HRP20050605A2 - Broadspectrum 2-amino-benzothiazole sulfonamide hiv protease inhibitors - Google Patents
Broadspectrum 2-amino-benzothiazole sulfonamide hiv protease inhibitors Download PDFInfo
- Publication number
- HRP20050605A2 HRP20050605A2 HR20050605A HRP20050605A HRP20050605A2 HR P20050605 A2 HRP20050605 A2 HR P20050605A2 HR 20050605 A HR20050605 A HR 20050605A HR P20050605 A HRP20050605 A HR P20050605A HR P20050605 A2 HRP20050605 A2 HR P20050605A2
- Authority
- HR
- Croatia
- Prior art keywords
- amino
- benzyl
- isobutyl
- sulfonyl
- benzothiazole
- Prior art date
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- 239000004030 hiv protease inhibitor Substances 0.000 title description 13
- XFMNXQKCYJXARU-UHFFFAOYSA-N 2-amino-3h-1,3-benzothiazole-2-sulfonamide Chemical compound C1=CC=C2SC(N)(S(N)(=O)=O)NC2=C1 XFMNXQKCYJXARU-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 211
- -1 hexahydrofuro [2,3-b] furanyl Chemical group 0.000 claims abstract description 109
- 108010010369 HIV Protease Proteins 0.000 claims abstract description 41
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 33
- 239000003814 drug Substances 0.000 claims abstract description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
- 239000001257 hydrogen Substances 0.000 claims abstract description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 19
- 125000002971 oxazolyl group Chemical group 0.000 claims abstract description 17
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 14
- 150000002367 halogens Chemical class 0.000 claims abstract description 14
- 125000001424 substituent group Chemical group 0.000 claims abstract description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 13
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims abstract description 12
- 241000124008 Mammalia Species 0.000 claims abstract description 11
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- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 11
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- UHGULLIUJBCTEF-UHFFFAOYSA-N 2-aminobenzothiazole Chemical compound C1=CC=C2SC(N)=NC2=C1 UHGULLIUJBCTEF-UHFFFAOYSA-N 0.000 claims abstract description 3
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 8
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
- 230000035772 mutation Effects 0.000 claims description 6
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- VDZQZWLVQAITRB-UHFFFAOYSA-N 3-hydroxy-n-[3-hydroxy-4-[[2-(methylamino)-1,3-benzothiazol-6-yl]sulfonyl-(2-methylpropyl)amino]-1-phenylbutan-2-yl]-2-methylbenzamide Chemical compound C1=C2SC(NC)=NC2=CC=C1S(=O)(=O)N(CC(C)C)CC(O)C(NC(=O)C=1C(=C(O)C=CC=1)C)CC1=CC=CC=C1 VDZQZWLVQAITRB-UHFFFAOYSA-N 0.000 claims description 4
- 150000001408 amides Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 239000002207 metabolite Substances 0.000 claims description 4
- NATWFOMFBYZWML-UHFFFAOYSA-N n-[4-[(2-amino-1,3-benzothiazol-6-yl)sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]-2-(4-iodo-2,6-dimethylphenoxy)acetamide Chemical compound C=1C=C2N=C(N)SC2=CC=1S(=O)(=O)N(CC(C)C)CC(O)C(NC(=O)COC=1C(=CC(I)=CC=1C)C)CC1=CC=CC=C1 NATWFOMFBYZWML-UHFFFAOYSA-N 0.000 claims description 4
- FSPHSOOHUVYFNS-UHFFFAOYSA-N n-[4-[(2-amino-1,3-benzothiazol-6-yl)sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]-2-[4-(aminomethyl)-2,6-dimethylphenoxy]acetamide Chemical compound C=1C=C2N=C(N)SC2=CC=1S(=O)(=O)N(CC(C)C)CC(O)C(NC(=O)COC=1C(=CC(CN)=CC=1C)C)CC1=CC=CC=C1 FSPHSOOHUVYFNS-UHFFFAOYSA-N 0.000 claims description 4
