MX2012005281A - Inhibicion de gpbp utilizando peptidomimeticos q2. - Google Patents
Inhibicion de gpbp utilizando peptidomimeticos q2.Info
- Publication number
- MX2012005281A MX2012005281A MX2012005281A MX2012005281A MX2012005281A MX 2012005281 A MX2012005281 A MX 2012005281A MX 2012005281 A MX2012005281 A MX 2012005281A MX 2012005281 A MX2012005281 A MX 2012005281A MX 2012005281 A MX2012005281 A MX 2012005281A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- alkoxy
- crc6
- hydroxy
- halo
- Prior art date
Links
- 239000000816 peptidomimetic Substances 0.000 title description 7
- 230000005764 inhibitory process Effects 0.000 title description 2
- 101100113051 Danio rerio cert1 gene Proteins 0.000 title 1
- 101100449199 Mus musculus Gpbp1 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 140
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
- 208000035475 disorder Diseases 0.000 claims abstract description 20
- 239000003814 drug Substances 0.000 claims abstract description 19
- 230000001404 mediated effect Effects 0.000 claims abstract description 17
- 229940079593 drug Drugs 0.000 claims abstract description 14
- 206010061218 Inflammation Diseases 0.000 claims abstract description 9
- 230000001594 aberrant effect Effects 0.000 claims abstract description 9
- 230000006907 apoptotic process Effects 0.000 claims abstract description 9
- 230000004054 inflammatory process Effects 0.000 claims abstract description 9
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 9
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 422
- 125000003545 alkoxy group Chemical group 0.000 claims description 297
- 125000005843 halogen group Chemical group 0.000 claims description 183
- -1 nitro, hydroxyl Chemical group 0.000 claims description 140
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 110
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 96
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 71
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 67
- 229910052736 halogen Inorganic materials 0.000 claims description 61
- 150000002367 halogens Chemical group 0.000 claims description 61
- 239000001257 hydrogen Substances 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 45
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 45
- 150000002431 hydrogen Chemical group 0.000 claims description 44
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 claims description 39
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 33
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 33
- 235000019260 propionic acid Nutrition 0.000 claims description 33
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 27
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 25
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 23
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 22
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 16
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000002671 adjuvant Substances 0.000 claims description 9
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 9
- 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
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- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims description 7
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- BWCFMQFJNLDWJE-UHFFFAOYSA-N 5-hydroxy-2-(3-methylphenyl)benzaldehyde Chemical compound CC1=CC=CC(C=2C(=CC(O)=CC=2)C=O)=C1 BWCFMQFJNLDWJE-UHFFFAOYSA-N 0.000 claims description 4
