JP4851328B2 - 新規なピリジン誘導体 - Google Patents

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Publication number

JP4851328B2

JP4851328B2 JP2006527332A JP2006527332A JP4851328B2 JP 4851328 B2 JP4851328 B2 JP 4851328B2 JP 2006527332 A JP2006527332 A JP 2006527332A JP 2006527332 A JP2006527332 A JP 2006527332A JP 4851328 B2 JP4851328 B2 JP 4851328B2

Authority

JP

Japan

Prior art keywords

alkyl

aryl

mmol

general formula

ethyl

Prior art date

2003-09-26

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.)

Expired - Fee Related

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• 150000003222 pyridines Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 162
• -1 2,5-dimethoxyphenyl Chemical group 0.000 claims description 153
• 229920006395 saturated elastomer Polymers 0.000 claims description 40
• 125000003118 aryl group Chemical group 0.000 claims description 37
• 239000001257 hydrogen Substances 0.000 claims description 28
• 229910052739 hydrogen Inorganic materials 0.000 claims description 28
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
• 150000003839 salts Chemical class 0.000 claims description 16
• 201000010099 disease Diseases 0.000 claims description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
• 125000001424 substituent group Chemical group 0.000 claims description 11
• 239000000126 substance Substances 0.000 claims description 9
• 238000011282 treatment Methods 0.000 claims description 9
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• 150000002367 halogens Chemical class 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
• 239000003814 drug 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
• 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
• 206010019280 Heart failures Diseases 0.000 claims description 4
• 206010020772 Hypertension Diseases 0.000 claims description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 3
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 3
• KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 3
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
• 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
• 239000004480 active ingredient Substances 0.000 claims description 3
• 125000000217 alkyl group Chemical group 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
• 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 3
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 3
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 2
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 2
• 206010016654 Fibrosis Diseases 0.000 claims description 2
• 208000001647 Renal Insufficiency Diseases 0.000 claims description 2
• 206010063897 Renal ischaemia Diseases 0.000 claims description 2
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
• 230000007882 cirrhosis Effects 0.000 claims description 2
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
• 208000033679 diabetic kidney disease Diseases 0.000 claims description 2
• 201000006370 kidney failure Diseases 0.000 claims description 2
• 208000007232 portal hypertension Diseases 0.000 claims description 2
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims 1
• 239000002671 adjuvant Substances 0.000 claims 1
• 230000001684 chronic effect Effects 0.000 claims 1
• 125000001188 haloalkyl group Chemical group 0.000 claims 1
• 210000003734 kidney Anatomy 0.000 claims 1
• 239000000203 mixture Substances 0.000 description 87
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
• 238000000034 method Methods 0.000 description 50
• 239000011734 sodium Substances 0.000 description 41
• XWRZCBIAXUHSIY-UHFFFAOYSA-N 1-(2-chloroethyl)-3-(2,6-dimethylpyridin-4-yl)urea Chemical compound CC1=CC(NC(=O)NCCCl)=CC(C)=N1 XWRZCBIAXUHSIY-UHFFFAOYSA-N 0.000 description 34
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 34
• 108010018369 Urotensin II Proteins 0.000 description 34
• 102000050488 Urotensin II Human genes 0.000 description 34
• 239000000243 solution Substances 0.000 description 33
