CA2325201A1

CA2325201A1 - Methods of administering apo b-secretion/mtp inhibitors

Methods of administering apo b-secretion/mtp inhibitors Download PDF

Info

Publication number: CA2325201A1
Authority: CA; Canada
Prior art keywords: phenyl; trifluoromethyl; carboxylic acid; biphenyl; alkylamino
Prior art date: 1999-11-10
Legal status : Abandoned

Application number

CA002325201A

Other languages

English (en)

French (fr)

Inventor

John Vincent

George Chang

Current Assignee

Pfizer Products Inc

Original Assignee

Pfizer Products Inc

Priority date

1999-11-10

Filing date

2000-11-08

Publication date

2001-05-10

2000-11-08 Application filed by Pfizer Products Inc filed Critical Pfizer Products Inc

2001-05-10 Publication of CA2325201A1 publication Critical patent/CA2325201A1/en

Status Abandoned legal-status Critical Current

Links

239000003112 inhibitor Substances 0.000 title claims abstract description 38
238000000034 method Methods 0.000 title description 24
102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 claims abstract description 44
108010038232 microsomal triglyceride transfer protein Proteins 0.000 claims abstract description 44
239000003814 drug Substances 0.000 claims abstract description 36
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 27
102000018616 Apolipoproteins B Human genes 0.000 claims abstract description 22
108010027006 Apolipoproteins B Proteins 0.000 claims abstract description 22
108010028554 LDL Cholesterol Proteins 0.000 claims abstract description 15
238000008214 LDL Cholesterol Methods 0.000 claims abstract description 15
230000009467 reduction Effects 0.000 claims abstract description 8
239000003085 diluting agent Substances 0.000 claims abstract description 7
239000003981 vehicle Substances 0.000 claims abstract description 7
102000007592 Apolipoproteins Human genes 0.000 claims abstract description 6
108010071619 Apolipoproteins Proteins 0.000 claims abstract description 6
239000003937 drug carrier Substances 0.000 claims abstract description 5
-1 cyano, nitro, oxo, thioxo, aminosulfonyl Chemical group 0.000 claims description 186
150000001875 compounds Chemical class 0.000 claims description 180
125000003282 alkyl amino group Chemical group 0.000 claims description 52
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 42
150000003839 salts Chemical class 0.000 claims description 39
125000000623 heterocyclic group Chemical group 0.000 claims description 36
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 32
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 32
125000002252 acyl group Chemical group 0.000 claims description 30
125000000217 alkyl group Chemical group 0.000 claims description 30
239000000651 prodrug Substances 0.000 claims description 30
229940002612 prodrug Drugs 0.000 claims description 30
125000001424 substituent group Chemical group 0.000 claims description 30
125000004423 acyloxy group Chemical group 0.000 claims description 28
229920001774 Perfluoroether Polymers 0.000 claims description 27
125000003118 aryl group Chemical group 0.000 claims description 27
125000005842 heteroatom Chemical group 0.000 claims description 26
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 25
125000004414 alkyl thio group Chemical group 0.000 claims description 25
229910052757 nitrogen Inorganic materials 0.000 claims description 25
229920006395 saturated elastomer Polymers 0.000 claims description 25
229910052736 halogen Inorganic materials 0.000 claims description 22
150000002367 halogens Chemical class 0.000 claims description 22
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 22
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 19
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 19
229910052760 oxygen Inorganic materials 0.000 claims description 19
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 18
125000004432 carbon atom Chemical group C* 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 18
239000001257 hydrogen Substances 0.000 claims description 18
