ES2532703T3 - Derivados de 3-amino-pirazol útiles contra la tuberculosis - Google Patents
Derivados de 3-amino-pirazol útiles contra la tuberculosis Download PDFInfo
- Publication number
- ES2532703T3 ES2532703T3 ES11771075.6T ES11771075T ES2532703T3 ES 2532703 T3 ES2532703 T3 ES 2532703T3 ES 11771075 T ES11771075 T ES 11771075T ES 2532703 T3 ES2532703 T3 ES 2532703T3
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- Prior art keywords
- methyl
- mmol
- compound
- nmr
- pyrazol
- Prior art date
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- 201000008827 tuberculosis Diseases 0.000 title claims description 29
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 203
- 150000003839 salts Chemical class 0.000 claims abstract description 50
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 25
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 17
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 13
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 11
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims abstract description 9
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 9
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 8
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 7
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 5
- -1 4-methyl-1,3-thiazol-2-yl Chemical group 0.000 claims description 111
- 238000011282 treatment Methods 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000005945 imidazopyridyl group Chemical group 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- RGYFTFFDGKEMOM-UHFFFAOYSA-N 1-(4-ethyl-1,3-thiazol-2-yl)-1-[5-[[1-[(2-methyl-1,3-thiazol-4-yl)methyl]pyrazol-3-yl]amino]-1,3,4-thiadiazol-2-yl]ethanol Chemical compound CCC1=CSC(C(C)(O)C=2SC(NC3=NN(CC=4N=C(C)SC=4)C=C3)=NN=2)=N1 RGYFTFFDGKEMOM-UHFFFAOYSA-N 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000000842 isoxazolyl 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
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- RPXZUCOCEKQSRG-INIZCTEOSA-N (1s)-1-(4-methyl-1,3-thiazol-2-yl)-1-[5-[[1-[(2-methyl-1,3-thiazol-4-yl)methyl]pyrazol-3-yl]amino]-1,3,4-thiadiazol-2-yl]ethanol Chemical compound CC1=CSC([C@](C)(O)C=2SC(NC3=NN(CC=4N=C(C)SC=4)C=C3)=NN=2)=N1 RPXZUCOCEKQSRG-INIZCTEOSA-N 0.000 claims 1
- CNNABHCCUHSVOG-KRWDZBQOSA-N (1s)-1-[5-[[1-[(3-fluoropyridin-2-yl)methyl]pyrazol-3-yl]amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethanol Chemical compound CC1=CSC([C@](C)(O)C=2SC(NC3=NN(CC=4C(=CC=CN=4)F)C=C3)=NN=2)=N1 CNNABHCCUHSVOG-KRWDZBQOSA-N 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 297
- 238000000132 electrospray ionisation Methods 0.000 description 153
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 91
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 85
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 58
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
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- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 19
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- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
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- 239000003480 eluent Substances 0.000 description 13
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 102000036639 antigens Human genes 0.000 description 12
- 108091007433 antigens Proteins 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 125000003373 pyrazinyl group Chemical group 0.000 description 11
- 239000000377 silicon dioxide Substances 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 241000282412 Homo Species 0.000 description 10
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 238000002953 preparative HPLC Methods 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 9
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- 150000002540 isothiocyanates Chemical class 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
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- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 8
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 7
- 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 description 7
