ES2645371T3 - Compuestos orgánicos - Google Patents
Compuestos orgánicos Download PDFInfo
- Publication number
- ES2645371T3 ES2645371T3 ES06772397.3T ES06772397T ES2645371T3 ES 2645371 T3 ES2645371 T3 ES 2645371T3 ES 06772397 T ES06772397 T ES 06772397T ES 2645371 T3 ES2645371 T3 ES 2645371T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- halogen
- pyrazolo
- pyrimidin
- carboxy
- 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.)
- Active
Links
- 150000002894 organic compounds Chemical class 0.000 title description 2
- -1 bicyclic aromatic hydrocarbon Chemical class 0.000 claims abstract description 59
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 52
- 125000003118 aryl group Chemical group 0.000 claims abstract description 51
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 51
- 150000002367 halogens Chemical group 0.000 claims abstract description 51
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 42
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 35
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 23
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
- 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 abstract description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 13
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 11
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 10
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 10
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims abstract description 4
- 125000004429 atom Chemical group 0.000 claims abstract description 4
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 4
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 4
- 239000011593 sulfur Substances 0.000 claims abstract description 4
- 229930195734 saturated hydrocarbon Natural products 0.000 claims abstract 3
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims description 137
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 47
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 23
- 125000004076 pyridyl group Chemical group 0.000 claims description 22
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 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 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 12
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 10
- 125000004512 1,2,3-thiadiazol-4-yl group Chemical group S1N=NC(=C1)* 0.000 claims description 9
- 208000018737 Parkinson disease Diseases 0.000 claims description 9
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 229910052702 rhenium Inorganic materials 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 230000019491 signal transduction Effects 0.000 claims description 6
- 208000028698 Cognitive impairment Diseases 0.000 claims description 5
- 208000010877 cognitive disease Diseases 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 4
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 4
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 4
- 208000005793 Restless legs syndrome Diseases 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000001769 aryl amino group Chemical group 0.000 claims description 4
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 4
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 4
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- TZYQTWHRLVDYPL-UHFFFAOYSA-N 5h-pyrimidin-4-one Chemical compound O=C1CC=NC=N1 TZYQTWHRLVDYPL-UHFFFAOYSA-N 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 150000002430 hydrocarbons Chemical group 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- NCGOHHUTVVTFHA-UHFFFAOYSA-N 5-anilino-8,11,11-trimethyl-3-[[4-(thiadiazol-4-yl)phenyl]methyl]-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2(6),4,9-trien-7-one Chemical compound O=C1N(C)C2=NC(C)(C)CN2C(N(N=2)CC=3C=CC(=CC=3)C=3N=NSC=3)=C1C=2NC1=CC=CC=C1 NCGOHHUTVVTFHA-UHFFFAOYSA-N 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 208000020925 Bipolar disease Diseases 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 208000012661 Dyskinesia Diseases 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 208000016285 Movement disease Diseases 0.000 claims description 2
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
- 206010044565 Tremor Diseases 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 201000010105 allergic rhinitis Diseases 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 230000001363 autoimmune Effects 0.000 claims description 2
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 2
- 125000002720 diazolyl group Chemical group 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 239000003368 psychostimulant agent Substances 0.000 claims description 2
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 2
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 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 2
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims 2
- 238000011084 recovery Methods 0.000 claims 2
- SRETYLZYPIDWJS-UHFFFAOYSA-N 3-benzyl-2-(biphenyl-4-ylmethyl)-7,8-dihydro-5,7,7-trimethyl-[2h]-imidazo-[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5h)-one Chemical compound C=1C=CC=CC=1CC1=C2C(=O)N(C)C3=NC(C)(C)CN3C2=NN1CC(C=C1)=CC=C1C1=CC=CC=C1 SRETYLZYPIDWJS-UHFFFAOYSA-N 0.000 claims 1
