JP2012518685A - 眼障害のためのｐｄｅ１阻害剤 - Google Patents
眼障害のためのｐｄｅ１阻害剤 Download PDFInfo
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- JP2012518685A JP2012518685A JP2011552026A JP2011552026A JP2012518685A JP 2012518685 A JP2012518685 A JP 2012518685A JP 2011552026 A JP2011552026 A JP 2011552026A JP 2011552026 A JP2011552026 A JP 2011552026A JP 2012518685 A JP2012518685 A JP 2012518685A
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- alkyl
- aryl
- cycloalkyl
- methyl
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- 229940121836 Phosphodiesterase 1 inhibitor Drugs 0.000 title claims abstract description 179
- 208000030533 eye disease Diseases 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 103
- 238000011282 treatment Methods 0.000 claims abstract description 54
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 43
- 230000004410 intraocular pressure Effects 0.000 claims abstract description 35
- 239000000203 mixture Substances 0.000 claims abstract description 32
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 19
- 206010030043 Ocular hypertension Diseases 0.000 claims abstract description 13
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 13
- 230000009885 systemic effect Effects 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 175
- -1 N-dialkylamino Inorganic materials 0.000 claims description 98
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 86
- 125000003118 aryl group Chemical group 0.000 claims description 83
- 229910052799 carbon Inorganic materials 0.000 claims description 79
- 238000000034 method Methods 0.000 claims description 78
- 150000003839 salts Chemical group 0.000 claims description 65
- 125000001072 heteroaryl group Chemical group 0.000 claims description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 46
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
- 125000005843 halogen group Chemical group 0.000 claims description 39
- 239000003814 drug Substances 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 33
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
- 229940079593 drug Drugs 0.000 claims description 31
- 125000001188 haloalkyl group Chemical group 0.000 claims description 31
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 31
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 229920006395 saturated elastomer Polymers 0.000 claims description 29
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 claims description 28
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 27
- 150000001721 carbon Chemical group 0.000 claims description 26
- 125000004076 pyridyl group Chemical group 0.000 claims description 26
- 150000003180 prostaglandins Chemical class 0.000 claims description 23
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 23
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 20
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 102100024318 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B Human genes 0.000 claims description 17
- 101001117099 Homo sapiens Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B Proteins 0.000 claims description 17
- 239000000651 prodrug Chemical group 0.000 claims description 17
- 229940002612 prodrug Drugs 0.000 claims description 17
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 16
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 16
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 15
- 150000002431 hydrogen Chemical group 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000004414 alkyl thio group Chemical group 0.000 claims description 14
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 14
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- AQOKCDNYWBIDND-FTOWTWDKSA-N bimatoprost Chemical compound CCNC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)CCC1=CC=CC=C1 AQOKCDNYWBIDND-FTOWTWDKSA-N 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
- 125000004512 1,2,3-thiadiazol-4-yl group Chemical group S1N=NC(=C1)* 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- IWEGDQUCWQFKHS-UHFFFAOYSA-N 1-(1,3-dioxolan-2-ylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(CC2OCCO2)N=C1 IWEGDQUCWQFKHS-UHFFFAOYSA-N 0.000 claims description 10
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 10
- 229960002470 bimatoprost Drugs 0.000 claims description 10
- 229960001724 brimonidine tartrate Drugs 0.000 claims description 10
- 239000000464 adrenergic agent Substances 0.000 claims description 9
- 125000004122 cyclic group Chemical group 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 239000003112 inhibitor Substances 0.000 claims description 9
- 229940054534 ophthalmic solution Drugs 0.000 claims description 9
- 239000002997 ophthalmic solution Substances 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 125000006682 monohaloalkyl group Chemical group 0.000 claims description 8
- 125000006684 polyhaloalkyl group Polymers 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 6
- 125000005110 aryl thio group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 102000012740 beta Adrenergic Receptors Human genes 0.000 claims description 6
