ZA200610783B - Substituted heteroaryl-and phenylsulfamoyl compounds - Google Patents
Substituted heteroaryl-and phenylsulfamoyl compounds Download PDFInfo
- Publication number
- ZA200610783B ZA200610783B ZA200610783A ZA200610783A ZA200610783B ZA 200610783 B ZA200610783 B ZA 200610783B ZA 200610783 A ZA200610783 A ZA 200610783A ZA 200610783 A ZA200610783 A ZA 200610783A ZA 200610783 B ZA200610783 B ZA 200610783B
- Authority
- ZA
- South Africa
- Prior art keywords
- phenyl
- compound
- inhibitor
- benzoic acid
- prepared
- Prior art date
Links
- -1 phenylsulfamoyl compounds Chemical class 0.000 title claims description 133
- 150000001875 compounds Chemical class 0.000 claims description 343
- 238000000034 method Methods 0.000 claims description 102
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 91
- 239000003112 inhibitor Substances 0.000 claims description 84
- 125000005843 halogen group Chemical group 0.000 claims description 66
- 150000003839 salts Chemical class 0.000 claims description 58
- 239000000203 mixture Substances 0.000 claims description 57
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 52
- 229910052799 carbon Inorganic materials 0.000 claims description 43
- 238000011282 treatment Methods 0.000 claims description 43
- 239000005711 Benzoic acid Substances 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 33
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- 125000000335 thiazolyl group Chemical group 0.000 claims description 28
- 102000004877 Insulin Human genes 0.000 claims description 26
- 108090001061 Insulin Proteins 0.000 claims description 26
- 229940125396 insulin Drugs 0.000 claims description 26
- 125000002971 oxazolyl group Chemical group 0.000 claims description 25
- 239000003981 vehicle Substances 0.000 claims description 24
- 201000001320 Atherosclerosis Diseases 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 206010012601 diabetes mellitus Diseases 0.000 claims description 20
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 18
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims description 15
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 235000001968 nicotinic acid Nutrition 0.000 claims description 14
- 239000011664 nicotinic acid Substances 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 claims description 13
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 claims description 13
- 150000002431 hydrogen Chemical group 0.000 claims description 13
- 230000028327 secretion Effects 0.000 claims description 13
- 108010000775 Hydroxymethylglutaryl-CoA synthase Proteins 0.000 claims description 12
- 229960003512 nicotinic acid Drugs 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 102100028888 Hydroxymethylglutaryl-CoA synthase, cytoplasmic Human genes 0.000 claims description 11
- 102000005782 Squalene Monooxygenase Human genes 0.000 claims description 11
- 229940123185 Squalene epoxidase inhibitor Drugs 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 229910052717 sulfur Chemical group 0.000 claims description 11
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims description 9
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 9
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 9
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 9
- 208000008589 Obesity Diseases 0.000 claims description 9
- 229940119502 Squalene cyclase inhibitor Drugs 0.000 claims description 9
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 9
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 9
- 229960004844 lovastatin Drugs 0.000 claims description 9
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 229940122498 Gene expression inhibitor Drugs 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 8
- 208000001132 Osteoporosis Diseases 0.000 claims description 8
- 238000010521 absorption reaction Methods 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 8
- 239000004059 squalene synthase inhibitor Substances 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 230000001225 therapeutic effect Effects 0.000 claims description 8
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 239000003963 antioxidant agent Substances 0.000 claims description 7
- 230000003078 antioxidant effect Effects 0.000 claims description 7
- 229920000080 bile acid sequestrant Polymers 0.000 claims description 7
- 229910052791 calcium Inorganic materials 0.000 claims description 7
- 125000002837 carbocyclic group Chemical group 0.000 claims description 7
- 208000029078 coronary artery disease Diseases 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 229940125753 fibrate Drugs 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 239000011593 sulfur Chemical group 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 claims description 6
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 6
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 6
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 6
- 229940123239 Cholesterol synthesis inhibitor Drugs 0.000 claims description 6
- 208000002249 Diabetes Complications Diseases 0.000 claims description 6
- 206010012655 Diabetic complications Diseases 0.000 claims description 6
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 6
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 6
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 6
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 6
- 229940123495 Squalene synthetase inhibitor Drugs 0.000 claims description 6
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 claims description 6
- YVPOVOVZCOOSBQ-AXHZAXLDSA-N [(1s,3r,7s,8s,8ar)-8-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2s)-2-methylbutanoate;pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1.C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 YVPOVOVZCOOSBQ-AXHZAXLDSA-N 0.000 claims description 6