- NSDAHLNHHJYAFQ-UHFFFAOYSA-N 8,11,11-trimethyl-3-[(4-phenylphenyl)methyl]-5-[N-[(4-phenylphenyl)methyl]anilino]-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2(6),4,9-trien-7-one Chemical compound O=C1N(C)C2=NC(C)(C)CN2C2=C1C(N(CC=1C=CC(=CC=1)C=1C=CC=CC=1)C=1C=CC=CC=1)=NN2CC(C=C1)=CC=C1C1=CC=CC=C1 NSDAHLNHHJYAFQ-UHFFFAOYSA-N 0.000 claims 1
- 206010012335 Dependence Diseases 0.000 claims 1
- 101001117089 Drosophila melanogaster Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1 Proteins 0.000 claims 1
- 230000018044 dehydration Effects 0.000 claims 1
- 238000006297 dehydration reaction Methods 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 abstract description 5
- 125000001183 hydrocarbyl group Chemical group 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000000243 solution Substances 0.000 description 28
- 239000000543 intermediate Substances 0.000 description 27
- 239000002904 solvent Substances 0.000 description 22
- 239000000047 product Substances 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 20
- 238000010438 heat treatment Methods 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 17
- 102100024318 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B Human genes 0.000 description 17
- 101001117099 Homo sapiens Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B Proteins 0.000 description 17
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 17
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 16
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- 101001117086 Dictyostelium discoideum cAMP/cGMP-dependent 3',5'-cAMP/cGMP phosphodiesterase A Proteins 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 15
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 15
- 238000001816 cooling Methods 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 238000001308 synthesis method Methods 0.000 description 14
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 8
- 229940058020 2-amino-2-methyl-1-propanol Drugs 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 235000015320 potassium carbonate Nutrition 0.000 description 6
- 238000010189 synthetic method Methods 0.000 description 6
- HZQLUIZFUXNFHK-UHFFFAOYSA-N 1-(bromomethyl)-4-phenylbenzene Chemical group C1=CC(CBr)=CC=C1C1=CC=CC=C1 HZQLUIZFUXNFHK-UHFFFAOYSA-N 0.000 description 5
- FCLQGHNSQXFQEG-UHFFFAOYSA-N 2-[4-(bromomethyl)phenyl]pyridine Chemical compound C1=CC(CBr)=CC=C1C1=CC=CC=N1 FCLQGHNSQXFQEG-UHFFFAOYSA-N 0.000 description 5
- DBTMQODRSDEGRZ-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-(2-oxoethyl)carbamate Chemical compound C1=CC=C2C(COC(=O)NCC=O)C3=CC=CC=C3C2=C1 DBTMQODRSDEGRZ-UHFFFAOYSA-N 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- 102000004076 Dopamine D1 Receptors Human genes 0.000 description 5
- 108090000511 Dopamine D1 Receptors Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 229910019213 POCl3 Inorganic materials 0.000 description 5
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 238000005660 chlorination reaction Methods 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 239000012024 dehydrating agents Substances 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 229960003638 dopamine Drugs 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 210000001577 neostriatum Anatomy 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- JFFOUICIRBXFRC-RFZPGFLSSA-N (1r,2r)-2-aminocyclopentan-1-ol Chemical compound N[C@@H]1CCC[C@H]1O JFFOUICIRBXFRC-RFZPGFLSSA-N 0.000 description 4
- RQFCJASXJCIDSX-UHFFFAOYSA-N 14C-Guanosin-5'-monophosphat Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(O)=O)C(O)C1O RQFCJASXJCIDSX-UHFFFAOYSA-N 0.000 description 4
- KTTPPSPBNHDDGN-UHFFFAOYSA-N 6-hydrazinyl-1-[(4-methoxyphenyl)methyl]-3-methylpyrimidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N(C)C(=O)C=C1NN KTTPPSPBNHDDGN-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 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
- 229910052786 argon Inorganic materials 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 229940125890 compound Ia Drugs 0.000 description 4
- 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 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 102000003678 AMPA Receptors Human genes 0.000 description 3
- 108090000078 AMPA Receptors Proteins 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- 102100024316 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Human genes 0.000 description 3
- 102100024317 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C Human genes 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 3
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001117044 Homo sapiens Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Proteins 0.000 description 3
- 101001117094 Homo sapiens Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C Proteins 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 229910006124 SOCl2 Inorganic materials 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 210000001638 cerebellum Anatomy 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 230000031146 intracellular signal transduction Effects 0.000 description 3
- 230000004068 intracellular signaling Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229940127557 pharmaceutical product Drugs 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- NWYYWIJOWOLJNR-YFKPBYRVSA-N (2r)-2-amino-3-methylbutan-1-ol Chemical compound CC(C)[C@@H](N)CO NWYYWIJOWOLJNR-YFKPBYRVSA-N 0.000 description 2
