JP2016509591A5 - - Google Patents
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- JP2016509591A5 JP2016509591A5 JP2015550788A JP2015550788A JP2016509591A5 JP 2016509591 A5 JP2016509591 A5 JP 2016509591A5 JP 2015550788 A JP2015550788 A JP 2015550788A JP 2015550788 A JP2015550788 A JP 2015550788A JP 2016509591 A5 JP2016509591 A5 JP 2016509591A5
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- JP
- Japan
- Prior art keywords
- optionally substituted
- diastereomer
- compound
- enantiomer
- acceptable salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 125000000217 alkyl group Chemical group 0.000 claims description 168
- 150000001875 compounds Chemical class 0.000 claims description 133
- 150000003839 salts Chemical class 0.000 claims description 116
- 229910052739 hydrogen Inorganic materials 0.000 claims description 88
- 239000001257 hydrogen Substances 0.000 claims description 76
- 150000002431 hydrogen Chemical class 0.000 claims description 72
- -1 OR 9 Chemical group 0.000 claims description 63
- 125000004429 atom Chemical group 0.000 claims description 48
- 239000012453 solvate Substances 0.000 claims description 47
- 229940002612 prodrug Drugs 0.000 claims description 42
- 239000000651 prodrug Substances 0.000 claims description 42
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 40
- 150000002367 halogens Chemical class 0.000 claims description 40
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 36
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 34
- 125000001072 heteroaryl group Chemical group 0.000 claims description 26
- 125000003107 substituted aryl group Chemical group 0.000 claims description 25
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 17
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 15
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
- 125000001153 fluoro group Chemical group F* 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 10
- 125000001246 bromo group Chemical group Br* 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 238000006467 substitution reaction Methods 0.000 claims description 8
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 230000019552 anatomical structure morphogenesis Effects 0.000 claims description 4
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 208000002672 hepatitis B Diseases 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000006384 methylpyridyl group Chemical group 0.000 claims description 4
- BVOCPVIXARZNQN-UHFFFAOYSA-N nipecotamide Chemical compound NC(=O)C1CCCNC1 BVOCPVIXARZNQN-UHFFFAOYSA-N 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 230000010076 replication Effects 0.000 claims description 3
- JNHULJPDNUCLHD-UHFFFAOYSA-N 5-[[3-[(4-methoxyphenyl)carbamoyl]phenyl]sulfonylamino]pentanoic acid Chemical compound C1=CC(OC)=CC=C1NC(=O)C1=CC=CC(S(=O)(=O)NCCCCC(O)=O)=C1 JNHULJPDNUCLHD-UHFFFAOYSA-N 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 2
- 206010016654 Fibrosis Diseases 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 150000004703 alkoxides Chemical class 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 150000001409 amidines Chemical class 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 230000007882 cirrhosis Effects 0.000 claims description 2
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
- 125000004342 dicyclopropylmethyl group Chemical group [H]C1([H])C([H])([H])C1([H])C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 208000019423 liver disease Diseases 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- FVMAYATYZSYSFZ-UHFFFAOYSA-N n-(3-methoxy-5-phenoxypyridin-2-yl)-3-pyrrolidin-1-ylsulfonylbenzamide Chemical compound C=1N=C(NC(=O)C=2C=C(C=CC=2)S(=O)(=O)N2CCCC2)C(OC)=CC=1OC1=CC=CC=C1 FVMAYATYZSYSFZ-UHFFFAOYSA-N 0.000 claims description 2