- YRTUHGQXTGJWMB-UHFFFAOYSA-N [3-formyl-4-(3-methylphenyl)phenyl] trifluoromethanesulfonate Chemical compound CC1=CC=CC(C=2C(=CC(OS(=O)(=O)C(F)(F)F)=CC=2)C=O)=C1 YRTUHGQXTGJWMB-UHFFFAOYSA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- NJFVDADRXPIWAV-UHFFFAOYSA-N 3-(difluoromethyl)-4-(3-methylphenyl)phenol Chemical compound CC1=CC=CC(C=2C(=CC(O)=CC=2)C(F)F)=C1 NJFVDADRXPIWAV-UHFFFAOYSA-N 0.000 claims description 3
- BAKPNKNKGYHUEB-UHFFFAOYSA-N 3-(difluoromethyl)-4-[3-(trifluoromethyl)phenyl]phenol Chemical compound FC(F)C1=CC(O)=CC=C1C1=CC=CC(C(F)(F)F)=C1 BAKPNKNKGYHUEB-UHFFFAOYSA-N 0.000 claims description 3
- FYKOSCNRBHHBLP-UHFFFAOYSA-N 3-[2-[3-(fluoromethyl)-4-pyridin-3-ylphenyl]-5-hydroxyphenyl]propanoic acid Chemical compound OC(=O)CCC1=CC(O)=CC=C1C1=CC=C(C=2C=NC=CC=2)C(CF)=C1 FYKOSCNRBHHBLP-UHFFFAOYSA-N 0.000 claims description 3
- JZPNWZYJYJTNMB-UHFFFAOYSA-N 3-[5-hydroxy-2-[3-(hydroxymethyl)-4-pyridin-3-ylphenyl]phenyl]propanoic acid Chemical compound OCC1=CC(C=2C(=CC(O)=CC=2)CCC(O)=O)=CC=C1C1=CC=CN=C1 JZPNWZYJYJTNMB-UHFFFAOYSA-N 0.000 claims description 3
- RHWGDKQUHQBNEA-UHFFFAOYSA-N 3-[5-methoxy-2-(3-methyl-4-pyridin-3-ylphenyl)phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC(OC)=CC=C1C1=CC=C(C=2C=NC=CC=2)C(C)=C1 RHWGDKQUHQBNEA-UHFFFAOYSA-N 0.000 claims description 3
- VEPCPUOMXQQXBQ-UHFFFAOYSA-N 3-methyl-4-pyridin-3-ylphenol Chemical compound CC1=CC(O)=CC=C1C1=CC=CN=C1 VEPCPUOMXQQXBQ-UHFFFAOYSA-N 0.000 claims description 3
- GTMZUVHAJXICBR-UHFFFAOYSA-N 4-(4-methoxy-3-methylphenyl)-3-methylphenol Chemical compound C1=C(C)C(OC)=CC=C1C1=CC=C(O)C=C1C GTMZUVHAJXICBR-UHFFFAOYSA-N 0.000 claims description 3
- HUKXVAXHIVDCPA-UHFFFAOYSA-N 5-hydroxy-2-[3-(trifluoromethyl)phenyl]benzaldehyde Chemical compound O=CC1=CC(O)=CC=C1C1=CC=CC(C(F)(F)F)=C1 HUKXVAXHIVDCPA-UHFFFAOYSA-N 0.000 claims description 3
- DTLWOCJITUYHLQ-UHFFFAOYSA-N 5-hydroxy-2-pyridin-3-ylbenzaldehyde Chemical compound O=CC1=CC(O)=CC=C1C1=CC=CN=C1 DTLWOCJITUYHLQ-UHFFFAOYSA-N 0.000 claims description 3
- 208000024869 Goodpasture syndrome Diseases 0.000 claims description 3
- 208000010159 IgA glomerulonephritis Diseases 0.000 claims description 3
- 206010021263 IgA nephropathy Diseases 0.000 claims description 3
- DEWXARKSCPBXTQ-UHFFFAOYSA-N [3-(difluoromethyl)-4-(3-methylphenyl)phenyl] trifluoromethanesulfonate Chemical compound CC1=CC=CC(C=2C(=CC(OS(=O)(=O)C(F)(F)F)=CC=2)C(F)F)=C1 DEWXARKSCPBXTQ-UHFFFAOYSA-N 0.000 claims description 3
- UCBVNQBPQXTVDE-UHFFFAOYSA-N [4-(4-methoxyphenyl)-3-methylphenyl] trifluoromethanesulfonate Chemical compound C1=CC(OC)=CC=C1C1=CC=C(OS(=O)(=O)C(F)(F)F)C=C1C UCBVNQBPQXTVDE-UHFFFAOYSA-N 0.000 claims description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 55
- 125000004103 aminoalkyl group Chemical group 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- ROTQIHSJPYGGGV-UHFFFAOYSA-N 3-[2-[3-(difluoromethyl)-4-pyridin-3-ylphenyl]-5-hydroxyphenyl]propanoic acid Chemical compound OC(=O)CCC1=CC(O)=CC=C1C(C=C1C(F)F)=CC=C1C1=CC=CN=C1 ROTQIHSJPYGGGV-UHFFFAOYSA-N 0.000 claims 1
- ZPDZUNDOTUCBKT-UHFFFAOYSA-N 3-[2-[3-(difluoromethyl)-4-pyridin-3-ylphenyl]-5-methoxyphenyl]propanoic acid Chemical compound OC(=O)CCC1=CC(OC)=CC=C1C(C=C1C(F)F)=CC=C1C1=CC=CN=C1 ZPDZUNDOTUCBKT-UHFFFAOYSA-N 0.000 claims 1
- LLEMOWNGBBNAJR-UHFFFAOYSA-N biphenyl-2-ol Chemical group OC1=CC=CC=C1C1=CC=CC=C1 LLEMOWNGBBNAJR-UHFFFAOYSA-N 0.000 claims 1
- 101710119334 Ceramide transfer protein Proteins 0.000 abstract description 31
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- 208000016691 refractory malignant neoplasm Diseases 0.000 abstract description 3
