JP2013507360A - ホスホジエステラーゼ１−標的トレーサーおよび方法 - Google Patents
ホスホジエステラーゼ１−標的トレーサーおよび方法 Download PDFInfo
- Publication number
- JP2013507360A JP2013507360A JP2012533137A JP2012533137A JP2013507360A JP 2013507360 A JP2013507360 A JP 2013507360A JP 2012533137 A JP2012533137 A JP 2012533137A JP 2012533137 A JP2012533137 A JP 2012533137A JP 2013507360 A JP2013507360 A JP 2013507360A
- Authority
- JP
- Japan
- Prior art keywords
- phosphodiesterase
- pyrazolo
- pde1
- methyl
- dione
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 22
- 239000000700 radioactive tracer Substances 0.000 title claims description 10
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title description 7
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title description 7
- 101001117086 Dictyostelium discoideum cAMP/cGMP-dependent 3',5'-cAMP/cGMP phosphodiesterase A Proteins 0.000 claims abstract description 32
- 239000000203 mixture Substances 0.000 claims abstract description 21
- 229940121836 Phosphodiesterase 1 inhibitor Drugs 0.000 claims abstract description 12
- 230000005855 radiation Effects 0.000 claims abstract description 6
- 238000001727 in vivo Methods 0.000 claims abstract description 3
- 239000003446 ligand Substances 0.000 claims description 16
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000003384 imaging method Methods 0.000 claims description 6
- 210000000056 organ Anatomy 0.000 claims description 6
- OOOBGFAUGXVKGI-UHFFFAOYSA-N 5,6-dihydropyrazolo[3,4-d]pyrimidin-4-one Chemical compound O=C1NCN=C2N=NC=C12 OOOBGFAUGXVKGI-UHFFFAOYSA-N 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 claims description 4
- 208000024891 symptom Diseases 0.000 claims description 4
- ZCYVEMRRCGMTRW-AHCXROLUSA-N Iodine-123 Chemical compound [123I] ZCYVEMRRCGMTRW-AHCXROLUSA-N 0.000 claims description 3
- GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 claims description 3
- KRHYYFGTRYWZRS-BJUDXGSMSA-N ac1l2y5h Chemical compound [18FH] KRHYYFGTRYWZRS-BJUDXGSMSA-N 0.000 claims description 3
- OKTJSMMVPCPJKN-BJUDXGSMSA-N carbon-11 Chemical group [11C] OKTJSMMVPCPJKN-BJUDXGSMSA-N 0.000 claims description 3
- 229940055742 indium-111 Drugs 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 238000002059 diagnostic imaging Methods 0.000 claims description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 238000003325 tomography Methods 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- 208000015114 central nervous system disease Diseases 0.000 claims 1
- 238000013507 mapping Methods 0.000 claims 1
- 238000002600 positron emission tomography Methods 0.000 claims 1
- 239000000651 prodrug Chemical group 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 claims 1
- 150000003839 salts Chemical group 0.000 claims 1
- 229940056501 technetium 99m Drugs 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 210000003169 central nervous system Anatomy 0.000 abstract description 6
- 230000002526 effect on cardiovascular system Effects 0.000 abstract description 6
- 238000002603 single-photon emission computed tomography Methods 0.000 abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 206010020772 Hypertension Diseases 0.000 abstract description 3
- 239000000090 biomarker Substances 0.000 abstract description 3
- 238000001514 detection method Methods 0.000 abstract description 3
- 201000010099 disease Diseases 0.000 abstract description 3
- 238000012631 diagnostic technique Methods 0.000 abstract description 2
- 230000008685 targeting Effects 0.000 abstract description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 210000001147 pulmonary artery Anatomy 0.000 abstract 1
