ZA200400057B - Cyclic nucleotide phosphodiesterase inhibitors, preparation and uses thereof. - Google Patents
Cyclic nucleotide phosphodiesterase inhibitors, preparation and uses thereof. Download PDFInfo
- Publication number
- ZA200400057B ZA200400057B ZA200400057A ZA200400057A ZA200400057B ZA 200400057 B ZA200400057 B ZA 200400057B ZA 200400057 A ZA200400057 A ZA 200400057A ZA 200400057 A ZA200400057 A ZA 200400057A ZA 200400057 B ZA200400057 B ZA 200400057B
- Authority
- ZA
- South Africa
- Prior art keywords
- dihydro
- benzodiazepin
- dimethoxy
- phenyl
- methyl
- Prior art date
Links
- 101000909851 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) cAMP/cGMP dual specificity phosphodiesterase Rv0805 Proteins 0.000 title claims description 10
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title description 2
- 239000002571 phosphodiesterase inhibitor Substances 0.000 title description 2
- 238000002360 preparation method Methods 0.000 title description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 202
- 150000001875 compounds Chemical class 0.000 claims description 196
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 176
- -1 34- dichalorophenyl Chemical group 0.000 claims description 81
- 125000000217 alkyl group Chemical group 0.000 claims description 70
- 125000003118 aryl group Chemical group 0.000 claims description 68
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 57
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 33
- 125000000623 heterocyclic group Chemical group 0.000 claims description 30
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 20
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 20
- 229910052702 rhenium Inorganic materials 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 16
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 16
- 238000010992 reflux Methods 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 230000005764 inhibitory process Effects 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- CIBFDTUUNLMFMC-UHFFFAOYSA-N 7,8-dimethoxy-1-phenyl-3,5-dihydro-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)NN=C1C1=CC=CC=C1 CIBFDTUUNLMFMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 230000007170 pathology Effects 0.000 claims description 7
- BBIXYYCWUHISQM-FQEVSTJZSA-N (3s)-3-benzyl-7,8-dimethoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C([C@H]1C(=O)NC=2C=C(C(=CC=2C(C=2C=CC=CC=2)=N1)OC)OC)C1=CC=CC=C1 BBIXYYCWUHISQM-FQEVSTJZSA-N 0.000 claims description 6
- QIYGTBUSLLNPAQ-UHFFFAOYSA-N 1-(4-iodophenyl)-7,8-dimethoxy-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C1=CC=C(I)C=C1 QIYGTBUSLLNPAQ-UHFFFAOYSA-N 0.000 claims description 6
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 6
- 230000002757 inflammatory effect Effects 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- GZHJMAVOLIEASV-UHFFFAOYSA-N 1-(1-benzothiophen-2-yl)-7,8-diethoxy-3,5-dihydro-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OCC)C(OCC)=CC=2CC(=O)NN=C1C1=CC2=CC=CC=C2S1 GZHJMAVOLIEASV-UHFFFAOYSA-N 0.000 claims description 5
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- YNQKOAZCUZKWBE-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-5-[4-(2-phenylethynyl)phenyl]-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CC)C2=CC(OC)=C(OC)C=C2C=1C(C=C1)=CC=C1C#CC1=CC=CC=C1 YNQKOAZCUZKWBE-UHFFFAOYSA-N 0.000 claims description 4
- MLZWVOXBBIWEQR-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-5-phenyl-3-[[3-(trifluoromethyl)phenyl]methyl]-3h-1,4-benzodiazepin-2-one Chemical group O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC(C(F)(F)F)=C1 MLZWVOXBBIWEQR-UHFFFAOYSA-N 0.000 claims description 4
- LIDAPGJWNNLPST-UHFFFAOYSA-N 3-benzyl-7,8-dimethoxy-1-phenyl-5h-2,3-benzodiazepin-4-one Chemical compound N1=C(C=2C=CC=CC=2)C=2C=C(OC)C(OC)=CC=2CC(=O)N1CC1=CC=CC=C1 LIDAPGJWNNLPST-UHFFFAOYSA-N 0.000 claims description 4
- LRICTWOHSPBXLD-UHFFFAOYSA-N 7,8-dimethoxy-1-[4-(2-methoxyphenyl)phenyl]-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=CC=C1OC LRICTWOHSPBXLD-UHFFFAOYSA-N 0.000 claims description 4
- XLAQCBYTYMNGDR-UHFFFAOYSA-N 7,8-dimethoxy-1-phenyl-3-propyl-5h-2,3-benzodiazepin-4-one Chemical compound C12=CC(OC)=C(OC)C=C2CC(=O)N(CCC)N=C1C1=CC=CC=C1 XLAQCBYTYMNGDR-UHFFFAOYSA-N 0.000 claims description 4
- GUDIDXQLBMNOSC-UHFFFAOYSA-N 7,8-dimethoxy-3,5-diphenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(=O)C(C=2C=CC=CC=2)N=C1C1=CC=CC=C1 GUDIDXQLBMNOSC-UHFFFAOYSA-N 0.000 claims description 4
- PICWHVLACPHMEF-UHFFFAOYSA-N 7-ethoxy-8-methoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=C(OC)C(OCC)=CC2=C1NC(=O)CN=C2C1=CC=CC=C1 PICWHVLACPHMEF-UHFFFAOYSA-N 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 4
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 claims description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 4
- 229930195733 hydrocarbon Natural products 0.000 claims description 4
- 150000002430 hydrocarbons Chemical class 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- RGGLEJFUEMKQSH-UHFFFAOYSA-N 1,4-benzodiazepin-2-one Chemical compound O=C1C=NC=C2C=CC=CC2=N1 RGGLEJFUEMKQSH-UHFFFAOYSA-N 0.000 claims description 3
- SJABLWFWDKABFZ-UHFFFAOYSA-N 1-(1-benzothiophen-2-yl)-7,8-diethoxy-5-propyl-3,5-dihydro-2,3-benzodiazepin-4-one Chemical compound N1C(=O)C(CCC)C2=CC(OCC)=C(OCC)C=C2C(C=2SC3=CC=CC=C3C=2)=N1 SJABLWFWDKABFZ-UHFFFAOYSA-N 0.000 claims description 3
- ICARBYJHFKZIFD-UHFFFAOYSA-N 1-[4-(4-acetylphenyl)phenyl]-7,8-dimethoxy-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=C(C(C)=O)C=C1 ICARBYJHFKZIFD-UHFFFAOYSA-N 0.000 claims description 3
- IQWQEVCQXDEINJ-UHFFFAOYSA-N 1-ethyl-3-[hydroxy(diphenyl)methyl]-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 IQWQEVCQXDEINJ-UHFFFAOYSA-N 0.000 claims description 3
- HCIKDGRDIWWCHS-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-3-[(2-methoxyphenyl)methyl]-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC=C1OC HCIKDGRDIWWCHS-UHFFFAOYSA-N 0.000 claims description 3
- KZOFGDXXMLUUFL-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-5-[3-(2-phenylethynyl)phenyl]-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CC)C2=CC(OC)=C(OC)C=C2C=1C(C=1)=CC=CC=1C#CC1=CC=CC=C1 KZOFGDXXMLUUFL-UHFFFAOYSA-N 0.000 claims description 3
- AFYOEJRCJMPOQK-UHFFFAOYSA-N 3-[(8-ethoxy-7-methoxy-1-methyl-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl)methyl]benzonitrile Chemical compound N1=C(C=2C=CC=CC=2)C=2C=C(OC)C(OCC)=CC=2N(C)C(=O)C1CC1=CC=CC(C#N)=C1 AFYOEJRCJMPOQK-UHFFFAOYSA-N 0.000 claims description 3
- FJLGAECREVUWAB-UHFFFAOYSA-N 3-benzyl-7,8-diethoxy-1-ethyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound N1=C(C=2C=CC=CC=2)C=2C=C(OCC)C(OCC)=CC=2N(CC)C(=O)C1CC1=CC=CC=C1 FJLGAECREVUWAB-UHFFFAOYSA-N 0.000 claims description 3
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 3
- AALFNMGUYPJUST-UHFFFAOYSA-N 5-[3,5-bis(trifluoromethyl)phenyl]-7,8-dimethoxy-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 AALFNMGUYPJUST-UHFFFAOYSA-N 0.000 claims description 3
- FVCLLYSNQRDQGL-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(=O)C(C)N=C1C1=CC=CC=C1 FVCLLYSNQRDQGL-UHFFFAOYSA-N 0.000 claims description 3
- 239000004215 Carbon black (E152) Substances 0.000 claims description 3
- 229910052684 Cerium Inorganic materials 0.000 claims description 3
- 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 3
- 239000012190 activator Substances 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 150000003857 carboxamides Chemical class 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 210000003169 central nervous system Anatomy 0.000 claims description 3
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 claims description 3
- 230000003959 neuroinflammation Effects 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- UKHBRHXBBYAMKX-UHFFFAOYSA-N 1-(1-benzothiophen-2-yl)-7,8-diethoxy-3-methyl-5-propyl-5h-2,3-benzodiazepin-4-one Chemical compound CN1C(=O)C(CCC)C2=CC(OCC)=C(OCC)C=C2C(C=2SC3=CC=CC=C3C=2)=N1 UKHBRHXBBYAMKX-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 150000002429 hydrazines Chemical class 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000002524 organometallic group Chemical group 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- YUYOVHKATDWYNX-UHFFFAOYSA-N 1-(1-benzothiophen-2-yl)-7,8-dimethoxy-3-methyl-5H-2,3-benzodiazepin-4-one 1-[4-(furan-2-yl)phenyl]-7,8-dimethoxy-3-methyl-5H-2,3-benzodiazepin-4-one Chemical compound O1C(=CC=C1)C1=CC=C(C=C1)C1=NN(C(CC2=C1C=C(C(=C2)OC)OC)=O)C.S2C1=C(C=C2C2=NN(C(CC3=C2C=C(C(=C3)OC)OC)=O)C)C=CC=C1 YUYOVHKATDWYNX-UHFFFAOYSA-N 0.000 claims 1
- RGEJQYAPVPRMKI-UHFFFAOYSA-N 3-benzyl-8-ethoxy-1-ethyl-7-methoxy-5-phenyl-3h-1,4-benzodiazepin-2-one;8-ethoxy-1-ethyl-7-methoxy-3,5-diphenyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OCC)=CC=2N(CC)C(=O)C(C=2C=CC=CC=2)N=C1C1=CC=CC=C1.N1=C(C=2C=CC=CC=2)C=2C=C(OC)C(OCC)=CC=2N(CC)C(=O)C1CC1=CC=CC=C1 RGEJQYAPVPRMKI-UHFFFAOYSA-N 0.000 claims 1
- IIYNEVNMWVPKJD-UHFFFAOYSA-N 5-(2-bromophenyl)-7,8-dimethoxy-1,3-dihydro-1,4-benzodiazepin-2-one 2-(1-ethyl-7,8-dimethoxy-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl)acetonitrile Chemical compound COc1cc2NC(=O)CN=C(c3ccccc3Br)c2cc1OC.CCN1c2cc(OC)c(OC)cc2C(=NC(CC#N)C1=O)c1ccccc1 IIYNEVNMWVPKJD-UHFFFAOYSA-N 0.000 claims 1