- 108010079452 beta Adrenergic Receptors Proteins 0.000 claims description 6
- 239000002876 beta blocker Substances 0.000 claims description 6
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 229960001160 latanoprost Drugs 0.000 claims description 6
- 229940094443 oxytocics prostaglandins Drugs 0.000 claims description 6
- 230000000699 topical effect Effects 0.000 claims description 6
- MKPLKVHSHYCHOC-AHTXBMBWSA-N travoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1 MKPLKVHSHYCHOC-AHTXBMBWSA-N 0.000 claims description 6
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 5
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 229960002368 travoprost Drugs 0.000 claims description 5
- 125000001425 triazolyl group Chemical group 0.000 claims description 5
- WLRMANUAADYWEA-NWASOUNVSA-N (S)-timolol maleate Chemical compound OC(=O)\C=C/C(O)=O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 WLRMANUAADYWEA-NWASOUNVSA-N 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 4
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 4
- 230000001668 ameliorated effect Effects 0.000 claims description 4
- 125000005122 aminoalkylamino group Chemical group 0.000 claims description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
- 125000001769 aryl amino group Chemical group 0.000 claims description 4
- 150000001540 azides Chemical class 0.000 claims description 4
- 239000006071 cream Substances 0.000 claims description 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 4
- 125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 4
- 239000000472 muscarinic agonist Substances 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 239000002674 ointment Substances 0.000 claims description 4
- 229940069265 ophthalmic ointment Drugs 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229940127293 prostanoid Drugs 0.000 claims description 4
- 150000003814 prostanoids Chemical class 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 229940124530 sulfonamide Drugs 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 150000003573 thiols Chemical class 0.000 claims description 4
- 229960005221 timolol maleate Drugs 0.000 claims description 4
- TVHAZVBUYQMHBC-SNHXEXRGSA-N unoprostone Chemical compound CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O TVHAZVBUYQMHBC-SNHXEXRGSA-N 0.000 claims description 4
- 229960004317 unoprostone Drugs 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000002720 diazolyl group Chemical group 0.000 claims description 3
- XXUPXHKCPIKWLR-JHUOEJJVSA-N isopropyl unoprostone Chemical group CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(=O)OC(C)C XXUPXHKCPIKWLR-JHUOEJJVSA-N 0.000 claims description 3
- 229940096984 ophthalmic cream Drugs 0.000 claims description 3
- 229940100654 ophthalmic suspension Drugs 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 229950008081 unoprostone isopropyl Drugs 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000005605 benzo group Chemical group 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 2
- 125000005518 carboxamido group Chemical group 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000003106 haloaryl group Chemical group 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 108060003345 Adrenergic Receptor Proteins 0.000 claims 4
- 102000017910 Adrenergic receptor Human genes 0.000 claims 4
- GZYKBCXBOOXTTM-UHFFFAOYSA-N 3-anilino-5-methyl-2-[(4-pyridin-2-ylphenyl)methyl]-1h-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C=1C=CC=CC=1NC1=C2C(=O)N(C)C(=O)NC2=NN1CC(C=C1)=CC=C1C1=CC=CC=N1 GZYKBCXBOOXTTM-UHFFFAOYSA-N 0.000 claims 2
- PKNOJFZRKNTJGM-UHFFFAOYSA-N 3-anilino-5-methyl-7-(2-methylpropyl)-2-[(4-phenylphenyl)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=C1C1=CC=CC=C1 PKNOJFZRKNTJGM-UHFFFAOYSA-N 0.000 claims 2
- NIEXVPSCWSOKOU-UHFFFAOYSA-N 3-anilino-5-methyl-7-(2-methylpropyl)-2-[(4-pyrazol-1-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=C1N1C=CC=N1 NIEXVPSCWSOKOU-UHFFFAOYSA-N 0.000 claims 2
- FOEJZFMBAIZVCL-UHFFFAOYSA-N 3-anilino-7-(2,2-dimethylpropyl)-5-methyl-2-[(4-pyridin-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)C)C2=NN1CC(C=C1)=CC=C1C1=CC=CC=N1 FOEJZFMBAIZVCL-UHFFFAOYSA-N 0.000 claims 2
- LKFJFBMOTUNCQS-UHFFFAOYSA-N 3-anilino-7-[(4-methoxyphenyl)methyl]-5-methyl-2-[(4-phenylphenyl)methyl]pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N(C)C(=O)C2=C(NC=3C=CC=CC=3)N(CC=3C=CC(=CC=3)C=3C=CC=CC=3)N=C21 LKFJFBMOTUNCQS-UHFFFAOYSA-N 0.000 claims 2
- AYFWOHAHSGBBKN-UHFFFAOYSA-N 3-anilino-7-[(4-methoxyphenyl)methyl]-5-methyl-2-[(4-pyridin-2-ylphenyl)methyl]pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N(C)C(=O)C2=C(NC=3C=CC=CC=3)N(CC=3C=CC(=CC=3)C=3N=CC=CC=3)N=C21 AYFWOHAHSGBBKN-UHFFFAOYSA-N 0.000 claims 2
- KXYRHKLJZOUTTR-UHFFFAOYSA-N 3-anilino-7-cyclopentyl-5-methyl-2-[(4-pyridin-2-ylphenyl)methyl]pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C12=NN(CC=3C=CC(=CC=3)C=3N=CC=CC=3)C(NC=3C=CC=CC=3)=C2C(=O)N(C)C(=O)N1C1CCCC1 KXYRHKLJZOUTTR-UHFFFAOYSA-N 0.000 claims 2
