JP5240899B2 - トリアゾロフタラジン - Google Patents

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Publication number

JP5240899B2

JP5240899B2 JP2007548843A JP2007548843A JP5240899B2 JP 5240899 B2 JP5240899 B2 JP 5240899B2 JP 2007548843 A JP2007548843 A JP 2007548843A JP 2007548843 A JP2007548843 A JP 2007548843A JP 5240899 B2 JP5240899 B2 JP 5240899B2

Authority

JP

Japan

Prior art keywords

phenyl

alkyl

methoxy

triazolo

phthalazin

Prior art date

2005-01-05

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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• SGTXILTYXULEQD-UHFFFAOYSA-N 2H-triazolo[4,5-f]phthalazine Chemical compound N1=NC=C2C3=NNN=C3C=CC2=C1 SGTXILTYXULEQD-UHFFFAOYSA-N 0.000 title description 8
• 150000001875 compounds Chemical class 0.000 claims description 261
• -1 cyano, tetrazol-5-yl Chemical group 0.000 claims description 114
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 102
• 229910052757 nitrogen Inorganic materials 0.000 claims description 80
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 64
• 125000000623 heterocyclic group Chemical group 0.000 claims description 50
• 150000003839 salts Chemical class 0.000 claims description 49
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 46
• 101100177165 Caenorhabditis elegans har-1 gene Proteins 0.000 claims description 44
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
• 229910052739 hydrogen Inorganic materials 0.000 claims description 40
• 239000001257 hydrogen Substances 0.000 claims description 40
• 229910052736 halogen Inorganic materials 0.000 claims description 33
• 150000002367 halogens Chemical class 0.000 claims description 33
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 33
• 125000004076 pyridyl group Chemical group 0.000 claims description 33
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 32
• 125000001544 thienyl group Chemical group 0.000 claims description 24
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 23
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
• 125000005842 heteroatom Chemical group 0.000 claims description 22
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 21
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 21
• 229910052760 oxygen Inorganic materials 0.000 claims description 21
• 239000001301 oxygen Substances 0.000 claims description 21
• 229910052717 sulfur Inorganic materials 0.000 claims description 21
• 239000011593 sulfur Substances 0.000 claims description 21
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 20
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 19
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 18
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 18
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 16
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 16
• ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 16
• 239000000460 chlorine Chemical group 0.000 claims description 16
• 239000008194 pharmaceutical composition Substances 0.000 claims description 16
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
• 125000004432 carbon atom Chemical group C* 0.000 claims description 15
• 125000003118 aryl group Chemical group 0.000 claims description 14
• 125000002950 monocyclic group Chemical group 0.000 claims description 14
• 229910052799 carbon Inorganic materials 0.000 claims description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
• 229910052801 chlorine Inorganic materials 0.000 claims description 12
• 201000010099 disease Diseases 0.000 claims description 12
• 125000003277 amino group Chemical group 0.000 claims description 11
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 10
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 10
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
• 229910052794 bromium Inorganic materials 0.000 claims description 10
• 125000004122 cyclic group Chemical group 0.000 claims description 10
• 239000011737 fluorine Chemical group 0.000 claims description 10
• 229910052731 fluorine Inorganic materials 0.000 claims description 10
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 10
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 9
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
• 230000000694 effects Effects 0.000 claims description 8
• 230000003511 endothelial effect Effects 0.000 claims description 8
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
• BUYUFJZVMVFQLQ-UHFFFAOYSA-N 4-[2-(5,5,8,8-tetramethyl-6,7-dihydroquinoxalin-2-yl)ethynyl]benzoic acid Chemical compound CC1(C=2N=CC(=NC=2C(CC1)(C)C)C#CC1=CC=C(C(=O)O)C=C1)C BUYUFJZVMVFQLQ-UHFFFAOYSA-N 0.000 claims description 6
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 6
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
• 230000033115 angiogenesis Effects 0.000 claims description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