- 239000000047 product Substances 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- -1 4- (1- [ 11 C] -methylpiperidin-2-yl) benzyl Chemical group 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 102100024317 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C Human genes 0.000 description 5
- 101001117094 Homo sapiens Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C Proteins 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 238000002372 labelling Methods 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- CDCURHBGLBNTSN-UHFFFAOYSA-N 3-anilino-5-methyl-7-(2-methylpropyl)-2-[(4-piperidin-2-ylphenyl)methyl]pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C=1C=CC=CC=1NC1=C2C(=O)N(C)C(=O)N(CC(C)C)C2=NN1CC(C=C1)=CC=C1C1CCCCN1 CDCURHBGLBNTSN-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000002285 radioactive effect Effects 0.000 description 4
- 239000002287 radioligand Substances 0.000 description 4
- 238000011894 semi-preparative HPLC Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 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 4
- QUGWAYNALWRAMD-UHFFFAOYSA-N 3-anilino-5-methyl-7-(2-methylpropyl)-2-[(4-pyrrolidin-2-ylphenyl)methyl]pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C=1C=CC=CC=1NC1=C2C(=O)N(C)C(=O)N(CC(C)C)C2=NN1CC(C=C1)=CC=C1C1CCCN1 QUGWAYNALWRAMD-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- LIYYCXVHZFDWSM-UHFFFAOYSA-N (4-piperidin-2-ylphenyl)methanol Chemical compound C1=CC(CO)=CC=C1C1NCCCC1 LIYYCXVHZFDWSM-UHFFFAOYSA-N 0.000 description 2
- BTUGGGLMQBJCBN-UHFFFAOYSA-N 1-iodo-2-methylpropane Chemical compound CC(C)CI BTUGGGLMQBJCBN-UHFFFAOYSA-N 0.000 description 2
- BYLOKEGWOSSBIT-UHFFFAOYSA-N 3-anilino-5-methyl-7-(2-methylpropyl)-2-[[4-(1-methylpyrrolidin-2-yl)phenyl]methyl]pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C=1C=CC=CC=1NC1=C2C(=O)N(C)C(=O)N(CC(C)C)C2=NN1CC(C=C1)=CC=C1C1CCCN1C BYLOKEGWOSSBIT-UHFFFAOYSA-N 0.000 description 2
- HTENNXXGAZOEPC-UHFFFAOYSA-N 3-anilino-5-methyl-7-(2-methylpropyl)-2h-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2NN=C1NC1=CC=CC=C1 HTENNXXGAZOEPC-UHFFFAOYSA-N 0.000 description 2
- NSZSICWLXFCCRN-UHFFFAOYSA-N 6-chloro-3-methyl-1-(2-methylpropyl)pyrimidine-2,4-dione Chemical compound CC(C)CN1C(Cl)=CC(=O)N(C)C1=O NSZSICWLXFCCRN-UHFFFAOYSA-N 0.000 description 2
- PTXRYWYSWRFJJO-UHFFFAOYSA-N 6-hydrazinyl-3-methyl-1-(2-methylpropyl)pyrimidine-2,4-dione Chemical compound CC(C)CN1C(NN)=CC(=O)N(C)C1=O PTXRYWYSWRFJJO-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 101001117099 Homo sapiens Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B Proteins 0.000 description 2
- 229910010082 LiAlH Inorganic materials 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- NZZFYRREKKOMAT-BJUDXGSMSA-N diiodo(111C)methane Chemical compound [11CH2](I)I NZZFYRREKKOMAT-BJUDXGSMSA-N 0.000 description 2
- 238000001952 enzyme assay Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- QSSVYRPOXMPNLG-UHFFFAOYSA-N fluoromethyl trifluoromethanesulfonate Chemical compound FCOS(=O)(=O)C(F)(F)F QSSVYRPOXMPNLG-UHFFFAOYSA-N 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- LDACBZMXDWYWPS-UHFFFAOYSA-N tert-butyl 2-[4-(hydroxymethyl)phenyl]piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1C1=CC=C(CO)C=C1 LDACBZMXDWYWPS-UHFFFAOYSA-N 0.000 description 2
- RXNZVNGSCCWIOT-UHFFFAOYSA-N tert-butyl 2-[4-(hydroxymethyl)phenyl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1C1=CC=C(CO)C=C1 RXNZVNGSCCWIOT-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 125000006545 (C1-C9) alkyl group Chemical group 0.000 description 1
- 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 1
- BEKHAMCNXMUUFQ-KTXUZGJCSA-N 3-anilino-5-methyl-2-[[4-(1-methylpiperidin-2-yl)phenyl]methyl]-7-(2-methylpropyl)pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C=1C=CC=CC=1NC1=C2C(=O)N(C)C(=O)N(CC(C)C)C2=NN1CC(C=C1)=CC=C1C1CCCCN1[11CH3] BEKHAMCNXMUUFQ-KTXUZGJCSA-N 0.000 description 1
