MXPA04011209A - Derivados de piridazin-3(2h)-ona como inhibidores de pde4. - Google Patents

Info

Publication number

MXPA04011209A

MXPA04011209A MXPA04011209A MXPA04011209A MXPA04011209A MX PA04011209 A MXPA04011209 A MX PA04011209A MX PA04011209 A MXPA04011209 A MX PA04011209A MX PA04011209 A MXPA04011209 A MX PA04011209A MX PA04011209 A MXPA04011209 A MX PA04011209A

Authority

MX

Mexico

Prior art keywords

acetyl

amino

ethyl

phenyl

pyridazin

Prior art date

2002-05-16

Links

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• Global Dossier
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• 238000000034 method Methods 0.000 claims abstract description 170
• AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 claims abstract description 22
• MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 claims abstract description 21
• 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims abstract description 21
• 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims abstract description 21
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
• 230000008569 process Effects 0.000 claims abstract description 6
• -1 cyano, difluoromethoxy Chemical group 0.000 claims description 250
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 250
• 150000001875 compounds Chemical class 0.000 claims description 224
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 68
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 56
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 45
• 125000001424 substituent group Chemical group 0.000 claims description 42
• 239000002253 acid Substances 0.000 claims description 37
• 125000000217 alkyl group Chemical group 0.000 claims description 34
• 125000003545 alkoxy group Chemical group 0.000 claims description 33
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 31
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
• VROMXVIODDASTK-UHFFFAOYSA-N 5-amino-1h-pyridazin-6-one Chemical compound NC1=CC=NNC1=O VROMXVIODDASTK-UHFFFAOYSA-N 0.000 claims description 24
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
• 125000004414 alkyl thio group Chemical group 0.000 claims description 21
• 125000000623 heterocyclic group Chemical group 0.000 claims description 20
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 18
• 150000003839 salts Chemical class 0.000 claims description 18
• 239000005711 Benzoic acid Substances 0.000 claims description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
• 239000003814 drug Substances 0.000 claims description 16
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 15
• 201000010099 disease Diseases 0.000 claims description 15
• 125000005843 halogen group Chemical group 0.000 claims description 15
• 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 15
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 14
• 238000011282 treatment Methods 0.000 claims description 14
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 13
• 125000002252 acyl group Chemical group 0.000 claims description 13
• 125000003118 aryl group Chemical group 0.000 claims description 13
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 13
• 230000005764 inhibitory process Effects 0.000 claims description 13
• 235000010233 benzoic acid Nutrition 0.000 claims description 12
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 10
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 10
• 125000004442 acylamino group Chemical group 0.000 claims description 10
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 10
