JP4851328B2 - 新規なピリジン誘導体 - Google Patents
新規なピリジン誘導体 Download PDFInfo
- 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
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- JP
- Japan
- Prior art keywords
- alkyl
- aryl
- mmol
- general formula
- ethyl
- Prior art date
- 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
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- 239000002244 precipitate Substances 0.000 description 5
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- 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
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
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- 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
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- 238000012360 testing method Methods 0.000 description 4
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- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
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- 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
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- 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
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- 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
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- 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
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- 239000012065 filter cake Substances 0.000 description 3
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- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
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| EPPCT/EP03/10746 | 2003-09-26 | ||
| EP0310746 | 2003-09-26 | ||
| PCT/EP2004/010559 WO2005030209A1 (en) | 2003-09-26 | 2004-09-21 | Pyridine derivatives and use thereof as urotensin ii antagonists |
Publications (4)
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| JP2007506692A JP2007506692A (ja) | 2007-03-22 |
| JP2007506692A6 JP2007506692A6 (ja) | 2007-07-12 |
| JP2007506692A5 JP2007506692A5 (enExample) | 2007-11-01 |
| JP4851328B2 true JP4851328B2 (ja) | 2012-01-11 |
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| TW (1) | TW200526630A (enExample) |
| WO (1) | WO2005030209A1 (enExample) |
| ZA (1) | ZA200602442B (enExample) |
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| EP1608319A4 (en) | 2003-04-03 | 2007-02-28 | Univ California | IMPROVED HEMMER FOR SOLUBLE EPOXY HYDROLASE |
| DE10358539A1 (de) * | 2003-12-15 | 2005-07-07 | Merck Patent Gmbh | Carbonsäureamidderivate |
| JP2007532484A (ja) | 2004-03-16 | 2007-11-15 | ザ・レジェンツ・オブ・ザ・ユニバーシティ・オブ・カリフォルニア | 可溶性エポキシド加水分解酵素の阻害剤およびエポキシエイコサノイドを用いて腎症を緩和する方法 |
| AR051213A1 (es) * | 2004-10-12 | 2006-12-27 | Actelion Pharmaceuticals Ltd | 1-(2-(4-bencil-4-hidroxi-piperidin-1-il)-etil)-3-(2-metil-quinolin-4-il)-urea como una sal sulfato cristalina |
| TW200630337A (en) * | 2004-10-14 | 2006-09-01 | Euro Celtique Sa | Piperidinyl compounds and the use thereof |
| EP1814875A4 (en) | 2004-10-20 | 2010-02-17 | Univ California | IMPROVED INHIBITORS OF SOLUBLE EPOXY HYDROLASE |
| SE0403084D0 (sv) * | 2004-12-17 | 2004-12-17 | Astrazeneca Ab | Chemical process |
| WO2006135694A2 (en) * | 2005-06-10 | 2006-12-21 | Acadia Pharmaceuticals Inc. | Uii-modulating compounds and their use |
| AR059826A1 (es) | 2006-03-13 | 2008-04-30 | Univ California | Inhibidores de urea conformacionalmente restringidos de epoxido hidrolasa soluble |
| US8247442B2 (en) * | 2006-03-29 | 2012-08-21 | Purdue Pharma L.P. | Benzenesulfonamide compounds and their use |
| TW200812963A (en) * | 2006-04-13 | 2008-03-16 | Euro Celtique Sa | Benzenesulfonamide compounds and the use thereof |
| TW200815353A (en) * | 2006-04-13 | 2008-04-01 | Euro Celtique Sa | Benzenesulfonamide compounds and their use |
| ES2380391T3 (es) * | 2006-12-22 | 2012-05-11 | Actelion Pharmaceuticals Ltd. | Derivados de 5,6,7,8-tetrahidro-imidazo[1,5-a]pirazina |
| US8399486B2 (en) | 2007-04-09 | 2013-03-19 | Purdue Pharma L.P. | Benzenesulfonyl compounds and the use thereof |
