EA013250B1 - Ингибиторы c-fms киназы - Google Patents

Info

Publication number

EA013250B1

EA013250B1 EA200700918A EA200700918A EA013250B1 EA 013250 B1 EA013250 B1 EA 013250B1 EA 200700918 A EA200700918 A EA 200700918A EA 200700918 A EA200700918 A EA 200700918A EA 013250 B1 EA013250 B1 EA 013250B1

Authority

EA

Eurasian Patent Office

Prior art keywords

amide

carboxylic acid

cyano

cyclohex

phenyl

Prior art date

2004-10-22

Links

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• 108010058398 Macrophage Colony-Stimulating Factor Receptor Proteins 0.000 title abstract 2
• 239000003112 inhibitor Substances 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 303
• 238000000034 method Methods 0.000 claims abstract description 76
• 150000003839 salts Chemical class 0.000 claims abstract description 35
• 239000012453 solvate Substances 0.000 claims abstract description 32
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 23
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 23
• 150000004677 hydrates Chemical class 0.000 claims abstract description 21
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
• 201000010099 disease Diseases 0.000 claims abstract description 11
• 206010027476 Metastases Diseases 0.000 claims abstract description 9
• 206010006187 Breast cancer Diseases 0.000 claims abstract description 7
• 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 7
• 230000002757 inflammatory effect Effects 0.000 claims abstract description 7
• 230000009401 metastasis Effects 0.000 claims abstract description 7
• 206010009944 Colon cancer Diseases 0.000 claims abstract description 6
• 206010033128 Ovarian cancer Diseases 0.000 claims abstract description 5
• 206010061535 Ovarian neoplasm Diseases 0.000 claims abstract description 5
• 208000002193 Pain Diseases 0.000 claims abstract description 5
• 208000029742 colonic neoplasm Diseases 0.000 claims abstract description 5
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 4
• 208000005718 Stomach Neoplasms Diseases 0.000 claims abstract description 4
• 206010017758 gastric cancer Diseases 0.000 claims abstract description 4
• 201000011549 stomach cancer Diseases 0.000 claims abstract description 4
• 208000006386 Bone Resorption Diseases 0.000 claims abstract description 3
• 206010006002 Bone pain Diseases 0.000 claims abstract description 3
• 206010065390 Inflammatory pain Diseases 0.000 claims abstract description 3
• 208000010191 Osteitis Deformans Diseases 0.000 claims abstract description 3
• 208000001132 Osteoporosis Diseases 0.000 claims abstract description 3
• 208000027868 Paget disease Diseases 0.000 claims abstract description 3
• 206010035226 Plasma cell myeloma Diseases 0.000 claims abstract description 3
• 206010039491 Sarcoma Diseases 0.000 claims abstract description 3
• 208000002495 Uterine Neoplasms Diseases 0.000 claims abstract description 3
• 206010003246 arthritis Diseases 0.000 claims abstract description 3
• 210000000988 bone and bone Anatomy 0.000 claims abstract description 3
• 230000024279 bone resorption Effects 0.000 claims abstract description 3
• 208000027202 mammary Paget disease Diseases 0.000 claims abstract description 3
• 201000000050 myeloid neoplasm Diseases 0.000 claims abstract description 3
• 208000004296 neuralgia Diseases 0.000 claims abstract description 3
• 201000008482 osteoarthritis Diseases 0.000 claims abstract description 3
• 230000000010 osteolytic effect Effects 0.000 claims abstract description 3
• 206010046766 uterine cancer Diseases 0.000 claims abstract description 3
• 230000009278 visceral effect Effects 0.000 claims abstract description 3