• 150000001412 amines Chemical class 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 150000002367 halogens Chemical class 0.000 claims description 10
• 125000002947 alkylene group Chemical group 0.000 claims description 9
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 9
• 239000001257 hydrogen Substances 0.000 claims description 9
• 229910052739 hydrogen Inorganic materials 0.000 claims description 9
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 8
• 125000004104 aryloxy group Chemical group 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 8
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 7
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 6
• 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
• 229910052757 nitrogen Inorganic materials 0.000 claims description 6
• 125000004043 oxo group Chemical group O=* 0.000 claims description 6
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 5
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 5
• 241001024304 Mino Species 0.000 claims description 5
• 125000005117 dialkylcarbamoyl group Chemical group 0.000 claims description 5
• 125000005842 heteroatom Chemical group 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 4
• 201000004681 Psoriasis Diseases 0.000 claims description 4
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
• 208000006673 asthma Diseases 0.000 claims description 4
• 201000008937 atopic dermatitis Diseases 0.000 claims description 4
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
• 230000001575 pathological effect Effects 0.000 claims description 4
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
• 125000003107 substituted aryl group Chemical group 0.000 claims description 4
• 229910052717 sulfur Chemical group 0.000 claims description 4
• PXINPBFBXVDMMC-UHFFFAOYSA-N 2-ethyl-5-(2-ethylbutanoyl)-4-(3-fluoroanilino)-6-(4-methylsulfanylphenyl)pyridazin-3-one Chemical compound O=C1N(CC)N=C(C=2C=CC(SC)=CC=2)C(C(=O)C(CC)CC)=C1NC1=CC=CC(F)=C1 PXINPBFBXVDMMC-UHFFFAOYSA-N 0.000 claims description 3
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
• OYBHIRQUMMJDIQ-UHFFFAOYSA-N 5-acetyl-2-ethyl-4-(naphthalen-1-ylamino)-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C3=CC=CC=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 OYBHIRQUMMJDIQ-UHFFFAOYSA-N 0.000 claims description 3
• XLQWKNMLDXHQPC-UHFFFAOYSA-N 5-acetyl-2-ethyl-6-phenyl-4-(5,6,7,8-tetrahydronaphthalen-1-ylamino)pyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C=3CCCCC=3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 XLQWKNMLDXHQPC-UHFFFAOYSA-N 0.000 claims description 3
• HQGAMAOHAUFYPD-UHFFFAOYSA-N 5-acetyl-4-(1,3-benzodioxol-5-ylamino)-2-ethyl-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C=C3OCOC3=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 HQGAMAOHAUFYPD-UHFFFAOYSA-N 0.000 claims description 3
• GGVPOCCNCPBSNB-UHFFFAOYSA-N 5-acetyl-4-(3-chloroanilino)-2-ethyl-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C=C(Cl)C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 GGVPOCCNCPBSNB-UHFFFAOYSA-N 0.000 claims description 3
• YEOVAVJQAGKESR-UHFFFAOYSA-N 5-acetyl-4-(naphthalen-1-ylamino)-6-phenyl-2-(pyridin-4-ylmethyl)pyridazin-3-one Chemical compound O=C1C(NC=2C3=CC=CC=C3C=CC=2)=C(C(=O)C)C(C=2C=CC=CC=2)=NN1CC1=CC=NC=C1 YEOVAVJQAGKESR-UHFFFAOYSA-N 0.000 claims description 3
• HBUMKFOVTJTPCX-UHFFFAOYSA-N C(C)(=O)C1=C(C(N(N=C1C1=CC=CC=C1)CC1CC1)=O)NC1=CC(=CC=C1)Cl.C(C)(=O)C1=C(C(N(N=C1C1=CC=CC=C1)CC1CC1)=O)NC1=CC(=CC=C1)F Chemical compound C(C)(=O)C1=C(C(N(N=C1C1=CC=CC=C1)CC1CC1)=O)NC1=CC(=CC=C1)Cl.C(C)(=O)C1=C(C(N(N=C1C1=CC=CC=C1)CC1CC1)=O)NC1=CC(=CC=C1)F HBUMKFOVTJTPCX-UHFFFAOYSA-N 0.000 claims description 3