- NSFKQWZKLQUICF-UHFFFAOYSA-N 7,8-dimethoxy-3-(2-methylsulfanylethyl)-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one;3-(1h-indol-3-ylmethyl)-7,8-dimethoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(=O)C(CCSC)N=C1C1=CC=CC=C1.C1=2C=C(OC)C(OC)=CC=2NC(=O)C(CC=2C3=CC=CC=C3NC=2)N=C1C1=CC=CC=C1 NSFKQWZKLQUICF-UHFFFAOYSA-N 0.000 claims 1
- KCYRYZYKPWHLIV-UHFFFAOYSA-N BrC1=CC2=C(C(=NCC(N2)=O)C2=CC=C(C=C2)Br)C=C1.BrC1=CC=C(C=C1)C1=NCC(NC2=C1C=C(C(=C2)OC)OC)=O Chemical compound BrC1=CC2=C(C(=NCC(N2)=O)C2=CC=C(C=C2)Br)C=C1.BrC1=CC=C(C=C1)C1=NCC(NC2=C1C=C(C(=C2)OC)OC)=O KCYRYZYKPWHLIV-UHFFFAOYSA-N 0.000 claims 1
- MSXQQBHAMHZOSF-UHFFFAOYSA-N C(C)OC=1C(=CC2=C(C(=NCC(N2)=O)C2=CC=CC=C2)C1)OCC.C(C1=CC=CC=C1)N1C(CN=C(C2=C1C=C(C(=C2)OC)OC)C2=CC=CC=C2)=O Chemical compound C(C)OC=1C(=CC2=C(C(=NCC(N2)=O)C2=CC=CC=C2)C1)OCC.C(C1=CC=CC=C1)N1C(CN=C(C2=C1C=C(C(=C2)OC)OC)C2=CC=CC=C2)=O MSXQQBHAMHZOSF-UHFFFAOYSA-N 0.000 claims 1
- GJBQXRBJGJSZGQ-UHFFFAOYSA-N C(C)OC=1C(=CC2=C(C(=NCC(N2CC)=O)C2=CC=CC=C2)C1)OCC.C(C)OC=1C(=CC2=C(C(=NCC(N2C)=O)C2=CC=CC=C2)C1)OCC Chemical compound C(C)OC=1C(=CC2=C(C(=NCC(N2CC)=O)C2=CC=CC=C2)C1)OCC.C(C)OC=1C(=CC2=C(C(=NCC(N2C)=O)C2=CC=CC=C2)C1)OCC GJBQXRBJGJSZGQ-UHFFFAOYSA-N 0.000 claims 1
- RGZATWPGZGJBNA-UHFFFAOYSA-N C(C1=CC=CC=C1)C1C(NC2=C(C(=N1)C1=CC=CC=C1)C=C(C(=C2)OC)OC)=O.COC=2C(=CC1=C(C(=NC(C(N1)=O)CC(C)C)C1=CC=CC=C1)C2)OC Chemical compound C(C1=CC=CC=C1)C1C(NC2=C(C(=N1)C1=CC=CC=C1)C=C(C(=C2)OC)OC)=O.COC=2C(=CC1=C(C(=NC(C(N1)=O)CC(C)C)C1=CC=CC=C1)C2)OC RGZATWPGZGJBNA-UHFFFAOYSA-N 0.000 claims 1
- ALCIOTMJXMIVGN-UHFFFAOYSA-N C(C1=CC=CC=C1)C1C(NC2=C(C(=N1)C1=CC=CC=C1)C=C(C(=C2)OCC)OC)=O.C2(=CC=CC=C2)C2C(NC1=C(C(=N2)C2=CC=CC=C2)C=C(C(=C1)OCC)OC)=O Chemical compound C(C1=CC=CC=C1)C1C(NC2=C(C(=N1)C1=CC=CC=C1)C=C(C(=C2)OCC)OC)=O.C2(=CC=CC=C2)C2C(NC1=C(C(=N2)C2=CC=CC=C2)C=C(C(=C1)OCC)OC)=O ALCIOTMJXMIVGN-UHFFFAOYSA-N 0.000 claims 1
- BVJHNHRFUUTGBH-UHFFFAOYSA-N COC=1C(=CC2=C(C(=NCC(N2)=O)C2=CC=CC=C2)C1)OC.COC=1C=CC2=C(C(=NCC(N2)=O)C2=CC(=CC=C2)C(F)(F)F)C1 Chemical compound COC=1C(=CC2=C(C(=NCC(N2)=O)C2=CC=CC=C2)C1)OC.COC=1C=CC2=C(C(=NCC(N2)=O)C2=CC(=CC=C2)C(F)(F)F)C1 BVJHNHRFUUTGBH-UHFFFAOYSA-N 0.000 claims 1
- MIRKNYSWZBBCFK-RRABGKBLSA-N COC=1C(=CC2=C(C(=NCC(N2C)=O)C#CC2=CC=CC=C2)C1)OC.COC=1C(=CC2=C(C(=NCC(N2C)=O)\C=C\C2=CC=CC=C2)C1)OC Chemical compound COC=1C(=CC2=C(C(=NCC(N2C)=O)C#CC2=CC=CC=C2)C1)OC.COC=1C(=CC2=C(C(=NCC(N2C)=O)\C=C\C2=CC=CC=C2)C1)OC MIRKNYSWZBBCFK-RRABGKBLSA-N 0.000 claims 1
- AGPDUKNQLNXZAI-UHFFFAOYSA-N ClC1=C(CC2C(N(C3=C(C(=N2)C2=CC=CC=C2)C=C(C(=C3)OC)OC)CC)=O)C=C(C=C1)Cl.ClC1=C(CC3C(N(C2=C(C(=N3)C3=CC=CC=C3)C=C(C(=C2)OC)OC)CC)=O)C=CC(=C1)Cl Chemical compound ClC1=C(CC2C(N(C3=C(C(=N2)C2=CC=CC=C2)C=C(C(=C3)OC)OC)CC)=O)C=C(C=C1)Cl.ClC1=C(CC3C(N(C2=C(C(=N3)C3=CC=CC=C3)C=C(C(=C2)OC)OC)CC)=O)C=CC(=C1)Cl AGPDUKNQLNXZAI-UHFFFAOYSA-N 0.000 claims 1
- XPCPMRHERAWHIA-UHFFFAOYSA-N ClC1=CC=C(C=C1)C1=NN(C(CC2=C1C=C(C(=C2)OC)OC)=O)C.COC=2C(=CC1=C(CC(N(N=C1C1=CC3=CC=CC=C3C=C1)C)=O)C2)OC Chemical compound ClC1=CC=C(C=C1)C1=NN(C(CC2=C1C=C(C(=C2)OC)OC)=O)C.COC=2C(=CC1=C(CC(N(N=C1C1=CC3=CC=CC=C3C=C1)C)=O)C2)OC XPCPMRHERAWHIA-UHFFFAOYSA-N 0.000 claims 1
- 229910019567 Re Re Inorganic materials 0.000 claims 1
- DXZDEAJXVCLRLE-UHFFFAOYSA-N azepin-2-one Chemical compound O=C1C=CC=CC=N1 DXZDEAJXVCLRLE-UHFFFAOYSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 181
- 239000000047 product Substances 0.000 description 177
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 99
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 46
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- 238000004587 chromatography analysis Methods 0.000 description 35
- 239000000243 solution Substances 0.000 description 32
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 29
- HXBMIQJOSHZCFX-UHFFFAOYSA-N 1-(bromomethyl)-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1CBr HXBMIQJOSHZCFX-UHFFFAOYSA-N 0.000 description 27
- 239000012298 atmosphere Substances 0.000 description 25
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 230000015572 biosynthetic process Effects 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- 238000003786 synthesis reaction Methods 0.000 description 22
- 239000000377 silicon dioxide Substances 0.000 description 21
- WNMYELHTHAILAM-UHFFFAOYSA-N (2-amino-4,5-dimethoxyphenyl)-phenylmethanone Chemical compound C1=C(OC)C(OC)=CC(N)=C1C(=O)C1=CC=CC=C1 WNMYELHTHAILAM-UHFFFAOYSA-N 0.000 description 20
- 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 description 19
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 19
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000000460 chlorine Substances 0.000 description 17
- ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 description 16
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 16
- VGESKMFUGWXWCQ-UHFFFAOYSA-N 5-(4-bromophenyl)-7,8-dimethoxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(=O)CN=C1C1=CC=C(Br)C=C1 VGESKMFUGWXWCQ-UHFFFAOYSA-N 0.000 description 16
- 101150065749 Churc1 gene Proteins 0.000 description 16
- 102100038239 Protein Churchill Human genes 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
- 239000000843 powder Substances 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- GIUTUZDGHNZVIA-UHFFFAOYSA-N 2-(ethylamino)acetic acid;hydrochloride Chemical compound Cl.CCNCC(O)=O GIUTUZDGHNZVIA-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000000284 extract Substances 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 10
- 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 10
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 9
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 9
- LGDHZCLREKIGKJ-UHFFFAOYSA-N 3,4-dimethoxyaniline Chemical compound COC1=CC=C(N)C=C1OC LGDHZCLREKIGKJ-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- NNNYJKWZQDHNLB-UHFFFAOYSA-N 5-(4-bromophenyl)-1-ethyl-7,8-dimethoxy-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CC)C2=CC(OC)=C(OC)C=C2C=1C1=CC=C(Br)C=C1 NNNYJKWZQDHNLB-UHFFFAOYSA-N 0.000 description 7
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- RBIMGKPHNCHXMS-UHFFFAOYSA-N 7,8-diethoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OCC)C(OCC)=CC=2NC(=O)CN=C1C1=CC=CC=C1 RBIMGKPHNCHXMS-UHFFFAOYSA-N 0.000 description 6
- JPTWVKXRRJCVIB-UHFFFAOYSA-N 7,8-dimethoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(=O)CN=C1C1=CC=CC=C1 JPTWVKXRRJCVIB-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 6
- 101100135868 Dictyostelium discoideum pde3 gene Proteins 0.000 description 6
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 229940095074 cyclic amp Drugs 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 208000027866 inflammatory disease Diseases 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- KBQFSUZPDHZXDF-UHFFFAOYSA-N (2-amino-4,5-diethoxyphenyl)-phenylmethanone Chemical compound C1=C(OCC)C(OCC)=CC(N)=C1C(=O)C1=CC=CC=C1 KBQFSUZPDHZXDF-UHFFFAOYSA-N 0.000 description 5
- IZQZWZCYWZVNLM-UHFFFAOYSA-N (2-amino-4-ethoxy-5-methoxyphenyl)-phenylmethanone Chemical compound C1=C(OC)C(OCC)=CC(N)=C1C(=O)C1=CC=CC=C1 IZQZWZCYWZVNLM-UHFFFAOYSA-N 0.000 description 5
- DPZCMNIHVJZAFB-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CC)C2=CC(OC)=C(OC)C=C2C=1C1=CC=CC=C1 DPZCMNIHVJZAFB-UHFFFAOYSA-N 0.000 description 5
- HFVCJTKFVFFUPZ-UHFFFAOYSA-N 3-[(2-aminophenyl)methyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC=C1N HFVCJTKFVFFUPZ-UHFFFAOYSA-N 0.000 description 5
- 108700012920 TNF Proteins 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- NSNPSJGHTQIXDO-UHFFFAOYSA-N naphthalene-1-carbonyl chloride Chemical compound C1=CC=C2C(C(=O)Cl)=CC=CC2=C1 NSNPSJGHTQIXDO-UHFFFAOYSA-N 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 4
- ZWVMLYRJXORSEP-LURJTMIESA-N (2s)-hexane-1,2,6-triol Chemical compound OCCCC[C@H](O)CO ZWVMLYRJXORSEP-LURJTMIESA-N 0.000 description 4
- UDCXBAXTPRFWEW-INIZCTEOSA-N (3s)-3-(4-aminobutyl)-7,8-dimethoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N([C@@H](CCCCN)C(=O)NC=1C=C(C(=CC=11)OC)OC)=C1C1=CC=CC=C1 UDCXBAXTPRFWEW-INIZCTEOSA-N 0.000 description 4
- IHVGHQMSDGPLJE-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-3-[(2-nitrophenyl)methyl]-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC=C1[N+]([O-])=O IHVGHQMSDGPLJE-UHFFFAOYSA-N 0.000 description 4
- WAXLSETXOXLXDV-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-5-(4-phenylphenyl)-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CC)C2=CC(OC)=C(OC)C=C2C=1C(C=C1)=CC=C1C1=CC=CC=C1 WAXLSETXOXLXDV-UHFFFAOYSA-N 0.000 description 4
- 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 4
- IYPFLJOJKBPBDC-UHFFFAOYSA-N 3-[(3-bromophenyl)methyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC(Br)=C1 IYPFLJOJKBPBDC-UHFFFAOYSA-N 0.000 description 4
- GHXSUOZEPFBJNH-UHFFFAOYSA-N 3-[(4-bromophenyl)methyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=C(Br)C=C1 GHXSUOZEPFBJNH-UHFFFAOYSA-N 0.000 description 4
- METKHLFZKUXAPB-UHFFFAOYSA-N 5-(3-bromophenyl)-1-ethyl-7,8-dimethoxy-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CC)C2=CC(OC)=C(OC)C=C2C=1C1=CC=CC(Br)=C1 METKHLFZKUXAPB-UHFFFAOYSA-N 0.000 description 4