150000001408 amides Chemical class 0.000 claims description 17
125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 claims description 15
125000004442 acylamino group Chemical group 0.000 claims description 15
125000000753 cycloalkyl group Chemical group 0.000 claims description 15
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 15
150000004677 hydrates Chemical class 0.000 claims description 14
229910052717 sulfur Chemical group 0.000 claims description 14
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
125000006413 ring segment Chemical group 0.000 claims description 13
239000011593 sulfur Chemical group 0.000 claims description 13
IQOMYCGTGFGDFN-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 IQOMYCGTGFGDFN-UHFFFAOYSA-N 0.000 claims description 12
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
125000001072 heteroaryl group Chemical group 0.000 claims description 12
239000001301 oxygen Substances 0.000 claims description 12
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 8
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
ZSOZYBIDCNHWSW-UHFFFAOYSA-N 2-[1-(3,3-diphenylpropyl)piperidin-4-yl]-3h-isoindol-1-one Chemical compound C1C2=CC=CC=C2C(=O)N1C(CC1)CCN1CCC(C=1C=CC=CC=1)C1=CC=CC=C1 ZSOZYBIDCNHWSW-UHFFFAOYSA-N 0.000 claims description 6
125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 6
125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 6
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
AEGLYZOILDLYDV-UHFFFAOYSA-N isoquinoline-1,4-dione Chemical compound C1=CC=C2C(=O)C=NC(=O)C2=C1 AEGLYZOILDLYDV-UHFFFAOYSA-N 0.000 claims description 6
XPSLLBXVEDRXQQ-UHFFFAOYSA-N 9-[4-[4-(3-oxo-1h-isoindol-2-yl)piperidin-1-yl]butyl]-n-propylfluorene-9-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCCC)CCCCN1CCC(N2C(C3=CC=CC=C3C2)=O)CC1 XPSLLBXVEDRXQQ-UHFFFAOYSA-N 0.000 claims description 5
101100295741 Gallus gallus COR4 gene Proteins 0.000 claims description 5
125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
125000004043 oxo group Chemical group O=* 0.000 claims description 5
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
125000000464 thioxo group Chemical group S=* 0.000 claims description 5
NCYWSQPTIIOKJI-UHFFFAOYSA-N 2-cyclopentyl-n-(2-hydroxy-1-phenylethyl)-2-[4-(quinolin-2-ylmethoxy)phenyl]acetamide Chemical compound C=1C=CC=CC=1C(CO)NC(=O)C(C=1C=CC(OCC=2N=C3C=CC=CC3=CC=2)=CC=1)C1CCCC1 NCYWSQPTIIOKJI-UHFFFAOYSA-N 0.000 claims description 4
JMZYIYGMXMSLEH-UHFFFAOYSA-N 9-[4-[4-[[2-(1,3-benzothiazol-2-yl)benzoyl]amino]piperidin-1-yl]butyl]-n-(2,2,2-trifluoroethyl)fluorene-9-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN1CCC(NC(=O)C=2C(=CC=CC=2)C=2SC3=CC=CC=C3N=2)CC1 JMZYIYGMXMSLEH-UHFFFAOYSA-N 0.000 claims description 4
125000004104 aryloxy group Chemical group 0.000 claims description 4
125000004465 cycloalkenyloxy group Chemical group 0.000 claims description 4
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
125000005592 polycycloalkyl group Polymers 0.000 claims description 4
125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 3
125000005110 aryl thio group Chemical group 0.000 claims description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
125000003107 substituted aryl group Chemical group 0.000 claims description 3
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 3
125000005309 thioalkoxy group Chemical group 0.000 claims description 3
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
229920002554 vinyl polymer Polymers 0.000 claims description 3
125000006554 (C4-C8) cycloalkenyl group Chemical group 0.000 claims description 2
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
229910052792 caesium Inorganic materials 0.000 claims description 2
RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 2
JMKISJRYGDIDDU-UHFFFAOYSA-N n,n-diethyl-7-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]quinoline-3-carboxamide Chemical compound C1=CC2=CC(C(=O)N(CC)CC)=CN=C2C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 JMKISJRYGDIDDU-UHFFFAOYSA-N 0.000 claims description 2
