ES2538386T3 - Compuestos bicíclicos y tricíclicos como inhibidores de KAT II - Google Patents
Compuestos bicíclicos y tricíclicos como inhibidores de KAT II Download PDFInfo
- Publication number
- ES2538386T3 ES2538386T3 ES10725875.8T ES10725875T ES2538386T3 ES 2538386 T3 ES2538386 T3 ES 2538386T3 ES 10725875 T ES10725875 T ES 10725875T ES 2538386 T3 ES2538386 T3 ES 2538386T3
- Authority
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- Spain
- Prior art keywords
- amino
- hydroxy
- dihydroquinolin
- alkyl
- aryl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 247
- 239000003112 inhibitor Substances 0.000 title description 11
- 125000002619 bicyclic group Chemical group 0.000 title description 3
- -1 heterocycloalkyloxy Chemical group 0.000 claims abstract description 355
- 125000003118 aryl group Chemical group 0.000 claims abstract description 111
- 125000001424 substituent group Chemical group 0.000 claims abstract description 108
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 104
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 88
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 61
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 61
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 60
- 125000005843 halogen group Chemical group 0.000 claims abstract description 57
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 53
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 31
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 27
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 26
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 25
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 23
- 239000011737 fluorine Substances 0.000 claims abstract description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 23
- 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 22
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 19
- 125000005553 heteroaryloxy group Chemical group 0.000 claims abstract description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 17
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 13
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 12
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 12
- 125000004171 alkoxy aryl group Chemical group 0.000 claims abstract description 10
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 9
- 125000005248 alkyl aryloxy group Chemical group 0.000 claims abstract description 7
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
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- 150000003839 salts Chemical class 0.000 claims description 73
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 14
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- AAKHAIQDMUELMT-UHFFFAOYSA-N 3-amino-7-bromo-1-hydroxy-3,4-dihydroquinolin-2-one Chemical group C1=C(Br)C=C2N(O)C(=O)C(N)CC2=C1 AAKHAIQDMUELMT-UHFFFAOYSA-N 0.000 claims description 6
- UAIVPPAGWHXQPR-UHFFFAOYSA-N 3-amino-7-chloro-1-hydroxy-3,4-dihydroquinolin-2-one Chemical group C1=C(Cl)C=C2N(O)C(=O)C(N)CC2=C1 UAIVPPAGWHXQPR-UHFFFAOYSA-N 0.000 claims description 6
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- QZIAGSLINPHDGO-UHFFFAOYSA-N 3-amino-1-hydroxy-4-methyl-3,4-dihydroquinolin-2-one Chemical compound C1=CC=C2C(C)C(N)C(=O)N(O)C2=C1 QZIAGSLINPHDGO-UHFFFAOYSA-N 0.000 claims description 5
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- KNSNOBBWEGQDRC-UHFFFAOYSA-N 3-amino-8-chloro-1-hydroxy-3,4-dihydroquinolin-2-one Chemical group C1=CC(Cl)=C2N(O)C(=O)C(N)CC2=C1 KNSNOBBWEGQDRC-UHFFFAOYSA-N 0.000 claims description 5
- GTGFQRUCAOHJGM-VIFPVBQESA-N [(3s)-3-amino-2-oxo-3,4-dihydroquinolin-1-yl] n,n-dimethylcarbamate Chemical compound C1=CC=C2N(OC(=O)N(C)C)C(=O)[C@@H](N)CC2=C1 GTGFQRUCAOHJGM-VIFPVBQESA-N 0.000 claims description 5
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- LNSCZIOIZZJMQP-UHFFFAOYSA-N 3-amino-7-fluoro-1-hydroxy-3,4-dihydroquinolin-2-one Chemical group C1=C(F)C=C2N(O)C(=O)C(N)CC2=C1 LNSCZIOIZZJMQP-UHFFFAOYSA-N 0.000 claims description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/58—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems with hetero atoms directly attached to the ring nitrogen atom
- C07D215/60—N-oxides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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| PCT/IB2010/052349 WO2010146488A1 (en) | 2009-06-18 | 2010-05-26 | Bicyclic and tricyclic compounds as kat ii inhibitors |
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| ES2524423T3 (es) * | 2010-12-01 | 2014-12-09 | Pfizer Inc. | Inhibidores de KAT II |
| WO2013005425A1 (ja) * | 2011-07-07 | 2013-01-10 | イハラケミカル工業株式会社 | ニトロベンゼン化合物の製造方法 |
| CN104364253A (zh) | 2012-06-15 | 2015-02-18 | 辉瑞公司 | 作为kat ii抑制剂的三环化合物 |
| EP2919788A4 (en) | 2012-11-14 | 2016-05-25 | Univ Johns Hopkins | METHOD AND COMPOSITIONS FOR TREATING SCHIZOPHRENIA |
| EP2746250B1 (en) * | 2012-12-21 | 2017-09-27 | ABX Advanced Biochemical Compounds GmbH | Precursors and process for the production of 18F-labelled amino acids |
| WO2014174745A1 (ja) * | 2013-04-26 | 2014-10-30 | 国立大学法人京都大学 | Eg5阻害剤 |
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| CN104592333B (zh) * | 2014-07-23 | 2017-06-27 | 江西科技师范大学 | 一种合成5‑羧基‑2’‑脱氧胞苷的方法 |
| JP6853782B2 (ja) * | 2015-10-22 | 2021-03-31 | 田辺三菱製薬株式会社 | 新規二環性複素環化合物 |
| GB201613163D0 (en) * | 2016-07-29 | 2016-09-14 | Autifony Therapeutics Ltd | Novel compounds |
| CN110291383B (zh) * | 2017-02-23 | 2021-12-28 | 株式会社Ihi | Oh自由基检测探测器、oh自由基测定装置以及oh自由基测定方法 |
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