JP7046959B2 - チエノピリミジン誘導体及び医薬におけるその使用 - Google Patents
チエノピリミジン誘導体及び医薬におけるその使用 Download PDFInfo
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- JP7046959B2 JP7046959B2 JP2019538620A JP2019538620A JP7046959B2 JP 7046959 B2 JP7046959 B2 JP 7046959B2 JP 2019538620 A JP2019538620 A JP 2019538620A JP 2019538620 A JP2019538620 A JP 2019538620A JP 7046959 B2 JP7046959 B2 JP 7046959B2
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- 239000003814 drug Substances 0.000 title description 7
- RBNBDIMXFJYDLQ-UHFFFAOYSA-N thieno[3,2-d]pyrimidine Chemical class C1=NC=C2SC=CC2=N1 RBNBDIMXFJYDLQ-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 319
- -1 hydroxy, amino Chemical group 0.000 claims description 315
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 143
- 125000000217 alkyl group Chemical group 0.000 claims description 102
- 229910052739 hydrogen Inorganic materials 0.000 claims description 72
- 229910052805 deuterium Inorganic materials 0.000 claims description 68
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 66
- 229910052794 bromium Inorganic materials 0.000 claims description 63
- 229910052801 chlorine Inorganic materials 0.000 claims description 62
- 125000000623 heterocyclic group Chemical group 0.000 claims description 62
- 229910052731 fluorine Inorganic materials 0.000 claims description 61
- 229910052740 iodine Inorganic materials 0.000 claims description 57
- 125000003545 alkoxy group Chemical group 0.000 claims description 56
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 51
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 51
- 125000001424 substituent group Chemical group 0.000 claims description 44
- 208000035475 disorder Diseases 0.000 claims description 36
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 36
- 125000004122 cyclic group Chemical group 0.000 claims description 35
- 102000000452 Acetyl-CoA carboxylase Human genes 0.000 claims description 34
- 108010016219 Acetyl-CoA carboxylase Proteins 0.000 claims description 34
- 108010018763 Biotin carboxylase Proteins 0.000 claims description 34
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 31
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 30
- 229920006395 saturated elastomer Polymers 0.000 claims description 29
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 28
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 27
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 26
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000002971 oxazolyl group Chemical group 0.000 claims description 18
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 18
- 150000001204 N-oxides Chemical class 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 17
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 17
- 125000002883 imidazolyl group Chemical group 0.000 claims description 17
- 125000001624 naphthyl group Chemical group 0.000 claims description 17
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 17
- 125000000335 thiazolyl group Chemical group 0.000 claims description 17
- 125000001544 thienyl group Chemical group 0.000 claims description 17
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000001425 triazolyl group Chemical group 0.000 claims description 16
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 15
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 15
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 15
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 15
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 15
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 14
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 13
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims description 12
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 12
- 230000001613 neoplastic effect Effects 0.000 claims description 12
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 12
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 12
- 206010022489 Insulin Resistance Diseases 0.000 claims description 11
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- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 235000020824 obesity Nutrition 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 10
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 10
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 9
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 9
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 9
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 9
- 125000002757 morpholinyl group Chemical group 0.000 claims description 9
- 125000004193 piperazinyl group Chemical group 0.000 claims description 9
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 9
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 9