- WFLQINZNNVGHIX-UHFFFAOYSA-N n-(3-methoxy-5-phenylsulfanylpyridin-2-yl)-3-pyrrolidin-1-ylsulfonylbenzamide Chemical compound C=1N=C(NC(=O)C=2C=C(C=CC=2)S(=O)(=O)N2CCCC2)C(OC)=CC=1SC1=CC=CC=C1 WFLQINZNNVGHIX-UHFFFAOYSA-N 0.000 claims description 2
- NPZTXJPMHHMWHQ-UHFFFAOYSA-N n-(5-bromo-3-methoxypyridin-2-yl)-3-piperidin-1-ylsulfonylbenzamide Chemical compound COC1=CC(Br)=CN=C1NC(=O)C1=CC=CC(S(=O)(=O)N2CCCCC2)=C1 NPZTXJPMHHMWHQ-UHFFFAOYSA-N 0.000 claims description 2
- SEFGEXQGNGLZAG-UHFFFAOYSA-N n-(5-ethenyl-3-methoxypyridin-2-yl)-3-piperidin-1-ylsulfonylbenzamide Chemical compound COC1=CC(C=C)=CN=C1NC(=O)C1=CC=CC(S(=O)(=O)N2CCCCC2)=C1 SEFGEXQGNGLZAG-UHFFFAOYSA-N 0.000 claims description 2
- MAQWAGCJOFDDNU-UHFFFAOYSA-N n-(5-ethyl-3-methoxypyridin-2-yl)-3-piperidin-1-ylsulfonylbenzamide Chemical compound COC1=CC(CC)=CN=C1NC(=O)C1=CC=CC(S(=O)(=O)N2CCCCC2)=C1 MAQWAGCJOFDDNU-UHFFFAOYSA-N 0.000 claims description 2
- 230000007170 pathology Effects 0.000 claims description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 150000004885 piperazines Chemical class 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 45
- 239000002904 solvent Substances 0.000 claims 24
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 4
- 150000004677 hydrates Chemical class 0.000 claims 3
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims 1
- 241000700605 Viruses Species 0.000 claims 1
- 150000001728 carbonyl compounds Chemical class 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 0 CC1=CCCC(C2(*)CC2)=C1 Chemical compound CC1=CCCC(C2(*)CC2)=C1 0.000 description 32
- 125000000753 cycloalkyl group Chemical group 0.000 description 15
- 238000000034 method Methods 0.000 description 5
- DQOGDQIDOONUSK-REOHCLBHSA-N C[C@H](C(F)(F)F)C(O)=O Chemical compound C[C@H](C(F)(F)F)C(O)=O DQOGDQIDOONUSK-REOHCLBHSA-N 0.000 description 4
- DQOGDQIDOONUSK-UWTATZPHSA-N C[C@@H](C(F)(F)F)C(O)=O Chemical compound C[C@@H](C(F)(F)F)C(O)=O DQOGDQIDOONUSK-UWTATZPHSA-N 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- FILOYPQPSRQLRL-NRFANRHFSA-N 3-piperidin-1-ylsulfonyl-n-[(1s)-1,2,3,4-tetrahydronaphthalen-1-yl]benzamide Chemical compound N([C@@H]1C2=CC=CC=C2CCC1)C(=O)C(C=1)=CC=CC=1S(=O)(=O)N1CCCCC1 FILOYPQPSRQLRL-NRFANRHFSA-N 0.000 description 1
- BGNWXRJWDQHCRB-UHFFFAOYSA-N CC(C)c1ncccn1 Chemical compound CC(C)c1ncccn1 BGNWXRJWDQHCRB-UHFFFAOYSA-N 0.000 description 1
- WPPZHQBTLCZSEY-UHFFFAOYSA-N CC1(C)N=CC=C(C)N1 Chemical compound CC1(C)N=CC=C(C)N1 WPPZHQBTLCZSEY-UHFFFAOYSA-N 0.000 description 1
- ZHUGZTZOGHQIOD-UHFFFAOYSA-N CC1(C)OC(C)=NC=C1 Chemical compound CC1(C)OC(C)=NC=C1 ZHUGZTZOGHQIOD-UHFFFAOYSA-N 0.000 description 1
- LRNKDEJJYFZZOV-SCSAIBSYSA-N C[C@@H](C(F)(F)F)C(OC1(CC1)C(O)=O)=O Chemical compound C[C@@H](C(F)(F)F)C(OC1(CC1)C(O)=O)=O LRNKDEJJYFZZOV-SCSAIBSYSA-N 0.000 description 1
- FZMPLKVGINKUJZ-UHFFFAOYSA-N Cc(cc1F)ccc1F Chemical compound Cc(cc1F)ccc1F FZMPLKVGINKUJZ-UHFFFAOYSA-N 0.000 description 1
- BPWJEVHPHKDCLD-UHFFFAOYSA-N O=C(c(cc1)cc(F)c1F)NC(CC1S(NC2CC2)(=O)=O)=CC=C1F Chemical compound O=C(c(cc1)cc(F)c1F)NC(CC1S(NC2CC2)(=O)=O)=CC=C1F BPWJEVHPHKDCLD-UHFFFAOYSA-N 0.000 description 1
- FABZZCLPYQXJEY-UHFFFAOYSA-N O=C(c(cc1)cc(F)c1F)Nc(cc1NS(C2CC2)(=O)=O)ccc1F Chemical compound O=C(c(cc1)cc(F)c1F)Nc(cc1NS(C2CC2)(=O)=O)ccc1F FABZZCLPYQXJEY-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261746552P | 2012-12-27 | 2012-12-27 | |
| US61/746,552 | 2012-12-27 | ||
