KR20050108379A - 이온 채널 조절제로서 유용한 퀴나졸린 - Google Patents
이온 채널 조절제로서 유용한 퀴나졸린 Download PDFInfo
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- KR20050108379A KR20050108379A KR1020057016287A KR20057016287A KR20050108379A KR 20050108379 A KR20050108379 A KR 20050108379A KR 1020057016287 A KR1020057016287 A KR 1020057016287A KR 20057016287 A KR20057016287 A KR 20057016287A KR 20050108379 A KR20050108379 A KR 20050108379A
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- South Korea
- Prior art keywords
- och
- optionally substituted
- compound
- ring
- phenyl
- Prior art date
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- 102000004310 Ion Channels Human genes 0.000 title description 14
- 150000003246 quinazolines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 560
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 claims abstract description 178
- 238000000034 method Methods 0.000 claims abstract description 68
- 239000000203 mixture Substances 0.000 claims abstract description 33
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 claims abstract description 19
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 claims abstract description 19
- 102000003922 Calcium Channels Human genes 0.000 claims abstract description 13
- 125000001931 aliphatic group Chemical group 0.000 claims description 257
- 229910052757 nitrogen Inorganic materials 0.000 claims description 233
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 221
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 188
- 229910052731 fluorine Inorganic materials 0.000 claims description 167
- 229910052801 chlorine Inorganic materials 0.000 claims description 164
- -1 2-phenyl-4-quinazolinyl Chemical group 0.000 claims description 161
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 153
- 125000003386 piperidinyl group Chemical group 0.000 claims description 140
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 135
- 125000005842 heteroatom Chemical group 0.000 claims description 135
- 229910052717 sulfur Inorganic materials 0.000 claims description 131
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 129
- 239000011593 sulfur Chemical group 0.000 claims description 128
- 229910052760 oxygen Inorganic materials 0.000 claims description 127
- 239000001301 oxygen Chemical group 0.000 claims description 127
- 229910052794 bromium Inorganic materials 0.000 claims description 126
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 124
- 125000003118 aryl group Chemical group 0.000 claims description 116
- 208000002193 Pain Diseases 0.000 claims description 104
- 229910052739 hydrogen Inorganic materials 0.000 claims description 103
- 239000001257 hydrogen Substances 0.000 claims description 102
- 125000002950 monocyclic group Chemical group 0.000 claims description 101
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 99
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 98
- 229910052736 halogen Inorganic materials 0.000 claims description 96
- 150000002367 halogens Chemical class 0.000 claims description 94
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 94
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 93
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 91
- 229920006395 saturated elastomer Polymers 0.000 claims description 90
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 79
- 229910004013 NO 2 Inorganic materials 0.000 claims description 75
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 72
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 66
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 63
- 230000036407 pain Effects 0.000 claims description 63
- 125000002619 bicyclic group Chemical group 0.000 claims description 58
- 125000001072 heteroaryl group Chemical group 0.000 claims description 58
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 53
- 125000004076 pyridyl group Chemical group 0.000 claims description 48
- 208000004296 neuralgia Diseases 0.000 claims description 45
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 43
- 150000002431 hydrogen Chemical class 0.000 claims description 43
- 125000004429 atom Chemical group 0.000 claims description 42
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
- 125000003545 alkoxy group Chemical group 0.000 claims description 37
- 125000004122 cyclic group Chemical group 0.000 claims description 37
- 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 36
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 36
- 125000000335 thiazolyl group Chemical group 0.000 claims description 34
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 31
- 229910052799 carbon Inorganic materials 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 29
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- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 27
- 206010015037 epilepsy Diseases 0.000 claims description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000005322 morpholin-1-yl group Chemical group 0.000 claims description 20
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 18
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 18
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 18
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 18
- 125000004434 sulfur atom Chemical group 0.000 claims description 18
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 16