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 9
- 125000006642 (C1-C6) cyanoalkyl group Chemical group 0.000 claims description 8
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 8
- 125000005936 piperidyl group Chemical group 0.000 claims description 8
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 7
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 7
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims description 6
- 206010029098 Neoplasm skin Diseases 0.000 claims description 6
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 6
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 6
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 6
- 201000001441 melanoma Diseases 0.000 claims description 6
- 201000002528 pancreatic cancer Diseases 0.000 claims description 6
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 239000003981 vehicle Substances 0.000 claims description 6
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 5
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
- 206010014733 Endometrial cancer Diseases 0.000 claims description 5
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 4
- 208000030159 metabolic disease Diseases 0.000 claims description 3
- 208000015347 renal cell adenocarcinoma Diseases 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 514
- 239000000203 mixture Substances 0.000 description 509
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 290
- 235000019439 ethyl acetate Nutrition 0.000 description 218
- 239000000243 solution Substances 0.000 description 171
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 155
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 152
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 116
- 238000001819 mass spectrum Methods 0.000 description 103
- 239000004698 Polyethylene Substances 0.000 description 102
- 239000000706 filtrate Substances 0.000 description 102
- 239000007787 solid Substances 0.000 description 100
- 150000002500 ions Chemical class 0.000 description 98
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 91
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
- 239000002904 solvent Substances 0.000 description 86
- 238000000967 suction filtration Methods 0.000 description 80
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 79
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 65
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 65
- 235000010290 biphenyl Nutrition 0.000 description 63
- 239000004305 biphenyl Substances 0.000 description 63
- 125000006267 biphenyl group Chemical group 0.000 description 63
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 63
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 62
- 238000010898 silica gel chromatography Methods 0.000 description 59
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 58
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 57
- 239000000741 silica gel Substances 0.000 description 55
- 229910002027 silica gel Inorganic materials 0.000 description 55
- 239000000460 chlorine Substances 0.000 description 49
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 47
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 44
- 239000003921 oil Substances 0.000 description 42
- 235000019198 oils Nutrition 0.000 description 42
- 239000011734 sodium Substances 0.000 description 42
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- 238000006243 chemical reaction Methods 0.000 description 40
- 239000012074 organic phase Substances 0.000 description 39
- 239000011541 reaction mixture Substances 0.000 description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 38
- 239000012044 organic layer Substances 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 239000012230 colorless oil Substances 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 239000002253 acid Substances 0.000 description 29
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
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- 125000004432 carbon atom Chemical group C* 0.000 description 23
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 22
- 239000000651 prodrug Substances 0.000 description 20
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- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 19
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- 229910000104 sodium hydride Inorganic materials 0.000 description 19
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- 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 8
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
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- Organic Chemistry (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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| PCT/CN2018/073581 WO2018133858A1 (en) | 2017-01-22 | 2018-01-22 | Thienopyrimidine derivative and use thereof in medicine |
