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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Applications Claiming Priority (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)
| Publication Number | Publication Date |
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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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| JP (1) | JP4851328B2 (enExample) |
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| CN (1) | CN1856305B (enExample) |
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| AT (1) | ATE427748T1 (enExample) |
| AU (1) | AU2004275488A1 (enExample) |
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| NO (1) | NO20061395L (enExample) |
| RU (1) | RU2006113948A (enExample) |
| TW (1) | TW200526630A (enExample) |
| WO (1) | WO2005030209A1 (enExample) |
| ZA (1) | ZA200602442B (enExample) |
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| WO2004089296A2 (en) | 2003-04-03 | 2004-10-21 | The Regents Of The University Of California | Improved inhibitors for the soluble epoxide hydrolase |
| DE10358539A1 (de) * | 2003-12-15 | 2005-07-07 | Merck Patent Gmbh | Carbonsäureamidderivate |
| EP1765311A4 (en) | 2004-03-16 | 2009-04-29 | Univ California | REDUCTION OF NEPHROPATHY WITH INHIBITORS OF SOLUBLE EPOXY HYDROLASE AND EPOXYEICOSANOIDS |
| 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 |
| WO2006045119A2 (en) | 2004-10-20 | 2006-04-27 | The Regents Of The University Of California | Improved inhibitors for the soluble epoxide 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 |
| WO2007110449A1 (en) | 2006-03-29 | 2007-10-04 | Euro-Celtique S.A. | Benzenesulfonamide compounds and their use |
| WO2007118853A1 (en) * | 2006-04-13 | 2007-10-25 | Euro-Celtique S.A. | Benzenesulfonamide compounds and their use as blockers of calcium channels |
| TW200812963A (en) | 2006-04-13 | 2008-03-16 | Euro Celtique Sa | Benzenesulfonamide compounds and the use thereof |
| AU2007337659A1 (en) * | 2006-12-22 | 2008-07-03 | Actelion Pharmaceuticals Ltd. | 5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine derivatives |
| WO2008124118A1 (en) | 2007-04-09 | 2008-10-16 | Purdue Pharma L.P. | Benzenesulfonyl compounds and the use therof |
| WO2009040659A2 (en) * | 2007-09-28 | 2009-04-02 | Purdue Pharma L.P. | Benzenesulfonamide compounds and the use thereof |
| AU2008335135A1 (en) | 2007-12-11 | 2009-06-18 | Cytopathfinder, Inc. | Carboxamide compounds and their use as chemokine receptor agonists |
| EP2528604B1 (en) | 2010-01-29 | 2017-11-22 | 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 |
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| FI97540C (fi) | 1989-11-06 | 1997-01-10 | Sanofi Sa | Menetelmä terapeuttisesti käyttökelpoisten, aromaattisesti substituoitujen piperidiini- ja piperatsiinijohdannaisten valmistamiseksi |
| 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 |
| AU6339200A (en) | 1999-07-28 | 2001-02-19 | Kirin Beer Kabushiki Kaisha | Urea derivatives as inhibitors of ccr-3 receptor |
| JP2003518059A (ja) | 1999-12-21 | 2003-06-03 | スミスクライン・ビーチャム・コーポレイション | ウロテンシン−ｉｉ受容体アンタゴニスト |
| US6544992B1 (en) | 1999-12-21 | 2003-04-08 | Smithkline Beecham Corporation | Urotensin-II receptor antagonists |
| CA2394603A1 (en) | 1999-12-21 | 2001-06-28 | Dashyant Dhanak | Urotensin-ii receptor antagonists |
| EP1262195A4 (en) | 2000-03-07 | 2003-05-21 | Takeda Chemical Industries Ltd | VASOACTIVE AGENTS |
| WO2002000606A1 (en) | 2000-06-28 | 2002-01-03 | Takeda Chemical Industries, Ltd. | Biphenyl compound |
