MX2007004847A - Nuevos derivados de acido dicarboxilico. - Google Patents

Info

Publication number

MX2007004847A

MX2007004847A MX2007004847A MX2007004847A MX2007004847A MX 2007004847 A MX2007004847 A MX 2007004847A MX 2007004847 A MX2007004847 A MX 2007004847A MX 2007004847 A MX2007004847 A MX 2007004847A MX 2007004847 A MX2007004847 A MX 2007004847A

Authority

MX

Mexico

Prior art keywords

dicarboxylic acid

acid

alkyl

cyclopentan

methylamino

Prior art date

2004-10-22

Links

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• 150000001990 dicarboxylic acid derivatives Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 132
• 238000002360 preparation method Methods 0.000 claims abstract description 40
• 238000000034 method Methods 0.000 claims abstract description 38
• 230000008569 process Effects 0.000 claims abstract description 18
• -1 polyfluoroalkyl Chemical group 0.000 claims description 179
• 239000002253 acid Substances 0.000 claims description 111
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 74
• 239000000203 mixture Substances 0.000 claims description 55
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 51
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 51
• 230000002829 reductive effect Effects 0.000 claims description 49
• 125000000217 alkyl group Chemical group 0.000 claims description 43
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 39
• 238000006243 chemical reaction Methods 0.000 claims description 31
• 125000005842 heteroatom Chemical group 0.000 claims description 26
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
• 150000003839 salts Chemical class 0.000 claims description 25
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims description 24
• 125000003118 aryl group Chemical group 0.000 claims description 24
• 125000004429 atom Chemical group 0.000 claims description 24
• JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 claims description 24
• 125000004494 ethyl ester group Chemical group 0.000 claims description 24
• 150000002148 esters Chemical class 0.000 claims description 22
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
• 125000001072 heteroaryl group Chemical group 0.000 claims description 19
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
• 125000004432 carbon atom Chemical group C* 0.000 claims description 14
• 239000003814 drug Substances 0.000 claims description 13
• 125000005843 halogen group Chemical group 0.000 claims description 13
• 102000005962 receptors Human genes 0.000 claims description 13
• 108020003175 receptors Proteins 0.000 claims description 13
• 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 11
• 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
• 125000000623 heterocyclic group Chemical group 0.000 claims description 11
• 150000004677 hydrates Chemical class 0.000 claims description 11
• 239000012453 solvate Substances 0.000 claims description 11
• 238000011282 treatment Methods 0.000 claims description 11
• 239000000556 agonist Substances 0.000 claims description 10
• 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 8
• 125000004122 cyclic group Chemical group 0.000 claims description 8
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
• GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 claims description 7
• 210000004698 lymphocyte Anatomy 0.000 claims description 7