• 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 5
• 229940124531 pharmaceutical excipient Drugs 0.000 claims description 5
• 230000002829 reductive effect Effects 0.000 claims description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• RBIIKVXVYVANCQ-CUWPLCDZSA-N (2s,4s,5s)-5-amino-n-(3-amino-2,2-dimethyl-3-oxopropyl)-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-propan-2-ylhexanamide Chemical compound C1C(C)(C)N(C[C@H](N)[C@@H](O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)CC(=O)N1C1=CC=CC=C1Cl RBIIKVXVYVANCQ-CUWPLCDZSA-N 0.000 claims description 4
• NENVQQVAZMKJJY-UHFFFAOYSA-N 3-n-[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]benzene-1,3-diamine Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(N)C=CC=1)C1=CC=CC=C12 NENVQQVAZMKJJY-UHFFFAOYSA-N 0.000 claims description 4
• 206010040070 Septic Shock Diseases 0.000 claims description 4
• 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 4
• 230000036303 septic shock Effects 0.000 claims description 4
• 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 4
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 3
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
• 208000028185 Angioedema Diseases 0.000 claims description 3
• 125000003545 alkoxy group Chemical group 0.000 claims description 3
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
• 230000002917 arthritic effect Effects 0.000 claims description 3
• 208000006673 asthma Diseases 0.000 claims description 3
• 230000000903 blocking effect Effects 0.000 claims description 3
• 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 3
• 125000002971 oxazolyl group Chemical group 0.000 claims description 3
• 208000023504 respiratory system disease Diseases 0.000 claims description 3
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims description 3
• YDGXEJJOEYTQEP-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-(3-pyrrolidin-1-ylsulfonylphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-amine Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(C=CC=1)S(=O)(=O)N1CCCC1)C1=CC=CC=C12 YDGXEJJOEYTQEP-UHFFFAOYSA-N 0.000 claims description 2
• OCYJKVRZVMCFDL-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-[4-(2h-tetrazol-5-yl)phenyl]-[1,2,4]triazolo[3,4-a]phthalazin-6-amine Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=CC(=CC=1)C1=NNN=N1)C1=CC=CC=C12 OCYJKVRZVMCFDL-UHFFFAOYSA-N 0.000 claims description 2
• YKQMVSZDYFMORE-UHFFFAOYSA-N 3-[(4-methoxyphenyl)methyl]-n-[3-(2h-tetrazol-5-yl)phenyl]-[1,2,4]triazolo[3,4-a]phthalazin-6-amine Chemical compound C1=CC(OC)=CC=C1CC1=NN=C2N1N=C(NC=1C=C(C=CC=1)C1=NNN=N1)C1=CC=CC=C12 YKQMVSZDYFMORE-UHFFFAOYSA-N 0.000 claims description 2
• COMATYKLCBVMLD-UHFFFAOYSA-N 3-[[3-(2-bromophenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]-n,n-dimethylbenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=CC(NC=2C3=CC=CC=C3C3=NN=C(N3N=2)C=2C(=CC=CC=2)Br)=C1 COMATYKLCBVMLD-UHFFFAOYSA-N 0.000 claims description 2
• APAPFHWEKMQZFO-UHFFFAOYSA-N 3-[[3-(2-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]-N,N-dimethylbenzenesulfonamide Chemical compound COC1=CC=CC=C1C1=NN=C2N1N=C(NC=1C=C(C=CC=1)S(=O)(=O)N(C)C)C1=CC=CC=C12 APAPFHWEKMQZFO-UHFFFAOYSA-N 0.000 claims description 2
• KFJMSIIDLJNVOT-UHFFFAOYSA-N 3-[[3-(4-bromophenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]-n,n-dimethylbenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=CC(NC=2C3=CC=CC=C3C3=NN=C(N3N=2)C=2C=CC(Br)=CC=2)=C1 KFJMSIIDLJNVOT-UHFFFAOYSA-N 0.000 claims description 2
• BERRTEMAKLHCEH-UHFFFAOYSA-N 3-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]-n,n-dimethylbenzenesulfonamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(C=CC=1)S(=O)(=O)N(C)C)C1=CC=CC=C12 BERRTEMAKLHCEH-UHFFFAOYSA-N 0.000 claims description 2
• SCBFCULYXKHFII-UHFFFAOYSA-N 3-methoxy-n-[3-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]benzenesulfonamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(NS(=O)(=O)C=3C=C(OC)C=CC=3)C=CC=1)C1=CC=CC=C12 SCBFCULYXKHFII-UHFFFAOYSA-N 0.000 claims description 2
• ZWLOLTMPNSGCHE-UHFFFAOYSA-N 4-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]-n,n-dimethylbenzenesulfonamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=CC(=CC=1)S(=O)(=O)N(C)C)C1=CC=CC=C12 ZWLOLTMPNSGCHE-UHFFFAOYSA-N 0.000 claims description 2
• PXAOPJAZZRRTMO-UHFFFAOYSA-N 4-acetyl-n-[3-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]benzenesulfonamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(NS(=O)(=O)C=3C=CC(=CC=3)C(C)=O)C=CC=1)C1=CC=CC=C12 PXAOPJAZZRRTMO-UHFFFAOYSA-N 0.000 claims description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
• 206010014561 Emphysema Diseases 0.000 claims description 2
• 206010035664 Pneumonia Diseases 0.000 claims description 2
• 230000001154 acute effect Effects 0.000 claims description 2
• 206010006451 bronchitis Diseases 0.000 claims description 2