| AU2001271018A1 (en) | 2000-07-04 | 2002-01-14 | Takeda Chemical Industries Ltd. | Gpr14 antagonist |
| EP1351688A4 (en) | 2000-12-11 | 2006-01-04 | Smithkline Beecham Corp | UROTENSIN-II RECEPTOR ANTAGONISTS |
| AU2002239506A1 (en) | 2000-12-11 | 2002-06-24 | Smith Kline Beecham Corporation | Urotensin-ii receptor antagonists |
| US6818655B2 (en) | 2001-01-26 | 2004-11-16 | Smithkline Beecham Corporation | Urotensin-II receptor antagonists |
| WO2002078707A1 (en) | 2001-03-29 | 2002-10-10 | Smithkline Beecham Corporation | Pyrrolidine sulfonamides |
| WO2002078641A2 (en) | 2001-03-29 | 2002-10-10 | Smithkline Beecham Corporation | Pyrrolidine sulfonamides |
| JP2004525156A (ja) | 2001-03-29 | 2004-08-19 | 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 |
| US20040152692A1 (en) | 2001-03-29 | 2004-08-05 | Dashyant Dhanak | Pyrrolidine 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 |
| 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 |
| WO2002090337A1 (en) | 2001-05-07 | 2002-11-14 | Smithkline Beecham Corporation | Sulfonamides |
| EP1387679A4 (en) | 2001-05-07 | 2004-08-11 | Smithkline Beecham Corp | SULPHONAMIDES |
| WO2002089740A2 (en) | 2001-05-07 | 2002-11-14 | Smithkline Beecham Corporation | Sulfonamides |
| US6849635B2 (en) | 2001-05-07 | 2005-02-01 | 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 |
| WO2004043369A2 (en) | 2002-11-06 | 2004-05-27 | Smithkline Beecham Corporation | Sulfonamides |
| WO2004043917A1 (en) | 2002-11-06 | 2004-05-27 | Smithkline Beecham Corporation | Sulfonamides |
| AU2003295408A1 (en) | 2002-11-06 | 2004-06-03 | Smithkline Beecham Corporation | Sulfonamides |
| WO2004043366A2 (en) | 2002-11-06 | 2004-05-27 | Smithkline Beecham Corporation | Sulfonamides |
| WO2004073634A2 (en) | 2003-02-20 | 2004-09-02 | Encysive Pharmaceuticals Inc. | Phenylenediamine urotensin-ii receptor antagonists and ccr-9 antagonists |
-
2004
- 2004-09-21 JP JP2006527332A patent/JP4851328B2/ja not_active Expired - Fee Related
- 2004-09-21 DE DE602004020486T patent/DE602004020486D1/de not_active Expired - Lifetime
- 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 EP EP04765436A patent/EP1670470B1/en not_active Expired - Lifetime
- 2004-09-21 AT AT04765436T patent/ATE427748T1/de not_active IP Right Cessation
- 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 US US10/573,516 patent/US7750161B2/en not_active Expired - Fee Related
- 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 WO PCT/EP2004/010559 patent/WO2005030209A1/en not_active Ceased
- 2004-09-21 CA CA2540196A patent/CA2540196C/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 |
|---|---|
| DE602004020486D1 (de) | 2009-05-20 |
| AR045949A1 (es) | 2005-11-16 |
| WO2005030209A1 (en) | 2005-04-07 |
| CA2540196A1 (en) | 2005-04-07 |
| CN1856305A (zh) | 2006-11-01 |
| US20070043081A1 (en) | 2007-02-22 |
| TW200526630A (en) | 2005-08-16 |
| IL174497A0 (en) | 2006-08-01 |
| WO2005030209A8 (en) | 2006-05-11 |
| CA2540196C (en) | 2012-03-20 |
| ATE427748T1 (de) | 2009-04-15 |
| JP2007506692A (ja) | 2007-03-22 |
| EP1670470A1 (en) | 2006-06-21 |
| RU2006113948A (ru) | 2007-11-10 |
| EP1670470B1 (en) | 2009-04-08 |
| AU2004275488A1 (en) | 2005-04-07 |
| MXPA06003264A (es) | 2006-06-08 |
| ZA200602442B (en) | 2007-09-26 |
| NO20061395L (no) | 2006-06-22 |
| KR20070014108A (ko) | 2007-01-31 |
| US7750161B2 (en) | 2010-07-06 |
| CN1856305B (zh) | 2010-04-28 |
| BRPI0414777A (pt) | 2006-11-21 |
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