| PCT/US2013/077940 WO2014106019A2 (en) | 2012-12-27 | 2013-12-27 | Novel antiviral agents against hbv infection |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018177094A Division JP2019034943A (ja) | 2012-12-27 | 2018-09-21 | Ｈｂｖ感染に対する新規抗ウイルス剤 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016509591A JP2016509591A (ja) | 2016-03-31 |
| JP2016509591A5 true JP2016509591A5 (enExample) | 2016-07-21 |
| JP6409001B2 JP6409001B2 (ja) | 2018-10-17 |
Family
ID=51022201
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015550788A Expired - Fee Related JP6409001B2 (ja) | 2012-12-27 | 2013-12-27 | Ｈｂｖ感染に対する新規抗ウイルス剤 |
| JP2018177094A Pending JP2019034943A (ja) | 2012-12-27 | 2018-09-21 | Ｈｂｖ感染に対する新規抗ウイルス剤 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018177094A Pending JP2019034943A (ja) | 2012-12-27 | 2018-09-21 | Ｈｂｖ感染に対する新規抗ウイルス剤 |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US9938236B2 (enExample) |
| EP (1) | EP2938338A4 (enExample) |
| JP (2) | JP6409001B2 (enExample) |
| KR (1) | KR101942151B1 (enExample) |
| CN (1) | CN105209031A (enExample) |
| AU (2) | AU2013370300B2 (enExample) |
| BR (1) | BR112015015584A2 (enExample) |
| CA (1) | CA2896554C (enExample) |
| EA (1) | EA201591220A1 (enExample) |
| HK (1) | HK1217649A1 (enExample) |
| IL (2) | IL239397B (enExample) |
| MX (1) | MX2015008471A (enExample) |
| PH (1) | PH12015501473A1 (enExample) |
| SG (2) | SG11201504740UA (enExample) |
| WO (1) | WO2014106019A2 (enExample) |
Families Citing this family (117)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA037918B1 (ru) | 2011-12-21 | 2021-06-07 | Новира Терапьютикс, Инк. | Противовирусные агенты против гепатита в |
| HK1208465A1 (en) | 2012-08-28 | 2016-03-04 | Janssen Sciences Ireland Uc | Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of hepatitis b |
| US9938236B2 (en) * | 2012-12-27 | 2018-04-10 | Drexel University | Antiviral agents against HBV infection |
| DK2961732T3 (en) | 2013-02-28 | 2017-07-10 | Janssen Sciences Ireland Uc | SULFAMOYLARYLAMIDS AND USE THEREOF AS MEDICINES TO TREAT HEPATITIS B |
| WO2014161888A1 (en) | 2013-04-03 | 2014-10-09 | Janssen R&D Ireland | N-phenyl-carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
| JO3603B1 (ar) | 2013-05-17 | 2020-07-05 | Janssen Sciences Ireland Uc | مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي |
| ES2774749T3 (es) | 2013-07-25 | 2020-07-22 | Janssen Sciences Ireland Unlimited Co | Derivados de pirrolamida sustituidos con glioxamida y su uso como medicamentos para el tratamiento de la hepatitis B |
| KR102290189B1 (ko) | 2013-10-23 | 2021-08-17 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 카르복스아미드 유도체 및 ｂ형 간염 치료용 의약으로서의 이의 용도 |
| US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| US10392349B2 (en) | 2014-01-16 | 2019-08-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| KR20160128305A (ko) | 2014-02-05 | 2016-11-07 | 노비라 테라퓨틱스, 인코포레이티드 | Hbv 감염의 치료를 위한 병용 요법 |
| DK3102572T3 (en) | 2014-02-06 | 2019-02-04 | Janssen Sciences Ireland Uc | SULFAMOYLPYRROLAMIDE DERIVATIVES AND THEIR USE AS MEDICINES TO TREAT HEPATITIS B |
| MX363600B (es) | 2014-03-13 | 2019-03-28 | Univ Indiana Res & Tech Corp | Moduladores alostericos de proteina nucleo de hepatitis b. |
| US9400280B2 (en) | 2014-03-27 | 2016-07-26 | Novira Therapeutics, Inc. | Piperidine derivatives and methods of treating hepatitis B infections |
| AU2015255656A1 (en) * | 2014-05-09 | 2016-11-10 | Assembly Biosciences, Inc. | Methods and compositions for treating hepatitis B virus infections |
| WO2016089990A1 (en) | 2014-12-02 | 2016-06-09 | Novira Therapeutics, Inc. | Sulfide alkyl and pyridyl reverse sulfonamide compounds for hbv treatment |
| US9597332B2 (en) | 2014-12-02 | 2017-03-21 | Novira Therapeutics, Inc. | Sulfide alkyl compounds for HBV treatment |
