EA023857B1 - Сочлененные производные пиримидиндионов в качестве модуляторов trpa1 - Google Patents
Сочлененные производные пиримидиндионов в качестве модуляторов trpa1 Download PDFInfo
- Publication number
- EA023857B1 EA023857B1 EA201190143A EA201190143A EA023857B1 EA 023857 B1 EA023857 B1 EA 023857B1 EA 201190143 A EA201190143 A EA 201190143A EA 201190143 A EA201190143 A EA 201190143A EA 023857 B1 EA023857 B1 EA 023857B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- acetamide
- thiazol
- pyrimidin
- dioxo
- phenyl
- Prior art date
Links
- 150000008512 pyrimidinediones Chemical class 0.000 title abstract description 3
- 101100482465 Caenorhabditis elegans trpa-1 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 222
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 300
- -1 2,2-dimethylpropoxy Chemical group 0.000 claims description 245
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 112
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 86
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 6
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 6
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 6
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 5
- PBMQQKUDOPKOMR-UHFFFAOYSA-N n-[4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(C=2C=C(F)C(=CC=2)C(F)(F)F)=C1 PBMQQKUDOPKOMR-UHFFFAOYSA-N 0.000 claims description 5
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 4
- 125000001331 3-methylbutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
- NLDCRIGVFPWIIR-UHFFFAOYSA-N n-[4-[4-(2,2-dimethylpropoxy)-3,5-difluorophenyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(C=2C=C(F)C(OCC(C)(C)C)=C(F)C=2)=C1 NLDCRIGVFPWIIR-UHFFFAOYSA-N 0.000 claims description 3
- WGSXKYXKAARAKD-UHFFFAOYSA-N 1-fluoro-3-isocyanato-5-(trifluoromethyl)benzene Chemical group FC1=CC(N=C=O)=CC(C(F)(F)F)=C1 WGSXKYXKAARAKD-UHFFFAOYSA-N 0.000 claims description 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- DUWJSLHJSLFDCX-UHFFFAOYSA-N N-[4-[4-(cyclopropylmethoxy)-3,5-difluorophenyl]-1,3-thiazol-2-yl]acetamide Chemical compound CC(=O)NC1=NC(=CS1)C1=CC(F)=C(OCC2CC2)C(F)=C1 DUWJSLHJSLFDCX-UHFFFAOYSA-N 0.000 claims 1
- 238000003776 cleavage reaction Methods 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 230000007017 scission Effects 0.000 claims 1
- XPDWGBQVDMORPB-UHFFFAOYSA-N trifluoromethane acid Natural products FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 217
- 239000000543 intermediate Substances 0.000 abstract description 132
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 28
- 230000015572 biosynthetic process Effects 0.000 abstract description 19
- 238000003786 synthesis reaction Methods 0.000 abstract description 17
- 201000010099 disease Diseases 0.000 abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 11
- 230000001052 transient effect Effects 0.000 abstract description 4
- 230000008569 process Effects 0.000 abstract description 3
- 239000007787 solid Substances 0.000 description 122
- 238000005160 1H NMR spectroscopy Methods 0.000 description 102
- 238000010168 coupling process Methods 0.000 description 94
- 230000008878 coupling Effects 0.000 description 89
- 238000005859 coupling reaction Methods 0.000 description 89
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- 239000011541 reaction mixture Substances 0.000 description 44
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 37
- 125000000217 alkyl group Chemical group 0.000 description 36
- 239000002904 solvent Substances 0.000 description 34
- 239000000047 product Substances 0.000 description 33
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- 239000000203 mixture Substances 0.000 description 28
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 239000002585 base Substances 0.000 description 25
- 229910052736 halogen Inorganic materials 0.000 description 25
