TW201718499A - 吡啶及嘧啶衍生物 - Google Patents
吡啶及嘧啶衍生物 Download PDFInfo
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- TW201718499A TW201718499A TW105125661A TW105125661A TW201718499A TW 201718499 A TW201718499 A TW 201718499A TW 105125661 A TW105125661 A TW 105125661A TW 105125661 A TW105125661 A TW 105125661A TW 201718499 A TW201718499 A TW 201718499A
- Authority
- TW
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- Prior art keywords
- butyl
- benzamide
- tert
- methyl
- compound
- Prior art date
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title description 13
- 150000003230 pyrimidines Chemical class 0.000 title description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 title description 7
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 160
- -1 1,1-dioxo-tetrahydro-thiophen-3-yl ring Chemical group 0.000 claims abstract description 73
- 150000003839 salts Chemical class 0.000 claims abstract description 52
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 41
- 239000000203 mixture Substances 0.000 claims abstract description 40
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 37
- 239000001257 hydrogen Substances 0.000 claims abstract description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 35
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 35
- 239000002253 acid Substances 0.000 claims abstract description 34
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 20
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 20
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims abstract description 19
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 18
- 230000003287 optical effect Effects 0.000 claims abstract description 18
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 17
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 17
- 208000029560 autism spectrum disease Diseases 0.000 claims abstract description 13
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 12
- 238000011282 treatment Methods 0.000 claims abstract description 10
- 208000020925 Bipolar disease Diseases 0.000 claims abstract description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 102
- 238000002360 preparation method Methods 0.000 claims description 30
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 23
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 22
- 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 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 6
- VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 claims description 5
- ZOEKRFACRKFNGN-UHFFFAOYSA-N N-(2-cyanopropan-2-yl)-3-(4-fluorophenyl)-5-(4-propan-2-ylpyrimidin-5-yl)benzamide Chemical compound CC(C)C1=C(C=NC=N1)C1=CC(=CC(=C1)C1=CC=C(F)C=C1)C(=O)NC(C)(C)C#N ZOEKRFACRKFNGN-UHFFFAOYSA-N 0.000 claims description 3
- VHDXYQYAVCLBLU-UHFFFAOYSA-N N-(2-cyclopropylpropan-2-yl)-3-(4-fluorophenyl)-5-(4-methylpyridin-3-yl)benzamide Chemical compound C1(CC1)C(C)(C)NC(C1=CC(=CC(=C1)C=1C=NC=CC=1C)C1=CC=C(C=C1)F)=O VHDXYQYAVCLBLU-UHFFFAOYSA-N 0.000 claims description 3
- ZZDLYPDMGQKRLK-UHFFFAOYSA-N N-(2-methylbutan-2-yl)-3-(4-methylphenyl)-5-(2-propan-2-ylpyridin-3-yl)benzamide Chemical compound CC(C)(CC)NC(C1=CC(=CC(=C1)C=1C(=NC=CC=1)C(C)C)C1=CC=C(C=C1)C)=O ZZDLYPDMGQKRLK-UHFFFAOYSA-N 0.000 claims description 3
- GJCVEQGIVIDHCS-UHFFFAOYSA-N N-(2-methylbutan-2-yl)-3-(4-methylphenyl)-5-(4-methylpyridin-3-yl)benzamide Chemical compound CC(C)(CC)NC(C1=CC(=CC(=C1)C=1C=NC=CC=1C)C1=CC=C(C=C1)C)=O GJCVEQGIVIDHCS-UHFFFAOYSA-N 0.000 claims description 3
- VGVOVXHQDJDEOX-UHFFFAOYSA-N N-(2-methylbutan-2-yl)-3-(4-methylphenyl)-5-(4-propan-2-ylpyridin-3-yl)benzamide Chemical compound CC(C)(CC)NC(C1=CC(=CC(=C1)C=1C=NC=CC=1C(C)C)C1=CC=C(C=C1)C)=O VGVOVXHQDJDEOX-UHFFFAOYSA-N 0.000 claims description 3