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| CN108699078A (zh) | 2016-03-02 | 2018-10-23 | 吉利德阿波罗公司 | 噻吩并嘧啶二酮acc抑制剂的固体形式及其制备方法 |
| ES2963841T3 (es) * | 2017-03-03 | 2024-04-02 | Gilead Sciences Inc | Procesos para preparar inhibidores de ACC y formas sólidas del mismo |
| EP4122464B1 (en) | 2017-03-28 | 2024-05-15 | Gilead Sciences, Inc. | Therapeutic combinations for treating liver diseases |
| CA3070525C (en) * | 2017-07-26 | 2022-03-15 | Nanjing Sanhome Pharmaceutical Co., Ltd. | Compound as acc inhibitor and use thereof |
| AU2019227823B2 (en) | 2018-02-28 | 2024-12-12 | The Regents Of The University Of Colorado, A Body Corporate | WEE1 kinase inhibitors and methods of treating cancer using the same |
| CN109810085B (zh) * | 2019-04-19 | 2019-07-19 | 上海皓元生物医药科技有限公司 | Acc抑制剂及其中间体的制备方法 |
| CN111848678A (zh) * | 2019-04-30 | 2020-10-30 | 正大天晴药业集团股份有限公司 | 含磷类噻吩并嘧啶衍生物 |
| EP3995498A4 (en) * | 2019-07-02 | 2023-03-01 | Sunshine Lake Pharma Co., Ltd. | THIENOPYRIMIDINE DERIVATIVES HAVING STEREO CONFIGURATION AND THEIR USE IN MEDICINE |
| AR119594A1 (es) * | 2019-08-09 | 2021-12-29 | Gilead Sciences Inc | Derivados de tienopirimidina como inhibidores acc y usos de los mismos |
| WO2022111517A1 (zh) * | 2020-11-24 | 2022-06-02 | 正大天晴药业集团股份有限公司 | 氘修饰的噻吩并吡啶酮化合物 |
| TW202233632A (zh) * | 2021-02-07 | 2022-09-01 | 大陸商正大天晴藥業集團股份有限公司 | 噻吩并嘧啶衍生物 |
| CN117126174B (zh) * | 2022-05-26 | 2025-12-05 | 广东东阳光药业股份有限公司 | 噻吩并嘧啶类化合物的共晶及其用途 |
| TW202400151A (zh) * | 2022-05-26 | 2024-01-01 | 大陸商廣東東陽光藥業股份有限公司 | 噻吩並嘧啶類化合物的晶型及其用途 |
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| JP2014533281A (ja) | 2011-11-11 | 2014-12-11 | ニンバス アポロ， インコーポレイテッド | Ａｃｃ阻害剤およびその使用 |
| WO2015007451A1 (en) | 2013-07-15 | 2015-01-22 | Syngenta Participations Ag | Microbiocidal heterobicyclic derivatives |
| WO2016096115A1 (en) | 2014-12-17 | 2016-06-23 | Gilead Sciences, Inc. | Hydroxy containing fxr (nr1h4) modulating compounds |
| WO2016112305A1 (en) | 2015-01-09 | 2016-07-14 | Nimbus Apollo, Inc. | Acc inhibitor combination therapy for the treatment of non-alcoholic fatty liver disease |
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| DE19644228A1 (de) | 1996-10-24 | 1998-04-30 | Merck Patent Gmbh | Thienopyrimidine |
| EP1989210A2 (en) | 2006-03-02 | 2008-11-12 | Cv Therapeutics, Inc. | A2a adenosine receptor antagonists |
| BR112015028173A2 (pt) | 2013-05-10 | 2017-07-25 | Nimbus Apollo Inc | inibidores de acc e usos dos mesmos |
| JP6417403B2 (ja) | 2013-05-10 | 2018-11-07 | ギリアド アポロ， エルエルシー | Ａｃｃ阻害剤及びその使用 |
| EP2994138A4 (en) | 2013-05-10 | 2016-12-28 | Nimbus Apollo Inc | ACC-HEMMER AND USES THEREOF |
| WO2015003881A1 (en) | 2013-07-08 | 2015-01-15 | Syngenta Participations Ag | Microbiocidal heterobicyclic derivatives |
| AR106472A1 (es) | 2015-10-26 | 2018-01-17 | Gilead Apollo Llc | Inhibidores de acc y usos de los mismos |
| ES2943235T3 (es) | 2015-11-25 | 2023-06-12 | Gilead Apollo Llc | Composiciones fungicidas que contienen derivados de 2,4-dioxo-1,4-dihidrotieno[2,3-d]pirimidina |
| MX2018006287A (es) | 2015-11-25 | 2018-09-07 | Gilead Apollo Llc | Inhibidores de acc de triazol y usos de los mismos. |
| AU2016361412A1 (en) | 2015-11-25 | 2018-05-24 | Gilead Apollo, Llc | Pyrazole ACC inhibitors and uses thereof |
| KR20180082558A (ko) | 2015-11-25 | 2018-07-18 | 길리어드 아폴로, 엘엘씨 | 에스테르 acc 억제제 및 그의 용도 |
| WO2017147161A1 (en) | 2016-02-23 | 2017-08-31 | Raju Mohan | Treatment of dermatological disorders or conditions |
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| CN110431144B (zh) | 2017-03-24 | 2022-08-05 | 浙江海正药业股份有限公司 | 氰基取代的杂芳基并嘧啶酮类衍生物及其制备方法和用途 |
| WO2018171698A1 (zh) | 2017-03-24 | 2018-09-27 | 浙江海正药业股份有限公司 | 杂芳基并嘧啶酮类衍生物及其制备方法和用途 |
| CN110709402B (zh) | 2017-06-15 | 2022-05-10 | 浙江海正药业股份有限公司 | 杂芳基并嘧啶酮类衍生物、其制备方法及其在医药上用途 |
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| JP2014533281A (ja) | 2011-11-11 | 2014-12-11 | ニンバス アポロ， インコーポレイテッド | Ａｃｃ阻害剤およびその使用 |
| WO2015007451A1 (en) | 2013-07-15 | 2015-01-22 | Syngenta Participations Ag | Microbiocidal heterobicyclic derivatives |
| WO2016096115A1 (en) | 2014-12-17 | 2016-06-23 | Gilead Sciences, Inc. | Hydroxy containing fxr (nr1h4) modulating compounds |
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| CN108341830B (zh) | 2021-03-02 |
| CN108341830A (zh) | 2018-07-31 |
| WO2018133858A1 (en) | 2018-07-26 |
| EP3571205A1 (en) | 2019-11-27 |
| US10759812B2 (en) | 2020-09-01 |
| CA3049816A1 (en) | 2018-07-26 |
| EP3571205B1 (en) | 2023-08-30 |
| EP3571205A4 (en) | 2020-06-03 |
| JP2020505356A (ja) | 2020-02-20 |
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