- 208000002193 Pain Diseases 0.000 description 21
- 125000003118 aryl group Chemical group 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 125000001188 haloalkyl group Chemical group 0.000 description 17
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 17
- 125000000753 cycloalkyl group Chemical group 0.000 description 16
- 229920002554 vinyl polymer Polymers 0.000 description 16
- 150000002367 halogens Chemical class 0.000 description 15
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000013256 coordination polymer Substances 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 229960000583 acetic acid Drugs 0.000 description 13
- 125000003342 alkenyl group Chemical group 0.000 description 13
- 125000000304 alkynyl group Chemical group 0.000 description 13
- 229910052740 iodine Inorganic materials 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 125000003545 alkoxy group Chemical group 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 12
- 125000004438 haloalkoxy group Chemical group 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 12
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 12
- 208000001321 ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 1 Diseases 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- SGLPRIIINMCHCW-UHFFFAOYSA-N 5h-pyrimidine-2,4-dione Chemical compound O=C1CC=NC(=O)N1 SGLPRIIINMCHCW-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 125000000392 cycloalkenyl group Chemical group 0.000 description 9
- 125000005843 halogen group Chemical group 0.000 description 9
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- 101150040795 EIS1 gene Proteins 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical class O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 125000003710 aryl alkyl group Chemical group 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 125000004093 cyano group Chemical group *C#N 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
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- 230000002152 alkylating effect Effects 0.000 description 6
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- 239000012043 crude product Substances 0.000 description 6
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- 239000011630 iodine Substances 0.000 description 6
- 210000000929 nociceptor Anatomy 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
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- 238000003756 stirring Methods 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
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- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 4
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- 238000004458 analytical method Methods 0.000 description 4
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
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- QGLVEAGMVUQOJP-UHFFFAOYSA-N prop-2-enylboronic acid Chemical compound OB(O)CC=C QGLVEAGMVUQOJP-UHFFFAOYSA-N 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- XLMRXVYIMICZOL-UHFFFAOYSA-N 2-(2-bromo-1,3-thiazol-4-yl)acetamide Chemical compound NC(=O)CC1=CSC(Br)=N1 XLMRXVYIMICZOL-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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| RU2674977C2 (ru) * | 2013-10-30 | 2018-12-14 | Шанхай Хэнжуй Фармасьютикал Ко., Лтд. | Производные пиразолопиримидона или пирролотриазона, способ их получения и их фармацевтические применения |
| RU2741788C1 (ru) * | 2017-07-28 | 2021-01-28 | Цзянсу Хэнжуй Медицин Ко., Лтд. | Способ получения гетероарильного производного пиримидона и промежуточного соединения гетероарильного производного пиримидона |
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| EA023857B1 (ru) | 2009-03-23 | 2016-07-29 | Гленмарк Фармасеутикалс С.А. | Сочлененные производные пиримидиндионов в качестве модуляторов trpa1 |