| MA41140A (fr) | 2014-12-12 | 2017-10-17 | Cancer Research Tech Ltd | Dérivés de 2,4-dioxo-quinazoline-6-sulfonamide en tant qu'inhibiteurs de la parg |
| MA41179A (fr) | 2014-12-19 | 2017-10-24 | Cancer Research Tech Ltd | Composés inhibiteurs de parg |
| EP3240537B1 (en) | 2014-12-30 | 2020-09-09 | F. Hoffmann-La Roche AG | Novel tetrahydropyridopyrimidines and tetrahydropyridopyridines for the treatment and prophylaxis of hepatitis b virus infection |
| US9765050B2 (en) | 2014-12-30 | 2017-09-19 | Novira Therapeutics, Inc. | Pyridyl reverse sulfonamides for HBV treatment |
| WO2016149581A1 (en) * | 2015-03-19 | 2016-09-22 | Novira Therapeutics, Inc. | Azocane and azonane derivatives and methods of treating hepatitis b infections |
| US10442788B2 (en) | 2015-04-01 | 2019-10-15 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| WO2016177655A1 (en) * | 2015-05-04 | 2016-11-10 | F. Hoffmann-La Roche Ag | Tetrahydropyridopyrimidines and tetrahydropyridopyridines as inhibitors of hbsag (hbv surface antigen) and hbv dna production for the treatment of hepatitis b virus infections |
| US10738035B2 (en) | 2015-05-13 | 2020-08-11 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| US10875876B2 (en) | 2015-07-02 | 2020-12-29 | Janssen Sciences Ireland Uc | Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| WO2017011552A1 (en) | 2015-07-13 | 2017-01-19 | Enanta Pharmaceuticals, Inc. | Hepatitis b antiviral agents |
| TWI721016B (zh) | 2015-09-15 | 2021-03-11 | 美商艾森伯利生物科學公司 | B型肝炎核心蛋白質調節劑 |
| HK1259410A1 (zh) | 2015-09-29 | 2019-11-29 | 诺维拉治疗公司 | 乙型肝炎抗病毒剂的晶体形式 |
| BR112018067964B1 (pt) * | 2016-03-07 | 2024-01-16 | Enanta Pharmaceuticals, Inc | Composto, composição farmacêutica que o compreende e uso do referido composto |
| EP3442524A2 (en) * | 2016-04-15 | 2019-02-20 | Novira Therapeutics Inc. | Combinations and methods comprising a capsid assembly inhibitor |
| CA3026252A1 (en) * | 2016-06-03 | 2017-12-07 | University Of Tennessee Research Foundation | Autotaxin inhibitors |
| MX2018015315A (es) | 2016-06-10 | 2019-04-25 | Enanta Pharm Inc | Agentes antivirales contra la hepatitis b. |
| MA45999A (fr) | 2016-08-22 | 2019-06-26 | Arbutus Biopharma Corp | Anticorps anti-pd-1, ou leurs fragments, pour le traitement de l'hépatite b |
| JOP20190024A1 (ar) | 2016-08-26 | 2019-02-19 | Gilead Sciences Inc | مركبات بيروليزين بها استبدال واستخداماتها |
| CA3036245C (en) | 2016-09-13 | 2021-07-20 | Arbutus Biopharma Corporation | Substituted chromane-8-carboxamide compounds and analogues thereof, and methods using same |
| US10987360B2 (en) | 2016-09-15 | 2021-04-27 | Assembly Biosciences, Inc. | Hepatitis B core protein modulators |
| US10821103B2 (en) | 2016-11-07 | 2020-11-03 | Arbutus Biopharma Corporation | Substituted pyridinone-containing trycyclic compounds, and methods using same |
| EA202190306A1 (ru) * | 2016-11-11 | 2021-08-17 | Новира Терапьютикс, Инк. | Комбинации и способы, включающие ингибитор сборки капсида |
| WO2018145620A1 (en) * | 2017-02-07 | 2018-08-16 | Janssen Pharmaceutica Nv | Sulphamoylaryl derivatives and use thereof as medicaments for the treatment of liver fibrosis |
| RU2650610C1 (ru) | 2017-02-28 | 2018-04-16 | Васильевич Иващенко Александр | Противовирусная композиция и способ ее применения |
| ES2898217T3 (es) | 2017-03-02 | 2022-03-04 | Assembly Biosciences Inc | Compuestos de sulfamida cíclica y métodos de uso de los mismos |
| MA49014A (fr) | 2017-03-21 | 2020-02-05 | Arbutus Biopharma Corp | Dihydroindène-4-carboxamides substitués, leurs analogues et procédés d'utilisation correspondant |
| JP7377718B2 (ja) | 2017-05-12 | 2023-11-10 | エナンタ ファーマシューティカルズ インコーポレイテッド | アポトーシスシグナル調節キナーゼ１阻害剤およびその使用方法 |