- BEKHAMCNXMUUFQ-UHFFFAOYSA-N 3-anilino-5-methyl-2-[[4-(1-methylpiperidin-2-yl)phenyl]methyl]-7-(2-methylpropyl)pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C=1C=CC=CC=1NC1=C2C(=O)N(C)C(=O)N(CC(C)C)C2=NN1CC(C=C1)=CC=C1C1CCCCN1C BEKHAMCNXMUUFQ-UHFFFAOYSA-N 0.000 description 1
- QEYDLHZXKWDABO-UHFFFAOYSA-N C1(=CC=CC=C1)N=C=S.C(C(C)C)N1C(N(C(C=2C1=NNC2NC2=CC=CC=C2)=O)C)=O Chemical compound C1(=CC=CC=C1)N=C=S.C(C(C)C)N1C(N(C(C=2C1=NNC2NC2=CC=CC=C2)=O)C)=O QEYDLHZXKWDABO-UHFFFAOYSA-N 0.000 description 1
- 102100024316 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Human genes 0.000 description 1
- 102100024318 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B Human genes 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 101001117044 Homo sapiens Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Proteins 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 241000282520 Papio Species 0.000 description 1
- 241001504519 Papio ursinus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- JXHYCCGOZUGBFD-UHFFFAOYSA-N benzoic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CC=C1 JXHYCCGOZUGBFD-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 150000001669 calcium Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000037326 chronic stress Effects 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- XGVXNTVBGYLJIR-UHFFFAOYSA-N fluoroiodomethane Chemical compound FCI XGVXNTVBGYLJIR-UHFFFAOYSA-N 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 210000002321 radial artery Anatomy 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- KOLWTYWGGAKGGU-UHFFFAOYSA-N tert-butyl 2-[4-[[3-anilino-5-methyl-7-(2-methylpropyl)-4,6-dioxopyrazolo[3,4-d]pyrimidin-2-yl]methyl]phenyl]piperidine-1-carboxylate Chemical compound C=1C=CC=CC=1NC1=C2C(=O)N(C)C(=O)N(CC(C)C)C2=NN1CC(C=C1)=CC=C1C1CCCCN1C(=O)OC(C)(C)C KOLWTYWGGAKGGU-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0459—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01T—MEASUREMENT OF NUCLEAR OR X-RADIATION
- G01T1/00—Measuring X-radiation, gamma radiation, corpuscular radiation, or cosmic radiation
- G01T1/16—Measuring radiation intensity
- G01T1/161—Applications in the field of nuclear medicine, e.g. in vivo counting
- G01T1/164—Scintigraphy
- G01T1/1641—Static instruments for imaging the distribution of radioactivity in one or two dimensions using one or several scintillating elements; Radio-isotope cameras
- G01T1/1642—Static instruments for imaging the distribution of radioactivity in one or two dimensions using one or several scintillating elements; Radio-isotope cameras using a scintillation crystal and position sensing photodetector arrays, e.g. ANGER cameras
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01T—MEASUREMENT OF NUCLEAR OR X-RADIATION
- G01T1/00—Measuring X-radiation, gamma radiation, corpuscular radiation, or cosmic radiation
- G01T1/29—Measurement performed on radiation beams, e.g. position or section of the beam; Measurement of spatial distribution of radiation
- G01T1/2914—Measurement of spatial distribution of radiation
- G01T1/2985—In depth localisation, e.g. using positron emitters; Tomographic imaging (longitudinal and transverse section imaging; apparatus for radiation diagnosis sequentially in different planes, steroscopic radiation diagnosis)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Optics & Photonics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Molecular Biology (AREA)
- High Energy & Nuclear Physics (AREA)
- Epidemiology (AREA)
- General Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Medical Informatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24985509P | 2009-10-08 | 2009-10-08 | |
