JP2007507514A - キノキサリン化合物 - Google Patents
キノキサリン化合物 Download PDFInfo
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- JP2007507514A JP2007507514A JP2006534060A JP2006534060A JP2007507514A JP 2007507514 A JP2007507514 A JP 2007507514A JP 2006534060 A JP2006534060 A JP 2006534060A JP 2006534060 A JP2006534060 A JP 2006534060A JP 2007507514 A JP2007507514 A JP 2007507514A
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- Prior art keywords
- independently
- alkyl
- butyl
- och
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- 125000001567 quinoxalinyl group Chemical class N1=C(C=NC2=CC=CC=C12)* 0.000 title abstract 2
- 238000000034 method Methods 0.000 claims abstract description 191
- 125000001424 substituent group Chemical group 0.000 claims abstract description 130
- 239000000203 mixture Substances 0.000 claims abstract description 93
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 57
- 102000005962 receptors Human genes 0.000 claims abstract description 54
- 108020003175 receptors Proteins 0.000 claims abstract description 54
- 201000010099 disease Diseases 0.000 claims abstract description 40
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 40
- 206010061218 Inflammation Diseases 0.000 claims abstract description 33
- 230000004054 inflammatory process Effects 0.000 claims abstract description 33
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 21
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 21
- 230000001404 mediated effect Effects 0.000 claims abstract description 18
- 210000000265 leukocyte Anatomy 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 230000007115 recruitment Effects 0.000 claims abstract description 10
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- 150000001875 compounds Chemical class 0.000 claims description 163
- -1 -NR a R b Chemical group 0.000 claims description 111
- 125000000217 alkyl group Chemical group 0.000 claims description 89
- 229910052799 carbon Inorganic materials 0.000 claims description 88
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 87
- 238000006243 chemical reaction Methods 0.000 claims description 65
- 229910052739 hydrogen Inorganic materials 0.000 claims description 55
- 150000002148 esters Chemical class 0.000 claims description 53
- 150000003839 salts Chemical class 0.000 claims description 41
- 230000028709 inflammatory response Effects 0.000 claims description 35
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 33
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 28
- 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 26
- 230000004044 response Effects 0.000 claims description 25
- 125000005843 halogen group Chemical group 0.000 claims description 24
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- 125000000304 alkynyl group Chemical group 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 19
- 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 17
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 17
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 12
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
- 238000003379 elimination reaction Methods 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 239000011968 lewis acid catalyst Substances 0.000 claims description 10
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 9
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 9
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 201000010105 allergic rhinitis Diseases 0.000 claims description 9
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- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 125000001246 bromo group Chemical group Br* 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 208000023275 Autoimmune disease Diseases 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 239000012429 reaction media Substances 0.000 claims description 8
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
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- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 7
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- 239000003377 acid catalyst Substances 0.000 claims description 6