- 229960005370 atorvastatin Drugs 0.000 claims description 6
- 229960005110 cerivastatin Drugs 0.000 claims description 6
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 claims description 6
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 claims description 6
- 229960003765 fluvastatin Drugs 0.000 claims description 6
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 6
- 239000003456 ion exchange resin Substances 0.000 claims description 6
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- 229960002965 pravastatin Drugs 0.000 claims description 6
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 229960000672 rosuvastatin Drugs 0.000 claims description 6
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 6
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- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 claims description 6
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 5
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- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
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- GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 claims description 3
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CN101828111B (zh) * | 2007-08-21 | 2014-07-23 | 塞诺米克斯公司 | 人t2r苦味受体及其用途 |
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WO2009086096A2 (en) * | 2007-12-21 | 2009-07-09 | University Of Cincinnati | Therapeutic use of carboxyl ester lipase inhibitors |
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EP2473515A4 (en) | 2009-09-04 | 2013-11-27 | Univ Toledo | METHODS OF MAKING OPTICALLY PURE BETA-LACTONES FROM ALDEHYDES AND COMPOSITIONS OBTAINED THEREFROM |
US9056835B2 (en) | 2012-08-27 | 2015-06-16 | The University Of Tennessee Research Foundation | LPA2 receptor-specific benzoic acid derivatives |
US9682085B2 (en) | 2013-02-22 | 2017-06-20 | Shifa Biomedical Corporation | Anti-proprotein convertase subtilisin kexin type 9 (anti-PCSK9) compounds and methods of using the same in the treatment and/or prevention of cardiovascular diseases |
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AU2014237312B2 (en) * | 2013-03-15 | 2019-03-28 | Shifa Biomedical Corporation | Anti-proprotein convertase subtilisin kexin type 9 (anti-PCSK9) compounds and methods of using the same in the treatment and/or prevention of cardiovascular diseases |
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-
2005
- 2005-02-24 US US11/065,774 patent/US20050288340A1/en not_active Abandoned
- 2005-06-17 WO PCT/IB2005/002007 patent/WO2006003495A1/en active Application Filing
- 2005-06-17 JP JP2007519911A patent/JP2008505170A/ja active Pending
- 2005-06-17 KR KR1020077001570A patent/KR20070030287A/ko not_active Application Discontinuation
- 2005-06-17 EP EP05755422A patent/EP1765796A1/en not_active Withdrawn
- 2005-06-17 CA CA002573193A patent/CA2573193A1/en not_active Abandoned
- 2005-06-17 AP AP2007003889A patent/AP2007003889A0/xx unknown
- 2005-06-17 EA EA200602273A patent/EA200602273A1/ru unknown
- 2005-06-17 AU AU2005258906A patent/AU2005258906A1/en not_active Abandoned
- 2005-06-17 CN CNA2005800252961A patent/CN101287718A/zh active Pending
- 2005-06-17 MX MX2007000289A patent/MX2007000289A/es unknown
- 2005-06-17 BR BRPI0512624-0A patent/BRPI0512624A/pt not_active IP Right Cessation
- 2005-06-24 TW TW094121240A patent/TW200611690A/zh unknown
- 2005-06-24 PE PE2005000739A patent/PE20060415A1/es not_active Application Discontinuation
- 2005-06-27 UY UY28988A patent/UY28988A1/es not_active Application Discontinuation
- 2005-06-27 GT GT200500173A patent/GT200500173A/es unknown
- 2005-06-27 AR ARP050102637A patent/AR054665A1/es unknown
- 2005-06-28 NL NL1029360A patent/NL1029360C2/nl not_active IP Right Cessation
- 2005-06-29 SV SV2005002158A patent/SV2006002158A/es not_active Application Discontinuation
- 2005-06-29 PA PA20058638001A patent/PA8638001A1/es unknown
-
2006
- 2006-06-16 US US11/424,623 patent/US20060229363A1/en not_active Abandoned
- 2006-12-20 ZA ZA200610783A patent/ZA200610783B/en unknown
- 2006-12-28 TN TNP2006000447A patent/TNSN06447A1/fr unknown
- 2006-12-28 EC EC2006007125A patent/ECSP067125A/es unknown
- 2006-12-28 IL IL180426A patent/IL180426A0/en unknown
- 2006-12-29 MA MA29590A patent/MA28703B1/fr unknown
-
2007
- 2007-01-26 CR CR8881A patent/CR8881A/es not_active Application Discontinuation
- 2007-01-26 NO NO20070511A patent/NO20070511L/no not_active Application Discontinuation
- 2007-12-07 US US11/952,608 patent/US20080090829A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
US20080090829A1 (en) | 2008-04-17 |
AR054665A1 (es) | 2007-07-11 |
CA2573193A1 (en) | 2006-01-12 |
PE20060415A1 (es) | 2006-06-02 |
MA28703B1 (fr) | 2007-06-01 |
CN101287718A (zh) | 2008-10-15 |
US20060229363A1 (en) | 2006-10-12 |
EP1765796A1 (en) | 2007-03-28 |
TW200611690A (en) | 2006-04-16 |
WO2006003495A1 (en) | 2006-01-12 |
KR20070030287A (ko) | 2007-03-15 |
AU2005258906A1 (en) | 2006-01-12 |
NO20070511L (no) | 2007-03-22 |
TNSN06447A1 (fr) | 2008-02-22 |
EA200602273A1 (ru) | 2007-06-29 |
UY28988A1 (es) | 2006-01-31 |
NL1029360C2 (nl) | 2006-07-12 |
US20050288340A1 (en) | 2005-12-29 |
AP2007003889A0 (en) | 2007-02-28 |
IL180426A0 (en) | 2007-06-03 |
PA8638001A1 (es) | 2006-06-02 |
GT200500173A (es) | 2006-03-02 |
JP2008505170A (ja) | 2008-02-21 |
NL1029360A1 (nl) | 2005-12-30 |
ECSP067125A (es) | 2007-03-29 |
SV2006002158A (es) | 2006-05-09 |
MX2007000289A (es) | 2007-04-10 |
BRPI0512624A (pt) | 2008-03-25 |
CR8881A (es) | 2007-03-19 |
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