JP7221217B2 - Ｄｕｂ阻害剤としての活性を有するスルホンアミド置換シアノピロリジン - Google Patents
Ｄｕｂ阻害剤としての活性を有するスルホンアミド置換シアノピロリジン Download PDFInfo
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- JP7221217B2 JP7221217B2 JP2019561718A JP2019561718A JP7221217B2 JP 7221217 B2 JP7221217 B2 JP 7221217B2 JP 2019561718 A JP2019561718 A JP 2019561718A JP 2019561718 A JP2019561718 A JP 2019561718A JP 7221217 B2 JP7221217 B2 JP 7221217B2
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- alkyl
- compound
- independently selected
- carbonitrile
- sulfonyl
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- 239000003112 inhibitor Substances 0.000 title description 18
- 230000000694 effects Effects 0.000 title description 10
- QJRYYOWARFCJQZ-UHFFFAOYSA-N pyrrolidine-1-carbonitrile Chemical class N#CN1CCCC1 QJRYYOWARFCJQZ-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 140
- -1 cyano, hydroxy Chemical group 0.000 claims description 71
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 56
- 125000000623 heterocyclic group Chemical group 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 36
- 229910052760 oxygen Inorganic materials 0.000 claims description 30
- 229910052717 sulfur Inorganic materials 0.000 claims description 30
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 28
- 125000005843 halogen group Chemical group 0.000 claims description 27
- 125000005842 heteroatom Chemical group 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 20
- 125000001153 fluoro group Chemical group F* 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
- 125000002837 carbocyclic group Chemical group 0.000 claims description 13
- 125000004043 oxo group Chemical group O=* 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 125000003386 piperidinyl group Chemical group 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 11
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 9
- 239000005977 Ethylene Substances 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- TYDQESZKNCOCEH-AEFFLSMTSA-N N1=CC(=CC=C1)C1=CC=C(C=C1)S(=O)(=O)N1[C@@H]2[C@H](CC1)CN(C2)C#N Chemical compound N1=CC(=CC=C1)C1=CC=C(C=C1)S(=O)(=O)N1[C@@H]2[C@H](CC1)CN(C2)C#N TYDQESZKNCOCEH-AEFFLSMTSA-N 0.000 claims description 8
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- BEEMGCAOXBWJIO-ZIAGYGMSSA-N (4aR,7aR)-4-(4-methylphenyl)sulfonyl-2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazine-6-carbonitrile Chemical compound C(#N)N1C[C@@H]2[C@H](N(S(=O)(=O)C3=CC=C(C=C3)C)CCO2)C1 BEEMGCAOXBWJIO-ZIAGYGMSSA-N 0.000 claims description 7
- JIFYKOUMBCOVFM-UHFFFAOYSA-N 4-[(4-methylphenyl)methylsulfonyl]-2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazine-6-carbonitrile Chemical compound CC1=CC=C(CS(=O)(=O)N2C3C(OCC2)CN(C3)C#N)C=C1 JIFYKOUMBCOVFM-UHFFFAOYSA-N 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 229940124530 sulfonamide Drugs 0.000 claims description 7
- 150000003456 sulfonamides Chemical group 0.000 claims description 7
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 6
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000006413 ring segment Chemical group 0.000 claims description 6
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 6
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 5
- QDICTGLHTPMYLM-UHFFFAOYSA-N 1-cyano-N-(4-phenylphenyl)pyrrolidine-3-sulfonamide Chemical compound C1(=CC=C(C=C1)NS(=O)(=O)C1CN(CC1)C#N)C1=CC=CC=C1 QDICTGLHTPMYLM-UHFFFAOYSA-N 0.000 claims description 5
- HBAOUZBEZQZDDA-UHFFFAOYSA-N C(C1=CC=CC=C1)C1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N Chemical compound C(C1=CC=CC=C1)C1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N HBAOUZBEZQZDDA-UHFFFAOYSA-N 0.000 claims description 5
- GOUNALIZYDVKHO-UHFFFAOYSA-N ClC1=CC=C(C=C1)C1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N Chemical compound ClC1=CC=C(C=C1)C1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N GOUNALIZYDVKHO-UHFFFAOYSA-N 0.000 claims description 5