| US61/249,855 | 2009-10-08 | ||
| PCT/US2010/002707 WO2011043816A1 (en) | 2009-10-08 | 2010-10-07 | Phosphodiesterase 1-targeting tracers and methods |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015254522A Division JP6224063B2 (ja) | 2009-10-08 | 2015-12-25 | ホスホジエステラーゼ１−標的トレーサーおよび方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2013507360A true JP2013507360A (ja) | 2013-03-04 |
Family
ID=43857046
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012533137A Withdrawn JP2013507360A (ja) | 2009-10-08 | 2010-10-07 | ホスホジエステラーゼ１−標的トレーサーおよび方法 |
| JP2015254522A Active JP6224063B2 (ja) | 2009-10-08 | 2015-12-25 | ホスホジエステラーゼ１−標的トレーサーおよび方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015254522A Active JP6224063B2 (ja) | 2009-10-08 | 2015-12-25 | ホスホジエステラーゼ１−標的トレーサーおよび方法 |
Country Status (4)
| Country | Link |
|---|---|
| US (2) | US8858911B2 (enExample) |
| EP (1) | EP2485771A4 (enExample) |
| JP (2) | JP2013507360A (enExample) |
| WO (1) | WO2011043816A1 (enExample) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2645371T3 (es) | 2005-06-06 | 2017-12-05 | Intra-Cellular Therapies, Inc. | Compuestos orgánicos |
| US9255099B2 (en) | 2006-06-06 | 2016-02-09 | Intra-Cellular Therapies, Inc. | Pyrazolo[3,4-D]pyrimidine-4,6(5H,7H)-diones as phosphodiesterase 1 inhibitors |
| US9006258B2 (en) | 2006-12-05 | 2015-04-14 | Intra-Cellular Therapies, Inc. | Method of treating female sexual dysfunction with a PDE1 inhibitor |
| KR101227738B1 (ko) | 2007-12-06 | 2013-01-29 | 다케다 야쿠힌 고교 가부시키가이샤 | 유기 화합물 |
| AU2008331833A1 (en) * | 2007-12-06 | 2009-06-11 | Intra-Cellular Therapies, Inc | Organic compounds |
| AU2009322903A1 (en) | 2008-12-06 | 2010-06-10 | Intra-Cellular Therapies, Inc. | Organic compounds |
| JP5784501B2 (ja) | 2008-12-06 | 2015-09-24 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
| ES2638912T3 (es) | 2008-12-06 | 2017-10-24 | Intra-Cellular Therapies, Inc. | Compuestos orgánicos |
| BRPI0922351A2 (pt) | 2008-12-06 | 2018-06-05 | Intracellular Therapies Inc | compostos orgânicos |
| MX2011005935A (es) | 2008-12-06 | 2011-12-16 | Intra Cellular Therapies Inc | Compuestos organicos. |
| MA32940B1 (fr) | 2008-12-06 | 2012-01-02 | Intra Cellular Therapies Inc | Composes organiques |
| US11464781B2 (en) | 2009-02-25 | 2022-10-11 | Intra-Cellular Therapies, Inc. | PDE1 inhibitors for ophthalmic disorders |
| EP2434895A4 (en) | 2009-05-13 | 2013-08-07 | Intra Cellular Therapies Inc | ORGANIC CONNECTIONS |
| JP5894148B2 (ja) | 2010-05-31 | 2016-03-23 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
| US9763948B2 (en) | 2010-05-31 | 2017-09-19 | Intra-Cellular Therapies, Inc. | PDE1 inhibitory compounds and methods |
| EP2575817A4 (en) | 2010-05-31 | 2014-01-08 | Intra Cellular Therapies Inc | ORGANIC CONNECTIONS |
| TW201206937A (en) | 2010-05-31 | 2012-02-16 | Intra Cellular Therapies Inc | Organic compounds |
| WO2012171016A1 (en) | 2011-06-10 | 2012-12-13 | Intra-Cellular Therapies, Inc. | Organic compounds |
| AR091507A1 (es) | 2012-06-21 | 2015-02-11 | Intra Cellular Therapies Inc | SALES DE (6aR,9aS)-5,6a,7,8,9,9a-HEXAHIDRO-5-METIL-3-(FENILAMINO)-2-((4-(6-FLUOROPIRIDIN-2-IL)FENIL)METIL)-CICLOPENT[4,5]IMIDAZO[1,2-a]PIRAZOLO[4,3-e]PIRIMIDIN-4(2H)-ONA |
| WO2014127331A1 (en) | 2013-02-17 | 2014-08-21 | Intra-Cellular Therapies, Inc. | Novel uses |
| ES2871327T3 (es) | 2013-03-15 | 2021-10-28 | Intra Cellular Therapies Inc | Inhibidores de la PDE1 para uso en el tratamiento y/o prevención de enfermedades o trastornos de SNC o SNP |
| RU2679142C2 (ru) | 2013-03-15 | 2019-02-06 | Интра-Селлулар Терапиз, Инк. | Органические соединения |