• 208000009935 visceral pain Diseases 0.000 claims abstract description 3
• -1 hetero radical Chemical class 0.000 claims description 307
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 98
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 71
• 150000001408 amides Chemical class 0.000 claims description 64
• 125000000217 alkyl group Chemical group 0.000 claims description 59
• XTDRPNJABDWQFI-UHFFFAOYSA-N 5-cyano-1h-imidazole-2-carboxylic acid Chemical compound OC(=O)C1=NC(C#N)=CN1 XTDRPNJABDWQFI-UHFFFAOYSA-N 0.000 claims description 50
• 229910052739 hydrogen Inorganic materials 0.000 claims description 41
• 239000001257 hydrogen Substances 0.000 claims description 40
• 125000003277 amino group Chemical group 0.000 claims description 38
• 239000000460 chlorine Substances 0.000 claims description 37
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 31
• 229920006395 saturated elastomer Polymers 0.000 claims description 26
• 125000003282 alkyl amino group Chemical group 0.000 claims description 24
• 125000003118 aryl group Chemical group 0.000 claims description 24
• 125000002883 imidazolyl group Chemical group 0.000 claims description 24
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 125000004076 pyridyl group Chemical group 0.000 claims description 22
• VGOKAEAIMLFTTI-UHFFFAOYSA-N 2-(cyclohexen-1-yl)-4-piperidin-4-ylaniline Chemical compound NC1=CC=C(C2CCNCC2)C=C1C1=CCCCC1 VGOKAEAIMLFTTI-UHFFFAOYSA-N 0.000 claims description 21
• 229910052757 nitrogen Inorganic materials 0.000 claims description 21
• 241000124008 Mammalia Species 0.000 claims description 20
• 239000002253 acid Substances 0.000 claims description 19
• 125000002541 furyl group Chemical group 0.000 claims description 19
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
• 229910052799 carbon Inorganic materials 0.000 claims description 17
• 239000011737 fluorine Substances 0.000 claims description 17
• 229910052731 fluorine Inorganic materials 0.000 claims description 17
• 150000002431 hydrogen Chemical class 0.000 claims description 17
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 17
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 16
• 125000003545 alkoxy group Chemical group 0.000 claims description 16
• 229910052801 chlorine Inorganic materials 0.000 claims description 16
• 125000004122 cyclic group Chemical group 0.000 claims description 16
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 15
• 125000001424 substituent group Chemical group 0.000 claims description 15
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 14
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 12
• BPMBNLJJRKCCRT-UHFFFAOYSA-N 4-phenylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1C1=CC=CC=C1 BPMBNLJJRKCCRT-UHFFFAOYSA-N 0.000 claims description 12
• VZNRRMBBFKLIET-UHFFFAOYSA-N 5-cyano-1h-imidazole-2-carboxamide Chemical compound NC(=O)C1=NC(C#N)=CN1 VZNRRMBBFKLIET-UHFFFAOYSA-N 0.000 claims description 12
• HHHCADSYQQJUGV-UHFFFAOYSA-N 5-cyanofuran-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(C#N)O1 HHHCADSYQQJUGV-UHFFFAOYSA-N 0.000 claims description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
• 125000005942 tetrahydropyridyl group Chemical group 0.000 claims description 12
• 230000015572 biosynthetic process Effects 0.000 claims description 11
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 150000002367 halogens Chemical group 0.000 claims description 10
• 125000001072 heteroaryl group Chemical group 0.000 claims description 10
• 125000002757 morpholinyl group Chemical group 0.000 claims description 10