- GOUNALIZYDVKHO-INIZCTEOSA-N ClC1=CC=C(C=C1)C1CCN(CC1)S(=O)(=O)[C@@H]1CN(CC1)C#N Chemical compound ClC1=CC=C(C=C1)C1CCN(CC1)S(=O)(=O)[C@@H]1CN(CC1)C#N GOUNALIZYDVKHO-INIZCTEOSA-N 0.000 claims description 5
- GOUNALIZYDVKHO-MRXNPFEDSA-N ClC1=CC=C(C=C1)C1CCN(CC1)S(=O)(=O)[C@H]1CN(CC1)C#N Chemical compound ClC1=CC=C(C=C1)C1CCN(CC1)S(=O)(=O)[C@H]1CN(CC1)C#N GOUNALIZYDVKHO-MRXNPFEDSA-N 0.000 claims description 5
- WRCNLCVEVZQITB-UHFFFAOYSA-N ClC1=CC=C(C=C1)C1CN(C1)S(=O)(=O)C1CN(CC1)C#N Chemical compound ClC1=CC=C(C=C1)C1CN(C1)S(=O)(=O)C1CN(CC1)C#N WRCNLCVEVZQITB-UHFFFAOYSA-N 0.000 claims description 5
- WRCNLCVEVZQITB-AWEZNQCLSA-N ClC1=CC=C(C=C1)C1CN(C1)S(=O)(=O)[C@@H]1CN(CC1)C#N Chemical compound ClC1=CC=C(C=C1)C1CN(C1)S(=O)(=O)[C@@H]1CN(CC1)C#N WRCNLCVEVZQITB-AWEZNQCLSA-N 0.000 claims description 5
- WRCNLCVEVZQITB-CQSZACIVSA-N ClC1=CC=C(C=C1)C1CN(C1)S(=O)(=O)[C@H]1CN(CC1)C#N Chemical compound ClC1=CC=C(C=C1)C1CN(C1)S(=O)(=O)[C@H]1CN(CC1)C#N WRCNLCVEVZQITB-CQSZACIVSA-N 0.000 claims description 5
- LWHZBVOWIRURSN-UHFFFAOYSA-N FC1=CC=C(C=C1)N1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N Chemical compound FC1=CC=C(C=C1)N1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N LWHZBVOWIRURSN-UHFFFAOYSA-N 0.000 claims description 5
- TWONXSWEDQMNGI-UHFFFAOYSA-N N1=C(C=CC=C1)N1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N Chemical compound N1=C(C=CC=C1)N1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N TWONXSWEDQMNGI-UHFFFAOYSA-N 0.000 claims description 5
- ZSDGNUMYZTWCOB-UHFFFAOYSA-N N1=C(N=CC=C1)N1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N Chemical compound N1=C(N=CC=C1)N1CCN(CC1)S(=O)(=O)C1CN(CC1)C#N ZSDGNUMYZTWCOB-UHFFFAOYSA-N 0.000 claims description 5
- 125000004450 alkenylene group Chemical group 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000002393 azetidinyl group Chemical group 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 5
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- VHNGRZVOMQENBT-UHFFFAOYSA-N O(C1=CC=CC=C1)C1CN(C1)S(=O)(=O)C1CN(CC1)C#N Chemical compound O(C1=CC=CC=C1)C1CN(C1)S(=O)(=O)C1CN(CC1)C#N VHNGRZVOMQENBT-UHFFFAOYSA-N 0.000 claims description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 31
- 238000000034 method Methods 0.000 description 29
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
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- 238000013518 transcription Methods 0.000 description 1
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- 238000001890 transfection Methods 0.000 description 1
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- 238000011830 transgenic mouse model Methods 0.000 description 1
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- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
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- 229960000281 trometamol Drugs 0.000 description 1
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- 150000003751 zinc Chemical class 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical class [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 to ring carbon atoms
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (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)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| GBGB1708652.1A GB201708652D0 (en) | 2017-05-31 | 2017-05-31 | Novel compounds and uses |
| GB1708652.1 | 2017-05-31 | ||
| PCT/GB2018/051454 WO2018220355A1 (en) | 2017-05-31 | 2018-05-30 | Sulfonamide-substituted cyanopyrrolidines with activity as dub inhibitors |
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| JP2020521730A JP2020521730A (ja) | 2020-07-27 |
| JP2020521730A5 JP2020521730A5 (enExample) | 2021-07-26 |
| JP7221217B2 true JP7221217B2 (ja) | 2023-02-13 |