• HFNHAPQMXICKCF-USJMABIRSA-N urotensin-ii Chemical compound N([C@@H](CC(O)=O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@@H](C(C)C)C(O)=O)C(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](N)CCC(O)=O)[C@@H](C)O HFNHAPQMXICKCF-USJMABIRSA-N 0.000 description 33
• 239000000284 extract Substances 0.000 description 23
• 239000000543 intermediate Substances 0.000 description 23
• 239000012071 phase Substances 0.000 description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 15
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 14
• 238000002360 preparation method Methods 0.000 description 14
• 239000000725 suspension Substances 0.000 description 14
• 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
• 102000012327 Urotensin II receptors Human genes 0.000 description 11
• 108050002984 Urotensin II receptors Proteins 0.000 description 11
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
• 235000013877 carbamide Nutrition 0.000 description 10
• 238000006243 chemical reaction Methods 0.000 description 10
• 238000004128 high performance liquid chromatography Methods 0.000 description 10
• 239000012074 organic phase Substances 0.000 description 10
• 239000002464 receptor antagonist Substances 0.000 description 10
• 229940044551 receptor antagonist Drugs 0.000 description 10
• 125000006413 ring segment Chemical group 0.000 description 10
• 239000007864 aqueous solution Substances 0.000 description 9
• 239000011780 sodium chloride Substances 0.000 description 9
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
• 229910004298 SiO 2 Inorganic materials 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 239000008346 aqueous phase Substances 0.000 description 8
• 239000004202 carbamide Substances 0.000 description 8
• 150000001721 carbon Chemical group 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 239000002904 solvent Chemical class 0.000 description 8
• 125000006701 (C1-C7) alkyl group Chemical group 0.000 description 7
• 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 description 7
• 150000001412 amines Chemical class 0.000 description 7
• 239000005557 antagonist Substances 0.000 description 7
• 230000027455 binding Effects 0.000 description 7
• 229910052799 carbon Inorganic materials 0.000 description 7
• 125000004432 carbon atom Chemical group C* 0.000 description 7
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 238000005859 coupling reaction Methods 0.000 description 7
• 239000012948 isocyanate Substances 0.000 description 7
• 150000002513 isocyanates Chemical class 0.000 description 7
• 229910052757 nitrogen Inorganic materials 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 230000002441 reversible effect Effects 0.000 description 7
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
• 101000841325 Homo sapiens Urotensin-2 Proteins 0.000 description 6
• 229910010082 LiAlH Inorganic materials 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 230000008878 coupling Effects 0.000 description 6
• 238000010168 coupling process Methods 0.000 description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• SEPRZKIMRGZVTI-UHFFFAOYSA-N 1-(2,6-dimethylpyridin-4-yl)-3-[2-[4-(methylamino)piperidin-1-yl]ethyl]urea Chemical compound C1CC(NC)CCN1CCNC(=O)NC1=CC(C)=NC(C)=C1 SEPRZKIMRGZVTI-UHFFFAOYSA-N 0.000 description 5
• ZJXMKPARTVOUAM-UHFFFAOYSA-N 2,6-dimethylpyridin-4-amine Chemical compound CC1=CC(N)=CC(C)=N1 ZJXMKPARTVOUAM-UHFFFAOYSA-N 0.000 description 5
• NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical class NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 5
• 230000009471 action Effects 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 5
• 150000002431 hydrogen Chemical class 0.000 description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 description 5
• 239000002798 polar solvent Substances 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 239000002516 radical scavenger Substances 0.000 description 5
• 239000011541 reaction mixture Substances 0.000 description 5
• 102000005962 receptors Human genes 0.000 description 5