• XWYNJZPDWLFBBL-UHFFFAOYSA-N 3-[(4-decyl-2,3-difluorophenyl)methylamino]cyclopentane-1,1-dicarboxylic acid Chemical compound FC1=C(F)C(CCCCCCCCCC)=CC=C1CNC1CC(C(O)=O)(C(O)=O)CC1 XWYNJZPDWLFBBL-UHFFFAOYSA-N 0.000 claims description 6
• NXXNOAZWICKDFY-UHFFFAOYSA-N 3-[2-(4-decyl-2,3-difluorophenyl)ethylamino]cyclopentane-1,1-dicarboxylic acid Chemical compound FC1=C(F)C(CCCCCCCCCC)=CC=C1CCNC1CC(C(O)=O)(C(O)=O)CC1 NXXNOAZWICKDFY-UHFFFAOYSA-N 0.000 claims description 6
• 125000000304 alkynyl group Chemical group 0.000 claims description 6
• YZFOGXKZTWZVFN-UHFFFAOYSA-N cyclopentane-1,1-dicarboxylic acid Chemical class OC(=O)C1(C(O)=O)CCCC1 YZFOGXKZTWZVFN-UHFFFAOYSA-N 0.000 claims description 6
• 210000000056 organ Anatomy 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 230000002265 prevention Effects 0.000 claims description 6
• 208000023275 Autoimmune disease Diseases 0.000 claims description 5
• 229910019142 PO4 Inorganic materials 0.000 claims description 5
• 238000005859 coupling reaction Methods 0.000 claims description 5
• 239000010452 phosphate Substances 0.000 claims description 5
• 125000001544 thienyl group Chemical group 0.000 claims description 5
• 238000002054 transplantation Methods 0.000 claims description 5
• RGSFGYAAUTVSQA-DICFDUPASA-N 1,1-dideuteriocyclopentane Chemical compound C1(CCCC1)([2H])[2H] RGSFGYAAUTVSQA-DICFDUPASA-N 0.000 claims description 4
• PKILXMOKFDNUJX-UHFFFAOYSA-N 3-[(4-decylphenyl)methylamino]cyclopentane-1,1-dicarboxylic acid Chemical class C1=CC(CCCCCCCCCC)=CC=C1CNC1CC(C(O)=O)(C(O)=O)CC1 PKILXMOKFDNUJX-UHFFFAOYSA-N 0.000 claims description 4
• BUPTZRZGUIGPQW-UHFFFAOYSA-N 3-[(4-nonylphenyl)methylamino]-1-(propylcarbamoyl)cyclopentane-1-carboxylic acid Chemical compound C1=CC(CCCCCCCCC)=CC=C1CNC1CC(C(=O)NCCC)(C(O)=O)CC1 BUPTZRZGUIGPQW-UHFFFAOYSA-N 0.000 claims description 4
• 206010052779 Transplant rejections Diseases 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 150000001413 amino acids Chemical class 0.000 claims description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• 125000006287 difluorobenzyl group Chemical group 0.000 claims description 4
• 208000035475 disorder Diseases 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 229910052739 hydrogen Inorganic materials 0.000 claims description 4
• 201000006417 multiple sclerosis Diseases 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 claims description 3
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 3
• DPEWOKOZTYDKCQ-UHFFFAOYSA-N 3-[(4-decylphenyl)methylamino]-1-(methylcarbamoyl)cyclopentane-1-carboxylic acid Chemical compound C1=CC(CCCCCCCCCC)=CC=C1CNC1CC(C(=O)NC)(C(O)=O)CC1 DPEWOKOZTYDKCQ-UHFFFAOYSA-N 0.000 claims description 3
• FBDDPQRVQWBJRV-UHFFFAOYSA-N 3-[(4-decylphenyl)methylamino]-1-ethoxycarbonylcyclopentane-1-carboxylic acid Chemical compound C1=CC(CCCCCCCCCC)=CC=C1CNC1CC(C(=O)OCC)(C(O)=O)CC1 FBDDPQRVQWBJRV-UHFFFAOYSA-N 0.000 claims description 3
• ZQCSXWIJERKDER-UHFFFAOYSA-N 3-[[3-fluoro-4-(4-heptylphenyl)phenyl]methylamino]cyclopentane-1,1-dicarboxylic acid Chemical compound C1=CC(CCCCCCC)=CC=C1C(C(=C1)F)=CC=C1CNC1CC(C(O)=O)(C(O)=O)CC1 ZQCSXWIJERKDER-UHFFFAOYSA-N 0.000 claims description 3
• 101100188553 Arabidopsis thaliana OCT4 gene Proteins 0.000 claims description 3
• 201000001320 Atherosclerosis Diseases 0.000 claims description 3