YPLIQPHSFOYEEJ-UHFFFAOYSA-N n-(1-phenylpropyl)-7-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]quinoline-3-carboxamide Chemical compound C=1C=CC=CC=1C(CC)NC(=O)C(C=C1C=C2)=CN=C1C=C2NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 YPLIQPHSFOYEEJ-UHFFFAOYSA-N 0.000 claims description 2
XPMZKGAEFVLLSP-UHFFFAOYSA-N n-(1-pyridin-2-ylpropyl)-7-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]quinoline-3-carboxamide Chemical compound C=1C=CC=NC=1C(CC)NC(=O)C(C=C1C=C2)=CN=C1C=C2NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 XPMZKGAEFVLLSP-UHFFFAOYSA-N 0.000 claims description 2
RIZRNFDHZHXBHE-UHFFFAOYSA-N n-(2-phenylpropan-2-yl)-7-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]quinoline-3-carboxamide Chemical compound C=1C=CC=CC=1C(C)(C)NC(=O)C(C=C1C=C2)=CN=C1C=C2NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 RIZRNFDHZHXBHE-UHFFFAOYSA-N 0.000 claims description 2
ASAGFWJDIJKUQY-UHFFFAOYSA-N n-(2-pyridin-2-ylethyl)-7-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]quinoline-3-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C=C(C=N2)C(=O)NCCC=3N=CC=CC=3)C2=C1 ASAGFWJDIJKUQY-UHFFFAOYSA-N 0.000 claims description 2
GHVZCYSYXCFJMA-OAQYLSRUSA-N n-[(1r)-1-phenylethyl]-6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinoline-2-carboxamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C(=O)N(CC1=CC=2)CCC1=CC=2NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 GHVZCYSYXCFJMA-OAQYLSRUSA-N 0.000 claims description 2
ZSNQHQMXRGECNB-HXUWFJFHSA-N n-[(1r)-1-phenylethyl]-7-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]quinoline-3-carboxamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C(=O)C(C=C1C=C2)=CN=C1C=C2NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 ZSNQHQMXRGECNB-HXUWFJFHSA-N 0.000 claims description 2
UUWFDGXBMPQLJG-UHFFFAOYSA-N n-[diphenyl(pyridin-2-yl)methyl]-7-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]quinoline-3-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C=C(C=N2)C(=O)NC(C=3C=CC=CC=3)(C=3C=CC=CC=3)C=3N=CC=CC=3)C2=C1 UUWFDGXBMPQLJG-UHFFFAOYSA-N 0.000 claims description 2
OWCKNHHEMYZRRW-UHFFFAOYSA-N n-[phenyl(pyridin-2-yl)methyl]-7-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]quinoline-3-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C=C(C=N2)C(=O)NC(C=3C=CC=CC=3)C=3N=CC=CC=3)C2=C1 OWCKNHHEMYZRRW-UHFFFAOYSA-N 0.000 claims description 2
QXJTXBKRBCDWSP-UHFFFAOYSA-N n-ethyl-7-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]quinoline-3-carboxamide Chemical compound C1=CC2=CC(C(=O)NCC)=CN=C2C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 QXJTXBKRBCDWSP-UHFFFAOYSA-N 0.000 claims description 2
CJSBRTIAHJNKHX-UHFFFAOYSA-N n-propan-2-yl-7-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]quinoline-3-carboxamide Chemical compound C1=CC2=CC(C(=O)NC(C)C)=CN=C2C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 CJSBRTIAHJNKHX-UHFFFAOYSA-N 0.000 claims description 2
125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims 20
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 16
125000004356 hydroxy functional group Chemical group O* 0.000 claims 16
125000000041 C6-C10 aryl group Chemical group 0.000 claims 10
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 4
125000006664 (C1-C3) perfluoroalkyl group Chemical group 0.000 claims 2
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 1
239000004615 ingredient Substances 0.000 claims 1
229940121649 protein inhibitor Drugs 0.000 claims 1
239000012268 protein inhibitor Substances 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 261
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 201
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 141
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
229910052799 carbon Inorganic materials 0.000 description 94
239000007787 solid Substances 0.000 description 76
238000005481 NMR spectroscopy Methods 0.000 description 61
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 55
238000003756 stirring Methods 0.000 description 49
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 47