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| Country | Link |
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| US (1) | US11414402B2 (enExample) |
| EP (1) | EP3630096A1 (enExample) |
| JP (1) | JP7221217B2 (enExample) |
| CN (1) | CN110678176B (enExample) |
| GB (1) | GB201708652D0 (enExample) |
| MA (1) | MA48765A (enExample) |
| WO (1) | WO2018220355A1 (enExample) |
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| US11014912B2 (en) | 2016-09-27 | 2021-05-25 | Mission Therapeutics Limited | Cyanopyrrolidine derivatives with activity as inhibitors of USP30 |
| GB201616511D0 (en) | 2016-09-29 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| GB201616627D0 (en) | 2016-09-30 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| TWI771327B (zh) | 2016-10-05 | 2022-07-21 | 英商使命醫療公司 | 新穎化合物 |
| WO2018234775A1 (en) | 2017-06-20 | 2018-12-27 | Mission Therapeutics Limited | Substituted cyanopyrrolidines with activity as dub inhibitors |
| CA3072362A1 (en) | 2017-10-06 | 2019-04-11 | Forma Therapeutics, Inc. | Inhibiting ubiquitin specific peptidase 30 |
| SG11202011299PA (en) | 2018-05-17 | 2020-12-30 | Forma Therapeutics Inc | Fused bicyclic compounds useful as ubiquitin-specific peptidase 30 inhibitors |
| MY209034A (en) | 2018-10-05 | 2025-06-17 | Forma Therapeutics Inc | Fused pyrrolines which act as ubiquitin-specific protease 30 (usp30) inhibitors |
| AU2020215510B2 (en) | 2019-01-28 | 2025-03-06 | Mitochondria Emotion, Inc. | Trans-4-hydroxycyclohexyl phenyl amide mitofusin activators and methods of use thereof |
| CA3127590A1 (en) | 2019-01-28 | 2020-08-06 | Mitochondria Emotion, Inc. | Mitofusin activators and methods of use thereof |
| GB201905375D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
| GB201905371D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
| GB201912674D0 (en) | 2019-09-04 | 2019-10-16 | Mission Therapeutics Ltd | Novel compounds |
| EP4132925A1 (en) | 2020-04-08 | 2023-02-15 | Mission Therapeutics Limited | N-cyanopyrrolidines with activity as usp30 inhibitors |
| MX2022014429A (es) | 2020-05-28 | 2022-12-07 | Mission Therapeutics Ltd | N-cianopirrolidinas con actividad como inhibidores de usp30. |
| KR20230019198A (ko) | 2020-06-04 | 2023-02-07 | 미션 테라퓨틱스 엘티디 | Usp30 억제제로서의 활성을 갖는 n-시아노피롤리딘 |
| HRP20250891T1 (hr) | 2020-06-08 | 2025-09-26 | Mission Therapeutics Limited | 1-(5-(2-cijanopiridin-4-il)oksazol-2-karbonil)-4-metilheksahidropirolo[3,4-b]pirol-5(1h)-karbonitril kao usp30 inhibitor za primjenu u liječenju mitohondrijske disfunkcije, raka i fibroze |
| GB202016800D0 (en) | 2020-10-22 | 2020-12-09 | Mission Therapeutics Ltd | Novel compounds |
| WO2022159566A1 (en) * | 2021-01-21 | 2022-07-28 | Icahn School Of Medicine At Mount Sinai | Benzenesulfonamide agonists of trap1 for treating organ fibrosis |
| EP4441044A1 (en) | 2021-12-01 | 2024-10-09 | Mission Therapeutics Limited | Substituted n-cyanopyrrolidines with activity as usp30 inhibitors |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009026197A1 (en) | 2007-08-20 | 2009-02-26 | Glaxo Group Limited | Novel cathepsin c inhibitors and their use |
| WO2009129365A1 (en) | 2008-04-18 | 2009-10-22 | Glaxo Group Limited | Cathepsin c inhibitors |
| WO2009129371A1 (en) | 2008-04-18 | 2009-10-22 | Glaxo Group Limited | Cathepsin c inhibitors |
| WO2009129370A1 (en) | 2008-04-18 | 2009-10-22 | Glaxo Group Limited | Cathepsin c inhibitors |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1272467A4 (en) * | 2000-04-06 | 2003-05-07 | Merck Frosst Canada Inc | Cathepsin cysteine protease inhibitors |
| US6867221B2 (en) * | 2001-08-30 | 2005-03-15 | Kowa Co., Ltd. | Cyclic amine compounds and pharmaceutical composition containing the same |
| CA2626190A1 (en) * | 2005-10-21 | 2007-05-03 | Vertex Pharmaceuticals Incorporated | Derivatives for modulation of ion channels |