- 102100034166 Vasculin Human genes 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 202
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- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
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| US25843209P | 2009-11-05 | 2009-11-05 | |
| PCT/EP2010/006757 WO2011054530A1 (en) | 2009-11-05 | 2010-11-05 | Gpbp inhibition using q2 peptidomimetics |
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| MX2012005281A true MX2012005281A (es) | 2012-06-19 |
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| MX2012005281A MX2012005281A (es) | 2009-11-05 | 2010-11-05 | Inhibicion de gpbp utilizando peptidomimeticos q2. |
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| CN103403030A (zh) | 2011-02-21 | 2013-11-20 | 菲布他丁有限合伙公司 | 治疗和诊断疾病的方法 |
| WO2014006020A1 (en) | 2012-07-02 | 2014-01-09 | Fibrostatin, S.L. | Gpbp-1 inhibition and its therapeutic use |
| ES2489815B1 (es) * | 2013-02-21 | 2015-08-10 | Centro De Investigación Príncipe Felipe | Nuevos p-terfenilos hexakis-sustituidos con grupos bilaterales para el tratamiento de la infección por el virus de la inmunodeficiencia humana tipo 1 (VIH-1) y otras enfermedades |
| JP6322704B2 (ja) * | 2013-06-27 | 2018-05-09 | エルジー・ケム・リミテッド | Gpr120アゴニストとしてのビアリール誘導体 |
| US20150093378A1 (en) * | 2013-09-27 | 2015-04-02 | Fibrostatin, S.L. | Goodpasture Antigen Binding Protein Detection and Inhibition and its Use in Diabetes |
| CN115925679A (zh) * | 2014-12-24 | 2023-04-07 | 株式会社Lg化学 | 作为gpr120激动剂的联芳基衍生物 |
| WO2016107906A1 (en) | 2014-12-31 | 2016-07-07 | Fibrostatin, S.L. | Methods for inhibiting mesenchymal phenotype after epithelial-to-mesenchymal transition |
| WO2017134146A1 (en) * | 2016-02-02 | 2017-08-10 | Fibrostatin, S.L. | Gpbp inhibitors and uses and scaleable synthesis thereof |
| CN112479941B (zh) * | 2020-11-30 | 2023-01-13 | 沧州维智达美制药有限公司 | 一种2-取代-3-芳基卤苄衍生物的制备方法 |
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| PT933346E (pt) * | 1996-07-31 | 2004-03-31 | Shionogi & Co | Novos compostos de p-terfenilo |
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| ATE316577T1 (de) | 1999-02-24 | 2006-02-15 | Juan Saus | Das goodpasture-antigen bindende protein |
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| JP4776279B2 (ja) * | 2005-06-09 | 2011-09-21 | 株式会社Adeka | 新規化合物及び液晶組成物 |
| CN101268029B (zh) * | 2005-10-07 | 2012-09-05 | 三菱化学株式会社 | 烃化合物、电荷传输材料、电荷传输材料组合物和有机电致发光元件 |
| JP5209325B2 (ja) * | 2006-01-25 | 2013-06-12 | 保土谷化学工業株式会社 | p−ターフェニル化合物混合物及び該化合物混合物を用いた電子写真用感光体 |
| WO2009008311A1 (ja) * | 2007-07-07 | 2009-01-15 | Idemitsu Kosan Co., Ltd. | クリセン誘導体及びそれを用いた有機エレクトロルミネッセンス素子 |
| EA201070422A1 (ru) * | 2007-10-04 | 2010-12-30 | Мерк Сероно С.А. | Производные оксадиазола |
| BRPI0817433A2 (pt) * | 2007-10-19 | 2015-06-16 | Janssen Pharmaceutica Nv | Moduladores de gama-secretase piperidinila e piperazinila |
| JP5662803B2 (ja) * | 2007-12-20 | 2015-02-04 | アストラゼネカ アクチボラグ | Dgat1阻害剤としてのカルバモイル化合物190 |
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| US20140080852A1 (en) | 2014-03-20 |
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| CN102781898B (zh) | 2014-12-24 |
| US20180179139A1 (en) | 2018-06-28 |
| US20110105545A1 (en) | 2011-05-05 |
| US9199936B2 (en) | 2015-12-01 |
| US20160083327A1 (en) | 2016-03-24 |
| WO2011054530A1 (en) | 2011-05-12 |
| EP2496544A1 (en) | 2012-09-12 |
| JP5883794B2 (ja) | 2016-03-15 |
| CN102781898A (zh) | 2012-11-14 |
| US8586776B2 (en) | 2013-11-19 |
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