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 3
• 206010025323 Lymphomas Diseases 0.000 claims description 3
• 208000009525 Myocarditis Diseases 0.000 claims description 3
• 206010035664 Pneumonia Diseases 0.000 claims description 3
• 201000004681 Psoriasis Diseases 0.000 claims description 3
• 206010040047 Sepsis Diseases 0.000 claims description 3
• 230000002378 acidificating effect Effects 0.000 claims description 3
• 208000006673 asthma Diseases 0.000 claims description 3
• 201000008937 atopic dermatitis Diseases 0.000 claims description 3
• 230000007812 deficiency Effects 0.000 claims description 3
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 3
• 229910052736 halogen Inorganic materials 0.000 claims description 3
• 206010025135 lupus erythematosus Diseases 0.000 claims description 3
• 230000004048 modification Effects 0.000 claims description 3
• 238000012986 modification Methods 0.000 claims description 3
• 238000006268 reductive amination reaction Methods 0.000 claims description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
• WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 claims description 3
• YOFHWDODVSEWGD-UHFFFAOYSA-N 2-[4-[(4-decyl-2,3-difluorophenyl)methylamino]but-2-ynyl]-2-methylpropanedioic acid Chemical compound CCCCCCCCCCC1=CC=C(CNCC#CCC(C)(C(O)=O)C(O)=O)C(F)=C1F YOFHWDODVSEWGD-UHFFFAOYSA-N 0.000 claims description 2
• ASDHRIBAVDPPLH-UHFFFAOYSA-N 3-[(2,3-difluoro-4-nonylphenyl)methylamino]-1-ethoxycarbonylcyclopentane-1-carboxylic acid Chemical compound FC1=C(F)C(CCCCCCCCC)=CC=C1CNC1CC(C(=O)OCC)(C(O)=O)CC1 ASDHRIBAVDPPLH-UHFFFAOYSA-N 0.000 claims description 2
• NAYVGWZZYCNTOL-UHFFFAOYSA-N 3-[(3-chloro-4-decoxyphenyl)methylamino]cyclopentane-1,1-dicarboxylic acid Chemical compound C1=C(Cl)C(OCCCCCCCCCC)=CC=C1CNC1CC(C(O)=O)(C(O)=O)CC1 NAYVGWZZYCNTOL-UHFFFAOYSA-N 0.000 claims description 2
• CIUXNPMCNUZPJD-UHFFFAOYSA-N 3-[2-(4-decylphenyl)ethylamino]cyclobutane-1,1-dicarboxylic acid Chemical compound C1=CC(CCCCCCCCCC)=CC=C1CCNC1CC(C(O)=O)(C(O)=O)C1 CIUXNPMCNUZPJD-UHFFFAOYSA-N 0.000 claims description 2
• 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
• 101000693265 Homo sapiens Sphingosine 1-phosphate receptor 1 Proteins 0.000 claims description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
• 230000033115 angiogenesis Effects 0.000 claims description 2
• 210000004369 blood Anatomy 0.000 claims description 2
• 239000008280 blood Substances 0.000 claims description 2
• 229910052799 carbon Inorganic materials 0.000 claims description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
• 206010012601 diabetes mellitus Diseases 0.000 claims description 2
• 238000006073 displacement reaction Methods 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 150000002367 halogens Chemical class 0.000 claims description 2
• 230000001771 impaired effect Effects 0.000 claims description 2
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• 230000002757 inflammatory effect Effects 0.000 claims description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 125000000468 ketone group Chemical group 0.000 claims description 2
• 208000003747 lymphoid leukemia Diseases 0.000 claims description 2
• 230000000269 nucleophilic effect Effects 0.000 claims description 2
• 125000003107 substituted aryl group Chemical group 0.000 claims description 2
