group consisting of oxygen and sulfur. ### Claim 22 (depends on 21) A method of treating cancer in a mammal, comprising administering to such mammal a therapeutically effective amount of a compound having the structure shown in claim 21 to inhibit telomerase activity in cancer cells is said mammal such that the telomeres of said cancer cells are reduced in length over successive cell divisions.