| WO2019001420A1 (en) | 2017-06-27 | 2019-01-03 | Janssen Pharmaceutica Nv | HETEROARYLDIHYDROPYRIMIDINE DERIVATIVES AND METHODS OF TREATING INFECTIONS WITH HEPATITIS B VIRUS |
| US10513515B2 (en) | 2017-08-25 | 2019-12-24 | Biotheryx, Inc. | Ether compounds and uses thereof |
| US10597382B2 (en) | 2017-08-28 | 2020-03-24 | Enanta Pharmaceuticals, Inc. | Tetrazole containing apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof |
| IL272941B2 (en) * | 2017-08-28 | 2023-03-01 | Enanta Pharm Inc | Antiviral agents for viral hepatitis b |
| TW201912153A (zh) * | 2017-08-30 | 2019-04-01 | 加拿大商愛彼特生物製藥公司 | 用於治療ｂ型肝炎的化合物、醫藥組合物及方法 |
| TW201927789A (zh) | 2017-12-06 | 2019-07-16 | 美商因那塔製藥公司 | B型肝炎抗病毒試劑 |
| TW201936192A (zh) | 2017-12-06 | 2019-09-16 | 美商因那塔製藥公司 | B 型肝炎抗病毒試劑 |
| US11058678B2 (en) | 2018-01-22 | 2021-07-13 | Enanta Pharmaceuticals, Inc. | Substituted heterocycles as antiviral agents |
| KR102526964B1 (ko) | 2018-02-26 | 2023-04-28 | 길리애드 사이언시즈, 인코포레이티드 | Hbv 복제 억제제로서의 치환된 피롤리진 화합물 |
| EA202092171A1 (ru) | 2018-03-14 | 2020-12-01 | Янссен Сайенсиз Айрлэнд Анлимитед Компани | Схема дозирования модулятора сборки капсида |
| WO2019191166A1 (en) | 2018-03-29 | 2019-10-03 | Enanta Pharmaceuticals, Inc. | Hepatitis b antiviral agents |
| WO2019206072A1 (zh) * | 2018-04-24 | 2019-10-31 | 浙江海正药业股份有限公司 | 磺酰胺芳基甲酰胺衍生物及其制备方法和用途 |
| WO2019213239A1 (en) * | 2018-05-02 | 2019-11-07 | Enanta Pharmaceuticals Inc. | Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof |
| KR102798464B1 (ko) | 2018-05-02 | 2025-04-21 | 이난타 파마슈티칼스, 인코포레이티드 | 아폽토시스 신호 조절 키나제 1 억제제를 포함하는 테트라졸 및 이의 사용 방법 |
| EP3597653A1 (en) | 2018-07-19 | 2020-01-22 | Irbm S.P.A. | Cyclic inhibitors of hepatitis b virus |
| EP3597637A1 (en) | 2018-07-19 | 2020-01-22 | Irbm S.P.A. | Inhibitors of hepatitis b virus |
| TWI869058B (zh) | 2018-07-27 | 2025-01-01 | 加拿大商愛彼特生物製藥公司 | 經取代四氫環戊[c]吡咯、經取代二氫吡咯，其類似物及使用其之方法 |
| CA3106239A1 (en) | 2018-07-27 | 2020-01-30 | Biotheryx, Inc. | Bifunctional compounds as cdk modulators |
| US11053235B2 (en) | 2018-08-09 | 2021-07-06 | Janssen Sciences Ireland Unlimited Company | Substituted 1,4-dihydropyrimidines for the treatment of HBV infection or HBV-induced diseases |
| EP3608326A1 (en) | 2018-08-10 | 2020-02-12 | Irbm S.P.A. | Tricyclic inhibitors of hepatitis b virus |
| US10968199B2 (en) | 2018-08-22 | 2021-04-06 | Enanta Pharmaceuticals, Inc. | Cycloalkyl-containing apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof |
| WO2020061435A1 (en) | 2018-09-21 | 2020-03-26 | Enanta Pharmaceuticals, Inc. | Functionalized heterocycles as antiviral agents |
| MX2021003150A (es) * | 2018-10-05 | 2021-07-06 | Univ Emory | Agentes monomericos y multimericos contra el vhb. |
| EP3870296A1 (en) | 2018-10-22 | 2021-09-01 | Assembly Biosciences, Inc. | 5-membered heteroaryl carboxamide compounds for treatment of hbv |
| AU2019373090B2 (en) | 2018-10-31 | 2023-05-25 | The University Of Sydney | Compositions and methods for treating viral infections |
| US11345699B2 (en) | 2018-11-19 | 2022-05-31 | Enanta Pharmaceuticals, Inc. | Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof |
| KR102819704B1 (ko) | 2018-11-21 | 2025-06-11 | 이난타 파마슈티칼스, 인코포레이티드 | 항바이러스제로서의 작용화된 헤테로사이클 |
| TW202415643A (zh) | 2018-12-12 | 2024-04-16 | 加拿大商愛彼特生物製藥公司 | 經取代之芳基甲基脲類及雜芳基甲基脲類、其類似物及其使用方法 |
| WO2020163479A1 (en) * | 2019-02-05 | 2020-08-13 | Board Of Regents, The University Of Texas System | Antibiotic ammonium compounds and methods for the treatment of bacterial infections |
| MA55020A (fr) | 2019-02-22 | 2021-12-29 | Janssen Sciences Ireland Unlimited Co | Dérivés d'amide utiles dans le traitement d'une infection par le virus de l'hépatite b ou de maladies induites par le virus de l'hépatite b |