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
239000011541 reaction mixture Substances 0.000 description 46
239000000243 solution Substances 0.000 description 39
239000000463 material Substances 0.000 description 38
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 37
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 37
239000012267 brine Substances 0.000 description 37
239000000203 mixture Substances 0.000 description 37
239000012074 organic phase Substances 0.000 description 37
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
239000000047 product Substances 0.000 description 35
238000012360 testing method Methods 0.000 description 31
239000000377 silicon dioxide Substances 0.000 description 26
238000012746 preparative thin layer chromatography Methods 0.000 description 25
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 25
HSOUMTLCFUJITE-UHFFFAOYSA-N 7-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]quinoline-3-carboxylic acid Chemical compound C1=CC2=CC(C(=O)O)=CN=C2C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 HSOUMTLCFUJITE-UHFFFAOYSA-N 0.000 description 24
150000003254 radicals Chemical class 0.000 description 21
125000003545 alkoxy group Chemical group 0.000 description 19
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 17
238000003828 vacuum filtration Methods 0.000 description 15
230000007423 decrease Effects 0.000 description 12
229940079593 drug Drugs 0.000 description 11
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 11
239000008194 pharmaceutical composition Substances 0.000 description 11
238000002360 preparation method Methods 0.000 description 11
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 10
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
235000012054 meals Nutrition 0.000 description 10
239000000902 placebo Substances 0.000 description 10
229940068196 placebo Drugs 0.000 description 10
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
230000028327 secretion Effects 0.000 description 9
239000002502 liposome Substances 0.000 description 8
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XDCDQCQNGONBDT-UHFFFAOYSA-N FC(C1=CC=C(C=C1)C=1C(=CC=CC1)C(=O)NC1=CC=C2C=C(C=NC2=C1)C(=O)O)(F)F.C(C)S(=O)(=O)O Chemical compound FC(C1=CC=C(C=C1)C=1C(=CC=CC1)C(=O)NC1=CC=C2C=C(C=NC2=C1)C(=O)O)(F)F.C(C)S(=O)(=O)O XDCDQCQNGONBDT-UHFFFAOYSA-N 0.000 description 7
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 7
229930006000 Sucrose Natural products 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
239000012131 assay buffer Substances 0.000 description 7
210000004369 blood Anatomy 0.000 description 7
239000008280 blood Substances 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
125000004122 cyclic group Chemical group 0.000 description 7
239000005720 sucrose Substances 0.000 description 7
102000004895 Lipoproteins Human genes 0.000 description 6
108090001030 Lipoproteins Proteins 0.000 description 6
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
150000002430 hydrocarbons Chemical group 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
230000003287 optical effect Effects 0.000 description 6
239000008188 pellet Substances 0.000 description 6
239000006228 supernatant Substances 0.000 description 6
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238000003786 synthesis reaction Methods 0.000 description 6
238000012546 transfer Methods 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
150000001540 azides Chemical class 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
239000006185 dispersion Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
ICWBNSHNWYOKSJ-UHFFFAOYSA-N ethyl 4-chloro-7-nitroquinoline-3-carboxylate Chemical compound C1=C([N+]([O-])=O)C=CC2=C(Cl)C(C(=O)OCC)=CN=C21 ICWBNSHNWYOKSJ-UHFFFAOYSA-N 0.000 description 5
ILSSELQOYSUBGG-UHFFFAOYSA-N ethyl 7-aminoquinoline-3-carboxylate Chemical compound C1=C(N)C=CC2=CC(C(=O)OCC)=CN=C21 ILSSELQOYSUBGG-UHFFFAOYSA-N 0.000 description 5
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
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