• 230000001684 chronic effect Effects 0.000 claims description 2
• 208000027866 inflammatory disease Diseases 0.000 claims description 2
• XKEMDWQSXAGUTA-UHFFFAOYSA-N n-[3-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(NS(=O)(=O)C=3C=CC(C)=CC=3)C=CC=1)C1=CC=CC=C12 XKEMDWQSXAGUTA-UHFFFAOYSA-N 0.000 claims description 2
• LWNBXONNCSDUJI-UHFFFAOYSA-N n-[4-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]-1-phenylmethanesulfonamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=CC(NS(=O)(=O)CC=3C=CC=CC=3)=CC=1)C1=CC=CC=C12 LWNBXONNCSDUJI-UHFFFAOYSA-N 0.000 claims description 2
• YJOFXVIATMLPER-UHFFFAOYSA-N n-[4-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=CC(NS(=O)(=O)C=3C=CC(C)=CC=3)=CC=1)C1=CC=CC=C12 YJOFXVIATMLPER-UHFFFAOYSA-N 0.000 claims description 2
• YZFXPFCBJYEBPC-UHFFFAOYSA-N n-[4-[[3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]amino]phenyl]morpholine-4-sulfonamide Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=CC(NS(=O)(=O)N3CCOCC3)=CC=1)C1=CC=CC=C12 YZFXPFCBJYEBPC-UHFFFAOYSA-N 0.000 claims description 2
• 206010039083 rhinitis Diseases 0.000 claims description 2
• 150000002431 hydrogen Chemical group 0.000 claims 4
• IZVSFCVCPDZGGF-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n-[3-(2-methyltetrazol-5-yl)phenyl]-[1,2,4]triazolo[3,4-a]phthalazin-6-amine Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(NC=1C=C(C=CC=1)C1=NN(C)N=N1)C1=CC=CC=C12 IZVSFCVCPDZGGF-UHFFFAOYSA-N 0.000 claims 1
• 101100135859 Dictyostelium discoideum regA gene Proteins 0.000 claims 1
• 101100082606 Plasmodium falciparum (isolate 3D7) PDEbeta gene Proteins 0.000 claims 1
• 101100135860 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PDE2 gene Proteins 0.000 claims 1
• 201000011510 cancer Diseases 0.000 claims 1
• 230000001575 pathological effect Effects 0.000 claims 1
• 230000007170 pathology Effects 0.000 claims 1
• BSXLLFUSNQCWJP-UHFFFAOYSA-N thiophene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CS1 BSXLLFUSNQCWJP-UHFFFAOYSA-N 0.000 claims 1
• 238000002844 melting Methods 0.000 description 55
• 230000008018 melting Effects 0.000 description 55
• 229910052740 iodine Inorganic materials 0.000 description 37
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 34
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 34
• 238000000034 method Methods 0.000 description 31
• 238000006243 chemical reaction Methods 0.000 description 27
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
• 230000005764 inhibitory process Effects 0.000 description 16
• 239000002904 solvent Substances 0.000 description 15
• 239000000203 mixture Substances 0.000 description 13
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 12
• ZHGVCXDOKBSJBV-UHFFFAOYSA-N 6-chloro-3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-a]phthalazine Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(Cl)C1=CC=CC=C12 ZHGVCXDOKBSJBV-UHFFFAOYSA-N 0.000 description 11
• 230000035699 permeability Effects 0.000 description 10
• 238000003752 polymerase chain reaction Methods 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 239000007787 solid Substances 0.000 description 10
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
• UQTJGZYAFKMABR-UHFFFAOYSA-N (4-chlorophthalazin-1-yl)hydrazine Chemical compound C1=CC=C2C(NN)=NN=C(Cl)C2=C1 UQTJGZYAFKMABR-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• 239000011541 reaction mixture Substances 0.000 description 9
• 239000000243 solution Substances 0.000 description 9
• 239000007858 starting material Substances 0.000 description 9
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 8
• 229940121828 Phosphodiesterase 2 inhibitor Drugs 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 108090000190 Thrombin Proteins 0.000 description 7
• 239000000443 aerosol Substances 0.000 description 7
• 150000001448 anilines Chemical class 0.000 description 7
• 230000002401 inhibitory effect Effects 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• 229960004072 thrombin Drugs 0.000 description 7
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 6
• ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 6
• NPFVRBCDMFKOPY-UHFFFAOYSA-N 3-(4-imidazol-1-ylthiophen-2-yl)-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC(N2C=NC=C2)=CS1 NPFVRBCDMFKOPY-UHFFFAOYSA-N 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 125000000217 alkyl group Chemical group 0.000 description 6
• 238000004440 column chromatography Methods 0.000 description 6
• ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 6
• 239000003814 drug Substances 0.000 description 6
• 238000004519 manufacturing process Methods 0.000 description 6
• 229950002910 motapizone Drugs 0.000 description 6
• 230000002265 prevention Effects 0.000 description 6
• QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 6
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