| CN105658222A (zh) | 2013-06-21 | 2016-06-08 | 细胞内治疗公司 | 游离碱晶体 |
| EP3091983B1 (en) | 2014-01-08 | 2019-10-02 | Intra-Cellular Therapies, Inc. | Pharmaceutical compositions comprising a pde-1 inhibitor and a pde-2 inhibitor |
| WO2015196186A1 (en) | 2014-06-20 | 2015-12-23 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US10285992B2 (en) | 2014-08-07 | 2019-05-14 | Intra-Cellular Therapies, Inc. | Combinations of PDE1 inhibitors and NEP inhibitors and associated methods |
| WO2016022893A1 (en) | 2014-08-07 | 2016-02-11 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US9546175B2 (en) | 2014-08-07 | 2017-01-17 | Intra-Cellular Therapies, Inc. | Organic compounds |
| EP3193878B1 (en) | 2014-09-17 | 2021-01-06 | Intra-Cellular Therapies, Inc. | 7,8-dihydro-[2h]-imidazo-[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5h)-one derivatives as phosphodiesterase 1 (pde1) inhibitors for treating diseases, disorders or injuries of the central nervous system (cns) |
| JP6608933B2 (ja) | 2014-12-06 | 2019-11-20 | イントラ−セルラー・セラピーズ・インコーポレイテッド | 有機化合物 |
| EP3226870B1 (en) | 2014-12-06 | 2019-09-25 | Intra-Cellular Therapies, Inc. | Organic compounds |
| JP2019510039A (ja) | 2016-03-28 | 2019-04-11 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 新規組成物および方法 |
| EP3970719A1 (en) | 2016-09-12 | 2022-03-23 | Intra-Cellular Therapies, Inc. | Pde1 inhibitor for use in a method of treatment or prophylaxis of inflammation and/or an inflammatory disease or disorder |
| JP7401442B2 (ja) | 2018-01-31 | 2023-12-19 | イントラ－セルラー・セラピーズ・インコーポレイテッド | 新規使用 |
| WO2020210614A1 (en) | 2019-04-12 | 2020-10-15 | Intra-Cellular Therapies, Inc. | Organic compounds |
| JP7612672B2 (ja) | 2019-09-03 | 2025-01-14 | イントラ－セルラー・セラピーズ・インコーポレイテッド | 新規化合物 |
| WO2021226407A1 (en) | 2020-05-06 | 2021-11-11 | Intra-Cellular Therapies, Inc. | Free base crystals |
| US12364695B2 (en) | 2020-06-02 | 2025-07-22 | Intra-Cellular Therapies, Inc. | Methods of treating inflammatory disease |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007143705A2 (en) * | 2006-06-06 | 2007-12-13 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US20080188492A1 (en) * | 2005-06-06 | 2008-08-07 | Intra-Cellular Therapies, Inc | Organic Compounds |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6334997B1 (en) * | 1994-03-25 | 2002-01-01 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
| US9198924B2 (en) * | 2006-11-13 | 2015-12-01 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US9006258B2 (en) | 2006-12-05 | 2015-04-14 | Intra-Cellular Therapies, Inc. | Method of treating female sexual dysfunction with a PDE1 inhibitor |
| GEP20125405B (en) * | 2007-05-11 | 2012-02-27 | Pfizer | Amino-heterocyclic compounds |
| AU2008331833A1 (en) | 2007-12-06 | 2009-06-11 | Intra-Cellular Therapies, Inc | Organic compounds |
| KR101227738B1 (ko) | 2007-12-06 | 2013-01-29 | 다케다 야쿠힌 고교 가부시키가이샤 | 유기 화합물 |
| US20120070443A1 (en) * | 2008-12-02 | 2012-03-22 | University Of Utah Research Foundation | Pde1 as a target therapeutic in heart disease |
| BRPI0922351A2 (pt) | 2008-12-06 | 2018-06-05 | Intracellular Therapies Inc | compostos orgânicos |
| JP5784501B2 (ja) | 2008-12-06 | 2015-09-24 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
| AU2009322903A1 (en) | 2008-12-06 | 2010-06-10 | Intra-Cellular Therapies, Inc. | Organic compounds |
| MA32940B1 (fr) | 2008-12-06 | 2012-01-02 | Intra Cellular Therapies Inc | Composes organiques |
| MX2011005935A (es) | 2008-12-06 | 2011-12-16 | Intra Cellular Therapies Inc | Compuestos organicos. |
| ES2638912T3 (es) | 2008-12-06 | 2017-10-24 | Intra-Cellular Therapies, Inc. | Compuestos orgánicos |
| US11464781B2 (en) | 2009-02-25 | 2022-10-11 | Intra-Cellular Therapies, Inc. | PDE1 inhibitors for ophthalmic disorders |