• 125000003386 piperidinyl group Chemical group 0.000 claims description 10
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 10
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
• 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 9
• 230000002401 inhibitory effect Effects 0.000 claims description 9
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
• 125000002971 oxazolyl group Chemical group 0.000 claims description 9
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 8
• 150000001721 carbon Chemical group 0.000 claims description 8
• UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 8
• 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 8
• 230000000694 effects Effects 0.000 claims description 8
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
• 125000004432 carbon atom Chemical group C* 0.000 claims description 7
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 7
• 125000005842 heteroatom Chemical group 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
• 201000011510 cancer Diseases 0.000 claims description 6
• 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 6
• KYWMCFOWDYFYLV-UHFFFAOYSA-N 1h-imidazole-2-carboxylic acid Chemical compound OC(=O)C1=NC=CN1 KYWMCFOWDYFYLV-UHFFFAOYSA-N 0.000 claims description 5
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 5
• 108091000080 Phosphotransferase Proteins 0.000 claims description 5
• 150000007513 acids Chemical class 0.000 claims description 5
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
• 206010012601 diabetes mellitus Diseases 0.000 claims description 5
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 5
• 102000020233 phosphotransferase Human genes 0.000 claims description 5
• BUZJFCFNJLVCDN-UHFFFAOYSA-N 1-[4-[4-amino-3-(cyclohexen-1-yl)phenyl]piperidin-1-yl]-2-pyridin-2-ylethanone Chemical compound NC1=CC=C(C2CCN(CC2)C(=O)CC=2N=CC=CC=2)C=C1C1=CCCCC1 BUZJFCFNJLVCDN-UHFFFAOYSA-N 0.000 claims description 4
• DSKOFFLMAAOSKB-UHFFFAOYSA-N 1-[4-[4-amino-3-(cyclohexen-1-yl)phenyl]piperidin-1-yl]-3-morpholin-4-ylpropan-1-one Chemical compound NC1=CC=C(C2CCN(CC2)C(=O)CCN2CCOCC2)C=C1C1=CCCCC1 DSKOFFLMAAOSKB-UHFFFAOYSA-N 0.000 claims description 4
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 4
• 125000002619 bicyclic group Chemical group 0.000 claims description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
• 125000005518 carboxamido group Chemical group 0.000 claims description 4
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
• 125000002950 monocyclic group Chemical group 0.000 claims description 4
• LJVQHXICFCZRJN-UHFFFAOYSA-N 1h-1,2,4-triazole-5-carboxylic acid Chemical compound OC(=O)C1=NC=NN1 LJVQHXICFCZRJN-UHFFFAOYSA-N 0.000 claims description 3
• CEQVSLWTDOIJFZ-UHFFFAOYSA-N 2-(4-methylcyclohexen-1-yl)-4-[1-(pyridin-2-ylmethyl)piperidin-4-yl]aniline Chemical compound C1C(C)CCC(C=2C(=CC=C(C=2)C2CCN(CC=3N=CC=CC=3)CC2)N)=C1 CEQVSLWTDOIJFZ-UHFFFAOYSA-N 0.000 claims description 3
• HCKNMNCOHLVBKP-UHFFFAOYSA-N 2-(cyclohexen-1-yl)-4-[1-(2-methylsulfonylethyl)piperidin-4-yl]aniline Chemical compound C1CN(CCS(=O)(=O)C)CCC1C1=CC=C(N)C(C=2CCCCC=2)=C1 HCKNMNCOHLVBKP-UHFFFAOYSA-N 0.000 claims description 3
• ASFAFOSQXBRFMV-LJQANCHMSA-N 3-n-(2-benzyl-1,3-dihydroxypropan-2-yl)-1-n-[(1r)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzene-1,3-dicarboxamide Chemical compound N([C@H](C)C=1C=CC(F)=CC=1)C(=O)C(C=1)=CC(N(C)S(C)(=O)=O)=CC=1C(=O)NC(CO)(CO)CC1=CC=CC=C1 ASFAFOSQXBRFMV-LJQANCHMSA-N 0.000 claims description 3
• VYVSSXVMKXXDFX-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)-2-(2-methylthiophen-3-yl)aniline Chemical compound C1CN(C)CCN1C1=CC=C(N)C(C2=C(SC=C2)C)=C1 VYVSSXVMKXXDFX-UHFFFAOYSA-N 0.000 claims description 3
