CZ304273B6 - 2-(Substitovaná-amino)benzothiazolsulfonamidová sloučenina, způsob její přípravy a farmaceutická kompozice s jejím obsahem - Google Patents
2-(Substitovaná-amino)benzothiazolsulfonamidová sloučenina, způsob její přípravy a farmaceutická kompozice s jejím obsahem Download PDFInfo
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- CZ304273B6 CZ304273B6 CZ2003-2415A CZ20032415A CZ304273B6 CZ 304273 B6 CZ304273 B6 CZ 304273B6 CZ 20032415 A CZ20032415 A CZ 20032415A CZ 304273 B6 CZ304273 B6 CZ 304273B6
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- alkyl
- het
- amino
- aryl
- formula
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- -1 2-(Substituted-amino)-benzothiazole sulfonamide compound Chemical class 0.000 title claims abstract description 139
- 238000000034 method Methods 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 16
- 230000008569 process Effects 0.000 title claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 227
- 241000725303 Human immunodeficiency virus Species 0.000 claims abstract description 37
- 239000003814 drug Substances 0.000 claims abstract description 36
- 241001430294 unidentified retrovirus Species 0.000 claims abstract description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 208000015181 infectious disease Diseases 0.000 claims abstract description 11
- 241000124008 Mammalia Species 0.000 claims abstract description 10
- 201000010099 disease Diseases 0.000 claims abstract description 10
- 108091005804 Peptidases Proteins 0.000 claims abstract description 6
- 239000004365 Protease Substances 0.000 claims abstract description 5
- 230000010076 replication Effects 0.000 claims abstract description 4
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract 2
- 230000001629 suppression Effects 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims description 304
- 239000000543 intermediate Substances 0.000 claims description 150
- 125000003118 aryl group Chemical group 0.000 claims description 76
- 239000000203 mixture Substances 0.000 claims description 56
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 53
- 239000001257 hydrogen Substances 0.000 claims description 51
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 48
- 125000003277 amino group Chemical group 0.000 claims description 43
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 39
- 125000001424 substituent group Chemical group 0.000 claims description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 31
- 150000002431 hydrogen Chemical class 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
- 125000002619 bicyclic group Chemical group 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 18
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 17
- 125000004043 oxo group Chemical group O=* 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 16
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 239000001301 oxygen Chemical group 0.000 claims description 14
- 229910052717 sulfur Chemical group 0.000 claims description 14
- 239000011593 sulfur Chemical group 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
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- 125000002911 monocyclic heterocycle group Chemical group 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
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims description 8
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
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- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
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- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 5
- 208000005074 Retroviridae Infections Diseases 0.000 claims description 5
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 5
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- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
- FODOUIXGKGNSMR-UHFFFAOYSA-L magnesium;2-oxidooxycarbonylbenzoate;hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[O-]OC(=O)C1=CC=CC=C1C([O-])=O FODOUIXGKGNSMR-UHFFFAOYSA-L 0.000 claims description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 3
- 101100219283 Amycolatopsis orientalis cyp165C4 gene Proteins 0.000 claims description 3
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- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims description 3
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- SAZIXRNDDOLEGS-UHFFFAOYSA-N CC=1C(=C(C(=O)OO)C=CC=1)Cl Chemical compound CC=1C(=C(C(=O)OO)C=CC=1)Cl SAZIXRNDDOLEGS-UHFFFAOYSA-N 0.000 claims description 2
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
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- 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 2
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- 125000005201 cycloalkylcarbonyloxy group Chemical group 0.000 claims description 2
- 125000003106 haloaryl group Chemical group 0.000 claims description 2
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
- QAGMBTAACMQRSS-MTULOOOASA-N [(2r,3s)-3,5-diacetyloxyoxolan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@H]1OC(OC(C)=O)C[C@@H]1OC(C)=O QAGMBTAACMQRSS-MTULOOOASA-N 0.000 claims 1
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- 230000005764 inhibitory process Effects 0.000 abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 224
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
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Classifications
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- 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
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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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
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- Engineering & Computer Science (AREA)
- AIDS & HIV (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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| AU2002226316B2 (en) | 2000-10-20 | 2008-06-26 | Virco Bvba | Mutational profiles in HIV-1 reverse transcriptase correlated with phenotypic drug resistance |
| EP1370543B1 (en) | 2001-02-14 | 2006-10-25 | Tibotec Pharmaceuticals Ltd. | Broadspectrum 2-(substituted-amino)-benzothiazole sulfonamide hiv protease inhibitors |
| US7109230B2 (en) | 2002-01-07 | 2006-09-19 | Sequoia Pharmaceuticals, Inc. | Resistance-repellent retroviral protease inhibitors |
| US7157489B2 (en) | 2002-03-12 | 2007-01-02 | The Board Of Trustees Of The University Of Illinois | HIV protease inhibitors |
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| EP1520247B1 (en) | 2002-07-01 | 2009-05-27 | Tibotec Pharmaceuticals Ltd. | Mutational profiles in hiv-1 protease correlated with phenotypic drug resistance |
| OA12893A (en) * | 2002-08-02 | 2006-10-13 | Tibotec Pharm Ltd | Broadspectrum 2-Amino-Benzothiazole Sulfonamide HIV Protease Inhibitors. |
| BR0305717A (pt) * | 2002-08-02 | 2004-09-28 | Tibotec Pharm Ltd | Inibidores da protease do hiv 2-amino-benzotiazol sulfonamida de amplo espectro |
| WO2005030739A1 (en) * | 2003-09-30 | 2005-04-07 | Tibotec Pharmaceuticals Ltd. | Methods for the preparation of benzoxazole sulfonamide compounds and intermediates thereof |
| DE10360835A1 (de) * | 2003-12-23 | 2005-07-21 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclische Imidazolverbindungen, deren Herstellung und deren Verwendung als Arzneimittel |
| AU2005244121B2 (en) * | 2004-05-07 | 2012-01-19 | Sequoia Pharmaceuticals, Inc. | Resistance-repellent retroviral protease inhibitors |
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Effective date: 20160214 |