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- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- KBGNMMALBRNKSH-UHFFFAOYSA-N tert-butyl n-[4-(bromomethyl)-1,3-thiazol-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=NC(CBr)=CS1 KBGNMMALBRNKSH-UHFFFAOYSA-N 0.000 description 1
- OWLBQQTUOQLZST-UHFFFAOYSA-N tert-butyl n-[4-(hydroxymethyl)-1,3-thiazol-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=NC(CO)=CS1 OWLBQQTUOQLZST-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229960003500 triclosan Drugs 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
Classifications
-
- 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
- C07D417/14—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 three or more hetero rings
-
- 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
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10382266 | 2010-10-13 | ||
| EP10382266 | 2010-10-13 | ||
| PCT/EP2011/067705 WO2012049161A1 (en) | 2010-10-13 | 2011-10-11 | 3 -amino- pyrazole derivatives useful against tuberculosis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2532703T3 true ES2532703T3 (es) | 2015-03-31 |
Family
ID=44924357
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11771075.6T Active ES2532703T3 (es) | 2010-10-13 | 2011-10-11 | Derivados de 3-amino-pirazol útiles contra la tuberculosis |
Country Status (5)
| Country | Link |
|---|---|
| US (3) | US8779153B2 (enExample) |
| EP (1) | EP2627653B1 (enExample) |
| JP (1) | JP5855668B2 (enExample) |
| ES (1) | ES2532703T3 (enExample) |
| WO (1) | WO2012049161A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8779153B2 (en) * | 2010-10-13 | 2014-07-15 | Glaxo Group Limited | 3-amino-pyrazole derivatives useful against tuberculosis |
| PT106651A (pt) * | 2012-11-20 | 2014-05-20 | Tecnimede Sociedade Tecnico Medicinal S A | Quinolil hidrazonas para o tratamento de tuberculose e doenças relacionadas |
| US9546138B2 (en) | 2012-12-13 | 2017-01-17 | Novartis Ag | Pyridone derivatives and uses thereof in the treatment of tuberculosis |
| WO2016138335A1 (en) | 2015-02-27 | 2016-09-01 | Lycera Corporation | Indazolyl thiadiazolamines and related compounds for inhibition of rho-associated protein kinase and the treatment of disease |
| WO2018039539A1 (en) | 2016-08-26 | 2018-03-01 | Lycera Corporation | Indazolyl-l,2,4-thiadiazolamines and related compounds for inhibition of rho-associated protein kinase and the treatment of disease |
| US12404265B2 (en) | 2020-08-04 | 2025-09-02 | Nura Bio, Inc. | Substituted pyridine derivatives as SARM1 inhibitors |
| WO2022060812A1 (en) * | 2020-09-16 | 2022-03-24 | Nura Bio, Inc. | Substituted pyridine derivatives as sarm1 inhibitors |
| CA3226869A1 (en) | 2021-07-28 | 2023-02-02 | Rao Kolluri | Substituted pyridine derivatives as sarm1 inhibitors |
| US11807640B1 (en) | 2023-03-28 | 2023-11-07 | King Faisal University | 7-isopropyl 1-ethyl/methyl 3-(substituted benzoyl)-2-substituted indolizine-1,7-dicarboxylates as anti-tubercular agents |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010058423A2 (en) * | 2008-11-20 | 2010-05-27 | Panacea Biotec Ltd. | Novel antimicrobials |
| US8779153B2 (en) * | 2010-10-13 | 2014-07-15 | Glaxo Group Limited | 3-amino-pyrazole derivatives useful against tuberculosis |
-
2011
- 2011-10-11 US US13/878,889 patent/US8779153B2/en active Active
- 2011-10-11 EP EP11771075.6A patent/EP2627653B1/en active Active
- 2011-10-11 ES ES11771075.6T patent/ES2532703T3/es active Active
- 2011-10-11 WO PCT/EP2011/067705 patent/WO2012049161A1/en not_active Ceased
- 2011-10-11 JP JP2013533184A patent/JP5855668B2/ja active Active
-
2014
- 2014-06-04 US US14/295,589 patent/US9000181B2/en active Active
-
2015
- 2015-03-05 US US14/639,241 patent/US9334265B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US8779153B2 (en) | 2014-07-15 |
| EP2627653A1 (en) | 2013-08-21 |
| US20130203802A1 (en) | 2013-08-08 |
| US20150307485A1 (en) | 2015-10-29 |
| US9000181B2 (en) | 2015-04-07 |
| US20140288133A1 (en) | 2014-09-25 |
| EP2627653B1 (en) | 2014-12-24 |
| WO2012049161A1 (en) | 2012-04-19 |
| JP5855668B2 (ja) | 2016-02-09 |
| US9334265B2 (en) | 2016-05-10 |
| JP2013539774A (ja) | 2013-10-28 |
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