• DNFSYUKZJKMDRE-UHFFFAOYSA-N 4-[4-[(5-cyano-1h-imidazole-2-carbonyl)amino]-3-(cyclohexen-1-yl)phenyl]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1C(C=C1C=2CCCCC=2)=CC=C1NC(=O)C1=NC=C(C#N)N1 DNFSYUKZJKMDRE-UHFFFAOYSA-N 0.000 claims description 3
• SAEZQFNKTQKVSM-UHFFFAOYSA-N 4-cyano-1h-pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC(C#N)=CN1 SAEZQFNKTQKVSM-UHFFFAOYSA-N 0.000 claims description 3
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
• 201000004681 Psoriasis Diseases 0.000 claims description 3
• 206010038802 Reticuloendothelial system stimulated Diseases 0.000 claims description 3
• 230000033115 angiogenesis Effects 0.000 claims description 3
• 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 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
• 239000008194 pharmaceutical composition Substances 0.000 claims description 3
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• YSACTRAHIJTMLP-UHFFFAOYSA-N 1-[4-[4-amino-3-(cyclohexen-1-yl)phenyl]piperidin-1-yl]-2-(1H-imidazol-5-yl)ethanone Chemical compound NC1=CC=C(C2CCN(CC2)C(=O)CC=2NC=NC=2)C=C1C1=CCCCC1 YSACTRAHIJTMLP-UHFFFAOYSA-N 0.000 claims description 2
• AXQQLAYDVUOVKN-UHFFFAOYSA-N 1-[4-[4-amino-3-(cyclohexen-1-yl)phenyl]piperidin-1-yl]-2-[2-hydroxyethyl(methyl)amino]ethanone Chemical compound C1CN(C(=O)CN(CCO)C)CCC1C1=CC=C(N)C(C=2CCCCC=2)=C1 AXQQLAYDVUOVKN-UHFFFAOYSA-N 0.000 claims description 2
• KHJUYNJKDOCLNH-UHFFFAOYSA-N 1-cyanoimidazole-2-carboxylic acid Chemical compound OC(=O)C1=NC=CN1C#N KHJUYNJKDOCLNH-UHFFFAOYSA-N 0.000 claims description 2
• HGFLHDKKRBSQHU-UHFFFAOYSA-N 2-(cyclopenten-1-yl)-4-[1-[(1-methylimidazol-2-yl)methyl]piperidin-4-yl]aniline Chemical compound CN1C=CN=C1CN1CCC(C=2C=C(C(N)=CC=2)C=2CCCC=2)CC1 HGFLHDKKRBSQHU-UHFFFAOYSA-N 0.000 claims description 2
• 208000024827 Alzheimer disease Diseases 0.000 claims description 2
• XRSYFGPQBZTPPS-UHFFFAOYSA-N CC1=C(C(C=C(C=C2)N3CCN(C)CC3)=C2C2=C(C(N)=O)OC(C#N)=C2)SC=C1 Chemical compound CC1=C(C(C=C(C=C2)N3CCN(C)CC3)=C2C2=C(C(N)=O)OC(C#N)=C2)SC=C1 XRSYFGPQBZTPPS-UHFFFAOYSA-N 0.000 claims description 2
• 206010012289 Dementia Diseases 0.000 claims description 2
• 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
• 208000031886 HIV Infections Diseases 0.000 claims description 2
• 208000037357 HIV infectious disease Diseases 0.000 claims description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
• 208000011623 Obstructive Lung disease Diseases 0.000 claims description 2
• 206010033645 Pancreatitis Diseases 0.000 claims description 2
• 208000021386 Sjogren Syndrome Diseases 0.000 claims description 2
• 206010046851 Uveitis Diseases 0.000 claims description 2
• 208000006673 asthma Diseases 0.000 claims description 2
• 239000004305 biphenyl Substances 0.000 claims description 2
• 235000010290 biphenyl Nutrition 0.000 claims description 2
• 125000001153 fluoro group Chemical group F* 0.000 claims description 2
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 2
• 208000002780 macular degeneration Diseases 0.000 claims description 2
• 230000001404 mediated effect Effects 0.000 claims description 2
• 201000006417 multiple sclerosis Diseases 0.000 claims description 2
• 201000000306 sarcoidosis Diseases 0.000 claims description 2
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 2
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 4
• DWZYHNROGDWFGE-UHFFFAOYSA-N 1-[4-[4-amino-3-(cyclohexen-1-yl)phenyl]piperidin-1-yl]-2-morpholin-4-ylethanone Chemical compound NC1=CC=C(C2CCN(CC2)C(=O)CN2CCOCC2)C=C1C1=CCCCC1 DWZYHNROGDWFGE-UHFFFAOYSA-N 0.000 claims 2