- OYNYOBLFISJYQY-UHFFFAOYSA-N N-tert-butyl-3-(4-fluorophenyl)-5-(4-methylpyridin-3-yl)benzamide Chemical compound C(C)(C)(C)NC(C1=CC(=CC(=C1)C=1C=NC=CC=1C)C1=CC=C(C=C1)F)=O OYNYOBLFISJYQY-UHFFFAOYSA-N 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 3
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- LTCIIZCLHRORFY-UHFFFAOYSA-N N-(1-hydroxy-2-methylpropan-2-yl)-3-(4-propan-2-ylpyrimidin-5-yl)-5-[4-(trifluoromethyl)phenyl]benzamide Chemical compound OCC(C)(C)NC(C1=CC(=CC(=C1)C1=CC=C(C=C1)C(F)(F)F)C=1C(=NC=NC=1)C(C)C)=O LTCIIZCLHRORFY-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- AXUWRUFYQMLMIM-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-(2-methylpyridin-3-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)benzamide Chemical compound ClC1=CC=C(C=C1)C=1C=C(C(=O)NC(C(F)(F)F)(C)C)C=C(C=1)C=1C(=NC=CC=1)C AXUWRUFYQMLMIM-UHFFFAOYSA-N 0.000 claims 1
- USLNCQVQNHETFF-UHFFFAOYSA-N C(C)(C)(C)NC(C1=CC(=CC(=C1)C=1C(=NC=NC1)CC)C1=CC=C(C=C1)Cl)=O.C(C)(C)(C)NC(C1=CC(=CC(=C1)C=1C(=NC=NC1)C1CC1)C1=CC=C(C=C1)Cl)=O Chemical compound C(C)(C)(C)NC(C1=CC(=CC(=C1)C=1C(=NC=NC1)CC)C1=CC=C(C=C1)Cl)=O.C(C)(C)(C)NC(C1=CC(=CC(=C1)C=1C(=NC=NC1)C1CC1)C1=CC=C(C=C1)Cl)=O USLNCQVQNHETFF-UHFFFAOYSA-N 0.000 claims 1
- IMEDBZZGWYBGQJ-UHFFFAOYSA-N N-tert-butyl-3-(4-tert-butylpyrimidin-5-yl)-5-(4-fluorophenyl)benzamide Chemical compound C(C)(C)(C)NC(C1=CC(=CC(=C1)C1=CC=C(C=C1)F)C=1C(=NC=NC=1)C(C)(C)C)=O IMEDBZZGWYBGQJ-UHFFFAOYSA-N 0.000 claims 1
- QTSOSPKKCFBTRE-UHFFFAOYSA-N N-tert-butyl-3-(4-tert-butylpyrimidin-5-yl)-5-[4-(trifluoromethyl)phenyl]benzamide N-tert-butyl-3-(4-ethylpyrimidin-5-yl)-5-(4-fluorophenyl)benzamide Chemical compound C(C)(C)(C)NC(C1=CC(=CC(=C1)C1=CC=C(C=C1)F)C=1C(=NC=NC1)CC)=O.C(C)(C)(C)NC(C1=CC(=CC(=C1)C1=CC=C(C=C1)C(F)(F)F)C=1C(=NC=NC1)C(C)(C)C)=O QTSOSPKKCFBTRE-UHFFFAOYSA-N 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 208000020016 psychiatric disease Diseases 0.000 abstract description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 abstract 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
- C07D239/36—One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
-
- 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
- C07D403/10—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 carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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| CN107207449B (zh) | 2015-04-23 | 2020-11-10 | 豪夫迈·罗氏有限公司 | 用于治疗精神障碍的四唑衍生物 |
| JP6831376B2 (ja) | 2015-10-06 | 2021-02-17 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | トリアゾール誘導体 |
| EP3368522B1 (en) * | 2015-10-28 | 2021-08-04 | F. Hoffmann-La Roche AG | Pyridine or pyrimidine derivatives |
| CN108473462B (zh) | 2016-02-02 | 2021-06-22 | 豪夫迈·罗氏有限公司 | 作为eaat3抑制剂的吡唑-吡啶衍生物 |
| EP3464246B1 (en) | 2016-05-27 | 2020-07-08 | H. Hoffnabb-La Roche Ag | Pyrazol compounds as eaat3 inhibitors |
| CN109563049B (zh) | 2016-10-14 | 2022-11-29 | 豪夫迈·罗氏有限公司 | 作为eaat3抑制剂的咪唑化合物 |
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| US20080021024A1 (en) * | 2006-06-29 | 2008-01-24 | Alantos Pharmaceuticals Holding, Inc. | Metalloprotease inhibitors |
| WO2010033168A2 (en) * | 2008-09-18 | 2010-03-25 | Renovis, Inc. | Amide compounds, compositions and uses thereof |
| US8598209B2 (en) * | 2008-10-31 | 2013-12-03 | Merck Sharp & Dohme Corp. | P2X3, receptor antagonists for treatment of pain |
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| US20180162824A1 (en) | 2018-06-14 |
| WO2017025523A1 (en) | 2017-02-16 |
| JP6754828B2 (ja) | 2020-09-16 |
| HK1251226A1 (zh) | 2019-01-25 |
| EP3334727B1 (en) | 2019-05-15 |
| JP2018522916A (ja) | 2018-08-16 |
| EP3334727A1 (en) | 2018-06-20 |
| CN107922391A (zh) | 2018-04-17 |
| US10005736B1 (en) | 2018-06-26 |
| AR105662A1 (es) | 2017-10-25 |
| CN107922391B (zh) | 2020-09-25 |
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