| EP2434895A4 (en) | 2009-05-13 | 2013-08-07 | Intra Cellular Therapies Inc | ORGANIC CONNECTIONS |
| KR101173440B1 (ko) * | 2010-11-05 | 2012-08-16 | (주)토마토시스템 | 서브그리드의 통합 트랜잭션 처리방법 및 이를 기록한 기록매체 |
-
2010
- 2010-10-07 EP EP10822355.3A patent/EP2485771A4/en not_active Withdrawn
- 2010-10-07 JP JP2012533137A patent/JP2013507360A/ja not_active Withdrawn
- 2010-10-07 WO PCT/US2010/002707 patent/WO2011043816A1/en not_active Ceased
- 2010-10-07 US US13/500,941 patent/US8858911B2/en active Active
-
2014
- 2014-09-22 US US14/492,879 patent/US20150139903A1/en not_active Abandoned
-
2015
- 2015-12-25 JP JP2015254522A patent/JP6224063B2/ja active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080188492A1 (en) * | 2005-06-06 | 2008-08-07 | Intra-Cellular Therapies, Inc | Organic Compounds |
| WO2007143705A2 (en) * | 2006-06-06 | 2007-12-13 | Intra-Cellular Therapies, Inc. | Organic compounds |
Non-Patent Citations (4)
| Title |
|---|
| JPN6014043237; Ａｃｔａ Ｎｅｕｒｏｌ Ｓｃａｎｄ．， ２００２， Ｖｏｌ．１０６ Ｎｏ．６， ｐ．３２５-３２． * |
| JPN6014043239; Ｊ Ｐｈａｒｍａｃｏｌ Ｅｘｐ Ｔｈｅｒ．， １９９７， Ｖｏｌ．２８３ Ｎｏ．２，ｐ．６１９-２４． * |
| JPN6014043240; Ｂｉｏ Ｃｌｉｎｉｃａ， ２００８， Ｖｏｌ．２３ Ｎｏ．１０， ｐ．５６-６３． * |
| JPN6014043242; Ｂｉｏｓｃｉ Ｂｉｏｔｅｃｈｎｏｌ Ｂｉｏｃｈｅｍ．， ２００３， Ｖｏｌ．６７ Ｎｏ．５， ｐ．９７３-９７９ * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2016056184A (ja) | 2016-04-21 |
| US20120201754A1 (en) | 2012-08-09 |
| EP2485771A1 (en) | 2012-08-15 |
| JP6224063B2 (ja) | 2017-11-01 |
| EP2485771A4 (en) | 2014-11-12 |
| US20150139903A1 (en) | 2015-05-21 |
| US8858911B2 (en) | 2014-10-14 |
| WO2011043816A1 (en) | 2011-04-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6224063B2 (ja) | ホスホジエステラーゼ１−標的トレーサーおよび方法 | |
| JP2016056184A5 (enExample) | ||
| US20220202963A1 (en) | Radiolabeled compounds | |
| TW200804363A (en) | Novel radioligands | |
| US11999710B2 (en) | Radiolabeled cannabinoid receptor 2 ligand | |
| BRPI0806621A2 (pt) | composto, uso de um composto, composição farmacêutica, e, método in vivo para medir depósitos amilóides em um indivìduo | |
| MX2013013946A (es) | Inhibidores de ciclasa de glutaminilo radioetiquetados. | |
| BRPI0808503B1 (pt) | Composto, uso de um composto, e, composição farmacêutica | |
| Prabhakaran et al. | Synthesis, in vitro and in vivo evaluation of [11C] MMTP: a potential PET ligand for mGluR1 receptors | |
| US10865195B2 (en) | Pet imaging agents | |
| JP2013543851A (ja) | 放射性標識されたフェニルイミダゾールベースのリガンド | |
| WO2012131037A1 (en) | Radiolabelled flumazenil derivatives | |
| Cao et al. | Synthesis and preliminary evaluation of 131I-9-iodovinyl-tetrabenazine targeting vesicular monoamine transporter 2 | |
| EP1545525B1 (en) | Radiolabeled neurokinin-1 receptor antagonists | |
| WO2026008606A1 (en) | Tdp-43 binding compounds and tdp-43 positron emission tomography imaging ligands | |
| JPH02286662A (ja) | ドーパミン受容体リガンド及び結像剤 | |
| WO2009046897A1 (en) | Chemical synthesis of i-124beta cit iodine-124 [2-beta-carbomethoxy-3beta- (4. -iodophenyl) -tropane] for pet investigations and for radiotherapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20131003 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20141021 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20141215 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150120 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150220 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150320 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150421 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150825 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170512 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170613 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170713 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20170809 |