TWI334414B - Tetrazole-substituted arylamides - Google Patents
Tetrazole-substituted arylamides Download PDFInfo
- Publication number
- TWI334414B TWI334414B TW096122982A TW96122982A TWI334414B TW I334414 B TWI334414 B TW I334414B TW 096122982 A TW096122982 A TW 096122982A TW 96122982 A TW96122982 A TW 96122982A TW I334414 B TWI334414 B TW I334414B
- Authority
- TW
- Taiwan
- Prior art keywords
- ethyl
- methyl
- biphenyl
- alkyl
- tetrazol
- Prior art date
Links
- -1 4-fluorenyl-phenyl group Chemical group 0.000 claims description 905
- 125000000217 alkyl group Chemical group 0.000 claims description 568
- 239000001257 hydrogen Substances 0.000 claims description 137
- 229910052739 hydrogen Inorganic materials 0.000 claims description 137
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 117
- 150000001875 compounds Chemical class 0.000 claims description 107
- 239000004305 biphenyl Substances 0.000 claims description 83
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 76
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
- 150000003839 salts Chemical class 0.000 claims description 63
- 239000002253 acid Substances 0.000 claims description 59
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 claims description 56
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 53
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 51
- 125000001072 heteroaryl group Chemical group 0.000 claims description 49
- 125000000623 heterocyclic group Chemical group 0.000 claims description 48
- 125000003545 alkoxy group Chemical group 0.000 claims description 44
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 43
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
- 150000001412 amines Chemical class 0.000 claims description 36
- 230000036407 pain Effects 0.000 claims description 36
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 35
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims description 32
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 32
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 32
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 28
- 125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 125000005842 heteroatom Chemical group 0.000 claims description 26
- 125000005843 halogen group Chemical group 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 125000004429 atom Chemical group 0.000 claims description 21
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 125000003277 amino group Chemical group 0.000 claims description 16
- 101710189970 P2X purinoceptor 3 Proteins 0.000 claims description 15
- 102000005962 receptors Human genes 0.000 claims description 15
- 108020003175 receptors Proteins 0.000 claims description 15
- 125000001188 haloalkyl group Chemical group 0.000 claims description 14
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 11
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
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- 101710189968 P2X purinoceptor 2 Proteins 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- 230000002496 gastric effect Effects 0.000 claims description 8
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 8
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- UGKMFEWOXCODEJ-UHFFFAOYSA-N N-(1-pyrazin-2-ylethyl)decan-1-amine Chemical compound CCCCCCCCCCNC(C)C1=CN=CC=N1 UGKMFEWOXCODEJ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 6
- KZSGEENZLZKOCP-UHFFFAOYSA-N N1=CN=CC(=C1)C(C)NCCCCCCCCCC Chemical compound N1=CN=CC(=C1)C(C)NCCCCCCCCCC KZSGEENZLZKOCP-UHFFFAOYSA-N 0.000 claims description 5
- 108010080192 Purinergic Receptors Proteins 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 5
- 229910052707 ruthenium Inorganic materials 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 5
- PFCRXWOJXUUPEM-UHFFFAOYSA-N C(C)(C)C1=NN=NN1C=1C=C(C=C(C1)C1=CC=C(C=C1)C)CCCCCCCCCC(=O)O Chemical compound C(C)(C)C1=NN=NN1C=1C=C(C=C(C1)C1=CC=C(C=C1)C)CCCCCCCCCC(=O)O PFCRXWOJXUUPEM-UHFFFAOYSA-N 0.000 claims description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 4
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 208000025609 Urogenital disease Diseases 0.000 claims description 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 claims description 2
- HPWXAGIVAMYDNU-UHFFFAOYSA-N N-(1-methylsulfanylpropan-2-yl)decan-1-amine Chemical compound CCCCCCCCCCNC(C)CSC HPWXAGIVAMYDNU-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 2
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 208000023504 respiratory system disease Diseases 0.000 claims description 2
- UOQIQIOJLZRPGE-UHFFFAOYSA-N 3-[5-(methoxymethyl)tetrazol-1-yl]-5-(4-methylphenyl)benzoic acid Chemical compound COCC1=NN=NN1C1=CC(C(O)=O)=CC(C=2C=CC(C)=CC=2)=C1 UOQIQIOJLZRPGE-UHFFFAOYSA-N 0.000 claims 1
- CSCPRNZZCOPLOR-UHFFFAOYSA-N C(C)C1=NN=NN1C=1C=CC=C(C1)C1=CC=C(C=C1)C Chemical group C(C)C1=NN=NN1C=1C=CC=C(C1)C1=CC=C(C=C1)C CSCPRNZZCOPLOR-UHFFFAOYSA-N 0.000 claims 1
- IIEYOAXVACSMOU-UHFFFAOYSA-N SC=1C=CN(NC1)CNCCCCCCCCCC Chemical compound SC=1C=CN(NC1)CNCCCCCCCCCC IIEYOAXVACSMOU-UHFFFAOYSA-N 0.000 claims 1
- FINHMKGKINIASC-UHFFFAOYSA-N Tetramethylpyrazine Chemical class CC1=NC(C)=C(C)N=C1C FINHMKGKINIASC-UHFFFAOYSA-N 0.000 claims 1
- NLMBNVBBHYNBQY-UHFFFAOYSA-N [C].[Ru] Chemical compound [C].[Ru] NLMBNVBBHYNBQY-UHFFFAOYSA-N 0.000 claims 1
- 208000027753 pain disease Diseases 0.000 claims 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 174
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 72
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 31
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| TWI696615B (zh) * | 2016-05-05 | 2020-06-21 | 瑞士商伊蘭科動物健康公司 | 雜芳基-1,2,4-三唑及雜芳基-三唑化合物 |
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| DE10312963A1 (de) * | 2003-03-24 | 2004-10-07 | Aventis Pharma Deutschland Gmbh | Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament |
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| EP1763509B1 (en) * | 2004-07-02 | 2018-02-21 | The Walter And Eliza Hall Institute Of Medical Research | Alpha-helical mimetics |
| EP1917262B1 (en) * | 2005-08-15 | 2011-12-14 | F. Hoffmann-La Roche AG | Piperidine and piperazine derivatives as p2x3 antagonists |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| TWI741040B (zh) * | 2016-10-20 | 2021-10-01 | 德商拜耳作物科學公司 | 製備3-烷基硫基-2-氯-n-(1-烷基-1h-四唑-5-基)-4-三氟甲基苯甲醯胺之方法 |
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