| US8765736B2 (en) * | 2007-09-28 | 2014-07-01 | Purdue Pharma L.P. | Benzenesulfonamide compounds and the use thereof |
| KR20100102646A (ko) | 2007-12-11 | 2010-09-24 | 가부시키가이샤 사이토파스파인더 | 카르복스아미드 화합물 및 케모카인 수용체 길항제로서의 이의 용도 |
| WO2012054093A2 (en) | 2010-01-29 | 2012-04-26 | The Regents Of The University Of California | Acyl piperidine inhibitors of soluble epoxide hydrolase |
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| WO2001098269A2 (en) * | 2000-06-21 | 2001-12-27 | Bristol-Myers Squibb Pharma Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| JP2002532427A (ja) * | 1998-12-18 | 2002-10-02 | デュポン ファーマシューティカルズ カンパニー | ケモカイン受容体活性のモジュレーターとしてのｎ−ウレイドアルキルピペリジン |
| WO2002076979A1 (en) * | 2001-03-27 | 2002-10-03 | Actelion Pharmaceuticals Ltd | 1,2,3,4-tetrahydroisoquinolines derivatives as urotensin ii receptor antagonists |
| WO2003048154A1 (en) * | 2001-12-04 | 2003-06-12 | Actelion Pharmaceuticals Ltd | 4-(piperidyl- and pyrrolidyl-alkyl-ureido) -quinolines as urotensin ii receptor antagonists |
| JP2006505533A (ja) * | 2002-09-17 | 2006-02-16 | アクテリオン ファマシューティカルズ リミテッド | １−ピリジン−４−イル−尿素誘導体 |
| JP2006525273A (ja) * | 2003-05-07 | 2006-11-09 | アクテリオン ファマシューティカルズ リミテッド | 新規なピペラジン誘導体 |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE903957A1 (en) | 1989-11-06 | 1991-05-08 | Sanofi Sa | Aromatic amine compounds, their method of preparation and¹pharmaceutical compositions in which they are present |
| US6159700A (en) | 1997-01-27 | 2000-12-12 | Smithkline Beecham Corporation | Method of finding agonist and antagonist to human and rat GPR14 |
| AUPP003197A0 (en) | 1997-09-03 | 1997-11-20 | Fujisawa Pharmaceutical Co., Ltd. | New heterocyclic compounds |
| US6331541B1 (en) * | 1998-12-18 | 2001-12-18 | Soo S. Ko | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| WO2001009088A1 (en) | 1999-07-28 | 2001-02-08 | Kirin Beer Kabushiki Kaisha | Urea derivatives as inhibitors of ccr-3 receptor |
| ATE279923T1 (de) | 1999-12-21 | 2004-11-15 | Smithkline Beecham Corp | Urotensin-ii rezeptorantagonisten |
| EP1244452B1 (en) | 1999-12-21 | 2003-09-17 | SmithKline Beecham Corporation | Carboxamide derivates of pyrrolidine and piperidine as urotensin-ii receptor antagonists |
| AU2441801A (en) | 1999-12-21 | 2001-07-03 | Smithkline Beecham Corporation | Urotensin-ii receptor antagonists |
| CA2402096A1 (en) | 2000-03-07 | 2001-09-13 | Takeda Chemical Industries, Ltd. | Vasoactive agents |
| EP1295867A4 (en) | 2000-06-28 | 2005-03-30 | Takeda Pharmaceutical | BIPHENYL COMPOUND |
| AU2001271018A1 (en) | 2000-07-04 | 2002-01-14 | Takeda Chemical Industries Ltd. | Gpr14 antagonist |
| EP1351687A4 (en) | 2000-12-11 | 2004-01-21 | Smithkline Beecham Corp | UROTENSIN II RECEPTOR ANTAGONISTS |
| EP1351688A4 (en) | 2000-12-11 | 2006-01-04 | Smithkline Beecham Corp | UROTENSIN-II RECEPTOR ANTAGONISTS |
| EP1359915A4 (en) | 2001-01-26 | 2004-07-21 | Smithkline Beecham | UROTENSIN-II RECEPTOR ANTAGONISTS |
| US20040152692A1 (en) | 2001-03-29 | 2004-08-05 | Dashyant Dhanak | Pyrrolidine sulfonamides |
| JP2004524355A (ja) | 2001-03-29 | 2004-08-12 | スミスクライン・ビーチャム・コーポレイション | ピロリジンスルホンアミド |
| JP2004529134A (ja) | 2001-03-29 | 2004-09-24 | スミスクライン・ビーチャム・コーポレイション | ピロリジンスルホンアミド |
| WO2002079188A1 (en) | 2001-03-29 | 2002-10-10 | Smithkline Beecham Corporation | Pyrrolidine sulfonamides |
| WO2002089740A2 (en) | 2001-05-07 | 2002-11-14 | Smithkline Beecham Corporation | Sulfonamides |
| JP2004529170A (ja) | 2001-05-07 | 2004-09-24 | スミスクライン・ビーチャム・コーポレイション | スルホンアミド |
| EP1387679A4 (en) | 2001-05-07 | 2004-08-11 | Smithkline Beecham Corp | SULPHONAMIDES |
| EP1385830A4 (en) | 2001-05-07 | 2005-08-17 | Smithkline Beecham Corp | SULPHONAMIDES |
| AR033879A1 (es) | 2001-05-07 | 2004-01-07 | Smithkline Beecham Corp | Compuesto sulfonamida, composicion farmaceutica que lo comprende, su uso para preparar dicha composicion y procedimiento para la obtencion de dicho compuesto |