- OUPKYSJIOYLADC-UHFFFAOYSA-N 5-(3-bromophenyl)-7,8-dimethoxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(=O)CN=C1C1=CC=CC(Br)=C1 OUPKYSJIOYLADC-UHFFFAOYSA-N 0.000 description 4
- JAFBIGGLFRQXES-UHFFFAOYSA-N 7,8-diethoxy-1-ethyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OCC)C(OCC)=CC=2N(CC)C(=O)CN=C1C1=CC=CC=C1 JAFBIGGLFRQXES-UHFFFAOYSA-N 0.000 description 4
- QLVZFXHPKMZWMK-UHFFFAOYSA-N 7,8-dimethoxy-1-methyl-3,4-dihydro-1,4-benzodiazepine-2,5-dione Chemical compound CN1C(=O)CNC(=O)C2=C1C=C(OC)C(OC)=C2 QLVZFXHPKMZWMK-UHFFFAOYSA-N 0.000 description 4
- PEACRWGRSQUWBX-UHFFFAOYSA-N 7-methoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(OC)=CC=C2NC(=O)CN=C1C1=CC=CC=C1 PEACRWGRSQUWBX-UHFFFAOYSA-N 0.000 description 4
- SITGILNKAQWBIB-UHFFFAOYSA-N 8-ethoxy-7-methoxy-3,5-diphenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OCC)=CC=2NC(=O)C(C=2C=CC=CC=2)N=C1C1=CC=CC=C1 SITGILNKAQWBIB-UHFFFAOYSA-N 0.000 description 4
- RPSHKCWYIAQKRC-UHFFFAOYSA-N 8-ethoxy-7-methoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OCC)=CC=2NC(=O)CN=C1C1=CC=CC=C1 RPSHKCWYIAQKRC-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- PAQVEXAFKDWGOT-UHFFFAOYSA-N prop-2-ynoxymethylbenzene Chemical compound C#CCOCC1=CC=CC=C1 PAQVEXAFKDWGOT-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- PRQNURIVOWEVEP-UHFFFAOYSA-N (2-amino-4,5-dimethoxyphenyl)-(2-bromophenyl)methanone Chemical compound C1=C(OC)C(OC)=CC(N)=C1C(=O)C1=CC=CC=C1Br PRQNURIVOWEVEP-UHFFFAOYSA-N 0.000 description 3
- NFTBFVFOCVDIMD-UHFFFAOYSA-N (2-amino-4-bromophenyl)-(4-bromophenyl)methanone Chemical compound NC1=CC(Br)=CC=C1C(=O)C1=CC=C(Br)C=C1 NFTBFVFOCVDIMD-UHFFFAOYSA-N 0.000 description 3
- UKDOBSYQTBSUQR-UHFFFAOYSA-N (2-amino-5-methoxyphenyl)-phenylmethanone Chemical compound COC1=CC=C(N)C(C(=O)C=2C=CC=CC=2)=C1 UKDOBSYQTBSUQR-UHFFFAOYSA-N 0.000 description 3
- DFWFNMPYVHZTMB-FQEVSTJZSA-N (3s)-3-benzyl-7,8-dimethoxy-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound C([C@H]1C(=O)N(C)C=2C=C(C(=CC=2C(C=2C=CC=CC=2)=N1)OC)OC)C1=CC=CC=C1 DFWFNMPYVHZTMB-FQEVSTJZSA-N 0.000 description 3
- ALKQZAYAWNIANE-UHFFFAOYSA-N (6-amino-2,3-dihydro-1,4-benzodioxin-7-yl)-phenylmethanone Chemical compound NC1=CC=2OCCOC=2C=C1C(=O)C1=CC=CC=C1 ALKQZAYAWNIANE-UHFFFAOYSA-N 0.000 description 3
- DTYUTSMRCQYVNW-UHFFFAOYSA-N 1,2-diethoxy-4-nitrobenzene Chemical compound CCOC1=CC=C([N+]([O-])=O)C=C1OCC DTYUTSMRCQYVNW-UHFFFAOYSA-N 0.000 description 3
- LFDSCLOSMHJNJH-UHFFFAOYSA-N 1-(1-benzothiophen-2-yl)-7,8-diethoxy-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OCC)C(OCC)=CC=2CC(=O)N(C)N=C1C1=CC2=CC=CC=C2S1 LFDSCLOSMHJNJH-UHFFFAOYSA-N 0.000 description 3
- MRIYEGFMPBTRHA-UHFFFAOYSA-N 1-(1-benzothiophen-2-yl)-7,8-diethoxy-5-ethyl-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OCC)C(OCC)=CC=2C(CC)C(=O)N(C)N=C1C1=CC2=CC=CC=C2S1 MRIYEGFMPBTRHA-UHFFFAOYSA-N 0.000 description 3
- RXKFGIJSAAGEOS-UHFFFAOYSA-N 1-(2-hydroxyethyl)-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(CCO)C(=O)CN=C1C1=CC=CC=C1 RXKFGIJSAAGEOS-UHFFFAOYSA-N 0.000 description 3
- RBWSNKAIGSTHNQ-UHFFFAOYSA-N 1-(4-bromophenyl)-7,8-dimethoxy-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C1=CC=C(Br)C=C1 RBWSNKAIGSTHNQ-UHFFFAOYSA-N 0.000 description 3
- HULIXCDYHMLUNC-UHFFFAOYSA-N 1-benzyl-7,8-diethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1CN=C(C=2C=CC=CC=2)C=2C=C(OCC)C(OCC)=CC=2N1CC1=CC=CC=C1 HULIXCDYHMLUNC-UHFFFAOYSA-N 0.000 description 3
- DBSPEUQZDHURPN-UHFFFAOYSA-N 1-benzyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1CN=C(C=2C=CC=CC=2)C=2C=C(OC)C(OC)=CC=2N1CC1=CC=CC=C1 DBSPEUQZDHURPN-UHFFFAOYSA-N 0.000 description 3
- HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 description 3
- XEGSKHDKMYFPCD-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-3-[(4-methylphenyl)methyl]-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=C(C)C=C1 XEGSKHDKMYFPCD-UHFFFAOYSA-N 0.000 description 3
- JIIPPKMAHMFTQN-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-5-[4-(2-phenylethyl)phenyl]-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CC)C2=CC(OC)=C(OC)C=C2C=1C(C=C1)=CC=C1CCC1=CC=CC=C1 JIIPPKMAHMFTQN-UHFFFAOYSA-N 0.000 description 3
- DNVLRCDPCFXSAQ-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-5-phenyl-3-[(4-phenylphenyl)methyl]-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC(C=C1)=CC=C1C1=CC=CC=C1 DNVLRCDPCFXSAQ-UHFFFAOYSA-N 0.000 description 3
- PAGHLFPRFADKFP-UHFFFAOYSA-N 2-ethoxy-1-methoxy-4-nitrobenzene Chemical compound CCOC1=CC([N+]([O-])=O)=CC=C1OC PAGHLFPRFADKFP-UHFFFAOYSA-N 0.000 description 3
- WRVUNDXYONRSPO-UHFFFAOYSA-N 3-(1h-indol-3-ylmethyl)-7,8-dimethoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(=O)C(CC=2C3=CC=CC=C3NC=2)N=C1C1=CC=CC=C1 WRVUNDXYONRSPO-UHFFFAOYSA-N 0.000 description 3
- KPXOZBSLTVTKAJ-UHFFFAOYSA-N 3-(3-hydroxypropyl)-7,8-dimethoxy-1-phenyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(CCCO)N=C1C1=CC=CC=C1 KPXOZBSLTVTKAJ-UHFFFAOYSA-N 0.000 description 3
- SJDHKJJWGILDIO-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC=C1Cl SJDHKJJWGILDIO-UHFFFAOYSA-N 0.000 description 3
- IQAKUMDPJRAVIK-UHFFFAOYSA-N 3-[(4-chlorophenyl)methyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=C(Cl)C=C1 IQAKUMDPJRAVIK-UHFFFAOYSA-N 0.000 description 3
- HMGUXGCHAZNRKQ-UHFFFAOYSA-N 3-[[2-(aminomethyl)phenyl]methyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC=C1CN HMGUXGCHAZNRKQ-UHFFFAOYSA-N 0.000 description 3
- RGGVIONSFAYEAU-UHFFFAOYSA-N 3-benzyl-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC=C1 RGGVIONSFAYEAU-UHFFFAOYSA-N 0.000 description 3
- USUFZAYMDBWDIX-UHFFFAOYSA-N 3-benzyl-7,8-diethoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N1=C(C=2C=CC=CC=2)C=2C=C(OCC)C(OCC)=CC=2NC(=O)C1CC1=CC=CC=C1 USUFZAYMDBWDIX-UHFFFAOYSA-N 0.000 description 3
- ZIDNWYSLKVVCCR-UHFFFAOYSA-N 3-benzyl-8-ethoxy-1-ethyl-7-methoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound N1=C(C=2C=CC=CC=2)C=2C=C(OC)C(OCC)=CC=2N(CC)C(=O)C1CC1=CC=CC=C1 ZIDNWYSLKVVCCR-UHFFFAOYSA-N 0.000 description 3
- BWIFWMKTQKKQAD-UHFFFAOYSA-N 3-benzyl-8-ethoxy-7-methoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N1=C(C=2C=CC=CC=2)C=2C=C(OC)C(OCC)=CC=2NC(=O)C1CC1=CC=CC=C1 BWIFWMKTQKKQAD-UHFFFAOYSA-N 0.000 description 3
- DHPLXTWXNFZRNP-UHFFFAOYSA-N 3-dodecyl-7,8-dimethoxy-1-phenyl-5h-2,3-benzodiazepin-4-one Chemical compound C12=CC(OC)=C(OC)C=C2CC(=O)N(CCCCCCCCCCCC)N=C1C1=CC=CC=C1 DHPLXTWXNFZRNP-UHFFFAOYSA-N 0.000 description 3
- JEKQFQAZBUJHAU-UHFFFAOYSA-N 3-ethyl-7,8-dimethoxy-1-phenyl-5h-2,3-benzodiazepin-4-one Chemical compound C12=CC(OC)=C(OC)C=C2CC(=O)N(CC)N=C1C1=CC=CC=C1 JEKQFQAZBUJHAU-UHFFFAOYSA-N 0.000 description 3
- MSNOOZDMPWOJAH-UHFFFAOYSA-N 5-(1h-indol-2-yl)-7,8-dimethoxy-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC2=CC=CC=C2N1 MSNOOZDMPWOJAH-UHFFFAOYSA-N 0.000 description 3
- IXVZTSJPZJXQPY-UHFFFAOYSA-N 5-(1h-indol-5-yl)-7,8-dimethoxy-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC=C(NC=C2)C2=C1 IXVZTSJPZJXQPY-UHFFFAOYSA-N 0.000 description 3
- CDFUJPZXXWWWOA-UHFFFAOYSA-N 5-(3,4-dimethoxyphenyl)-7,8-dimethoxy-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1C1=NCC(=O)N(C)C2=CC(OC)=C(OC)C=C12 CDFUJPZXXWWWOA-UHFFFAOYSA-N 0.000 description 3
- NXYWSJCICDUCEQ-UHFFFAOYSA-N 5-(3-bromophenyl)-7,8-dimethoxy-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC=CC(Br)=C1 NXYWSJCICDUCEQ-UHFFFAOYSA-N 0.000 description 3
- KDLPXRWGSXHDDB-UHFFFAOYSA-N 5-(4-bromophenyl)-7,8-dimethoxy-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC=C(Br)C=C1 KDLPXRWGSXHDDB-UHFFFAOYSA-N 0.000 description 3
- JMAIHPNISRFSSW-UHFFFAOYSA-N 6,7-dimethoxy-1-methyl-3,1-benzoxazine-2,4-dione Chemical compound CN1C(=O)OC(=O)C2=C1C=C(OC)C(OC)=C2 JMAIHPNISRFSSW-UHFFFAOYSA-N 0.000 description 3
- UMPZEODMQVWKCC-UHFFFAOYSA-N 7,8-diethoxy-3-methyl-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OCC)C(OCC)=CC=2NC(=O)C(C)N=C1C1=CC=CC=C1 UMPZEODMQVWKCC-UHFFFAOYSA-N 0.000 description 3
- JEFSPAVNHMTXPS-UHFFFAOYSA-N 7,8-dimethoxy-1-[4-(4-methoxyphenyl)phenyl]-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CC=C(C=2C3=CC(OC)=C(OC)C=C3CC(=O)N(C)N=2)C=C1 JEFSPAVNHMTXPS-UHFFFAOYSA-N 0.000 description 3
- LTCMYALFHUJZML-UHFFFAOYSA-N 7,8-dimethoxy-1-methyl-5-(2-methylphenyl)-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC=CC=C1C LTCMYALFHUJZML-UHFFFAOYSA-N 0.000 description 3
- TVYHGRSGZGTTLT-UHFFFAOYSA-N 7,8-dimethoxy-1-methyl-5-(2-phenylethyl)-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1CCC1=CC=CC=C1 TVYHGRSGZGTTLT-UHFFFAOYSA-N 0.000 description 3
- JNSUWWWQGPXZBN-UHFFFAOYSA-N 7,8-dimethoxy-1-methyl-5-(2-phenylethynyl)-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C#CC1=CC=CC=C1 JNSUWWWQGPXZBN-UHFFFAOYSA-N 0.000 description 3
- QNTRIAZKHXMTKW-MDZDMXLPSA-N 7,8-dimethoxy-1-methyl-5-[(e)-2-phenylethenyl]-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1\C=C\C1=CC=CC=C1 QNTRIAZKHXMTKW-MDZDMXLPSA-N 0.000 description 3
- UHYVPWDNMXWRNH-UHFFFAOYSA-N 7,8-dimethoxy-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC=CC=C1 UHYVPWDNMXWRNH-UHFFFAOYSA-N 0.000 description 3