| WO2020198214A1 (en) | 2019-03-25 | 2020-10-01 | Enanta Pharmaceuticals, Inc. | Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof |
| BR112021021454A2 (pt) | 2019-05-06 | 2021-12-21 | Janssen Sciences Ireland Unlimited Co | Derivados de amida úteis no tratamento da infecção por hbv ou doenças induzidas por hbv |
| EP3825318A1 (en) | 2019-11-25 | 2021-05-26 | Promidis S.r.l. | Oxalamido-substituted tricyclic inhibitors of hepatitis b virus |
| EP3741762A1 (en) | 2019-05-23 | 2020-11-25 | Irbm S.P.A. | Oxalamido-substituted tricyclic inhibitors of hepatitis b virus |
| UY38705A (es) | 2019-05-23 | 2020-12-31 | Irbm S P A | Inhibidores tricíclicos sustituidos con oxalamido del virus de hepatitis b |
| BR112021023622A2 (pt) | 2019-05-24 | 2022-04-19 | Assembly Biosciences Inc | Composições farmaceuticas para o tratamento de hbv |
| US11236111B2 (en) | 2019-06-03 | 2022-02-01 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| US11472808B2 (en) | 2019-06-04 | 2022-10-18 | Enanta Pharmaceuticals, Inc. | Substituted pyrrolo[1,2-c]pyrimidines as hepatitis B antiviral agents |
| US11760755B2 (en) | 2019-06-04 | 2023-09-19 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| WO2020255013A1 (en) | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and capsid assembly modulators being amide derivatives |
| US11738019B2 (en) | 2019-07-11 | 2023-08-29 | Enanta Pharmaceuticals, Inc. | Substituted heterocycles as antiviral agents |
| WO2021055425A2 (en) | 2019-09-17 | 2021-03-25 | Enanta Pharmaceuticals, Inc. | Functionalized heterocycles as antiviral agents |
| EP4048807A1 (en) | 2019-09-23 | 2022-08-31 | Omega Therapeutics, Inc. | Compositions and methods for modulating apolipoprotein b (apob) gene expression |
| CA3147643A1 (en) | 2019-09-23 | 2021-04-01 | Omega Therapeutics, Inc. | Compositions and methods for modulating hepatocyte nuclear factor 4-alpha (hnf4.alpha.) gene expression |
| NZ790488A (en) | 2019-12-20 | 2026-01-30 | Arbutus Biopharma Corp | Synthetic processes and intermediates |
| EP4118207A1 (en) | 2020-03-11 | 2023-01-18 | Omega Therapeutics, Inc. | Compositions and methods for modulating forkhead box p3 (foxp3) gene expression |
| WO2021188414A1 (en) | 2020-03-16 | 2021-09-23 | Enanta Pharmaceuticals, Inc. | Functionalized heterocyclic compounds as antiviral agents |
| KR20210126507A (ko) | 2020-04-10 | 2021-10-20 | 주식회사 스탠다임 | 벤즈아미드 화합물을 포함하는 암 예방 또는 치료용 조성물 |
| CN111349056B (zh) * | 2020-04-16 | 2022-08-02 | 南京安纳康生物科技有限公司 | 用于乙型肝炎病毒感染的抗病毒剂 |
| CN111393391B (zh) * | 2020-04-16 | 2022-07-26 | 南京安纳康生物科技有限公司 | 用于乙型肝炎病毒感染的抗病毒剂 |
| CN121248511A (zh) | 2020-04-22 | 2026-01-02 | 组装生物科学股份有限公司 | 用于治疗hbv的5元杂芳基甲酰胺化合物 |
| EP4139000A1 (en) | 2020-04-22 | 2023-03-01 | Assembly Biosciences, Inc. | Pyrazole carboxamide compounds for treatment of hbv |
| WO2021216660A1 (en) | 2020-04-22 | 2021-10-28 | Assembly Biosciences, Inc. | 5-membered heteroaryl carboxamide compounds for treatment of hbv |
| WO2021216661A1 (en) | 2020-04-22 | 2021-10-28 | Assembly Biosciences, Inc. | Pyrazole carboxamide compounds for treatment of hbv |
| EP4143329A4 (en) | 2020-04-28 | 2024-10-16 | Anwita Biosciences, Inc. | Interleukin-2 polypeptides and fusion proteins thereof, and their pharmaceutical compositions and therapeutic applications |
| EP4244213A4 (en) * | 2020-11-10 | 2024-11-20 | Foghorn Therapeutics Inc. | COMPOUNDS AND USES THEREOF |
| WO2023283359A2 (en) | 2021-07-07 | 2023-01-12 | Omega Therapeutics, Inc. | Compositions and methods for modulating secreted frizzled receptor protein 1 (sfrp1) gene expression |