• 108020003175 receptors Proteins 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• HFNHAPQMXICKCF-FDMLFMOBSA-N (4s)-4-amino-5-[[(2s,3r)-1-[(2r)-2-[[(2s)-1-[[(4r,7s,10r,13s,16r,19s)-10-(4-aminobutyl)-16-benzyl-4-[[(1s)-1-carboxy-2-methylpropyl]carbamoyl]-7-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloi Chemical compound N([C@@H](CC(O)=O)C(=O)N[C@@H]1CSSC[C@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](CCCCN)NC(=O)[C@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@@H](C(C)C)C(O)=O)C(=O)[C@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](N)CCC(O)=O)[C@@H](C)O HFNHAPQMXICKCF-FDMLFMOBSA-N 0.000 description 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
• FWIYLQRKWQFKQR-UHFFFAOYSA-N 2-[(2-methylpyridin-4-yl)carbamoylamino]acetic acid Chemical compound CC1=CC(NC(=O)NCC(O)=O)=CC=N1 FWIYLQRKWQFKQR-UHFFFAOYSA-N 0.000 description 4
• ZGZMEKHQIZSZOH-UHFFFAOYSA-N 2-chloro-6-methylpyridine-4-carboxylic acid Chemical compound CC1=CC(C(O)=O)=CC(Cl)=N1 ZGZMEKHQIZSZOH-UHFFFAOYSA-N 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
• 238000012512 characterization method Methods 0.000 description 4
• 230000008602 contraction Effects 0.000 description 4
• 229960004979 fampridine Drugs 0.000 description 4
• 239000005556 hormone Substances 0.000 description 4
• 229940088597 hormone Drugs 0.000 description 4
• 102000047478 human UTS2 Human genes 0.000 description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
• 230000000877 morphologic effect Effects 0.000 description 4
• BEAXPGCVGRGDFG-UHFFFAOYSA-N n-ethyl-4-methoxy-n-piperidin-4-ylbenzenesulfonamide Chemical compound C=1C=C(OC)C=CC=1S(=O)(=O)N(CC)C1CCNCC1 BEAXPGCVGRGDFG-UHFFFAOYSA-N 0.000 description 4
• 239000002953 phosphate buffered saline Substances 0.000 description 4
• 229920005862 polyol Polymers 0.000 description 4
• 150000003077 polyols Chemical class 0.000 description 4
• 150000003141 primary amines Chemical class 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
• 238000004809 thin layer chromatography Methods 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• YZYUZPNQBOSTAO-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) carbamate Chemical compound NC(=O)OC1=C(F)C(F)=C(F)C(F)=C1F YZYUZPNQBOSTAO-UHFFFAOYSA-N 0.000 description 3
• TVXKJXUEPNLDFS-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) n-(2-ethyl-6-methylpyridin-4-yl)carbamate Chemical compound CC1=NC(CC)=CC(NC(=O)OC=2C(=C(F)C(F)=C(F)C=2F)F)=C1 TVXKJXUEPNLDFS-UHFFFAOYSA-N 0.000 description 3
• PCNDXYHWLSHXMV-UHFFFAOYSA-N 2-(4-benzylpiperidin-1-yl)ethanamine Chemical compound C1CN(CCN)CCC1CC1=CC=CC=C1 PCNDXYHWLSHXMV-UHFFFAOYSA-N 0.000 description 3
• CBYORPBSXNQQLX-UHFFFAOYSA-N 2-chloro-4-isocyanatopyridine Chemical compound ClC1=CC(N=C=O)=CC=N1 CBYORPBSXNQQLX-UHFFFAOYSA-N 0.000 description 3
• JYDLVIFFRRSJNQ-UHFFFAOYSA-N 2-ethyl-6-methylpyridin-4-amine Chemical compound CCC1=CC(N)=CC(C)=N1 JYDLVIFFRRSJNQ-UHFFFAOYSA-N 0.000 description 3
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
• SGGYDYGRESJMHW-BQYQJAHWSA-N 4-isocyanato-2-methyl-6-[(e)-2-phenylethenyl]pyridine Chemical compound CC1=CC(N=C=O)=CC(\C=C\C=2C=CC=CC=2)=N1 SGGYDYGRESJMHW-BQYQJAHWSA-N 0.000 description 3
• NEQLVBPHUSLUJK-UHFFFAOYSA-N 4-phenyl-1-phenylmethoxycarbonylpiperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)(C=2C=CC=CC=2)CCN1C(=O)OCC1=CC=CC=C1 NEQLVBPHUSLUJK-UHFFFAOYSA-N 0.000 description 3
• FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 241000251468 Actinopterygii Species 0.000 description 3
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
• 102000026557 Urotensins Human genes 0.000 description 3
• 108010011107 Urotensins Proteins 0.000 description 3
• 150000001299 aldehydes Chemical class 0.000 description 3
• 239000000010 aprotic solvent Substances 0.000 description 3
• HREXFDIZSAUXBO-UHFFFAOYSA-N benzyl n-(2-bromoethyl)carbamate Chemical compound BrCCNC(=O)OCC1=CC=CC=C1 HREXFDIZSAUXBO-UHFFFAOYSA-N 0.000 description 3
• 125000002837 carbocyclic group Chemical group 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 230000002708 enhancing effect Effects 0.000 description 3
• 239000012065 filter cake Substances 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
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