| CA2689989A1 (en) | 2007-06-04 | 2008-12-11 | Avila Therapeutics, Inc. | Heterocyclic compounds and uses thereof |
| EP2565186A1 (en) | 2011-09-02 | 2013-03-06 | Hybrigenics S.A. | Selective and reversible inhibitors of ubiquitin specific protease 7 |
| CN103183673B (zh) | 2011-12-30 | 2016-09-14 | 浙江新和成股份有限公司 | (s,s)-2,8-二氮杂双环[4,3,0]壬烷的合成方法 |
| SG11201600159TA (en) | 2013-07-31 | 2016-02-26 | Merck Patent Gmbh | Pyridines, pyrimidines, and pyrazines, as btk inhibitors and uses thereof |
| WO2015179190A1 (en) | 2014-05-19 | 2015-11-26 | Northeastern University | N-acylethanolamine hydrolyzing acid amidase (naaa) inhibitors and their use thereof |
| EP3148572A4 (en) | 2014-05-27 | 2017-12-27 | Pharmakea, Inc. | Compositions and methods of delivery of deubiquitinase inhibitors |
| WO2016019237A2 (en) | 2014-07-31 | 2016-02-04 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| GB201416754D0 (en) | 2014-09-23 | 2014-11-05 | Mission Therapeutics Ltd | Novel compounds |
| RU2717238C2 (ru) | 2015-03-30 | 2020-03-19 | Мишн Терапьютикс Лимитед | Соединения 1-циано-пирролидинов в качестве ингибиторов USP30 |
| US10669234B2 (en) * | 2015-07-14 | 2020-06-02 | Mission Therapeutics Limited | Cyanopyrrolidines as dub inhibitors for the treatment of cancer |
| GB201521109D0 (en) | 2015-11-30 | 2016-01-13 | Mission Therapeutics Ltd | Novel compounds |
| GB201522267D0 (en) | 2015-12-17 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| GB201522768D0 (en) | 2015-12-23 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| GB201602854D0 (en) | 2016-02-18 | 2016-04-06 | Mission Therapeutics Ltd | Novel compounds |
| GB201603779D0 (en) | 2016-03-04 | 2016-04-20 | Mission Therapeutics Ltd | Novel compounds |
| GB201604638D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| GB201604647D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| JP6959252B2 (ja) | 2016-03-24 | 2021-11-02 | ミッション セラピューティクス リミティド | Ｄｕｂ阻害剤としての１−シアノピロリジン誘導体 |
| US11014912B2 (en) | 2016-09-27 | 2021-05-25 | Mission Therapeutics Limited | Cyanopyrrolidine derivatives with activity as inhibitors of USP30 |
| GB201616511D0 (en) | 2016-09-29 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| GB201616627D0 (en) | 2016-09-30 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| TWI771327B (zh) | 2016-10-05 | 2022-07-21 | 英商使命醫療公司 | 新穎化合物 |
| WO2018234775A1 (en) | 2017-06-20 | 2018-12-27 | Mission Therapeutics Limited | Substituted cyanopyrrolidines with activity as dub inhibitors |
-
2017
- 2017-05-31 GB GBGB1708652.1A patent/GB201708652D0/en not_active Ceased
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2018
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- 2018-05-30 MA MA048765A patent/MA48765A/fr unknown
- 2018-05-30 JP JP2019561718A patent/JP7221217B2/ja active Active
- 2018-05-30 CN CN201880035657.8A patent/CN110678176B/zh active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009026197A1 (en) | 2007-08-20 | 2009-02-26 | Glaxo Group Limited | Novel cathepsin c inhibitors and their use |
| WO2009129365A1 (en) | 2008-04-18 | 2009-10-22 | Glaxo Group Limited | Cathepsin c inhibitors |
| WO2009129371A1 (en) | 2008-04-18 | 2009-10-22 | Glaxo Group Limited | Cathepsin c inhibitors |
| WO2009129370A1 (en) | 2008-04-18 | 2009-10-22 | Glaxo Group Limited | Cathepsin c inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| ACS Med. Chem. Lett.，2011年，Vol.2，pp.142-147 |
Also Published As
| Publication number | Publication date |
|---|---|
| MA48765A (fr) | 2020-04-08 |
| EP3630096A1 (en) | 2020-04-08 |
| CN110678176A (zh) | 2020-01-10 |
| GB201708652D0 (en) | 2017-07-12 |
| WO2018220355A1 (en) | 2018-12-06 |
| US20200172518A1 (en) | 2020-06-04 |
| US11414402B2 (en) | 2022-08-16 |
| JP2020521730A (ja) | 2020-07-27 |
| CN110678176B (zh) | 2023-03-14 |
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