ES2604542T3 - Arilamidas con sustitución tetrazol - Google Patents
Arilamidas con sustitución tetrazol Download PDFInfo
- Publication number
- ES2604542T3 ES2604542T3 ES07730213.1T ES07730213T ES2604542T3 ES 2604542 T3 ES2604542 T3 ES 2604542T3 ES 07730213 T ES07730213 T ES 07730213T ES 2604542 T3 ES2604542 T3 ES 2604542T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- tetrazol
- ethyl
- biphenyl
- pyridin
- 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.)
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- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical group C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 title 1
- -1 chloro, amino , methylamino Chemical group 0.000 abstract description 83
- 150000001875 compounds Chemical class 0.000 abstract description 46
- 125000000217 alkyl group Chemical group 0.000 abstract description 34
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 14
- 239000001257 hydrogen Substances 0.000 abstract description 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 9
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 8
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 4
- 125000002098 pyridazinyl group Chemical group 0.000 abstract description 4
- 125000004076 pyridyl group Chemical group 0.000 abstract description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 abstract description 4
- 125000004429 atom Chemical group 0.000 abstract description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 3
- 125000001072 heteroaryl group Chemical group 0.000 abstract description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 abstract description 3
- 125000003373 pyrazinyl group Chemical group 0.000 abstract description 3
- 125000003226 pyrazolyl group Chemical group 0.000 abstract description 3
- 150000003839 salts Chemical class 0.000 abstract description 3
- 125000000335 thiazolyl group Chemical group 0.000 abstract description 3
- 150000002431 hydrogen Chemical group 0.000 abstract 5
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract 3
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 3
- 125000003884 phenylalkyl group Chemical group 0.000 abstract 3
- 125000003545 alkoxy group Chemical group 0.000 abstract 2
- 125000005843 halogen group Chemical group 0.000 abstract 2
- 125000004404 heteroalkyl group Chemical group 0.000 abstract 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract 2
- 125000004442 acylamino group Chemical group 0.000 abstract 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 abstract 1
- 125000001153 fluoro group Chemical group F* 0.000 abstract 1
- 125000004438 haloalkoxy group Chemical group 0.000 abstract 1
- 125000001188 haloalkyl group Chemical group 0.000 abstract 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- 125000003831 tetrazolyl group Chemical group 0.000 abstract 1
- 125000001544 thienyl group Chemical group 0.000 abstract 1
- 150000003840 hydrochlorides Chemical class 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- 239000000203 mixture Substances 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 239000007787 solid Substances 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 16
- 238000000034 method Methods 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 208000002193 Pain Diseases 0.000 description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 150000004702 methyl esters Chemical class 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- MPBCUCGKHDEUDD-UHFFFAOYSA-N (5-methylpyrazin-2-yl)methanamine Chemical compound CC1=CN=C(CN)C=N1 MPBCUCGKHDEUDD-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000007832 Na2SO4 Substances 0.000 description 5