- XRGUXDBXZXGOMC-UHFFFAOYSA-N 7,8-dimethoxy-1-methyl-5-piperidin-1-yl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1N1CCCCC1 XRGUXDBXZXGOMC-UHFFFAOYSA-N 0.000 description 3
- ZYNNEDGJJJTFMD-UHFFFAOYSA-N 7,8-dimethoxy-1-methyl-5-pyridin-4-yl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC=NC=C1 ZYNNEDGJJJTFMD-UHFFFAOYSA-N 0.000 description 3
- RUIDJCJYWFYLGT-UHFFFAOYSA-N 7,8-dimethoxy-1-methyl-5-thiophen-2-yl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC=CS1 RUIDJCJYWFYLGT-UHFFFAOYSA-N 0.000 description 3
- BRMKLBBTWJKINP-UHFFFAOYSA-N 7,8-dimethoxy-3-(2-methylpropyl)-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(=O)C(CC(C)C)N=C1C1=CC=CC=C1 BRMKLBBTWJKINP-UHFFFAOYSA-N 0.000 description 3
- DMPHKSRLDAUROB-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-1-[4-(2-methylphenyl)phenyl]-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=CC=C1C DMPHKSRLDAUROB-UHFFFAOYSA-N 0.000 description 3
- CCEIGWZSQJRJEM-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-1-[4-(4-methylphenyl)phenyl]-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=C(C)C=C1 CCEIGWZSQJRJEM-UHFFFAOYSA-N 0.000 description 3
- QTGCBGWMWURTNG-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-1-naphthalen-1-yl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C1=CC=CC2=CC=CC=C12 QTGCBGWMWURTNG-UHFFFAOYSA-N 0.000 description 3
- NDGQQCWWACOEMD-UHFFFAOYSA-N 7,8-dimethoxy-5-(2-methoxyphenyl)-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC=CC=C1OC NDGQQCWWACOEMD-UHFFFAOYSA-N 0.000 description 3
- DJQGTGLYMQOBAQ-UHFFFAOYSA-N 7,8-dimethoxy-5-(6-methoxynaphthalen-2-yl)-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1C(=O)N(C)C2=CC(OC)=C(OC)C=C2C(C2=CC3=CC=C(C=C3C=C2)OC)=N1 DJQGTGLYMQOBAQ-UHFFFAOYSA-N 0.000 description 3
- ZNGYNNFXIKDGEM-UHFFFAOYSA-N 8-bromo-5-(4-bromophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=CC(Br)=CC=C1C1=NCC(=O)NC2=CC(Br)=CC=C12 ZNGYNNFXIKDGEM-UHFFFAOYSA-N 0.000 description 3
- GETNXSJEFJMXMA-UHFFFAOYSA-N 8-ethoxy-1-ethyl-7-methoxy-3,5-diphenyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OCC)=CC=2N(CC)C(=O)C(C=2C=CC=CC=2)N=C1C1=CC=CC=C1 GETNXSJEFJMXMA-UHFFFAOYSA-N 0.000 description 3
- RVPJDPWFXUFDQJ-UHFFFAOYSA-N 8-ethoxy-7-methoxy-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OCC)=CC=2N(C)C(=O)CN=C1C1=CC=CC=C1 RVPJDPWFXUFDQJ-UHFFFAOYSA-N 0.000 description 3
- GVWCSZJBGUTVJA-UHFFFAOYSA-N 8-methoxy-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound C=1C(OC)=CC=C2C=1N(C)C(=O)CN=C2C1=CC=CC=C1 GVWCSZJBGUTVJA-UHFFFAOYSA-N 0.000 description 3
- 101100135859 Dictyostelium discoideum regA gene Proteins 0.000 description 3
- 101150085511 PEDS1 gene Proteins 0.000 description 3
- 101150003085 Pdcl gene Proteins 0.000 description 3
- 102100037592 Plasmanylethanolamine desaturase Human genes 0.000 description 3
- 101100082606 Plasmodium falciparum (isolate 3D7) PDEbeta gene Proteins 0.000 description 3
- 101100135860 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PDE2 gene Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- LKIOIDUSXIBIKG-UHFFFAOYSA-N methyl 12-(7,8-dimethoxy-4-oxo-1-phenyl-5h-2,3-benzodiazepin-3-yl)dodecanoate Chemical compound C12=CC(OC)=C(OC)C=C2CC(=O)N(CCCCCCCCCCCC(=O)OC)N=C1C1=CC=CC=C1 LKIOIDUSXIBIKG-UHFFFAOYSA-N 0.000 description 3
- GSAZXWNBULMSQA-UHFFFAOYSA-N n-[3-[4-(7,8-dimethoxy-3-methyl-4-oxo-5h-2,3-benzodiazepin-1-yl)phenyl]phenyl]acetamide Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=CC(NC(C)=O)=C1 GSAZXWNBULMSQA-UHFFFAOYSA-N 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229920003199 poly(diethylsiloxane) Polymers 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- HXTDCSNZXQTBAD-UHFFFAOYSA-N (2-amino-4,5-dimethoxyphenyl)-(3-bromophenyl)methanone Chemical compound C1=C(OC)C(OC)=CC(N)=C1C(=O)C1=CC=CC(Br)=C1 HXTDCSNZXQTBAD-UHFFFAOYSA-N 0.000 description 2
- WFQVKQBWROLGIR-UHFFFAOYSA-N (2-amino-4,5-dimethoxyphenyl)-(4-bromophenyl)methanone Chemical compound C1=C(OC)C(OC)=CC(N)=C1C(=O)C1=CC=C(Br)C=C1 WFQVKQBWROLGIR-UHFFFAOYSA-N 0.000 description 2
- GFHWOKUXKUUKQJ-UHFFFAOYSA-N (2-amino-4-methoxyphenyl)-phenylmethanone Chemical compound NC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 GFHWOKUXKUUKQJ-UHFFFAOYSA-N 0.000 description 2
- TWJWFECRFISHHB-UHFFFAOYSA-N (2-amino-5-ethoxy-4-methoxyphenyl)-phenylmethanone Chemical compound C1=C(OC)C(OCC)=CC(C(=O)C=2C=CC=CC=2)=C1N TWJWFECRFISHHB-UHFFFAOYSA-N 0.000 description 2
- NAKVSMGYGQEWPC-UHFFFAOYSA-N (2-amino-5-hydroxy-4-methoxyphenyl)-phenylmethanone Chemical compound C1=C(O)C(OC)=CC(N)=C1C(=O)C1=CC=CC=C1 NAKVSMGYGQEWPC-UHFFFAOYSA-N 0.000 description 2
- YFUREOKAZJCOMQ-UHFFFAOYSA-N (2-amino-5-iodophenyl)-[3-(trifluoromethyl)phenyl]methanone Chemical compound NC1=CC=C(I)C=C1C(=O)C1=CC=CC(C(F)(F)F)=C1 YFUREOKAZJCOMQ-UHFFFAOYSA-N 0.000 description 2
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 2
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 2
- OBQRODBYVNIZJU-UHFFFAOYSA-N (4-acetylphenyl)boronic acid Chemical compound CC(=O)C1=CC=C(B(O)O)C=C1 OBQRODBYVNIZJU-UHFFFAOYSA-N 0.000 description 2
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 2
- BAVAZRNEAWBRLO-UHFFFAOYSA-N 1,2-benzodiazepin-4-one Chemical compound O=C1C=NN=C2C=CC=CC2=C1 BAVAZRNEAWBRLO-UHFFFAOYSA-N 0.000 description 2
- ZCVXDIHBWICLSH-UHFFFAOYSA-N 1-(1-benzothiophen-2-yl)-7,8-diethoxy-5-ethyl-3,5-dihydro-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OCC)C(OCC)=CC=2C(CC)C(=O)NN=C1C1=CC2=CC=CC=C2S1 ZCVXDIHBWICLSH-UHFFFAOYSA-N 0.000 description 2
- LTSMOMLGNZXVPA-UHFFFAOYSA-N 1-(1-benzothiophen-2-yl)-7,8-dimethoxy-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C1=CC2=CC=CC=C2S1 LTSMOMLGNZXVPA-UHFFFAOYSA-N 0.000 description 2
- HHEQXECGPUADEG-UHFFFAOYSA-N 1-(1-benzothiophen-2-yl)-7,8-dimethoxy-5,5-dimethyl-3h-2,3-benzodiazepin-4-one Chemical compound C1=C(OC)C(OC)=CC2=C1C(C)(C)C(=O)NN=C2C1=CC2=CC=CC=C2S1 HHEQXECGPUADEG-UHFFFAOYSA-N 0.000 description 2
- KQNBRMUBPRGXSL-UHFFFAOYSA-N 1-(bromomethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CBr)C=C1 KQNBRMUBPRGXSL-UHFFFAOYSA-N 0.000 description 2
- VQJSSLAQHFVHJH-UHFFFAOYSA-N 1-[4-(3-acetylphenyl)phenyl]-7,8-dimethoxy-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=CC(C(C)=O)=C1 VQJSSLAQHFVHJH-UHFFFAOYSA-N 0.000 description 2
- ZFBLKBAGSSRDAP-UHFFFAOYSA-N 1-[4-(furan-2-yl)phenyl]-7,8-dimethoxy-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=CO1 ZFBLKBAGSSRDAP-UHFFFAOYSA-N 0.000 description 2
- OWTKSBICDHTGEY-UHFFFAOYSA-N 1-[4-[3,5-bis(trifluoromethyl)phenyl]phenyl]-7,8-dimethoxy-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 OWTKSBICDHTGEY-UHFFFAOYSA-N 0.000 description 2
- FRLQEZGVOSOIOV-UHFFFAOYSA-N 1-benzyl-7,8-dimethoxy-3,4-dihydro-1,4-benzodiazepine-2,5-dione Chemical compound O=C1CNC(=O)C=2C=C(OC)C(OC)=CC=2N1CC1=CC=CC=C1 FRLQEZGVOSOIOV-UHFFFAOYSA-N 0.000 description 2
- OUWMQCZHCUEXLS-UHFFFAOYSA-N 1-ethyl-7,8-dihydroxy-5-phenyl-3H-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CC)C2=CC(O)=C(O)C=C2C=1C1=CC=CC=C1 OUWMQCZHCUEXLS-UHFFFAOYSA-N 0.000 description 2
- BJFZFRGUSAEHBG-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-3-[(3-methoxyphenyl)methyl]-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC(OC)=C1 BJFZFRGUSAEHBG-UHFFFAOYSA-N 0.000 description 2
- PKLOQQDQBJEJQS-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-5-phenyl-3-[(3-phenylphenyl)methyl]-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC(C=1)=CC=CC=1C1=CC=CC=C1 PKLOQQDQBJEJQS-UHFFFAOYSA-N 0.000 description 2
- WQQPGMSAJNSWML-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-5-phenyl-3-prop-2-ynyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1C(CC#C)C(=O)N(CC)C2=CC(OC)=C(OC)C=C2C=1C1=CC=CC=C1 WQQPGMSAJNSWML-UHFFFAOYSA-N 0.000 description 2
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- GYYOUAWPCTYJIG-UHFFFAOYSA-N 2-(2-hydrazinyl-2-oxoethyl)-4,5-dimethoxybenzoic acid Chemical compound COC1=CC(CC(=O)NN)=C(C(O)=O)C=C1OC GYYOUAWPCTYJIG-UHFFFAOYSA-N 0.000 description 2
- QGXNHCXKWFNKCG-UHFFFAOYSA-N 2-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=CC=C1C#N QGXNHCXKWFNKCG-UHFFFAOYSA-N 0.000 description 2
- NOUUHGZLGUYQON-UHFFFAOYSA-N 2-(carboxymethyl)-4,5-dimethoxybenzoic acid Chemical compound COC1=CC(CC(O)=O)=C(C(O)=O)C=C1OC NOUUHGZLGUYQON-UHFFFAOYSA-N 0.000 description 2
- FFRMJYMNIWFUCU-UHFFFAOYSA-N 2-[(1-ethyl-7,8-dimethoxy-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl)methyl]benzonitrile Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC=C1C#N FFRMJYMNIWFUCU-UHFFFAOYSA-N 0.000 description 2
- BNICRIHXXAVPBH-UHFFFAOYSA-N 2-[2-(1-benzothiophene-2-carbonyl)-4,5-diethoxyphenyl]ethyl pentanoate Chemical compound CCCCC(=O)OCCC1=CC(OCC)=C(OCC)C=C1C(=O)C1=CC2=CC=CC=C2S1 BNICRIHXXAVPBH-UHFFFAOYSA-N 0.000 description 2
- IKYZLUAAOLUOFW-UHFFFAOYSA-N 3,4-diethoxyaniline Chemical compound CCOC1=CC=C(N)C=C1OCC IKYZLUAAOLUOFW-UHFFFAOYSA-N 0.000 description 2
- CSBZWVNBMFQYTQ-UHFFFAOYSA-N 3,5-dibenzyl-7,8-dimethoxy-1-phenyl-5h-2,3-benzodiazepin-4-one Chemical compound O=C1N(CC=2C=CC=CC=2)N=C(C=2C=CC=CC=2)C=2C=C(OC)C(OC)=CC=2C1CC1=CC=CC=C1 CSBZWVNBMFQYTQ-UHFFFAOYSA-N 0.000 description 2