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- 239000003054 catalyst Substances 0.000 claims description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 208000004732 Systemic Vasculitis Diseases 0.000 claims description 5
- 206010047115 Vasculitis Diseases 0.000 claims description 5
- 230000009285 allergic inflammation Effects 0.000 claims description 5
- 230000001363 autoimmune Effects 0.000 claims description 5
- 201000004339 autoimmune neuropathy Diseases 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
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- 208000037976 chronic inflammation Diseases 0.000 claims description 4
- 230000006020 chronic inflammation Effects 0.000 claims description 4
- 229940044551 receptor antagonist Drugs 0.000 claims description 4
- 239000002464 receptor antagonist Substances 0.000 claims description 4
- 229940075993 receptor modulator Drugs 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 claims description 3
- 208000009137 Behcet syndrome Diseases 0.000 claims description 3
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 3
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 208000007465 Giant cell arteritis Diseases 0.000 claims description 3
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 claims description 3
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims description 3
- 201000011152 Pemphigus Diseases 0.000 claims description 3
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- 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 206010039710 Scleroderma Diseases 0.000 claims description 3
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 206010047642 Vitiligo Diseases 0.000 claims description 3
- 230000001919 adrenal effect Effects 0.000 claims description 3
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- 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims description 3
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 239000004031 partial agonist Substances 0.000 claims description 3
- 201000001976 pemphigus vulgaris Diseases 0.000 claims description 3
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 3
- 150000004885 piperazines Chemical class 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 claims description 3
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- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 2
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- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 2
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
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- 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
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50717603P | 2003-09-30 | 2003-09-30 | |
| PCT/US2004/032003 WO2005033088A1 (en) | 2003-09-30 | 2004-09-29 | Quinoxaline compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007507514A true JP2007507514A (ja) | 2007-03-29 |
| JP2007507514A5 JP2007507514A5 (OSRAM) | 2007-11-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006534060A Pending JP2007507514A (ja) | 2003-09-30 | 2004-09-29 | キノキサリン化合物 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20050070527A1 (OSRAM) |
| EP (1) | EP1670774A1 (OSRAM) |
| JP (1) | JP2007507514A (OSRAM) |
| KR (1) | KR20060111466A (OSRAM) |
| CN (1) | CN1886389B (OSRAM) |
| AU (2) | AU2004278372B2 (OSRAM) |
| CA (1) | CA2540638A1 (OSRAM) |
| IL (1) | IL174629A0 (OSRAM) |
| MX (1) | MXPA06003578A (OSRAM) |
| WO (1) | WO2005033088A1 (OSRAM) |
| ZA (1) | ZA200603410B (OSRAM) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0525068D0 (en) | 2005-12-08 | 2006-01-18 | Novartis Ag | Organic compounds |
| JP5066175B2 (ja) | 2006-03-31 | 2012-11-07 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ヒスタミンｈ４受容体のモジュレーターとしてのベンゾイミダゾール−２−イルピリミジンおよびピラジン |
| US20090069343A1 (en) * | 2006-04-10 | 2009-03-12 | Dunford Paul J | Combination Histamine H1R and H4R Antagonist Therapy for Treating Pruritus |
| US20100016293A1 (en) * | 2006-07-03 | 2010-01-21 | Rogier Adriaan Smits | Quinazolines and Related Heterocyclic Compounds, and Their Therapeutic Use |
| GB0614471D0 (en) | 2006-07-20 | 2006-08-30 | Syngenta Ltd | Herbicidal Compounds |
| US7985745B2 (en) | 2006-10-02 | 2011-07-26 | Abbott Laboratories | Method for pain treatment |
