JP2007519754A - 化合物 - Google Patents
化合物 Download PDFInfo
- Publication number
- JP2007519754A JP2007519754A JP2006551626A JP2006551626A JP2007519754A JP 2007519754 A JP2007519754 A JP 2007519754A JP 2006551626 A JP2006551626 A JP 2006551626A JP 2006551626 A JP2006551626 A JP 2006551626A JP 2007519754 A JP2007519754 A JP 2007519754A
- Authority
- JP
- Japan
- Prior art keywords
- benzamide
- pyrimidinyl
- amino
- methyl
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 106
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 239000012453 solvate Substances 0.000 claims abstract description 16
- -1 2-amino-4-pyrimidinyl Chemical group 0.000 claims description 120
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 46
- 238000000034 method Methods 0.000 claims description 34
- 125000000217 alkyl 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 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 21
- 230000000694 effects Effects 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000002950 monocyclic group Chemical group 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000004104 aryloxy group Chemical group 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 8
- 230000001404 mediated effect Effects 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 7
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- TURLOSKPJBPGOR-UHFFFAOYSA-N n-[(3-methoxyphenyl)methyl]-4-[6-(prop-2-enylamino)pyrimidin-4-yl]benzamide Chemical compound COC1=CC=CC(CNC(=O)C=2C=CC(=CC=2)C=2N=CN=C(NCC=C)C=2)=C1 TURLOSKPJBPGOR-UHFFFAOYSA-N 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 5
- IRGOHKRWMGVGCR-UHFFFAOYSA-N 4-(2-aminopyrimidin-4-yl)-n-[(3-methoxyphenyl)methyl]benzamide Chemical compound COC1=CC=CC(CNC(=O)C=2C=CC(=CC=2)C=2N=C(N)N=CC=2)=C1 IRGOHKRWMGVGCR-UHFFFAOYSA-N 0.000 claims description 5
- FTEKOWMGBWHZSA-UHFFFAOYSA-N 4-(6-aminopyrimidin-4-yl)-n-[(3-methoxyphenyl)methyl]benzamide Chemical compound COC1=CC=CC(CNC(=O)C=2C=CC(=CC=2)C=2N=CN=C(N)C=2)=C1 FTEKOWMGBWHZSA-UHFFFAOYSA-N 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- JBLPUDJLELBRHC-UHFFFAOYSA-N n-[(3-methoxyphenyl)methyl]-4-pyridin-4-ylbenzamide Chemical compound COC1=CC=CC(CNC(=O)C=2C=CC(=CC=2)C=2C=CN=CC=2)=C1 JBLPUDJLELBRHC-UHFFFAOYSA-N 0.000 claims description 5
- SYSUZXPGQXEWCZ-UHFFFAOYSA-N n-benzyl-4-pyridin-4-ylbenzamide Chemical compound C=1C=C(C=2C=CN=CC=2)C=CC=1C(=O)NCC1=CC=CC=C1 SYSUZXPGQXEWCZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 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 4
- OQXPFQFKBILBEF-UHFFFAOYSA-N 4-(1h-indazol-5-yl)-n-[(3-methoxyphenyl)methyl]benzamide Chemical compound COC1=CC=CC(CNC(=O)C=2C=CC(=CC=2)C=2C=C3C=NNC3=CC=2)=C1 OQXPFQFKBILBEF-UHFFFAOYSA-N 0.000 claims description 4
- JZIIWVNIBYGBPC-UHFFFAOYSA-N 4-(2-aminopyrimidin-4-yl)-n-[(4-methoxyphenyl)methyl]benzamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC=C(C=2N=C(N)N=CC=2)C=C1 JZIIWVNIBYGBPC-UHFFFAOYSA-N 0.000 claims description 4
- NAPIHYHPUPRPDF-UHFFFAOYSA-N 4-(2-chloropyridin-4-yl)-n-[(3-methoxyphenyl)methyl]benzamide Chemical compound COC1=CC=CC(CNC(=O)C=2C=CC(=CC=2)C=2C=C(Cl)N=CC=2)=C1 NAPIHYHPUPRPDF-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- VCCHIIPGONQZHJ-UHFFFAOYSA-N n-[(3-methoxyphenyl)methyl]-4-(1h-pyrazol-4-yl)benzamide Chemical compound COC1=CC=CC(CNC(=O)C=2C=CC(=CC=2)C2=CNN=C2)=C1 VCCHIIPGONQZHJ-UHFFFAOYSA-N 0.000 claims description 4
- BHWQEVXWYHXNMX-UHFFFAOYSA-N n-[(3-methoxyphenyl)methyl]-4-pyrimidin-4-ylbenzamide Chemical compound COC1=CC=CC(CNC(=O)C=2C=CC(=CC=2)C=2N=CN=CC=2)=C1 BHWQEVXWYHXNMX-UHFFFAOYSA-N 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 3
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
- ATYMIQGWWSULBL-UHFFFAOYSA-N 5-(2-aminopyrimidin-4-yl)-2-benzyl-3h-isoindol-1-one Chemical compound NC1=NC=CC(C=2C=C3CN(CC=4C=CC=CC=4)C(=O)C3=CC=2)=N1 ATYMIQGWWSULBL-UHFFFAOYSA-N 0.000 claims description 2
- OFDXNOMIOCNAHC-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)-2-benzylisoquinolin-1-one Chemical compound NC1=NC=CC(C=2C=C3C(C(N(CC=4C=CC=CC=4)C=C3)=O)=CC=2)=N1 OFDXNOMIOCNAHC-UHFFFAOYSA-N 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- 125000006574 non-aromatic ring group Chemical group 0.000 claims 1
- 238000001819 mass spectrum Methods 0.000 description 51
- 239000000203 mixture Substances 0.000 description 40
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- 239000007787 solid Substances 0.000 description 31
- 235000002639 sodium chloride Nutrition 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 239000002904 solvent Substances 0.000 description 24
- 239000011435 rock Substances 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 14
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- 239000002253 acid Substances 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 10