| WO2023069545A1 (en) | 2021-10-20 | 2023-04-27 | Assembly Biosciences, Inc. | 5-membered heteroaryl carboxamide compounds for treatment of hbv |
| WO2023069547A1 (en) | 2021-10-20 | 2023-04-27 | Assembly Biosciences, Inc. | 5-membered heteroaryl carboxamide compounds for treatment of hbv |
| WO2023069544A1 (en) | 2021-10-20 | 2023-04-27 | Assembly Biosciences, Inc. | 5-membered heteroaryl carboxamide compounds for treatment of hbv |
| KR102617049B1 (ko) | 2021-12-30 | 2023-12-21 | 장고옥 | 헤어고데기 |
| WO2023164181A1 (en) | 2022-02-25 | 2023-08-31 | Assembly Biosciences, Inc. | Benzothia(dia)zepine compounds for treatment of hbv and hdv |
| WO2023164183A1 (en) | 2022-02-25 | 2023-08-31 | Assembly Biosciences, Inc. | Benzothia(dia)zepine compounds for treatment of hbv and hdv |
| WO2023164179A1 (en) | 2022-02-25 | 2023-08-31 | Assembly Biosciences, Inc. | Benzothia(dia)zepine compounds for treatment of hbv and hdv |
| WO2023164186A1 (en) | 2022-02-25 | 2023-08-31 | Assembly Biosciences, Inc. | Benzothia(dia)zepine compounds for treatment of hbv and hdv |
| AR128846A1 (es) | 2022-03-23 | 2024-06-19 | Ideaya Biosciences Inc | Compuestos de indazol sustituidos con piperazina como inhibidores de parg |
| CN119584960A (zh) * | 2022-08-01 | 2025-03-07 | 国立研究开发法人理化学研究所 | 抗hbv剂 |
| EP4580618A2 (en) * | 2022-08-30 | 2025-07-09 | Pannex Therapeutics Inc. | Pannexin-1 modulators and methods of treating disorders in which pannexin-1 is implicated |
| CN115677545B (zh) * | 2022-10-28 | 2024-03-15 | 潍坊医学院 | 一种抗hbv磺胺苯甲酰胺类衍生物及其制备方法和应用 |
| CN116410106B (zh) * | 2023-04-13 | 2024-12-06 | 山东第二医科大学 | 一种苯甲酰胺类hbv衣壳蛋白抑制剂及其制备方法与应用 |
| WO2024243438A2 (en) | 2023-05-23 | 2024-11-28 | Omega Therapeutics, Inc. | Compositions and methods for reducing cxcl9, cxcl10, and cxcl11 gene expression |
| WO2025043094A1 (en) | 2023-08-23 | 2025-02-27 | Assembly Biosciences, Inc. | Benzothia(dia)zepine compounds for treatment of hbv and hdv |
| WO2026038156A1 (en) | 2024-08-15 | 2026-02-19 | Assembly Biosciences, Inc. | Novel crystalline forms |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2891938A (en) * | 1957-03-29 | 1959-06-23 | Geigy Ag J R | Chromium-containing monoazo dyestuffs |
| US3557111A (en) * | 1968-03-29 | 1971-01-19 | Bola Vithal Shetty | N and n,n-alkyl,acyl and arylsulfamyl-tetrahydroquinazolinones |
| US3567746A (en) * | 1968-07-10 | 1971-03-02 | Pennwalt Corp | N-aryl benzamides |
| JPH0625106B2 (ja) | 1985-07-24 | 1994-04-06 | 三共株式会社 | イソインドリン−１，３−ジオン誘導体およびその製造法 |
| JP2000212157A (ja) * | 1999-01-13 | 2000-08-02 | Warner Lambert Co | ジアリ―ルアミン |
| AU2201500A (en) * | 1999-01-13 | 2000-08-01 | Warner-Lambert Company | Benzenesulfonamide derivatives and their use as mek inhibitors |
| ATE538794T1 (de) | 1999-01-13 | 2012-01-15 | Bayer Healthcare Llc | Gamma carboxyarylsubstituierte diphenylharnstoffverbindungen als p38 kinasehemmer |
| WO2007056016A2 (en) * | 2005-11-02 | 2007-05-18 | Kemia, Inc. | Bisamide cytokine inhibitors |
| JP2009518442A (ja) * | 2005-12-05 | 2009-05-07 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 可溶性エポキシド加水分解酵素インヒビターとして有益な置換ピラゾール化合物 |
| US7842713B2 (en) | 2006-04-20 | 2010-11-30 | Pfizer Inc | Fused phenyl amido heterocyclic compounds |
| WO2008070707A1 (en) * | 2006-12-05 | 2008-06-12 | Smithkline Beecham Corporation | Il-8 receptor antagonists |
| JP2008184403A (ja) * | 2007-01-29 | 2008-08-14 | Japan Health Science Foundation | 新規ｃ型肝炎ウイルス阻害剤 |
| EA019524B1 (ru) * | 2007-05-04 | 2014-04-30 | Айрм Ллк | СОЕДИНЕНИЯ И КОМПОЗИЦИИ КАК ИНГИБИТОРЫ КИНАЗЫ с-kit И PDGFR |
| AP2009005070A0 (en) * | 2007-05-23 | 2009-12-31 | Siga Technologies Inc | Antiviral drugs for treatment or prevention of dengue infection |