| JP5694560B2 (ja) | 2010-12-20 | 2015-04-01 | グレンマーク ファーマシューティカルズ， エセ．アー． | Ｔｒｐａ１アンタゴニストとしての２−アミノ−４−アリールチアゾール化合物 |
| AR084433A1 (es) | 2010-12-22 | 2013-05-15 | Ironwood Pharmaceuticals Inc | Inhibidores de la faah y composiciones farmaceuticas que los contienen |
| EP2520566A1 (en) | 2011-05-06 | 2012-11-07 | Orion Corporation | New Pharmaceutical Compounds |
| CN103826637A (zh) | 2011-06-13 | 2014-05-28 | 格兰马克药品股份有限公司 | 使用trpa1拮抗剂治疗呼吸疾患 |
| US20140107113A1 (en) | 2011-06-22 | 2014-04-17 | Glenmark Pharmaceuticals S.A. | Pharmaceutical composition comprising a trpa1 antagonist and a beta-2 agonist |
| WO2012176105A1 (en) | 2011-06-22 | 2012-12-27 | Glenmark Pharmaceuticals Sa | Pharmaceutical composition comprising a trpa1 antagonist and a leukotriene receptor antagonist |
| WO2013014597A1 (en) | 2011-07-25 | 2013-01-31 | Glenmark Pharmaceuticals Sa | Pharmaceutical composition comprising a trpa1 antagonist and a steroid |
| CN103265543A (zh) | 2011-08-09 | 2013-08-28 | 丘比斯特药物股份有限公司 | 抑制瞬时受体电位离子通道trpa1 |
| EP2787991A1 (en) | 2011-12-05 | 2014-10-15 | Glenmark Pharmaceuticals S.A. | Pharmaceutical composition comprising a trpa1 antagonist and an anticholinergic agent |
| JP6182072B2 (ja) | 2012-01-17 | 2017-08-16 | Ｅａファーマ株式会社 | 複素環アミド誘導体及びそれを含有する医薬 |
| NZ701721A (en) | 2012-06-08 | 2016-03-31 | Glenmark Pharmaceuticals Sa | Amides of 2-amino-4-arylthiazole compounds and their salts |
| NZ706989A (en) | 2012-10-01 | 2018-07-27 | Orion Corp | N-prop-2-ynyl carboxamide derivatives and their use as trpa1 antagonists |
| US9394308B2 (en) | 2013-01-18 | 2016-07-19 | Merck Sharp & Dohme Corp. | Inhibiting the transient receptor potential A1 ion channel |
| US9532988B2 (en) | 2013-10-15 | 2017-01-03 | Glenmark Pharmaceuticals S.A. | Pharmaceutical composition comprising a TRPA1 antagonist and an analgesic agent |
| CN103755705B (zh) * | 2014-02-17 | 2017-02-15 | 上海佰特因医药科技有限公司 | 一种天然产物四甲基尿酸的全合成方法 |
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| WO2016042501A1 (en) | 2014-09-16 | 2016-03-24 | Glenmark Pharmaceuticals S.A. | Trpa1 antagonist for the treatment of pain associated to diabetic neuropathic pain |
| CN105001170A (zh) * | 2015-07-13 | 2015-10-28 | 佛山市赛维斯医药科技有限公司 | 末端腈基取代的三氮唑亚砜类化合物、其制备方法及其用途 |
| WO2017060488A1 (en) | 2015-10-09 | 2017-04-13 | Almirall, S.A. | New trpa1 antagonists |
| WO2017064068A1 (en) | 2015-10-14 | 2017-04-20 | Almirall, S.A. | New trpa1 antagonists |
| CN109422749B (zh) * | 2017-08-21 | 2023-01-24 | 重庆医药工业研究院有限责任公司 | 一种抑制单羧酸转运蛋白的嘧啶二酮衍生物 |
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| CN108558836A (zh) * | 2018-05-14 | 2018-09-21 | 东南大学 | 一类具有双重作用机制的dpp-4抑制剂及其用途 |
| WO2023096915A1 (en) * | 2021-11-24 | 2023-06-01 | Slap Pharmaceuticals Llc | Multicyclic compounds |
| MX2024009581A (es) * | 2022-02-03 | 2024-08-13 | De Shaw Res Llc | Compuestos de uracilo n3-sustituidos como inhibidores de trpa1. |
| JP2025510646A (ja) * | 2022-03-14 | 2025-04-15 | スラップ ファーマシューティカルズ エルエルシー | 多環式化合物 |
| CN114656472B (zh) * | 2022-04-27 | 2023-07-04 | 成都施贝康生物医药科技有限公司 | 吡唑并嘧啶类化合物、异构体或盐及其制备方法和用途 |
| CN114656473B (zh) * | 2022-04-27 | 2023-09-29 | 成都施贝康生物医药科技有限公司 | 吡咯并嘧啶类化合物、异构体或盐及其制备方法和用途 |
| CN114656480B (zh) * | 2022-04-27 | 2024-01-26 | 成都施贝康生物医药科技有限公司 | 噻吩并嘧啶类化合物、异构体或盐及其制备方法和用途 |
| CN118373832B (zh) * | 2023-01-20 | 2025-01-28 | 深圳晶蛋生物医药科技有限公司 | 大环类化合物、其药物组合物及其应用 |
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| RU2674977C2 (ru) * | 2013-10-30 | 2018-12-14 | Шанхай Хэнжуй Фармасьютикал Ко., Лтд. | Производные пиразолопиримидона или пирролотриазона, способ их получения и их фармацевтические применения |
| RU2741788C1 (ru) * | 2017-07-28 | 2021-01-28 | Цзянсу Хэнжуй Медицин Ко., Лтд. | Способ получения гетероарильного производного пиримидона и промежуточного соединения гетероарильного производного пиримидона |
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