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
Classifications
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- 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
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- C07—ORGANIC CHEMISTRY
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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- C07—ORGANIC CHEMISTRY
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
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- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Communicable Diseases (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
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- Physical Education & Sports Medicine (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US54062104P | 2004-01-30 | 2004-01-30 | |
| PCT/US2005/003479 WO2005074643A2 (en) | 2004-01-30 | 2005-01-28 | Benzamide compounds useful as rock inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007519754A true JP2007519754A (ja) | 2007-07-19 |
| JP2007519754A5 JP2007519754A5 (OSRAM) | 2008-03-13 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006551626A Pending JP2007519754A (ja) | 2004-01-30 | 2005-01-28 | 化合物 |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US20080275062A1 (OSRAM) |
| EP (1) | EP1713775A4 (OSRAM) |
| JP (1) | JP2007519754A (OSRAM) |
| WO (1) | WO2005074643A2 (OSRAM) |
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| JP2010536925A (ja) * | 2007-08-27 | 2010-12-02 | アボット ゲーエムベーハー ウント カンパニー カーゲー | 4−(4−ピリジニル)−ベンズアミドおよびrock活性調節因子としてのこれらの使用 |
| JP2013510110A (ja) * | 2009-11-04 | 2013-03-21 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | 5−(2−アミノ−ピリミジン−4−イル)−2−アリール−1h−ピロール−3−カルボキサミドの調製方法 |
| JP2013533879A (ja) * | 2010-06-29 | 2013-08-29 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Wntシグナル伝達経路調節のための組成物および方法 |
| JP2016510033A (ja) * | 2013-02-28 | 2016-04-04 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 強力なrock1およびrock2阻害剤としてのフェニルピラゾール誘導体 |
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| WO2025224050A1 (en) | 2024-04-22 | 2025-10-30 | Institut National de la Santé et de la Recherche Médicale | Methods of treatment of patients suffering from hypomelanosis of ito |
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- 2005-01-28 EP EP05712794A patent/EP1713775A4/en not_active Withdrawn
- 2005-01-28 WO PCT/US2005/003479 patent/WO2005074643A2/en not_active Ceased
- 2005-01-28 US US10/597,473 patent/US20080275062A1/en not_active Abandoned
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| WO2002064545A1 (en) * | 2001-02-13 | 2002-08-22 | Aventis Pharma Deutschland Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
| WO2003024448A2 (en) * | 2001-09-14 | 2003-03-27 | Methylgene, Inc. | Inhibitors of histone deacetylase |
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| US8895749B2 (en) | 2007-08-27 | 2014-11-25 | Abbvie Inc. | 4-(4-pyridinyl)-benzamides and their use as rock activity modulators |
| JP2010536925A (ja) * | 2007-08-27 | 2010-12-02 | アボット ゲーエムベーハー ウント カンパニー カーゲー | 4−(4−ピリジニル)−ベンズアミドおよびrock活性調節因子としてのこれらの使用 |
| JP2013510110A (ja) * | 2009-11-04 | 2013-03-21 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | 5−(2−アミノ−ピリミジン−4−イル)−2−アリール−1h−ピロール−3−カルボキサミドの調製方法 |
| JP2013533879A (ja) * | 2010-06-29 | 2013-08-29 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Wntシグナル伝達経路調節のための組成物および方法 |
| JP2016510033A (ja) * | 2013-02-28 | 2016-04-04 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 強力なrock1およびrock2阻害剤としてのフェニルピラゾール誘導体 |
| JP2016510032A (ja) * | 2013-02-28 | 2016-04-04 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 強力なrock1およびrock2阻害剤としてのフェニルピラゾール誘導体 |
| JP7076022B2 (ja) | 2013-12-11 | 2022-05-26 | バイオジェン・エムエイ・インコーポレイテッド | 腫瘍学、神経学及び免疫学におけるヒト疾患の治療に有用なビアリール化合物 |
| JP2019163280A (ja) * | 2013-12-11 | 2019-09-26 | バイオジェン・エムエイ・インコーポレイテッドBiogen MA Inc. | 腫瘍学、神経学及び免疫学におけるヒト疾患の治療に有用なビアリール化合物 |
| JP2021091733A (ja) * | 2013-12-11 | 2021-06-17 | バイオジェン・エムエイ・インコーポレイテッドBiogen MA Inc. | 腫瘍学、神経学及び免疫学におけるヒト疾患の治療に有用なビアリール化合物 |
| JP2017524026A (ja) * | 2014-08-21 | 2017-08-24 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 強力なrock阻害剤としてのタイドバックのベンズアミド誘導体 |
| JP2021522201A (ja) * | 2018-04-18 | 2021-08-30 | メッドシャイン ディスカバリー インコーポレイテッド | Rhoキナーゼ阻害剤としてのベンゾピラゾール系化合物 |
| JP7187575B2 (ja) | 2018-04-18 | 2022-12-12 | メッドシャイン ディスカバリー インコーポレイテッド | Rhoキナーゼ阻害剤としてのベンゾピラゾール系化合物 |
| JP2024517533A (ja) * | 2021-01-06 | 2024-04-23 | ジェノスコ インク. | Rock1およびrock2タンパク質キナーゼの選択的阻害剤およびその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1713775A2 (en) | 2006-10-25 |
| US20080275062A1 (en) | 2008-11-06 |
| WO2005074643A3 (en) | 2006-03-09 |
| EP1713775A4 (en) | 2009-08-12 |
| WO2005074643A2 (en) | 2005-08-18 |
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