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims 2
- 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 claims 1
- BDABEQSQUPAQLG-UHFFFAOYSA-N 3-(n-cyclopentylanilino)-5-methyl-2-[(4-pyridin-2-ylphenyl)methyl]-1h-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1CCCC1N(C=1C=CC=CC=1)C1=C2C(=O)N(C)C(=O)NC2=NN1CC(C=C1)=CC=C1C1=CC=CC=N1 BDABEQSQUPAQLG-UHFFFAOYSA-N 0.000 claims 1
- NUGDPTDTOCLGNC-UHFFFAOYSA-N 3-anilino-2-[[4-(5-fluoropyrimidin-2-yl)phenyl]methyl]-5-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=C1C1=NC=C(F)C=N1 NUGDPTDTOCLGNC-UHFFFAOYSA-N 0.000 claims 1
- YQDNWIPJGMMJDQ-UHFFFAOYSA-N 3-anilino-5-methyl-2-[(4-pyridin-2-ylphenyl)methyl]-7-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C=1C=CC=CC=1NC1=C2C(=O)N(C)C(=O)N(CC(F)(F)F)C2=NN1CC(C=C1)=CC=C1C1=CC=CC=N1 YQDNWIPJGMMJDQ-UHFFFAOYSA-N 0.000 claims 1
- FMAYUZFAJQOADP-UHFFFAOYSA-N 3-anilino-5-methyl-2-[[4-(5-methyl-1,2,4-oxadiazol-3-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=C1C1=NOC(C)=N1 FMAYUZFAJQOADP-UHFFFAOYSA-N 0.000 claims 1
- RWTYIOFOSAVNPW-UHFFFAOYSA-N 3-anilino-5-methyl-7-(2-methylpropyl)-2-[(4-methylsulfonylphenyl)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=NN1CC1=CC=C(S(C)(=O)=O)C=C1 RWTYIOFOSAVNPW-UHFFFAOYSA-N 0.000 claims 1
- NYUOFLITHDBQSA-UHFFFAOYSA-N 3-anilino-5-methyl-7-(2-methylpropyl)-2-[(4-pyridin-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=C1C1=CC=CC=N1 NYUOFLITHDBQSA-UHFFFAOYSA-N 0.000 claims 1
- QZFJKIQSVOUYTI-UHFFFAOYSA-N 3-anilino-7-(2,2-dimethylpropyl)-5-methyl-2-[[6-(trifluoromethyl)pyridin-3-yl]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)C)C2=NN1CC1=CC=C(C(F)(F)F)N=C1 QZFJKIQSVOUYTI-UHFFFAOYSA-N 0.000 claims 1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
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- 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
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- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
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| PCT/US2010/000534 WO2010098839A1 (en) | 2009-02-25 | 2010-02-24 | Pde 1 inhibitors for ophthalmic disorders |
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| JP2017527598A (ja) * | 2014-09-17 | 2017-09-21 | 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． | 化合物および方法 |
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| ES2645371T3 (es) | 2005-06-06 | 2017-12-05 | Intra-Cellular Therapies, Inc. | Compuestos orgánicos |
| 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 |
| 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 |
| MX2011005935A (es) | 2008-12-06 | 2011-12-16 | Intra Cellular Therapies Inc | Compuestos organicos. |
| AU2009322903A1 (en) | 2008-12-06 | 2010-06-10 | Intra-Cellular Therapies, Inc. | Organic compounds |
| ES2638912T3 (es) | 2008-12-06 | 2017-10-24 | Intra-Cellular Therapies, Inc. | Compuestos orgánicos |
| 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 |
| 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 |
| EP2485771A4 (en) | 2009-10-08 | 2014-11-12 | Intra Cellular Therapies Inc | TRACER AND METHODS TAGGED ON PHOSPHODIESTERASE 1 |
| 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 |
| 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 |
| 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 |
| SG11201408397SA (en) | 2012-06-18 | 2015-01-29 | Dart Neuroscience Cayman Ltd | Substituted thiophene- and furan-fused azolopyrimidine-5-(6h)-one 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 |
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| 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 |
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| WO2015196186A1 (en) | 2014-06-20 | 2015-12-23 | Intra-Cellular Therapies, Inc. | Organic compounds |
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| EP3226870B1 (en) | 2014-12-06 | 2019-09-25 | Intra-Cellular Therapies, Inc. | Organic compounds |
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| 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 |
| CA3117148A1 (en) | 2018-10-21 | 2020-04-30 | Intra-Cellular Therapies, Inc. | Novel uses |
| US20220125791A1 (en) * | 2019-01-30 | 2022-04-28 | Intra-Cellular Therapies, Inc. | Novel devices |
| 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 |
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2010
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- 2010-02-24 WO PCT/US2010/000534 patent/WO2010098839A1/en not_active Ceased
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2015
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| JP2017527598A (ja) * | 2014-09-17 | 2017-09-21 | 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． | 化合物および方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2015212262A (ja) | 2015-11-26 |
| US20110312978A1 (en) | 2011-12-22 |
| US11464781B2 (en) | 2022-10-11 |
| WO2010098839A1 (en) | 2010-09-02 |
| JP6247249B2 (ja) | 2017-12-13 |
| EP2400970A1 (en) | 2012-01-04 |
| EP2400970A4 (en) | 2012-07-18 |
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