| US6849635B2 (en) | 2001-05-07 | 2005-02-01 | Smithkline Beecham Corporation | Sulfonamides |
| WO2004043368A2 (en) | 2002-11-06 | 2004-05-27 | Smithkline Beecham Corporation | Sulfonamides |
| AR041885A1 (es) | 2002-11-06 | 2005-06-01 | Smithkline Beecham Corp | Compuesto de sulfonamida, composicion farmaceutica que lo comprende y su uso para preparar dicha composicion |
| AU2003291303A1 (en) | 2002-11-06 | 2004-06-03 | Smithkline Beecham Corporation | Sulfonamides |
| AU2003291262A1 (en) | 2002-11-06 | 2004-06-03 | Smithkline Beecham Corporation | Sulfonamides |
| AU2003291255A1 (en) | 2002-11-06 | 2004-06-03 | Smithkline Beecham Corporation | Sulfonamides |
| CA2515780C (en) | 2003-02-20 | 2012-12-11 | Encysive Pharmaceuticals Inc. | Phenylenediamine urotensin-ii receptor antagonists and ccr-9 antagonists |
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2004
- 2004-09-21 CA CA2540196A patent/CA2540196C/en not_active Expired - Fee Related
- 2004-09-21 DE DE602004020486T patent/DE602004020486D1/de not_active Expired - Lifetime
- 2004-09-21 KR KR1020067005848A patent/KR20070014108A/ko not_active Withdrawn
- 2004-09-21 AU AU2004275488A patent/AU2004275488A1/en not_active Abandoned
- 2004-09-21 AT AT04765436T patent/ATE427748T1/de not_active IP Right Cessation
- 2004-09-21 RU RU2006113948/04A patent/RU2006113948A/ru unknown
- 2004-09-21 CN CN2004800277254A patent/CN1856305B/zh not_active Expired - Fee Related
- 2004-09-21 BR BRPI0414777-4A patent/BRPI0414777A/pt not_active Application Discontinuation
- 2004-09-21 MX MXPA06003264A patent/MXPA06003264A/es unknown
- 2004-09-21 JP JP2006527332A patent/JP4851328B2/ja not_active Expired - Fee Related
- 2004-09-21 WO PCT/EP2004/010559 patent/WO2005030209A1/en not_active Ceased
- 2004-09-21 EP EP04765436A patent/EP1670470B1/en not_active Expired - Lifetime
- 2004-09-21 US US10/573,516 patent/US7750161B2/en not_active Expired - Fee Related
- 2004-09-24 AR ARP040103475A patent/AR045949A1/es unknown
- 2004-09-24 TW TW093129149A patent/TW200526630A/zh unknown
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2006
- 2006-03-22 IL IL174497A patent/IL174497A0/en unknown
- 2006-03-24 ZA ZA200602442A patent/ZA200602442B/en unknown
- 2006-03-27 NO NO20061395A patent/NO20061395L/no not_active Application Discontinuation
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002532427A (ja) * | 1998-12-18 | 2002-10-02 | デュポン ファーマシューティカルズ カンパニー | ケモカイン受容体活性のモジュレーターとしてのｎ−ウレイドアルキルピペリジン |
| WO2001098269A2 (en) * | 2000-06-21 | 2001-12-27 | Bristol-Myers Squibb Pharma Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| WO2002076979A1 (en) * | 2001-03-27 | 2002-10-03 | Actelion Pharmaceuticals Ltd | 1,2,3,4-tetrahydroisoquinolines derivatives as urotensin ii receptor antagonists |
| WO2003048154A1 (en) * | 2001-12-04 | 2003-06-12 | Actelion Pharmaceuticals Ltd | 4-(piperidyl- and pyrrolidyl-alkyl-ureido) -quinolines as urotensin ii receptor antagonists |
| JP2006505533A (ja) * | 2002-09-17 | 2006-02-16 | アクテリオン ファマシューティカルズ リミテッド | １−ピリジン−４−イル−尿素誘導体 |
| JP2006525273A (ja) * | 2003-05-07 | 2006-11-09 | アクテリオン ファマシューティカルズ リミテッド | 新規なピペラジン誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1670470B1 (en) | 2009-04-08 |
| BRPI0414777A (pt) | 2006-11-21 |
| KR20070014108A (ko) | 2007-01-31 |
| EP1670470A1 (en) | 2006-06-21 |
| WO2005030209A8 (en) | 2006-05-11 |
| NO20061395L (no) | 2006-06-22 |
| JP2007506692A (ja) | 2007-03-22 |
| ZA200602442B (en) | 2007-09-26 |
| US20070043081A1 (en) | 2007-02-22 |
| DE602004020486D1 (de) | 2009-05-20 |
| RU2006113948A (ru) | 2007-11-10 |
| CA2540196A1 (en) | 2005-04-07 |
| MXPA06003264A (es) | 2006-06-08 |
| TW200526630A (en) | 2005-08-16 |
| US7750161B2 (en) | 2010-07-06 |
| CN1856305B (zh) | 2010-04-28 |
| CN1856305A (zh) | 2006-11-01 |
| WO2005030209A1 (en) | 2005-04-07 |
| AR045949A1 (es) | 2005-11-16 |
| CA2540196C (en) | 2012-03-20 |
| IL174497A0 (en) | 2006-08-01 |
| AU2004275488A1 (en) | 2005-04-07 |
| ATE427748T1 (de) | 2009-04-15 |
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