- ZEKZWMAZSZKUMS-UHFFFAOYSA-N 3-(1-benzyl-4-hydroxypiperidin-4-yl)-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1C(CC1)(O)CCN1CC1=CC=CC=C1 ZEKZWMAZSZKUMS-UHFFFAOYSA-N 0.000 description 2
- ASJOGLHFOISWHA-UHFFFAOYSA-N 3-(1h-imidazol-5-ylmethyl)-7,8-dimethoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N1=C(C=2C=CC=CC=2)C=2C=C(OC)C(OC)=CC=2NC(=O)C1CC1=CNC=N1 ASJOGLHFOISWHA-UHFFFAOYSA-N 0.000 description 2
- CVKOOKPNCVYHNY-UHFFFAOYSA-N 3-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=CC(C#N)=C1 CVKOOKPNCVYHNY-UHFFFAOYSA-N 0.000 description 2
- OGOBINRVCUWLGN-UHFFFAOYSA-N 3-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)C1=CC=CC(C#N)=C1 OGOBINRVCUWLGN-UHFFFAOYSA-N 0.000 description 2
- NIIXULBXOKLVNO-UHFFFAOYSA-N 3-[(2,4-dichlorophenyl)methyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=C(Cl)C=C1Cl NIIXULBXOKLVNO-UHFFFAOYSA-N 0.000 description 2
- KAIVUBLYJNIMRK-UHFFFAOYSA-N 3-[(2,5-dichlorophenyl)methyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC(Cl)=CC=C1Cl KAIVUBLYJNIMRK-UHFFFAOYSA-N 0.000 description 2
- OHFLKROAUPNRAB-UHFFFAOYSA-N 3-[(2-bromophenyl)methyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC=C1Br OHFLKROAUPNRAB-UHFFFAOYSA-N 0.000 description 2
- ZFYBWAVBGULGRO-UHFFFAOYSA-N 3-[[3-(aminomethyl)phenyl]methyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC(CN)=C1 ZFYBWAVBGULGRO-UHFFFAOYSA-N 0.000 description 2
- BBIXYYCWUHISQM-UHFFFAOYSA-N 3-benzyl-7,8-dimethoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N1=C(C=2C=CC=CC=2)C=2C=C(OC)C(OC)=CC=2NC(=O)C1CC1=CC=CC=C1 BBIXYYCWUHISQM-UHFFFAOYSA-N 0.000 description 2
- BEFRVRWYSAQETM-UHFFFAOYSA-N 3-ethoxy-4-methoxyaniline Chemical compound CCOC1=CC(N)=CC=C1OC BEFRVRWYSAQETM-UHFFFAOYSA-N 0.000 description 2
- HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 2
- UKYPTPMYUZTCNB-UHFFFAOYSA-N 5-(1-benzofuran-2-yl)-7,8-dimethoxy-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC2=CC=CC=C2O1 UKYPTPMYUZTCNB-UHFFFAOYSA-N 0.000 description 2
- BIFHZUCGQTZVPT-UHFFFAOYSA-N 5-(1-benzothiophen-2-yl)-7,8-dimethoxy-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC2=CC=CC=C2S1 BIFHZUCGQTZVPT-UHFFFAOYSA-N 0.000 description 2
- ZOKLVYBIKSORDC-UHFFFAOYSA-N 5-(2-bromophenyl)-7,8-dimethoxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(=O)CN=C1C1=CC=CC=C1Br ZOKLVYBIKSORDC-UHFFFAOYSA-N 0.000 description 2
- ONHNOXFEIIWTCK-UHFFFAOYSA-N 5-(4-acetylphenyl)-7,8-dimethoxy-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC=C(C(C)=O)C=C1 ONHNOXFEIIWTCK-UHFFFAOYSA-N 0.000 description 2
- HAOKXTLRQQFEST-UHFFFAOYSA-N 5-(4-fluorophenyl)-7,8-dimethoxy-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC=C(F)C=C1 HAOKXTLRQQFEST-UHFFFAOYSA-N 0.000 description 2
- ZRSAERBPVHGIPW-UHFFFAOYSA-N 5-(furan-2-yl)-7,8-dimethoxy-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC=CO1 ZRSAERBPVHGIPW-UHFFFAOYSA-N 0.000 description 2
- XEZRPKWKRMROBK-UHFFFAOYSA-N 6,7-dimethoxy-1,4-dihydroisochromen-3-one Chemical compound C1OC(=O)CC2=C1C=C(OC)C(OC)=C2 XEZRPKWKRMROBK-UHFFFAOYSA-N 0.000 description 2
- SHWCMBUPQTWNES-UHFFFAOYSA-N 6,7-dimethoxy-1h-3,1-benzoxazine-2,4-dione Chemical compound N1C(=O)OC(=O)C2=C1C=C(OC)C(OC)=C2 SHWCMBUPQTWNES-UHFFFAOYSA-N 0.000 description 2
- AATKSLBQUSPGJS-UHFFFAOYSA-N 6,7-dimethoxy-4h-isochromene-1,3-dione Chemical class C1C(=O)OC(=O)C2=C1C=C(OC)C(OC)=C2 AATKSLBQUSPGJS-UHFFFAOYSA-N 0.000 description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
- NALNPEFGPDBRCS-UHFFFAOYSA-N 7,8-diethoxy-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OCC)C(OCC)=CC=2N(C)C(=O)CN=C1C1=CC=CC=C1 NALNPEFGPDBRCS-UHFFFAOYSA-N 0.000 description 2
- IWMABSNJKZRWFO-UHFFFAOYSA-N 7,8-dimethoxy-1-[4-(3-methoxyphenyl)phenyl]-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound COC1=CC=CC(C=2C=CC(=CC=2)C=2C3=CC(OC)=C(OC)C=C3CC(=O)N(C)N=2)=C1 IWMABSNJKZRWFO-UHFFFAOYSA-N 0.000 description 2
- FZQNVHBWKUYPMO-UHFFFAOYSA-N 7,8-dimethoxy-1-methyl-5-(6-phenylmethoxynaphthalen-2-yl)-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C(C=C1C=C2)=CC=C1C=C2OCC1=CC=CC=C1 FZQNVHBWKUYPMO-UHFFFAOYSA-N 0.000 description 2
- RVDWKXIFMDTSOO-UHFFFAOYSA-N 7,8-dimethoxy-1-propyl-3,4-dihydro-1,4-benzodiazepine-2,5-dione Chemical compound O=C1NCC(=O)N(CCC)C2=CC(OC)=C(OC)C=C21 RVDWKXIFMDTSOO-UHFFFAOYSA-N 0.000 description 2
- RLBVNENZMLRKLR-UHFFFAOYSA-N 7,8-dimethoxy-3,5-dihydro-2h-2,3-benzodiazepine-1,4-dione Chemical compound C1C(=O)NNC(=O)C2=C1C=C(OC)C(OC)=C2 RLBVNENZMLRKLR-UHFFFAOYSA-N 0.000 description 2
- INRWZZJCVLANKR-UHFFFAOYSA-N 7,8-dimethoxy-3-(2-methylsulfanylethyl)-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(=O)C(CCSC)N=C1C1=CC=CC=C1 INRWZZJCVLANKR-UHFFFAOYSA-N 0.000 description 2
- CBZDWXSMWJWFGA-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-1-(4-thiophen-2-ylphenyl)-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=CS1 CBZDWXSMWJWFGA-UHFFFAOYSA-N 0.000 description 2
- UJSOHZFFVQFFQG-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-1-[4-(3-nitrophenyl)phenyl]-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=CC([N+]([O-])=O)=C1 UJSOHZFFVQFFQG-UHFFFAOYSA-N 0.000 description 2
- ACXGWEHMIUPNGX-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-1-[4-[3-(trifluoromethyl)phenyl]phenyl]-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=CC(C(F)(F)F)=C1 ACXGWEHMIUPNGX-UHFFFAOYSA-N 0.000 description 2
- URRSFRMIDFVNLG-UHFFFAOYSA-N 7,8-dimethoxy-5-(3-methoxyphenyl)-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound COC1=CC=CC(C=2C3=CC(OC)=C(OC)C=C3N(C)C(=O)CN=2)=C1 URRSFRMIDFVNLG-UHFFFAOYSA-N 0.000 description 2
- DUMABVVGUSIGPX-UHFFFAOYSA-N 7,8-dimethoxy-5-(4-methoxyphenyl)-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=CC(OC)=CC=C1C1=NCC(=O)N(C)C2=CC(OC)=C(OC)C=C12 DUMABVVGUSIGPX-UHFFFAOYSA-N 0.000 description 2
- LUIUBCACSPXTPV-UHFFFAOYSA-N 7,8-dimethoxy-5-phenyl-1-propyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CCC)C2=CC(OC)=C(OC)C=C2C=1C1=CC=CC=C1 LUIUBCACSPXTPV-UHFFFAOYSA-N 0.000 description 2
- DDEUQSKXBUAGMW-UHFFFAOYSA-N 7-methoxy-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound C12=CC(OC)=CC=C2N(C)C(=O)CN=C1C1=CC=CC=C1 DDEUQSKXBUAGMW-UHFFFAOYSA-N 0.000 description 2
- YVYPNFLCTISLMV-UHFFFAOYSA-N 7-methoxy-5-[3-(trifluoromethyl)phenyl]-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(OC)=CC=C2NC(=O)CN=C1C1=CC=CC(C(F)(F)F)=C1 YVYPNFLCTISLMV-UHFFFAOYSA-N 0.000 description 2
- OGDLFFYXUKTNDD-UHFFFAOYSA-N 8-methoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C=1C(OC)=CC=C2C=1NC(=O)CN=C2C1=CC=CC=C1 OGDLFFYXUKTNDD-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 101001117089 Drosophila melanogaster Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1 Proteins 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- 229910019201 POBr3 Inorganic materials 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 125000005024 alkenyl aryl group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 150000001557 benzodiazepines Chemical class 0.000 description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 235000013681 dietary sucrose Nutrition 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- FNNXQLSKQSVNLL-UHFFFAOYSA-N ethyl 2-amino-2-phenylacetate;hydrochloride Chemical compound Cl.CCOC(=O)C(N)C1=CC=CC=C1 FNNXQLSKQSVNLL-UHFFFAOYSA-N 0.000 description 2
- DABYEOZXRSTEGL-UHFFFAOYSA-N ethyl 2-amino-3-(1h-indol-3-yl)propanoate Chemical compound C1=CC=C2C(CC(N)C(=O)OCC)=CNC2=C1 DABYEOZXRSTEGL-UHFFFAOYSA-N 0.000 description 2
- QIGLJVBIRIXQRN-UHFFFAOYSA-N ethyl 2-amino-4-methylpentanoate Chemical compound CCOC(=O)C(N)CC(C)C QIGLJVBIRIXQRN-UHFFFAOYSA-N 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical compound OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- WUAXWQRULBZETB-UHFFFAOYSA-N homoveratric acid Chemical compound COC1=CC=C(CC(O)=O)C=C1OC WUAXWQRULBZETB-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- WVKIFIROCHIWAY-UHFFFAOYSA-N hydron;2-(methylamino)acetic acid;chloride Chemical compound Cl.CNCC(O)=O WVKIFIROCHIWAY-UHFFFAOYSA-N 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 210000002464 muscle smooth vascular Anatomy 0.000 description 2
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 2
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- QVCOXWYMPCBIMH-UHFFFAOYSA-N prop-2-ynyl carbamate Chemical compound NC(=O)OCC#C QVCOXWYMPCBIMH-UHFFFAOYSA-N 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- DSPYCWLYGXGJNJ-UHFFFAOYSA-N tert-butyl n-prop-2-ynylcarbamate Chemical group CC(C)(C)OC(=O)NCC#C DSPYCWLYGXGJNJ-UHFFFAOYSA-N 0.000 description 2
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 2
- 235000019798 tripotassium phosphate Nutrition 0.000 description 2
- 229940070710 valerate Drugs 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical class CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- NCMNTRBEBJCETB-UHFFFAOYSA-N (2-amino-3-bromo-4,5-dimethoxyphenyl)-phenylmethanone Chemical compound BrC1=C(OC)C(OC)=CC(C(=O)C=2C=CC=CC=2)=C1N NCMNTRBEBJCETB-UHFFFAOYSA-N 0.000 description 1
- AFDXETYIZYYCEH-UHFFFAOYSA-N (2-amino-5-methoxyphenyl)-[3-(trifluoromethyl)phenyl]methanone Chemical compound COC1=CC=C(N)C(C(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 AFDXETYIZYYCEH-UHFFFAOYSA-N 0.000 description 1