| EP2077263A1 (en) * | 2008-01-02 | 2009-07-08 | Vereniging voor christelijk hoger onderwijs, wetenschappelijk onderzoek en patiëntenzorg | Quinazolines and related heterocyclic compounds and their therapeutic use |
| NZ603072A (en) * | 2008-06-12 | 2013-01-25 | Janssen Pharmaceutica Nv | Use of histamine H4 antagonist for the treatment of post-operative tissue adhesions after surgical procedures |
| US9371311B2 (en) | 2008-06-30 | 2016-06-21 | Janssen Pharmaceutica Nv | Benzoimidazol-2-yl pyrimidine derivatives |
| EP2201982A1 (en) | 2008-12-24 | 2010-06-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Histamine H4 receptor antagonists for the treatment of vestibular disorders |
| US8349852B2 (en) | 2009-01-13 | 2013-01-08 | Novartis Ag | Quinazolinone derivatives useful as vanilloid antagonists |
| WO2011092293A2 (en) | 2010-02-01 | 2011-08-04 | Novartis Ag | Cyclohexyl amide derivatives as crf receptor antagonists |
| CN102762572A (zh) | 2010-02-01 | 2012-10-31 | 诺瓦提斯公司 | 作为CRF-1受体拮抗剂的吡唑并[5,1b]*唑衍生物 |
| US8835444B2 (en) | 2010-02-02 | 2014-09-16 | Novartis Ag | Cyclohexyl amide derivatives as CRF receptor antagonists |
| UY34094A (es) | 2011-05-27 | 2013-01-03 | Novartis Ag | Derivados de la piperidina 3-espirocíclica como agonistas de receptores de la ghrelina |
| EA201491990A1 (ru) | 2012-05-03 | 2015-02-27 | Новартис Аг | L-малатная соль 2,7-диазаспиро[4.5]дец-7-иловых производных и их кристаллические формы в качестве агонистов грелиновых рецепторов |
| ES2683380T3 (es) | 2012-06-08 | 2018-09-26 | Sensorion | Inhibidores del receptor H4 para tratar el tinnitus |
| EA201591648A1 (ru) | 2013-03-06 | 2016-02-29 | Янссен Фармацевтика Нв | Бензимидазол-2-ил-пиримидиновые модуляторы рецептора гистамина h4 |
| CN105001169B (zh) * | 2015-07-09 | 2017-07-21 | 华侨大学 | 一种3‑氨基喹喔啉‑2(1h)‑酮类化合物的合成方法 |
| CN110092760B (zh) * | 2019-06-04 | 2020-11-13 | 杭州师范大学 | 一种3-氟代烷氧基-2(1h)-喹喔啉酮及其合成方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3493572A (en) * | 1968-07-05 | 1970-02-03 | Pfizer & Co C | Process for producing quinoxaline-di-n-oxides |
| FI193974A7 (OSRAM) * | 1973-07-13 | 1975-01-14 | Merck & Co Inc | |
| EP0008864A1 (en) * | 1978-08-15 | 1980-03-19 | FISONS plc | Pyridopyrazine and quinoxaline derivatives, processes for their preparation, and pharmaceutical compositions containing them |
| DK716188D0 (da) * | 1988-12-22 | 1988-12-22 | Ferrosan As | Quinoxalinforbindelser, deres fremstilling og anvendelse |
| DE4342024A1 (de) * | 1993-12-09 | 1995-06-14 | Hoechst Ag | Kombinationspräparate, enthaltend ein Chinoxalin und ein Nukleosid |
| MY132385A (en) * | 1995-08-31 | 2007-10-31 | Novartis Ag | 2,3-dioxo-1,2,3,4-tetrahydro-quinoxalinyl derivatives |
| KR20050025628A (ko) * | 2002-07-19 | 2005-03-14 | 바이오비트럼 에이비 | 5-ｈｔ2ａ 수용체 관련 장애의 치료를 위한 신규피페라지닐-피라지논 유도체 |
-
2004
- 2004-09-29 EP EP04789260A patent/EP1670774A1/en not_active Withdrawn
- 2004-09-29 WO PCT/US2004/032003 patent/WO2005033088A1/en not_active Ceased
- 2004-09-29 KR KR1020067008422A patent/KR20060111466A/ko not_active Withdrawn
- 2004-09-29 AU AU2004278372A patent/AU2004278372B2/en not_active Ceased
- 2004-09-29 US US10/953,126 patent/US20050070527A1/en not_active Abandoned
- 2004-09-29 CN CN2004800348033A patent/CN1886389B/zh not_active Expired - Fee Related
- 2004-09-29 JP JP2006534060A patent/JP2007507514A/ja active Pending
- 2004-09-29 MX MXPA06003578A patent/MXPA06003578A/es unknown
- 2004-09-29 CA CA002540638A patent/CA2540638A1/en not_active Abandoned
-
2006
- 2006-03-29 IL IL174629A patent/IL174629A0/en unknown
- 2006-04-28 ZA ZA200603410A patent/ZA200603410B/en unknown
-
2010
- 2010-05-18 AU AU2010202009A patent/AU2010202009A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| KR20060111466A (ko) | 2006-10-27 |
| AU2010202009A1 (en) | 2010-06-10 |
| AU2004278372A1 (en) | 2005-04-14 |
| US20050070527A1 (en) | 2005-03-31 |
| MXPA06003578A (es) | 2006-08-31 |
| IL174629A0 (en) | 2006-08-20 |
| WO2005033088A1 (en) | 2005-04-14 |
| EP1670774A1 (en) | 2006-06-21 |
| ZA200603410B (en) | 2007-07-25 |
| CN1886389B (zh) | 2010-07-21 |
| AU2004278372B2 (en) | 2010-02-18 |
| CN1886389A (zh) | 2006-12-27 |
| CA2540638A1 (en) | 2005-04-14 |
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