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- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 14
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- 230000000694 effects Effects 0.000 claims description 14
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- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 12
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
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- 208000004404 Intractable Pain Diseases 0.000 claims description 11
- 230000001684 chronic effect Effects 0.000 claims description 11
- 230000002981 neuropathic effect Effects 0.000 claims description 11
- 206010003591 Ataxia Diseases 0.000 claims description 10
- 108090000312 Calcium Channels Proteins 0.000 claims description 10
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- 231100000869 headache Toxicity 0.000 claims description 10
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 10
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 10
- 208000009935 visceral pain Diseases 0.000 claims description 10
- 208000004550 Postoperative Pain Diseases 0.000 claims description 9
- 208000008765 Sciatica Diseases 0.000 claims description 9
- 201000006417 multiple sclerosis Diseases 0.000 claims description 9
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 8
- RAUWPNXIALNKQM-UHFFFAOYSA-N 4-nitro-1,2-phenylenediamine Chemical compound NC1=CC=C([N+]([O-])=O)C=C1N RAUWPNXIALNKQM-UHFFFAOYSA-N 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 8
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 8
- 208000006561 Cluster Headache Diseases 0.000 claims description 8
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 8
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- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 8
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 8
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 8
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
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- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 6
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 6
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- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 6
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- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical group O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 claims description 4
- 208000012661 Dyskinesia Diseases 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 4
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- NGXSWUFDCSEIOO-SCSAIBSYSA-N (3r)-pyrrolidin-3-amine Chemical compound N[C@@H]1CCNC1 NGXSWUFDCSEIOO-SCSAIBSYSA-N 0.000 claims description 2
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 2
- KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 claims description 2
- PWZDJIUQHUGFRJ-UHFFFAOYSA-N 1-(2-chlorophenyl)piperazine Chemical compound ClC1=CC=CC=C1N1CCNCC1 PWZDJIUQHUGFRJ-UHFFFAOYSA-N 0.000 claims description 2
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 claims description 2
- KVYOWXUQJLOCIA-UHFFFAOYSA-N 1-oxa-8-azaspiro[4.5]decane Chemical compound C1CCOC21CCNCC2 KVYOWXUQJLOCIA-UHFFFAOYSA-N 0.000 claims description 2
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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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- A61P25/00—Drugs for disorders of the nervous system
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR20120125978A (ko) * | 2009-09-03 | 2012-11-19 | 브리스톨-마이어스 스큅 컴퍼니 | 칼륨 이온 채널 억제제로서의 퀴나졸린 |
| KR20180105926A (ko) * | 2017-03-16 | 2018-10-01 | 기초과학연구원 | 퀴나졸린, 퀴놀린 유도체 및 egfr 키나제 억제제로서의 용도 |
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- 2004-03-03 BR BR0408026-2A patent/BRPI0408026A/pt not_active IP Right Cessation
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- 2004-03-03 KR KR1020057016287A patent/KR20050108379A/ko not_active Ceased
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- 2004-03-03 AT AT04716887T patent/ATE453629T1/de active
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20120125978A (ko) * | 2009-09-03 | 2012-11-19 | 브리스톨-마이어스 스큅 컴퍼니 | 칼륨 이온 채널 억제제로서의 퀴나졸린 |
| KR20180105926A (ko) * | 2017-03-16 | 2018-10-01 | 기초과학연구원 | 퀴나졸린, 퀴놀린 유도체 및 egfr 키나제 억제제로서의 용도 |
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| US8343980B2 (en) | 2013-01-01 |
| NZ542664A (en) | 2009-03-31 |
| ES2338553T3 (es) | 2010-05-10 |
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| UY28215A1 (es) | 2004-09-30 |
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| CL2004000409A1 (es) | 2005-01-07 |
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| RU2378260C2 (ru) | 2010-01-10 |
| AU2004217891B2 (en) | 2011-06-23 |
| DE602004024873D1 (de) | 2010-02-11 |
| JP5247027B2 (ja) | 2013-07-24 |
| JP2006522119A (ja) | 2006-09-28 |
| AU2004217891A1 (en) | 2004-09-16 |
| EP1608632B1 (en) | 2009-12-30 |
| IL170636A (en) | 2012-08-30 |
| AR044502A1 (es) | 2005-09-14 |
| US20110021495A1 (en) | 2011-01-27 |
| PE20041059A1 (es) | 2005-02-07 |
| CA2517844A1 (en) | 2004-09-16 |
| NO20054546D0 (no) | 2005-10-03 |
| EP1608632A1 (en) | 2005-12-28 |
| ATE453629T1 (de) | 2010-01-15 |
| US7678802B2 (en) | 2010-03-16 |
| RU2005130486A (ru) | 2006-05-10 |
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