- RCVDPBFUMYUKPB-UHFFFAOYSA-N (3,4-dimethoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1OC RCVDPBFUMYUKPB-UHFFFAOYSA-N 0.000 description 1
- AFSSVCNPDKKSRR-UHFFFAOYSA-N (3-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Br)=C1 AFSSVCNPDKKSRR-UHFFFAOYSA-N 0.000 description 1
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 1
- VYEWTHXZHHATTA-UHFFFAOYSA-N (4-acetamidophenyl)boronic acid Chemical compound CC(=O)NC1=CC=C(B(O)O)C=C1 VYEWTHXZHHATTA-UHFFFAOYSA-N 0.000 description 1
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 1
- GZFAVYWCPSMLCM-UHFFFAOYSA-N (6-methoxynaphthalen-2-yl)boronic acid Chemical compound C1=C(B(O)O)C=CC2=CC(OC)=CC=C21 GZFAVYWCPSMLCM-UHFFFAOYSA-N 0.000 description 1
- ZVHAZMUBLCEMGG-UHFFFAOYSA-N (6-phenylmethoxynaphthalen-2-yl)boronic acid Chemical compound C1=CC2=CC(B(O)O)=CC=C2C=C1OCC1=CC=CC=C1 ZVHAZMUBLCEMGG-UHFFFAOYSA-N 0.000 description 1
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- ZHYMGSPDEVXULU-UHFFFAOYSA-N 1,2-benzodiazepin-3-one Chemical class N1=NC(=O)C=CC2=CC=CC=C21 ZHYMGSPDEVXULU-UHFFFAOYSA-N 0.000 description 1
- XYRIXOUEUNLESN-UHFFFAOYSA-N 1,2-benzodiazepin-7-one Chemical compound N1=CC=CC2=CC(=O)C=CC2=N1 XYRIXOUEUNLESN-UHFFFAOYSA-N 0.000 description 1
- PWTFRUXTAFBWBW-UHFFFAOYSA-N 1,3-dibromo-5-(bromomethyl)benzene Chemical compound BrCC1=CC(Br)=CC(Br)=C1 PWTFRUXTAFBWBW-UHFFFAOYSA-N 0.000 description 1
- ASCRLTIXZKFQJI-UHFFFAOYSA-N 1-(1-benzothiophen-2-yl)-7,8-diethoxy-3-ethyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OCC)C(OCC)=CC=2CC(=O)N(CC)N=C1C1=CC2=CC=CC=C2S1 ASCRLTIXZKFQJI-UHFFFAOYSA-N 0.000 description 1
- FPSXKAJUOFGDNX-UHFFFAOYSA-N 1-(4-chlorophenyl)-7,8-diethoxy-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OCC)C(OCC)=CC=2CC(=O)N(C)N=C1C1=CC=C(Cl)C=C1 FPSXKAJUOFGDNX-UHFFFAOYSA-N 0.000 description 1
- GYYVSPASTBUVCR-UHFFFAOYSA-N 1-(4-chlorophenyl)-7,8-dimethoxy-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C1=CC=C(Cl)C=C1 GYYVSPASTBUVCR-UHFFFAOYSA-N 0.000 description 1
- FVZWOEXGLBRPHR-UHFFFAOYSA-N 1-(4-hept-1-ynylphenyl)-7,8-dimethoxy-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=CC(C#CCCCCC)=CC=C1C1=NN(C)C(=O)CC2=CC(OC)=C(OC)C=C12 FVZWOEXGLBRPHR-UHFFFAOYSA-N 0.000 description 1
- RGLQSFFFIREZFV-UHFFFAOYSA-N 1-(bromomethyl)-2,4-dichlorobenzene Chemical compound ClC1=CC=C(CBr)C(Cl)=C1 RGLQSFFFIREZFV-UHFFFAOYSA-N 0.000 description 1
- PURSZYWBIQIANP-UHFFFAOYSA-N 1-(bromomethyl)-2-chlorobenzene Chemical compound ClC1=CC=CC=C1CBr PURSZYWBIQIANP-UHFFFAOYSA-N 0.000 description 1
- WAUNFWSVXRPCDQ-UHFFFAOYSA-N 1-(bromomethyl)-2-methoxybenzene Chemical compound COC1=CC=CC=C1CBr WAUNFWSVXRPCDQ-UHFFFAOYSA-N 0.000 description 1
- WGVYCXYGPNNUQA-UHFFFAOYSA-N 1-(bromomethyl)-2-methylbenzene Chemical compound CC1=CC=CC=C1CBr WGVYCXYGPNNUQA-UHFFFAOYSA-N 0.000 description 1
- MYYYZNVAUZVXBO-UHFFFAOYSA-N 1-(bromomethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CBr)=C1 MYYYZNVAUZVXBO-UHFFFAOYSA-N 0.000 description 1
- ZKSOJQDNSNJIQW-UHFFFAOYSA-N 1-(bromomethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CBr)=C1 ZKSOJQDNSNJIQW-UHFFFAOYSA-N 0.000 description 1
- WZRKSPFYXUXINF-UHFFFAOYSA-N 1-(bromomethyl)-4-methylbenzene Chemical compound CC1=CC=C(CBr)C=C1 WZRKSPFYXUXINF-UHFFFAOYSA-N 0.000 description 1
- GOWMBYUZXIZENX-CAUSLRQDSA-N 1-[(2r,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-(hexadecylamino)pyrimidin-2-one Chemical compound O=C1N=C(NCCCCCCCCCCCCCCCC)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 GOWMBYUZXIZENX-CAUSLRQDSA-N 0.000 description 1
- MIXIYVAEJDWEGL-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)phenyl]-7,8-dimethoxy-3-methyl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 MIXIYVAEJDWEGL-UHFFFAOYSA-N 0.000 description 1
- PKRRNTJIHGOMRC-UHFFFAOYSA-N 1-benzofuran-2-ylboronic acid Chemical compound C1=CC=C2OC(B(O)O)=CC2=C1 PKRRNTJIHGOMRC-UHFFFAOYSA-N 0.000 description 1
- DNGLRCHMGDDHNC-UHFFFAOYSA-N 1-benzothiophene-2-carbonyl chloride Chemical compound C1=CC=C2SC(C(=O)Cl)=CC2=C1 DNGLRCHMGDDHNC-UHFFFAOYSA-N 0.000 description 1
- ZTXYRZOIOISELI-UHFFFAOYSA-N 1-benzyl-5-chloro-7,8-dimethoxy-3h-1,4-benzodiazepin-2-one Chemical compound O=C1CN=C(Cl)C=2C=C(OC)C(OC)=CC=2N1CC1=CC=CC=C1 ZTXYRZOIOISELI-UHFFFAOYSA-N 0.000 description 1
- SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 1
- ZPCJPJQUVRIILS-UHFFFAOYSA-N 1-bromo-3-(bromomethyl)benzene Chemical compound BrCC1=CC=CC(Br)=C1 ZPCJPJQUVRIILS-UHFFFAOYSA-N 0.000 description 1
- YLRBJYMANQKEAW-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)benzene Chemical compound BrCC1=CC=C(Br)C=C1 YLRBJYMANQKEAW-UHFFFAOYSA-N 0.000 description 1
- PBLNBZIONSLZBU-UHFFFAOYSA-N 1-bromododecane Chemical compound CCCCCCCCCCCCBr PBLNBZIONSLZBU-UHFFFAOYSA-N 0.000 description 1
- CYTYSYYPAYFDSR-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-3-[(2-methylphenyl)methyl]-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC=C1C CYTYSYYPAYFDSR-UHFFFAOYSA-N 0.000 description 1
- WNWRPVFIEUZBNY-UHFFFAOYSA-N 1-ethyl-7,8-dimethoxy-5-[4-(3-phenylmethoxyprop-1-ynyl)phenyl]-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CC)C2=CC(OC)=C(OC)C=C2C=1C(C=C1)=CC=C1C#CCOCC1=CC=CC=C1 WNWRPVFIEUZBNY-UHFFFAOYSA-N 0.000 description 1
- LXWQJQHNSJLQTO-UHFFFAOYSA-N 10-phenyl-2,3,6,8-tetrahydro-[1,4]dioxino[2,3-h][1,4]benzodiazepin-7-one Chemical compound C12=CC=3OCCOC=3C=C2NC(=O)CN=C1C1=CC=CC=C1 LXWQJQHNSJLQTO-UHFFFAOYSA-N 0.000 description 1
- BZKOZYWGZKRTIB-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-6-amine Chemical compound O1CCOC2=CC(N)=CC=C21 BZKOZYWGZKRTIB-UHFFFAOYSA-N 0.000 description 1
- MAGIXZPMCBHOFV-UHFFFAOYSA-N 2-(1-ethyl-7,8-dimethoxy-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl)acetamide Chemical compound N=1C(CC(N)=O)C(=O)N(CC)C2=CC(OC)=C(OC)C=C2C=1C1=CC=CC=C1 MAGIXZPMCBHOFV-UHFFFAOYSA-N 0.000 description 1
- XQRQKIPYUCJWBO-UHFFFAOYSA-N 2-(3,4-diethoxyphenyl)ethyl butanoate Chemical compound CCCC(=O)OCCC1=CC=C(OCC)C(OCC)=C1 XQRQKIPYUCJWBO-UHFFFAOYSA-N 0.000 description 1
- UUVDOPTUDWJHFK-UHFFFAOYSA-N 2-(bromomethyl)-1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C(CBr)=C1 UUVDOPTUDWJHFK-UHFFFAOYSA-N 0.000 description 1
- ONANEURZGVLNCQ-UHFFFAOYSA-N 2-[(8-ethoxy-7-methoxy-1-methyl-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl)methyl]benzonitrile Chemical compound N1=C(C=2C=CC=CC=2)C=2C=C(OC)C(OCC)=CC=2N(C)C(=O)C1CC1=CC=CC=C1C#N ONANEURZGVLNCQ-UHFFFAOYSA-N 0.000 description 1
- AFMPMSCZPVNPEM-UHFFFAOYSA-N 2-bromobenzonitrile Chemical compound BrC1=CC=CC=C1C#N AFMPMSCZPVNPEM-UHFFFAOYSA-N 0.000 description 1
- OLAITAANNRHOLM-UHFFFAOYSA-N 2-ethoxy-5-nitrophenol Chemical compound CCOC1=CC=C([N+]([O-])=O)C=C1O OLAITAANNRHOLM-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 102000001707 3',5'-Cyclic-AMP Phosphodiesterases Human genes 0.000 description 1
- 108010054479 3',5'-Cyclic-AMP Phosphodiesterases Proteins 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- MOLLMKZLHNWYJJ-UHFFFAOYSA-N 3-[(1-ethyl-7,8-dimethoxy-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl)methyl]benzonitrile Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC=CC(C#N)=C1 MOLLMKZLHNWYJJ-UHFFFAOYSA-N 0.000 description 1
- CGOMMLCWBCUVIU-UHFFFAOYSA-N 3-[(3,5-dibromophenyl)methyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1CC1=CC(Br)=CC(Br)=C1 CGOMMLCWBCUVIU-UHFFFAOYSA-N 0.000 description 1
- MYUOCABMOOQGAE-UHFFFAOYSA-N 3-[(3-bromophenyl)-hydroxymethyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1C(O)C1=CC=CC(Br)=C1 MYUOCABMOOQGAE-UHFFFAOYSA-N 0.000 description 1
- FGMBQTNFQLFNRR-UHFFFAOYSA-N 3-[1,2-bis(4-bromophenyl)ethyl]-1-ethyl-7,8-dimethoxy-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound O=C1N(CC)C2=CC(OC)=C(OC)C=C2C(C=2C=CC=CC=2)=NC1C(C=1C=CC(Br)=CC=1)CC1=CC=C(Br)C=C1 FGMBQTNFQLFNRR-UHFFFAOYSA-N 0.000 description 1
- SJGGDZCTGBKBCK-UHFFFAOYSA-N 3-acetylphenylboronic acid Chemical compound CC(=O)C1=CC=CC(B(O)O)=C1 SJGGDZCTGBKBCK-UHFFFAOYSA-N 0.000 description 1
- DHYHYLGCQVVLOQ-UHFFFAOYSA-N 3-bromoaniline Chemical compound NC1=CC=CC(Br)=C1 DHYHYLGCQVVLOQ-UHFFFAOYSA-N 0.000 description 1
- FURFVPBUGLPPFW-UHFFFAOYSA-N 3-bromobenzaldehyde hydrobromide Chemical compound Br.BrC1=CC=CC(C=O)=C1 FURFVPBUGLPPFW-UHFFFAOYSA-N 0.000 description 1
- STXAVEHFKAXGOX-UHFFFAOYSA-N 3-bromobenzonitrile Chemical compound BrC1=CC=CC(C#N)=C1 STXAVEHFKAXGOX-UHFFFAOYSA-N 0.000 description 1
- RUROFEVDCUGKHD-UHFFFAOYSA-N 3-bromoprop-1-enylbenzene Chemical compound BrCC=CC1=CC=CC=C1 RUROFEVDCUGKHD-UHFFFAOYSA-N 0.000 description 1
- ZNRGSYUVFVNSAW-UHFFFAOYSA-N 3-nitrophenylboronic acid Chemical compound OB(O)C1=CC=CC([N+]([O-])=O)=C1 ZNRGSYUVFVNSAW-UHFFFAOYSA-N 0.000 description 1
- DENKGPBHLYFNGK-UHFFFAOYSA-N 4-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Br)C=C1 DENKGPBHLYFNGK-UHFFFAOYSA-N 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- VLVCDUSVTXIWGW-UHFFFAOYSA-N 4-iodoaniline Chemical compound NC1=CC=C(I)C=C1 VLVCDUSVTXIWGW-UHFFFAOYSA-N 0.000 description 1
- NJAKCIUOTIPYED-UHFFFAOYSA-N 4-iodobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(I)C=C1 NJAKCIUOTIPYED-UHFFFAOYSA-N 0.000 description 1