- 125000004103 aminoalkyl group Chemical group 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000004305 biphenyl Substances 0.000 description 5
- 235000010290 biphenyl Nutrition 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- UGSDNFUJFOBREZ-UHFFFAOYSA-N 3-(1-ethyltetrazol-5-yl)-5-(4-methylphenyl)benzoic acid Chemical compound CCN1N=NN=C1C1=CC(C(O)=O)=CC(C=2C=CC(C)=CC=2)=C1 UGSDNFUJFOBREZ-UHFFFAOYSA-N 0.000 description 4
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 208000002551 irritable bowel syndrome Diseases 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- YWTUCRBEYQHQGN-UHFFFAOYSA-N methyl 3-amino-5-(5-methylpyridin-2-yl)benzoate Chemical compound COC(=O)C1=CC(N)=CC(C=2N=CC(C)=CC=2)=C1 YWTUCRBEYQHQGN-UHFFFAOYSA-N 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 125000006002 1,1-difluoroethyl group Chemical group 0.000 description 3
- DKUHRMQFVUOLMW-UHFFFAOYSA-N 3-(5-chloropyridin-2-yl)-5-(5-propan-2-yltetrazol-1-yl)benzoic acid Chemical compound CC(C)C1=NN=NN1C1=CC(C(O)=O)=CC(C=2N=CC(Cl)=CC=2)=C1 DKUHRMQFVUOLMW-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- 208000004454 Hyperalgesia Diseases 0.000 description 3
- 206010020853 Hypertonic bladder Diseases 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 206010053552 allodynia Diseases 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 230000007123 defense Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 210000002414 leg Anatomy 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- LGTLTQGYTMMNDL-UHFFFAOYSA-N methyl 3-(4-methyl-2-oxopyridin-1-yl)-5-nitrobenzoate Chemical compound [O-][N+](=O)C1=CC(C(=O)OC)=CC(N2C(C=C(C)C=C2)=O)=C1 LGTLTQGYTMMNDL-UHFFFAOYSA-N 0.000 description 3
- CXEKTDHWRDMRBU-UHFFFAOYSA-N methyl 3-amino-5-(4-methyl-2-oxopyridin-1-yl)benzoate Chemical compound COC(=O)C1=CC(N)=CC(N2C(C=C(C)C=C2)=O)=C1 CXEKTDHWRDMRBU-UHFFFAOYSA-N 0.000 description 3
- USWIIRNZLBTCSP-UHFFFAOYSA-N methyl 3-iodo-5-(4-methylphenyl)benzoate Chemical compound COC(=O)C1=CC(I)=CC(C=2C=CC(C)=CC=2)=C1 USWIIRNZLBTCSP-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 2
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 2
- NXMXETCTWNXSFG-UHFFFAOYSA-N 1-methoxypropan-2-amine Chemical compound COCC(C)N NXMXETCTWNXSFG-UHFFFAOYSA-N 0.000 description 2
- IIGXIHLJMZQHJY-UHFFFAOYSA-N 1-pyrazin-2-ylethanamine Chemical compound CC(N)C1=CN=CC=N1 IIGXIHLJMZQHJY-UHFFFAOYSA-N 0.000 description 2
- HIZMJYQEHFJWQY-UHFFFAOYSA-N 1-pyridin-4-ylethanamine Chemical compound CC(N)C1=CC=NC=C1 HIZMJYQEHFJWQY-UHFFFAOYSA-N 0.000 description 2
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 2
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 2
- ZVLHHXBKTMUUNR-UHFFFAOYSA-N 3-(4-methylphenyl)-n-[(5-methylpyrazin-2-yl)methyl]-5-(5-propan-2-yltetrazol-1-yl)benzamide Chemical compound CC(C)C1=NN=NN1C1=CC(C(=O)NCC=2N=CC(C)=NC=2)=CC(C=2C=CC(C)=CC=2)=C1 ZVLHHXBKTMUUNR-UHFFFAOYSA-N 0.000 description 2
- IPYYWXRGBBYBNO-UHFFFAOYSA-N 3-(5-chloropyridin-2-yl)-n-[(5-methylpyrazin-2-yl)methyl]-5-(5-propan-2-yltetrazol-1-yl)benzamide Chemical compound CC(C)C1=NN=NN1C1=CC(C(=O)NCC=2N=CC(C)=NC=2)=CC(C=2N=CC(Cl)=CC=2)=C1 IPYYWXRGBBYBNO-UHFFFAOYSA-N 0.000 description 2
- KWGCQTSLXZTWIR-UHFFFAOYSA-N 3-(5-ethyltetrazol-1-yl)-5-(4-methylphenyl)-n-pyridazin-4-ylbenzamide Chemical compound CCC1=NN=NN1C1=CC(C(=O)NC=2C=NN=CC=2)=CC(C=2C=CC(C)=CC=2)=C1 KWGCQTSLXZTWIR-UHFFFAOYSA-N 0.000 description 2