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 3
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
• 125000002619 bicyclic group Chemical group 0.000 claims description 3
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 125000002950 monocyclic group Chemical group 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 3
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
• 239000001301 oxygen Chemical group 0.000 claims description 3
• 239000011593 sulfur Chemical group 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• PNRNDNPESUNOLE-UHFFFAOYSA-N 2-ethyl-5-(2-ethylbutanoyl)-6-(4-methylsulfanylphenyl)-4-(naphthalen-1-ylamino)pyridazin-3-one Chemical compound CCC(CC)C(=O)C1=C(NC=2C3=CC=CC=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=C(SC)C=C1 PNRNDNPESUNOLE-UHFFFAOYSA-N 0.000 claims description 2
• IQJXVUYRDWSYRO-UHFFFAOYSA-N 5-(3-chloroanilino)-1-ethyl-6-oxo-3-phenylpyridazine-4-carbaldehyde Chemical compound O=CC1=C(NC=2C=C(Cl)C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 IQJXVUYRDWSYRO-UHFFFAOYSA-N 0.000 claims description 2
• IGINFKNVKRSJHU-UHFFFAOYSA-N 5-acetyl-2-ethyl-4-(3-hydroxyanilino)-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C=C(O)C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 IGINFKNVKRSJHU-UHFFFAOYSA-N 0.000 claims description 2
• MSRCVYFZYDCIGD-UHFFFAOYSA-N 5-acetyl-4-(3,5-dichloroanilino)-2-ethyl-6-phenylpyridazin-3-one;5-acetyl-4-(3,5-difluoroanilino)-2-ethyl-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C=C(F)C=C(F)C=2)C(=O)N(CC)N=C1C1=CC=CC=C1.CC(=O)C1=C(NC=2C=C(Cl)C=C(Cl)C=2)C(=O)N(CC)N=C1C1=CC=CC=C1 MSRCVYFZYDCIGD-UHFFFAOYSA-N 0.000 claims description 2
• WVYCSADQTVBOTB-UHFFFAOYSA-N 5-acetyl-4-(3-chloro-n-(3-chlorophenyl)anilino)-2-ethyl-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(N(C=2C=C(Cl)C=CC=2)C=2C=C(Cl)C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 WVYCSADQTVBOTB-UHFFFAOYSA-N 0.000 claims description 2
• BKJXBIOCSNNPJU-UHFFFAOYSA-N 5-acetyl-4-(3-chloroanilino)-2-ethyl-6-(4-fluorophenyl)pyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C=C(Cl)C=CC=2)C(=O)N(CC)N=C1C1=CC=C(F)C=C1 BKJXBIOCSNNPJU-UHFFFAOYSA-N 0.000 claims description 2
• ANLZZGTWBDRRPB-UHFFFAOYSA-N 5-nitro-1h-pyridazin-6-one Chemical class [O-][N+](=O)C1=CC=NNC1=O ANLZZGTWBDRRPB-UHFFFAOYSA-N 0.000 claims description 2
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 2
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
• 239000004202 carbamide Substances 0.000 claims description 2
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• KILMWYKRIUZJHI-UHFFFAOYSA-N C(C)(=O)C1=C(C(N(N=C1C1=CC(=CC=C1)F)CC)=O)NC1=CC(=CC=C1)Cl.C(C)(=O)C1=C(C(N(N=C1C1=CC(=CC=C1)F)CC)=O)NC1=CC(=CC=C1)F Chemical compound C(C)(=O)C1=C(C(N(N=C1C1=CC(=CC=C1)F)CC)=O)NC1=CC(=CC=C1)Cl.C(C)(=O)C1=C(C(N(N=C1C1=CC(=CC=C1)F)CC)=O)NC1=CC(=CC=C1)F KILMWYKRIUZJHI-UHFFFAOYSA-N 0.000 claims 2
• IPRJXAGUEGOFGG-UHFFFAOYSA-N N-butylbenzenesulfonamide Chemical compound CCCCNS(=O)(=O)C1=CC=CC=C1 IPRJXAGUEGOFGG-UHFFFAOYSA-N 0.000 claims 2
• CGMKBLVWNRNBDX-UHFFFAOYSA-N 5-(3-cyanoanilino)-1-ethyl-6-oxo-3-phenylpyridazine-4-carboxamide Chemical compound NC(=O)C1=C(NC=2C=C(C=CC=2)C#N)C(=O)N(CC)N=C1C1=CC=CC=C1 CGMKBLVWNRNBDX-UHFFFAOYSA-N 0.000 claims 1
• DPAWOYZTVRDBPD-UHFFFAOYSA-N 5-acetyl-2-(cyclopropylmethyl)-4-(3-fluoroanilino)-6-phenylpyridazin-3-one Chemical compound O=C1N(CC2CC2)N=C(C=2C=CC=CC=2)C(C(=O)C)=C1NC1=CC=CC(F)=C1 DPAWOYZTVRDBPD-UHFFFAOYSA-N 0.000 claims 1