- XJNPNXSISMKQEX-UHFFFAOYSA-N 4-nitrocatechol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1O XJNPNXSISMKQEX-UHFFFAOYSA-N 0.000 description 1
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- POCQPJWWSXAJHM-UHFFFAOYSA-N 5-(4-chlorophenyl)-7,8-dimethoxy-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N(C)C(=O)CN=C1C1=CC=C(Cl)C=C1 POCQPJWWSXAJHM-UHFFFAOYSA-N 0.000 description 1
- HRBONWTYLGDUKT-UHFFFAOYSA-N 5-[3-(hydroxymethyl)phenyl]-7,8-dimethoxy-1-methyl-3-propyl-3h-1,4-benzodiazepin-2-one Chemical compound C12=CC(OC)=C(OC)C=C2N(C)C(=O)C(CCC)N=C1C1=CC=CC(CO)=C1 HRBONWTYLGDUKT-UHFFFAOYSA-N 0.000 description 1
- LEWTUQQUNJVNSJ-UHFFFAOYSA-N 5-chloro-7,8-dimethoxy-1,3-dimethyl-3h-1,4-benzodiazepin-2-one Chemical compound CN1C(=O)C(C)N=C(Cl)C2=C1C=C(OC)C(OC)=C2 LEWTUQQUNJVNSJ-UHFFFAOYSA-N 0.000 description 1
- VRWXHCGIOURJAL-UHFFFAOYSA-N 5-chloro-7,8-dimethoxy-1-propyl-3h-1,4-benzodiazepin-2-one Chemical compound ClC1=NCC(=O)N(CCC)C2=CC(OC)=C(OC)C=C21 VRWXHCGIOURJAL-UHFFFAOYSA-N 0.000 description 1
- BHQWWGQGYZTSJN-UHFFFAOYSA-N 7,8-dimethoxy-1,3-dimethyl-3,4-dihydro-1,4-benzodiazepine-2,5-dione Chemical compound CN1C(=O)C(C)NC(=O)C2=C1C=C(OC)C(OC)=C2 BHQWWGQGYZTSJN-UHFFFAOYSA-N 0.000 description 1
- HBNQJZPTBMBXCX-UHFFFAOYSA-N 7,8-dimethoxy-3,4-dihydro-1h-1,4-benzodiazepine-2,5-dione Chemical compound N1C(=O)CNC(=O)C2=C1C=C(OC)C(OC)=C2 HBNQJZPTBMBXCX-UHFFFAOYSA-N 0.000 description 1
- NIDQDDGVVNCHFH-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-1-(4-pyridin-3-ylphenyl)-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=CN=C1 NIDQDDGVVNCHFH-UHFFFAOYSA-N 0.000 description 1
- XKJBVKQYRHXRAS-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-1-[4-(3-methylphenyl)phenyl]-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C(C=C1)=CC=C1C1=CC=CC(C)=C1 XKJBVKQYRHXRAS-UHFFFAOYSA-N 0.000 description 1
- FZBQSODPIDLQDZ-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-1-naphthalen-2-yl-5h-2,3-benzodiazepin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CC(=O)N(C)N=C1C1=CC=C(C=CC=C2)C2=C1 FZBQSODPIDLQDZ-UHFFFAOYSA-N 0.000 description 1
- DFIUPVPLSDQFHP-UHFFFAOYSA-N 7,8-dimethoxy-3-methyl-2,5-dihydro-2,3-benzodiazepine-1,4-dione Chemical class C1C(=O)N(C)NC(=O)C2=C1C=C(OC)C(OC)=C2 DFIUPVPLSDQFHP-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- RGVPILAQNDITHR-UHFFFAOYSA-N B(O)O.FC(C=1C=CC=C(C1)C(F)(F)F)(F)F Chemical compound B(O)O.FC(C=1C=CC=C(C1)C(F)(F)F)(F)F RGVPILAQNDITHR-UHFFFAOYSA-N 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- GMBZSPAGJJUOSB-UHFFFAOYSA-N C(C)N1CC(N=C(C2=C1C=C(C(=C2)OC)OC)C2=CC=CC=C2)CC2=C(C=CC=C2)C Chemical compound C(C)N1CC(N=C(C2=C1C=C(C(=C2)OC)OC)C2=CC=CC=C2)CC2=C(C=CC=C2)C GMBZSPAGJJUOSB-UHFFFAOYSA-N 0.000 description 1
- 125000006519 CCH3 Chemical group 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 108010078321 Guanylate Cyclase Proteins 0.000 description 1
- 102000014469 Guanylate cyclase Human genes 0.000 description 1
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100039065 Interleukin-1 beta Human genes 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 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 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
- VKIJXFIYBAYHOE-VOTSOKGWSA-N [(e)-2-phenylethenyl]boronic acid Chemical compound OB(O)\C=C\C1=CC=CC=C1 VKIJXFIYBAYHOE-VOTSOKGWSA-N 0.000 description 1
- BPTABBGLHGBJQR-UHFFFAOYSA-N [3,5-bis(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 BPTABBGLHGBJQR-UHFFFAOYSA-N 0.000 description 1
- WOAORAPRPVIATR-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C(F)(F)F)=C1 WOAORAPRPVIATR-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- PWUBONDMIMDOQY-UHFFFAOYSA-N acetonitrile;hydrochloride Chemical compound Cl.CC#N PWUBONDMIMDOQY-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000005025 alkynylaryl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 125000005018 aryl alkenyl group Chemical group 0.000 description 1
- 125000005015 aryl alkynyl group Chemical group 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- YNCYPMUJDDXIRH-UHFFFAOYSA-N benzo[b]thiophene-2-boronic acid Chemical compound C1=CC=C2SC(B(O)O)=CC2=C1 YNCYPMUJDDXIRH-UHFFFAOYSA-N 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 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 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 1
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000000095 emetic effect Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- VSCJXMLDRWWDOQ-UHFFFAOYSA-N ethoxysulfonylmethanesulfonic acid;hydrochloride Chemical compound Cl.CCOS(=O)(=O)CS(O)(=O)=O VSCJXMLDRWWDOQ-UHFFFAOYSA-N 0.000 description 1
- PNJYCUHMPBXTOJ-UHFFFAOYSA-N ethyl 2-(1-ethyl-7,8-dimethoxy-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl)acetate Chemical compound C12=CC(OC)=C(OC)C=C2N(CC)C(=O)C(CC(=O)OCC)N=C1C1=CC=CC=C1 PNJYCUHMPBXTOJ-UHFFFAOYSA-N 0.000 description 1
- IEMGWBMVQLVHEY-UHFFFAOYSA-N ethyl 2-(3-amino-6,7-dihydro-5h-cyclopenta[b]pyridin-7-yl)acetate Chemical compound NC1=CN=C2C(CC(=O)OCC)CCC2=C1 IEMGWBMVQLVHEY-UHFFFAOYSA-N 0.000 description 1
- ACHWEOLUTJAHLV-UHFFFAOYSA-N ethyl 2-amino-3-(1h-imidazol-5-yl)propanoate Chemical compound CCOC(=O)C(N)CC1=CN=CN1 ACHWEOLUTJAHLV-UHFFFAOYSA-N 0.000 description 1
- UACSTJFVSYFIPA-UHFFFAOYSA-N ethyl acetate;hydrobromide Chemical compound Br.CCOC(C)=O UACSTJFVSYFIPA-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
- 235000013928 guanylic acid Nutrition 0.000 description 1
- YVXHZKKCZYLQOP-UHFFFAOYSA-N hept-1-yne Chemical compound CCCCCC#C YVXHZKKCZYLQOP-UHFFFAOYSA-N 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000037041 intracellular level Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 1
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
- 239000011654 magnesium acetate Substances 0.000 description 1
- 235000011285 magnesium acetate Nutrition 0.000 description 1
- 229940069446 magnesium acetate Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- IYUKFAFDFHZKPI-DFWYDOINSA-N methyl (2s)-2-aminopropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](C)N IYUKFAFDFHZKPI-DFWYDOINSA-N 0.000 description 1
- QNXOHINFQALBQN-UHFFFAOYSA-N methyl 12-bromododecanoate Chemical compound COC(=O)CCCCCCCCCCCBr QNXOHINFQALBQN-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 108010028584 nucleotidase Proteins 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 125000003367 polycyclic group Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- MUIMMFVCYYVISV-UHFFFAOYSA-N propan-1-ol;hydrobromide Chemical compound Br.CCCO MUIMMFVCYYVISV-UHFFFAOYSA-N 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/02—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Rheumatology (AREA)
- Child & Adolescent Psychology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0107458 | 2001-06-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200400057B true ZA200400057B (en) | 2005-02-21 |
Family
ID=8864056
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200400057A ZA200400057B (en) | 2001-06-07 | 2004-01-06 | Cyclic nucleotide phosphodiesterase inhibitors, preparation and uses thereof. |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7250410B2 (fr) |
| EP (1) | EP1392663A2 (fr) |
| JP (1) | JP2005503356A (fr) |
| AU (2) | AU2002317910B2 (fr) |
| CA (1) | CA2446696A1 (fr) |
| IL (2) | IL159105A0 (fr) |
| NZ (1) | NZ529582A (fr) |
| WO (1) | WO2002098865A2 (fr) |
| ZA (1) | ZA200400057B (fr) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060025388A1 (en) * | 1999-04-30 | 2006-02-02 | Glick Gary D | Compositions and methods relating to novel compounds and targets thereof |
| US7144880B2 (en) | 1999-04-30 | 2006-12-05 | Regents Of The University Of Michigan | Compositions relating to novel compounds and targets thereof |
| US20050113460A1 (en) * | 1999-04-30 | 2005-05-26 | The Regents Of The University Of Michigan | Compositions and methods relating to novel compounds and targets thereof |
| EP2062583B1 (fr) * | 1999-04-30 | 2012-12-26 | The Regents of the University of Michigan | Applications thérapeutiques de benzodiazépines pro-apoptotiques |
| US20030119029A1 (en) * | 1999-04-30 | 2003-06-26 | Regents Of The University Of Michigan | Compositions and methods relating to novel benzodiazepine compounds and targets thereof |
| EP1546089A2 (fr) * | 2002-08-09 | 2005-06-29 | TransTech Pharma Inc. | Composes aryle et heteroaryle et procedes de modulation de la coagulation |
| FR2846653B1 (fr) * | 2002-10-30 | 2007-04-20 | Neuro3D | Inhibiteurs des phosphodiesterases des nucleotides cycliques, preparation et utilisations |
| US20060128695A1 (en) * | 2002-10-30 | 2006-06-15 | Neuro3D | Cyclic nucleotide phosphodiesterase inhibitors, preparation and uses |
| US7459472B2 (en) * | 2003-08-08 | 2008-12-02 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds, compositions, and methods of use |
| US7208601B2 (en) * | 2003-08-08 | 2007-04-24 | Mjalli Adnan M M | Aryl and heteroaryl compounds, compositions, and methods of use |
| EP1548011A1 (fr) | 2003-12-23 | 2005-06-29 | Neuro3D | Dérivés de 1,4-benzodiazépine-2-one comme inhibiteurs de PDE2 phosphodiesterase, leurs préparation et utilisation thérapeutique |