- FRFZNYNKHCCNGI-UHFFFAOYSA-N 3-(5-methylpyridin-2-yl)-5-(tetrazol-1-yl)benzoic acid Chemical compound N1=CC(C)=CC=C1C1=CC(C(O)=O)=CC(N2N=NN=C2)=C1 FRFZNYNKHCCNGI-UHFFFAOYSA-N 0.000 description 2
- JYPLNXGNHJXDCN-UHFFFAOYSA-N 3-[5-(1-methoxyethyl)tetrazol-1-yl]-5-(4-methylphenyl)-n-(1-pyrimidin-5-ylethyl)benzamide Chemical compound COC(C)C1=NN=NN1C1=CC(C(=O)NC(C)C=2C=NC=NC=2)=CC(C=2C=CC(C)=CC=2)=C1 JYPLNXGNHJXDCN-UHFFFAOYSA-N 0.000 description 2
- KUBQSAXEBSTXMS-UHFFFAOYSA-N 3-amino-5-(5-chloropyridin-2-yl)benzoic acid Chemical compound NC=1C=C(C(=O)O)C=C(C=1)C1=NC=C(C=C1)Cl KUBQSAXEBSTXMS-UHFFFAOYSA-N 0.000 description 2
- YBDRFJXGJQULGH-UHFFFAOYSA-N 4-methyl-1h-pyridin-2-one Chemical compound CC1=CC=NC(O)=C1 YBDRFJXGJQULGH-UHFFFAOYSA-N 0.000 description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 208000009722 Overactive Urinary Bladder Diseases 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
- 229910003910 SiCl4 Inorganic materials 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- DMVOXQPQNTYEKQ-UHFFFAOYSA-N biphenyl-4-amine Chemical compound C1=CC(N)=CC=C1C1=CC=CC=C1 DMVOXQPQNTYEKQ-UHFFFAOYSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000009610 hypersensitivity Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- PVJQXUVHPGMIDF-UHFFFAOYSA-N methyl 3-(1-ethyltetrazol-5-yl)-5-(4-methylphenyl)benzoate Chemical compound CCN1N=NN=C1C1=CC(C(=O)OC)=CC(C=2C=CC(C)=CC=2)=C1 PVJQXUVHPGMIDF-UHFFFAOYSA-N 0.000 description 2
- VJWXJLPFRFVDKA-UHFFFAOYSA-N methyl 3-(5-chloropyridin-2-yl)-5-(2-methylpropanoylamino)benzoate Chemical compound COC(=O)C1=CC(NC(=O)C(C)C)=CC(C=2N=CC(Cl)=CC=2)=C1 VJWXJLPFRFVDKA-UHFFFAOYSA-N 0.000 description 2
- JIOVBBWGOIGBJI-UHFFFAOYSA-N methyl 3-(5-chloropyridin-2-yl)-5-(5-propan-2-yltetrazol-1-yl)benzoate Chemical compound C=1C(C(=O)OC)=CC(C=2N=CC(Cl)=CC=2)=CC=1N1N=NN=C1C(C)C JIOVBBWGOIGBJI-UHFFFAOYSA-N 0.000 description 2
- LIYIMALWYSIVOY-UHFFFAOYSA-N methyl 3-(5-methylpyridin-2-yl)-5-(tetrazol-1-yl)benzoate Chemical compound C=1C(C(=O)OC)=CC(C=2N=CC(C)=CC=2)=CC=1N1C=NN=N1 LIYIMALWYSIVOY-UHFFFAOYSA-N 0.000 description 2
- BVGDAFNOZXSBTL-UHFFFAOYSA-N methyl 3-(ethylcarbamoyl)-5-(4-methylphenyl)benzoate Chemical compound CCNC(=O)C1=CC(C(=O)OC)=CC(C=2C=CC(C)=CC=2)=C1 BVGDAFNOZXSBTL-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- CAWHJQAVHZEVTJ-UHFFFAOYSA-N methylpyrazine Chemical compound CC1=CN=CC=N1 CAWHJQAVHZEVTJ-UHFFFAOYSA-N 0.000 description 2
- SHYDILMVZHYOJU-UHFFFAOYSA-N n-(2-aminopyridin-4-yl)-3-(4-methylphenyl)-5-(5-propan-2-yltetrazol-1-yl)benzamide Chemical compound CC(C)C1=NN=NN1C1=CC(C(=O)NC=2C=C(N)N=CC=2)=CC(C=2C=CC(C)=CC=2)=C1 SHYDILMVZHYOJU-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 208000020629 overactive bladder Diseases 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 201000007094 prostatitis Diseases 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- FDNAPBUWERUEDA-UHFFFAOYSA-N silicon tetrachloride Chemical compound Cl[Si](Cl)(Cl)Cl FDNAPBUWERUEDA-UHFFFAOYSA-N 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 210000000689 upper leg Anatomy 0.000 description 2
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Classifications
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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| JP5685203B2 (ja) * | 2009-05-29 | 2015-03-18 | ラクオリア創薬株式会社 | カルシウムチャネル遮断薬またはナトリウムチャネル遮断薬としてのアリール置換カルボキサミド誘導体 |
| AR077033A1 (es) * | 2009-06-11 | 2011-07-27 | Hoffmann La Roche | Compuestos inhibidores de las quinasas de janus y su uso en el tratamiento de enfermedades inmunologicas |
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