• MZNKWROACLNWAZ-UHFFFAOYSA-N 5-acetyl-2-ethyl-4-(3-methylanilino)-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C=C(C)C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 MZNKWROACLNWAZ-UHFFFAOYSA-N 0.000 claims 1
• DAFCVMJHEGNTLP-UHFFFAOYSA-N 5-acetyl-2-ethyl-4-(naphthalen-1-ylamino)-6-(3-nitrophenyl)pyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C3=CC=CC=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC([N+]([O-])=O)=C1 DAFCVMJHEGNTLP-UHFFFAOYSA-N 0.000 claims 1
• CFPMORWIVOOHAP-UHFFFAOYSA-N 5-acetyl-2-ethyl-4-[(1-oxo-2,3-dihydroinden-5-yl)amino]-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C=C3CCC(=O)C3=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 CFPMORWIVOOHAP-UHFFFAOYSA-N 0.000 claims 1
• IDGKQVZCCDXRRF-UHFFFAOYSA-N 5-acetyl-2-methyl-4-(naphthalen-1-ylamino)-6-phenylpyridazin-3-one Chemical compound N=1N(C)C(=O)C(NC=2C3=CC=CC=C3C=CC=2)=C(C(=O)C)C=1C1=CC=CC=C1 IDGKQVZCCDXRRF-UHFFFAOYSA-N 0.000 claims 1
• QRAHDPXJBHBZSK-UHFFFAOYSA-N 5-acetyl-4-(2-chloroanilino)-2-ethyl-6-phenylpyridazin-3-one;5-acetyl-2-ethyl-4-(naphthalen-1-ylamino)-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C(=CC=CC=2)Cl)C(=O)N(CC)N=C1C1=CC=CC=C1.CC(=O)C1=C(NC=2C3=CC=CC=C3C=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 QRAHDPXJBHBZSK-UHFFFAOYSA-N 0.000 claims 1
• PSXXPZUUDYZRIO-UHFFFAOYSA-N 5-acetyl-4-(3,4-dimethoxyanilino)-2-ethyl-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C=C(OC)C(OC)=CC=2)C(=O)N(CC)N=C1C1=CC=CC=C1 PSXXPZUUDYZRIO-UHFFFAOYSA-N 0.000 claims 1
• GOTRFKPRTIEMCF-UHFFFAOYSA-N 5-acetyl-4-(3,5-dichloro-n-(3,5-dichlorophenyl)anilino)-2-ethyl-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(N(C=2C=C(Cl)C=C(Cl)C=2)C=2C=C(Cl)C=C(Cl)C=2)C(=O)N(CC)N=C1C1=CC=CC=C1 GOTRFKPRTIEMCF-UHFFFAOYSA-N 0.000 claims 1
• SZQUONFMSGCEGH-UHFFFAOYSA-N 5-acetyl-4-(5-chloro-2-methoxyanilino)-2-ethyl-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C(NC=2C(=CC=C(Cl)C=2)OC)C(=O)N(CC)N=C1C1=CC=CC=C1 SZQUONFMSGCEGH-UHFFFAOYSA-N 0.000 claims 1
• IIUIGCROACYZLP-UHFFFAOYSA-N C(C)(=O)C1=C(C(N(N=C1C1=CC=CC=C1)C)=O)NC1=CC(=CC=C1)F.C(C)(=O)C1=C(C(N(N=C1C1=CC=CC=C1)CC1CC1)=O)NC1=CC(=CC(=C1)F)F Chemical compound C(C)(=O)C1=C(C(N(N=C1C1=CC=CC=C1)C)=O)NC1=CC(=CC=C1)F.C(C)(=O)C1=C(C(N(N=C1C1=CC=CC=C1)CC1CC1)=O)NC1=CC(=CC(=C1)F)F IIUIGCROACYZLP-UHFFFAOYSA-N 0.000 claims 1
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
• METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 238000002360 preparation method Methods 0.000 abstract description 232
• 239000003112 inhibitor Substances 0.000 abstract description 3
• 239000000126 substance Substances 0.000 abstract description 2
• 238000002560 therapeutic procedure Methods 0.000 abstract 1
• 239000007787 solid Substances 0.000 description 93
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 82
• 239000000203 mixture Substances 0.000 description 79
• 230000014759 maintenance of location Effects 0.000 description 63
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
• BWVQSFMROMRENR-UHFFFAOYSA-N 5-acetyl-2-ethyl-4-nitro-6-phenylpyridazin-3-one Chemical compound CC(=O)C1=C([N+]([O-])=O)C(=O)N(CC)N=C1C1=CC=CC=C1 BWVQSFMROMRENR-UHFFFAOYSA-N 0.000 description 50
• 238000002474 experimental method Methods 0.000 description 43
• 239000000243 solution Substances 0.000 description 35
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
• 239000000047 product Substances 0.000 description 26
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
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