• KASAITPLPKXDDM-UHFFFAOYSA-N 1-[4-[4-amino-3-(cyclohexen-1-yl)phenyl]piperidin-1-yl]-2-pyridin-4-ylethanone Chemical compound NC1=CC=C(C2CCN(CC2)C(=O)CC=2C=CN=CC=2)C=C1C1=CCCCC1 KASAITPLPKXDDM-UHFFFAOYSA-N 0.000 claims 2
• UVUBZUPVNPMHQF-UHFFFAOYSA-N 2-(cyclohexen-1-yl)-4-(1-pyridin-2-ylpiperidin-4-yl)aniline Chemical compound NC1=CC=C(C2CCN(CC2)C=2N=CC=CC=2)C=C1C1=CCCCC1 UVUBZUPVNPMHQF-UHFFFAOYSA-N 0.000 claims 2
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 2
• 239000002552 dosage form Substances 0.000 claims 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
• CLEIDFUPZUOMRS-UHFFFAOYSA-N 1-[4-[4-amino-3-(cyclohexen-1-yl)phenyl]piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C1CN(C(=O)CN(C)C)CCC1C1=CC=C(N)C(C=2CCCCC=2)=C1 CLEIDFUPZUOMRS-UHFFFAOYSA-N 0.000 claims 1
• HZSRIOTZWOAUJE-UHFFFAOYSA-N 1-[4-[4-amino-3-(cyclohexen-1-yl)phenyl]piperidin-1-yl]-2-methylsulfonylethanone Chemical compound C1CN(C(=O)CS(=O)(=O)C)CCC1C1=CC=C(N)C(C=2CCCCC=2)=C1 HZSRIOTZWOAUJE-UHFFFAOYSA-N 0.000 claims 1
• DESNPSZBZHRHAM-UHFFFAOYSA-N 1-[4-[4-amino-3-(cyclohexen-1-yl)phenyl]piperidin-1-yl]-2-pyridin-3-ylethanone Chemical compound NC1=CC=C(C2CCN(CC2)C(=O)CC=2C=NC=CC=2)C=C1C1=CCCCC1 DESNPSZBZHRHAM-UHFFFAOYSA-N 0.000 claims 1
• PGPDHIFTNPJUBA-UHFFFAOYSA-N 1-[4-[4-amino-3-(cyclohexen-1-yl)phenyl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=CC=C(N)C(C=2CCCCC=2)=C1 PGPDHIFTNPJUBA-UHFFFAOYSA-N 0.000 claims 1
• RCTPNXUPRHOSSW-UHFFFAOYSA-N 2-(3,6-dihydro-2H-pyran-4-yl)-4-(4-methylpiperazin-1-yl)aniline Chemical compound C1CN(C)CCN1C1=CC=C(N)C(C=2CCOCC=2)=C1 RCTPNXUPRHOSSW-UHFFFAOYSA-N 0.000 claims 1
• DDHAFYWTHXVSLP-UHFFFAOYSA-N 2-(cyclohexen-1-yl)-4-[1-(pyridin-2-ylmethyl)piperidin-4-yl]aniline Chemical compound NC1=CC=C(C2CCN(CC=3N=CC=CC=3)CC2)C=C1C1=CCCCC1 DDHAFYWTHXVSLP-UHFFFAOYSA-N 0.000 claims 1
• 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims 1
• YZICFVIUVMCCOC-UHFFFAOYSA-N 3-piperidin-1-ylpropanenitrile Chemical compound N#CCCN1CCCCC1 YZICFVIUVMCCOC-UHFFFAOYSA-N 0.000 claims 1
• OPXXQBVGRCBQHS-UHFFFAOYSA-N 4-cyano-1-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]imidazole-2-carboxamide Chemical compound C1(=CCCCC1)C1=C(C=CC(=C1)C1CCN(CC1)C(CN(C)C)=O)N1C(=NC(=C1)C#N)C(=O)N OPXXQBVGRCBQHS-UHFFFAOYSA-N 0.000 claims 1
• GGTTVHXACHERJR-UHFFFAOYSA-N C1(=CCCCC1)C1=C(C=CC(=C1)C1CCN(CC1)CCN1CCOCC1)N1C(=NC(=C1)C#N)C(=O)N Chemical compound C1(=CCCCC1)C1=C(C=CC(=C1)C1CCN(CC1)CCN1CCOCC1)N1C(=NC(=C1)C#N)C(=O)N GGTTVHXACHERJR-UHFFFAOYSA-N 0.000 claims 1
• 101100479039 Caenorhabditis elegans aars-1 gene Proteins 0.000 claims 1
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• 208000017442 Retinal disease Diseases 0.000 claims 1
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• 125000005037 alkyl phenyl group Chemical group 0.000 claims 1
• 239000013256 coordination polymer Substances 0.000 claims 1
• 230000004054 inflammatory process Effects 0.000 claims 1
• WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 claims 1
• 229910052702 rhenium Inorganic materials 0.000 claims 1
• WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 claims 1
• 208000037408 Device failure Diseases 0.000 abstract 1
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• 239000000203 mixture Substances 0.000 description 124
• 239000000243 solution Substances 0.000 description 113
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 94
• 238000001819 mass spectrum Methods 0.000 description 93
• 239000011541 reaction mixture Substances 0.000 description 86
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 85
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