• 230000002792 vascular Effects 0.000 claims description 2
• HJBLEOMQDLLYAZ-UHFFFAOYSA-N 3-[2-(2,3-difluoro-4-nonylphenyl)ethylamino]-1-(methylcarbamoyl)cyclopentane-1-carboxylic acid Chemical compound FC1=C(F)C(CCCCCCCCC)=CC=C1CCNC1CC(C(=O)NC)(C(O)=O)CC1 HJBLEOMQDLLYAZ-UHFFFAOYSA-N 0.000 claims 2
• 125000004175 fluorobenzyl group Chemical group 0.000 claims 2
• HJAHIIUFDFDBHD-UHFFFAOYSA-N (3-chloro-4-nonoxyphenyl)methanamine Chemical compound CCCCCCCCCOC1=CC=C(CN)C=C1Cl HJAHIIUFDFDBHD-UHFFFAOYSA-N 0.000 claims 1
• OVSQGRPUVXCGGX-UHFFFAOYSA-N 1-(methylcarbamoyl)-3-[(4-nonylphenyl)methylamino]cyclopentane-1-carboxylic acid;hydrochloride Chemical compound Cl.C1=CC(CCCCCCCCC)=CC=C1CNC1CC(C(=O)NC)(C(O)=O)CC1 OVSQGRPUVXCGGX-UHFFFAOYSA-N 0.000 claims 1
• LVNMEDFRUGYQEB-UHFFFAOYSA-N 1-butoxycarbonyl-3-[(4-nonylphenyl)methylamino]cyclopentane-1-carboxylic acid 3-[2-(4-decylphenyl)ethylamino]cyclopentane-1,1-dicarboxylic acid Chemical compound C(CCC)OC(=O)C1(CC(CC1)NCC1=CC=C(C=C1)CCCCCCCCC)C(=O)O.C(CCCCCCCCC)C1=CC=C(CCNC2CC(CC2)(C(=O)O)C(=O)O)C=C1 LVNMEDFRUGYQEB-UHFFFAOYSA-N 0.000 claims 1
• SMIYHPHDBDKZTR-UHFFFAOYSA-N 1-ethoxycarbonylcyclopentane-1-carboxylic acid Chemical compound CCOC(=O)C1(C(O)=O)CCCC1 SMIYHPHDBDKZTR-UHFFFAOYSA-N 0.000 claims 1
• JKIMHSXYHSPQIL-UHFFFAOYSA-N 2-methyl-2-[4-[(4-nonylphenyl)methyl-propan-2-ylamino]but-2-ynyl]propanedioic acid Chemical compound CCCCCCCCCC1=CC=C(CN(CC#CCC(C)(C(O)=O)C(O)=O)C(C)C)C=C1 JKIMHSXYHSPQIL-UHFFFAOYSA-N 0.000 claims 1
• WDBRDCFUVVEIER-UHFFFAOYSA-N 3-[(4-octylphenyl)methylamino]cyclopentane-1,1-dicarboxylic acid Chemical compound C1=CC(CCCCCCCC)=CC=C1CNC1CC(C(O)=O)(C(O)=O)CC1 WDBRDCFUVVEIER-UHFFFAOYSA-N 0.000 claims 1
• FGERXQYSFOUIDO-UHFFFAOYSA-N 3-[[3-fluoro-4-(4-heptylphenyl)phenyl]methylamino]-1-(methylcarbamoyl)cyclobutane-1-carboxylic acid Chemical class C1=CC(CCCCCCC)=CC=C1C(C(=C1)F)=CC=C1CNC1CC(C(=O)NC)(C(O)=O)C1 FGERXQYSFOUIDO-UHFFFAOYSA-N 0.000 claims 1
• KCCXPBBPGJTACM-UHFFFAOYSA-N 3-[cyclopropyl-[(4-nonylphenyl)methyl]amino]cyclopentane-1,1-dicarboxylic acid 3-[[3-fluoro-4-(4-heptylphenyl)phenyl]methyl-methylamino]cyclopentane-1,1-dicarboxylic acid Chemical compound FC1=C(C=CC(=C1)CN(C1CC(CC1)(C(=O)O)C(=O)O)C)C1=CC=C(C=C1)CCCCCCC.C1(CC1)N(C1CC(CC1)(C(=O)O)C(=O)O)CC1=CC=C(C=C1)CCCCCCCCC KCCXPBBPGJTACM-UHFFFAOYSA-N 0.000 claims 1
• 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 claims 1
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• 206010048908 Seasonal allergy Diseases 0.000 claims 1
• 125000002877 alkyl aryl group Chemical group 0.000 claims 1
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
• XOVJAYNMQDTIJD-UHFFFAOYSA-N cyclopentobarbital Chemical compound C1CC=CC1C1(CC=C)C(=O)NC(=O)NC1=O XOVJAYNMQDTIJD-UHFFFAOYSA-N 0.000 claims 1
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• DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 abstract 2
• 230000001270 agonistic effect Effects 0.000 abstract 1
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• 238000005481 NMR spectroscopy Methods 0.000 description 108
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• 239000002904 solvent Substances 0.000 description 50
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• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 41
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