- PCSRGJKSOMKGGM-UHFFFAOYSA-N 2-(2,6-dimethylphenoxy)-n-[3-hydroxy-4-[[2-(methylamino)-1,3-benzothiazol-6-yl]sulfonyl-(2-methylpropyl)amino]-1-phenylbutan-2-yl]acetamide Chemical compound C1=C2SC(NC)=NC2=CC=C1S(=O)(=O)N(CC(C)C)CC(O)C(NC(=O)COC=1C(=CC=CC=1C)C)CC1=CC=CC=C1 PCSRGJKSOMKGGM-UHFFFAOYSA-N 0.000 claims description 3
- RQQJAOWBNMYRRI-ZCYQVOJMSA-N 3-amino-4-[(2s,3r)-4-[(2-amino-1,3-benzothiazol-6-yl)sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]-2-methylbenzamide Chemical compound C([C@H]([C@@H](O)CN(CC(C)C)S(=O)(=O)C=1C=C2SC(N)=NC2=CC=1)C=1C(=C(C)C(C(N)=O)=CC=1)N)C1=CC=CC=C1 RQQJAOWBNMYRRI-ZCYQVOJMSA-N 0.000 claims description 3
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/82—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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AU2005244121B2 (en) * | 2004-05-07 | 2012-01-19 | Sequoia Pharmaceuticals, Inc. | Resistance-repellent retroviral protease inhibitors |
JO2841B1 (en) * | 2006-06-23 | 2014-09-15 | تيبوتيك فارماسيوتيكالز ليمتد | 2-(substituted-amino) -benzothiazole sulfonamide as protease inhibitors HIV (HIV) |
US8267163B2 (en) * | 2008-03-17 | 2012-09-18 | Visteon Global Technologies, Inc. | Radiator tube dimple pattern |
WO2011061590A1 (en) | 2009-11-17 | 2011-05-26 | Hetero Research Foundation | Novel carboxamide derivatives as hiv inhibitors |
CN103209963A (zh) | 2010-07-02 | 2013-07-17 | 吉里德科学公司 | 作为hiv抗病毒化合物的2-喹啉基-乙酸衍生物 |
KR20130135826A (ko) | 2010-07-02 | 2013-12-11 | 길리애드 사이언시즈, 인코포레이티드 | Aids를 치료하기 위한 나프트-2-일아세트산 유도체 |
US9024038B2 (en) | 2010-12-27 | 2015-05-05 | Purdue Research Foundation | Compunds and methods for treating HIV |
WO2012145728A1 (en) | 2011-04-21 | 2012-10-26 | Gilead Sciences, Inc. | Benzothiazole compounds and their pharmaceutical use |
WO2013103738A1 (en) | 2012-01-04 | 2013-07-11 | Gilead Sciences, Inc. | Napthalene acetic acid derivatives against hiv infection |
US9376392B2 (en) | 2012-01-04 | 2016-06-28 | Gilead Sciences, Inc. | 2-(tert-butoxy)-2-(7-methylquinolin-6-yl) acetic acid derivatives for treating AIDS |
CA2850881C (en) | 2012-04-20 | 2021-02-16 | Gilead Sciences, Inc. | Benzothiazol-6-yl acetic acid derivatives and their use for treating an hiv infection |
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US5968942A (en) * | 1992-08-25 | 1999-10-19 | G. D. Searle & Co. | α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors |
EP0715618B1 (en) * | 1993-08-24 | 1998-12-16 | G.D. Searle & Co. | Hydroxyethylamino sulphonamides useful as retroviral protease inhibitors |
WO1999067254A2 (en) * | 1998-06-23 | 1999-12-29 | The United States Of America Represented By The Secretary, Department Of Health And Human Services | Multi-drug resistant retroviral protease inhibitors and use thereof |
EE05385B1 (et) * | 2001-02-14 | 2011-02-15 | Tibotec�Pharmaceuticals�Ltd. | LaiaspektrilisedÁ2-(asendatudÁamino)bensotiasoolsulfoonamiididÁkuiÁHIVÁproteaasiÁinhibiitorid,ÁnendeÁvalmistamismeetodÁjaÁkasutamineÁningÁfarmatseutilineÁkompositsioon |
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CA2492832C (en) | 2012-05-22 |
CN1671380B (zh) | 2010-05-26 |
MXPA05001275A (es) | 2005-04-28 |
EP1545518A1 (en) | 2005-06-29 |
IL166257A (en) | 2013-04-30 |
IL166257A0 (en) | 2006-01-15 |
KR20050025647A (ko) | 2005-03-14 |
AP2005003242A0 (en) | 2005-03-31 |
PL374948A1 (en) | 2005-11-14 |
WO2004014371A1 (en) | 2004-02-19 |
BR0305717A (pt) | 2004-09-28 |
CN1671380A (zh) | 2005-09-21 |
CA2492832A1 (en) | 2004-02-19 |
NO20051089L (no) | 2005-05-02 |
EA008594B1 (ru) | 2007-06-29 |
US20050267156A1 (en) | 2005-12-01 |
AU2003262561A1 (en) | 2004-02-25 |
AP1878A (en) | 2008-08-13 |
NZ538488A (en) | 2007-10-26 |
US20090203742A1 (en) | 2009-08-13 |
EA200500298A1 (ru) | 2005-08-25 |
AU2003262561B2 (en) | 2008-10-16 |
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