| US20090275099A1 (en) * | 2004-04-27 | 2009-11-05 | Regents Of The University Of Michigan | Methods and compositions for treating diseases and conditions associated with mitochondrial function |
| US20050272723A1 (en) * | 2004-04-27 | 2005-12-08 | The Regents Of The University Of Michigan | Methods and compositions for treating diseases and conditions associated with mitochondrial function |
| FR2870539B1 (fr) * | 2004-05-19 | 2006-08-04 | Greenpharma Sa Sa | Nouvelles methodes et medicaments |
| CA2577060A1 (fr) | 2004-08-13 | 2006-02-23 | Amgen Inc. | Heterocycles benzo-condenses substitues |
| US20060052369A1 (en) * | 2004-09-07 | 2006-03-09 | The Regents Of The University Of Michigan | Compositions and methods relating to novel compounds and targets thereof |
| WO2007053193A2 (fr) * | 2005-06-01 | 2007-05-10 | The Regents Of The University Of Michigan | Préparations de benzodiazépine non solvatées et méthodes |
| US20070105844A1 (en) * | 2005-10-26 | 2007-05-10 | Regents Of The University Of Michigan | Therapeutic compositions and methods |
| AU2006308655B2 (en) * | 2005-11-01 | 2010-09-23 | The Regents Of The University Of Michigan | Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties |
| US7759338B2 (en) * | 2006-04-27 | 2010-07-20 | The Regents Of The University Of Michigan | Soluble 1,4 benzodiazepine compounds and stable salts thereof |
| WO2007146167A1 (fr) | 2006-06-09 | 2007-12-21 | The Regents Of The University Of Michigan | Compositions et procédés associés à de nouveaux composés et leurs cibles |
| JP5383513B2 (ja) | 2007-03-09 | 2014-01-08 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | 化合物およびその標的に関連する組成物ならびに方法 |
| EP2146722A4 (fr) * | 2007-05-10 | 2011-08-03 | Amr Technology Inc | Tétrahydrobenzo-l,4-diazépines substituées par un aryle ou un hétéroaryle et utilisation desdites dans le blocage de la réassimilation de la norépinéphrine, de la dopamine et de la sérotonine |
| WO2009036175A2 (fr) * | 2007-09-14 | 2009-03-19 | The Regents Of The University Of Michigan | Inhibiteur de f1f0-atpase et procédés associés |
| WO2009037302A1 (fr) * | 2007-09-18 | 2009-03-26 | Via Pharmaceuticals, Inc. | 1,4-benzodiazépines 5-substituées en tant qu'inhibiteurs de phosphodiestérase |
| RU2010122902A (ru) | 2007-11-06 | 2011-12-20 | Дзе Риджентс оф дзе Юниверсити оф Мичиган (US) | Бензодиапениноновые соединения, применимые в лечении кожных состояний |
| EP2352724B1 (fr) | 2008-09-11 | 2015-04-22 | The Regents of the University of Michigan | Aryle guanidines comme inhibiteurs de la f1f0-atpase et leur utilisation medicale |
| US8604023B2 (en) | 2009-04-17 | 2013-12-10 | The Regents Of The University Of Michigan | 1,4-benzodiazepinone compounds and their use in treating cancer |
| EP2470020A4 (fr) | 2009-09-18 | 2013-03-13 | Univ Michigan | Composés de benzodiazépinone et méthodes de traitement les utilisant |
| US8815845B2 (en) | 2009-11-17 | 2014-08-26 | The Regents Of The University Of Michigan | 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties |
| CA2780333C (fr) | 2009-11-17 | 2016-05-24 | The Regents Of The University Of Michigan | 1,4-benzodiazepine-2,5-diones et composes apparentes presentant des proprietes therapeutiques |
| AR084070A1 (es) | 2010-12-02 | 2013-04-17 | Constellation Pharmaceuticals Inc | Inhibidores del bromodominio y usos de los mismos |
| US9249161B2 (en) | 2010-12-02 | 2016-02-02 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
| EP2705039B1 (fr) | 2011-05-04 | 2017-07-26 | Constellation Pharmaceuticals, Inc. | Inhibiteurs de bromodomaines et leurs utilisations |
| WO2012174487A2 (fr) | 2011-06-17 | 2012-12-20 | Constellation Pharmaceuticals, Inc. | Inhibiteurs à bromodomaine et leurs utilisations |
| US9624244B2 (en) | 2012-06-06 | 2017-04-18 | Constellation Pharmaceuticals, Inc. | Benzo [B] isoxazoloazepine bromodomain inhibitors and uses thereof |
| TWI602820B (zh) | 2012-06-06 | 2017-10-21 | 星宿藥物公司 | 溴域抑制劑及其用途 |
| LT3157928T (lt) | 2014-06-20 | 2019-05-27 | Constellation Pharmaceuticals, Inc. | 2-((4s)-6-(4-chlorfenil)-1-metil-4h-benzo[c]iizoksazolo[4,5-e]azepin-4-il)acetamido kristalinės formos |
| US20250313537A1 (en) * | 2022-05-13 | 2025-10-09 | University Of Cincinnati | Benzodiazepine analogs and methods of use in treating cancer |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH408940A (de) * | 1959-12-10 | 1966-03-15 | Hoffmann La Roche | Verfahren zur Herstellung von 1,4-Benzodiazepin-Derivaten |
| NL131733C (fr) * | 1961-06-20 | |||
| US3182067A (en) * | 1964-04-09 | 1965-05-04 | Hoffmann La Roche | Benzodiazepine compounds |
| FR1497456A (fr) * | 1964-06-15 | 1967-10-13 | Clin Byla Ets | Ortho-amino aryl cétimines, composés hétérocycliques qui s'y rattachent et prépaation de ces divers corps |
| IL29988A0 (en) * | 1967-06-23 | 1968-07-25 | American Cyanamid Co | Novel 7-trifluoromethoxybenzo-1,4-diazepines |
| US3631029A (en) * | 1967-12-01 | 1971-12-28 | Sumitomo Chemical Co | Process for producing benzodiazepine derivatives |
| FR2085645A1 (en) * | 1970-04-22 | 1971-12-31 | Chimidrog | 1-phenyl-2,3-benzodiazepin-4-ones - as tranquillizers |
| US3801569A (en) * | 1973-01-15 | 1974-04-02 | Hoffmann La Roche | 7-(1,1-difluoroalkyl)-1,4-benzodiazepines |
| DE3119874A1 (de) | 1981-05-19 | 1982-12-09 | Dr. Karl Thomae Gmbh, 7950 Biberach | "benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel" |
| IL93401A (en) * | 1989-03-08 | 1994-08-26 | Kali Chemie Pharma Gmbh | H1 - Indole - 2 - Carboxylic acid 1, 7 - Consolidated N -) 1, 4 - Benzodiazepine - 3 - Il (amides, their preparation and drugs containing them |
| TW221687B (fr) * | 1992-01-24 | 1994-03-11 | Hoffmann La Roche | |
| DE19604920A1 (de) * | 1996-02-01 | 1997-08-07 | Schering Ag | Neue 2,3-Benzodiazepinderivate, deren Herstellung und Verwendung als Arzneimittel |
| US5891871A (en) | 1996-03-21 | 1999-04-06 | Cocensys, Inc. | Substituted 2,3-benzodiazepin-4-ones and the use thereof |
| AU4565600A (en) * | 1999-06-18 | 2001-01-09 | Synt:Em (S.A.) | Identifying active molecules using physico-chemical parameters |
| WO2002051232A2 (fr) | 2000-12-27 | 2002-07-04 | Actelion Pharmaceuticals Ltd. | Nouvelles benzazepines et derives heterocycliques associes |
-
2002
- 2002-06-07 WO PCT/FR2002/001952 patent/WO2002098865A2/fr not_active Ceased
- 2002-06-07 US US10/479,000 patent/US7250410B2/en not_active Expired - Fee Related
- 2002-06-07 AU AU2002317910A patent/AU2002317910B2/en not_active Ceased
- 2002-06-07 JP JP2003501989A patent/JP2005503356A/ja active Pending
- 2002-06-07 EP EP02747514A patent/EP1392663A2/fr not_active Withdrawn
- 2002-06-07 IL IL15910502A patent/IL159105A0/xx unknown
- 2002-06-07 NZ NZ529582A patent/NZ529582A/en unknown
- 2002-06-07 CA CA002446696A patent/CA2446696A1/fr not_active Abandoned
-
2003
- 2003-11-27 IL IL159105A patent/IL159105A/en not_active IP Right Cessation
-
2004
- 2004-01-06 ZA ZA200400057A patent/ZA200400057B/en unknown
-
2008
- 2008-09-18 AU AU2008221554A patent/AU2008221554A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20040152888A1 (en) | 2004-08-05 |
| JP2005503356A (ja) | 2005-02-03 |
| IL159105A0 (en) | 2004-05-12 |
| WO2002098865A3 (fr) | 2003-02-27 |
| US7250410B2 (en) | 2007-07-31 |
| CA2446696A1 (fr) | 2002-12-12 |
| EP1392663A2 (fr) | 2004-03-03 |
| NZ529582A (en) | 2006-10-27 |
| AU2002317910B2 (en) | 2008-06-19 |
| AU2008221554A1 (en) | 2008-10-09 |
| IL159105A (en) | 2009-05-04 |
| WO2002098865A2 (fr) | 2002-12-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ZA200400057B (en) | Cyclic nucleotide phosphodiesterase inhibitors, preparation and uses thereof. | |
| US10123993B2 (en) | Cyclic ureas as inhibitors of rock | |
| KR102457933B1 (ko) | Rock의 억제제로서의 트리아졸론 및 테트라졸론 | |
| ES2325045T3 (es) | Nuevos derivados de pirazol heterociclilmetil sustituidos y su uso en el tratamiento de enfermedades cardiovasculares. | |
| ES2315546T3 (es) | Inhibidores delas fosfodiesterasas de los nucleotidos ciclicos, que presentan una estructura de benzodiazepina, y su uso en terapia. | |
| JP5474153B2 (ja) | Gabaa受容体調節物質としての置換シンノリン誘導体 | |
| US7410963B2 (en) | Benzo-1,4-diazepin-2-one derivatives as phosphodiesterase PDE2 inhibitors, preparation and therapeutic use thereof | |
| KR20030045187A (ko) | 도파민 d₃수용체 조절제 (정신병 치료제)로서 유용한테트라히드로벤즈아제핀 유도체 | |
| MX2011004680A (es) | Moduladores de beta amiloide. | |
| CA2216882A1 (fr) | Agents amidino cycliques utiles en tant qu'inhibiteurs de synthase de l'oxyde nitrique | |
| CA3201456A1 (fr) | Composes tricycliques | |
| JP2001503408A (ja) | GABA▲下A▼α5受容体サブタイプに対するリガンドとしてのチエニルシクロヘキサノン誘導体 | |
| TW202110845A (zh) | 三環化合物 | |
| ES2309493T3 (es) | 3compuestos de triazol y su uso terapeutico. | |
| EP0719264B1 (fr) | Derives d'imidazolone et d'oxazolone utilises comme antagonistes de la dopamine | |
| CA2476164C (fr) | Composes d'imidazole 4-carboxamide a activite d'inhibition de l'adenosine deaminase | |
| CA3185263A1 (fr) | Agonistes du recepteur 2 du peptide formyle de pyrazolone | |
| FR2846653A1 (fr) | Inhibiteurs des phosphodiesterases des nucleotides cycliques, preparation et utilisations |