| CN101765425A (zh) * | 2007-08-02 | 2010-06-30 | 弗·哈夫曼-拉罗切有限公司 | 苯甲酰胺衍生物用于治疗cns障碍的用途 |
| DE102007041116A1 (de) * | 2007-08-30 | 2009-03-05 | Merck Patent Gmbh | 1,3-Dihydro-isoindolderivate |
| US8642660B2 (en) * | 2007-12-21 | 2014-02-04 | The University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| US20090197787A1 (en) | 2008-02-04 | 2009-08-06 | Eurotab | Multilayer Detergent Tablet |
| PE20091553A1 (es) * | 2008-02-06 | 2009-10-30 | Glaxo Group Ltd | Farmacoforos duales - antagonistas muscarinicos de pde4 |
| US8263642B2 (en) | 2008-06-25 | 2012-09-11 | Vanderbilt University | Antimicrobial compounds and methods of use thereof |
| EP2236505A1 (de) * | 2009-04-03 | 2010-10-06 | Bayer CropScience AG | Acylierte Aminopyridine und - pyridazine als Insektizide |
| WO2010123139A1 (ja) * | 2009-04-24 | 2010-10-28 | 持田製薬株式会社 | スルファモイル基を有するアリールカルボキサミド誘導体 |
| CN105853415A (zh) | 2009-05-12 | 2016-08-17 | 罗马克实验室有限公司 | 卤代烷基杂芳基苯甲酰胺化合物 |
| WO2011088561A1 (en) | 2010-01-20 | 2011-07-28 | University Of Manitoba | Anti-viral compounds and compositions |
| KR20130108543A (ko) | 2010-08-05 | 2013-10-04 | 암젠 인코포레이션 | 역형성 림프종 키나제를 억제하는 벤즈이미다졸 및 아자벤즈이미다졸 화합물 |
| US8987307B2 (en) * | 2011-03-03 | 2015-03-24 | Hoffmann-La Roche Inc. | 3-amino-pyridines as GPBAR1 agonists |
| WO2012122391A1 (en) * | 2011-03-08 | 2012-09-13 | 3-V Biosciences, Inc. | Heterocyclic modulators of lipid synthesis |
| JP5977347B2 (ja) * | 2011-07-01 | 2016-08-24 | バルーク エス．ブルームバーグ インスティテュート | Ｈｂｖ感染に対する抗ウイルス剤としてのスルファモイルベンズアミド誘導体 |
| EA037918B1 (ru) | 2011-12-21 | 2021-06-07 | Новира Терапьютикс, Инк. | Противовирусные агенты против гепатита в |
| EP2819671A4 (en) | 2012-02-29 | 2016-05-11 | Baruch S Blumberg Inst | INHIBITORS OF HEPATITIS B VIRUS WITH COVALENT CLOSED CIRCULAR DNA PREPARATION AND ITS USE METHOD |
| HK1208465A1 (en) | 2012-08-28 | 2016-03-04 | Janssen Sciences Ireland Uc | Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of hepatitis b |
| CA2892606A1 (en) | 2012-12-06 | 2014-06-12 | Baruch S. Blumberg Institute | Functionalized benzamide derivatives as antiviral agents against hbv infection |
| US9938236B2 (en) * | 2012-12-27 | 2018-04-10 | Drexel University | Antiviral agents against HBV infection |
-
2013
- 2013-12-27 US US14/759,385 patent/US9938236B2/en not_active Expired - Fee Related
- 2013-12-27 EP EP13868405.5A patent/EP2938338A4/en not_active Withdrawn
- 2013-12-27 HK HK16105705.7A patent/HK1217649A1/zh unknown
- 2013-12-27 SG SG11201504740UA patent/SG11201504740UA/en unknown
- 2013-12-27 JP JP2015550788A patent/JP6409001B2/ja not_active Expired - Fee Related
- 2013-12-27 AU AU2013370300A patent/AU2013370300B2/en not_active Ceased
- 2013-12-27 CN CN201380072796.5A patent/CN105209031A/zh active Pending
- 2013-12-27 WO PCT/US2013/077940 patent/WO2014106019A2/en not_active Ceased
- 2013-12-27 CA CA2896554A patent/CA2896554C/en not_active Expired - Fee Related
- 2013-12-27 EA EA201591220A patent/EA201591220A1/ru unknown
- 2013-12-27 BR BR112015015584A patent/BR112015015584A2/pt not_active Application Discontinuation
- 2013-12-27 SG SG10201803698UA patent/SG10201803698UA/en unknown
- 2013-12-27 MX MX2015008471A patent/MX2015008471A/es unknown
- 2013-12-27 KR KR1020157020432A patent/KR101942151B1/ko not_active Expired - Fee Related
-
2015
- 2015-06-14 IL IL239397A patent/IL239397B/en not_active IP Right Cessation
- 2015-06-26 PH PH12015501473A patent/PH12015501473A1/en unknown
-
2018
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- 2018-03-22 US US15/933,098 patent/US20180230092A1/en not_active Abandoned
- 2018-09-21 JP JP2018177094A patent/JP2019034943A/ja active Pending
-
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