- 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 2
- DDZRORQHXHMKDZ-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]-3-methyl-6-[2-[(4-phenylphenyl)methylidene]hydrazinyl]pyrimidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N(C)C(=O)C=C1NN=CC1=CC=C(C=2C=CC=CC=2)C=C1 DDZRORQHXHMKDZ-UHFFFAOYSA-N 0.000 description 2
- DCGGMHIZEAHUJL-UHFFFAOYSA-N 1-methyl-1,3-diazinane-2,4,6-trione Chemical compound CN1C(=O)CC(=O)NC1=O DCGGMHIZEAHUJL-UHFFFAOYSA-N 0.000 description 2
- QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical compound C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 2
- URIOKNBMKROHSV-UHFFFAOYSA-N 2-(biphenyl-4-ylmethyl)-7,8-dihydro-5,7,7-trimethyl-[2h]-imidazo-[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5h)-one Chemical compound C1=C2C(=O)N(C)C3=NC(C)(C)CN3C2=NN1CC(C=C1)=CC=C1C1=CC=CC=C1 URIOKNBMKROHSV-UHFFFAOYSA-N 0.000 description 2
- VAPROOBYXGIIII-CHWSQXEVSA-N 3-anilino-6-[[(1R,2R)-2-hydroxycyclohexyl]amino]-5-methyl-2H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound N=1C2=NNC(NC=3C=CC=CC=3)=C2C(=O)N(C)C=1N[C@@H]1CCCC[C@H]1O VAPROOBYXGIIII-CHWSQXEVSA-N 0.000 description 2
- UXGFENPVRDNBEZ-UHFFFAOYSA-N 3-anilino-6-chloro-5-methyl-2h-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=2C(=O)N(C)C(Cl)=NC=2NN=C1NC1=CC=CC=C1 UXGFENPVRDNBEZ-UHFFFAOYSA-N 0.000 description 2
- LORJEVCVIWOZTJ-UHFFFAOYSA-N 3-benzyl-5-methyl-2-[(4-phenylphenyl)methyl]-1h-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C=1C=CC=CC=1CC1=C2C(=O)N(C)C(=O)NC2=NN1CC(C=C1)=CC=C1C1=CC=CC=C1 LORJEVCVIWOZTJ-UHFFFAOYSA-N 0.000 description 2
- JSOKOOPXJFFDOL-UHFFFAOYSA-N 3-benzyl-6-chloro-5-methyl-2-[(4-phenylphenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C=1C=CC=CC=1CC1=C2C(=O)N(C)C(Cl)=NC2=NN1CC(C=C1)=CC=C1C1=CC=CC=C1 JSOKOOPXJFFDOL-UHFFFAOYSA-N 0.000 description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 2
- ISDBWOPVZKNQDW-UHFFFAOYSA-N 4-phenylbenzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CC=CC=C1 ISDBWOPVZKNQDW-UHFFFAOYSA-N 0.000 description 2
- SPIZYPSHBCPKFF-UHFFFAOYSA-N 5-methyl-2-[(4-phenylphenyl)methyl]-1h-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=C2C(=O)N(C)C(=O)NC2=NN1CC(C=C1)=CC=C1C1=CC=CC=C1 SPIZYPSHBCPKFF-UHFFFAOYSA-N 0.000 description 2
- SGLXGFAZAARYJY-UHFFFAOYSA-N 6-Chloro-3-methyluracil Chemical compound CN1C(=O)C=C(Cl)NC1=O SGLXGFAZAARYJY-UHFFFAOYSA-N 0.000 description 2
- NINZAMOQCXMUNF-UHFFFAOYSA-N 6-chloro-1-[(4-methoxyphenyl)methyl]-3-methylpyrimidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N(C)C(=O)C=C1Cl NINZAMOQCXMUNF-UHFFFAOYSA-N 0.000 description 2
- OKELOWNXOVOLDX-UHFFFAOYSA-N 6-chloro-5-methyl-2-[(4-phenylphenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=C2C(=O)N(C)C(Cl)=NC2=NN1CC(C=C1)=CC=C1C1=CC=CC=C1 OKELOWNXOVOLDX-UHFFFAOYSA-N 0.000 description 2
- JVYBHXSIAJRNGN-UHFFFAOYSA-N 7-[(4-methoxyphenyl)methyl]-5-methyl-1h-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N(C)C(=O)C2=C1NN=C2 JVYBHXSIAJRNGN-UHFFFAOYSA-N 0.000 description 2
- WVVWJZXPWNPJJQ-UHFFFAOYSA-N 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=CN(CC=3C=CC(=CC=3)C=3C=CC=CC=3)N=C21 WVVWJZXPWNPJJQ-UHFFFAOYSA-N 0.000 description 2
- AEOBEOJCBAYXBA-UHFFFAOYSA-N A2P5P Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1OP(O)(O)=O AEOBEOJCBAYXBA-UHFFFAOYSA-N 0.000 description 2
- 101150051188 Adora2a gene Proteins 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 102000000584 Calmodulin Human genes 0.000 description 2
- 108010041952 Calmodulin Proteins 0.000 description 2
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 2
- 108050007331 Cannabinoid receptor Proteins 0.000 description 2
- 102000012749 Dopamine and cAMP-Regulated Phosphoprotein 32 Human genes 0.000 description 2
- 108010090047 Dopamine and cAMP-Regulated Phosphoprotein 32 Proteins 0.000 description 2
- 102000009025 Endorphins Human genes 0.000 description 2
- 108010049140 Endorphins Proteins 0.000 description 2
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 2
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 2
- 108020001621 Natriuretic Peptide Proteins 0.000 description 2
- 102000004571 Natriuretic peptide Human genes 0.000 description 2
- 101800001814 Neurotensin Proteins 0.000 description 2
- 102000050267 Neurotensin Human genes 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 210000004227 basal ganglia Anatomy 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- MDKCFLQDBWCQCV-UHFFFAOYSA-N benzyl isothiocyanate Chemical compound S=C=NCC1=CC=CC=C1 MDKCFLQDBWCQCV-UHFFFAOYSA-N 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- LQCIDLXXSFUYSA-UHFFFAOYSA-N cerium(4+);tetranitrate Chemical compound [Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O LQCIDLXXSFUYSA-UHFFFAOYSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002875 fluorescence polarization Methods 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 description 2
- 229960004502 levodopa Drugs 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000000692 natriuretic peptide Substances 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 230000002474 noradrenergic effect Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229940117953 phenylisothiocyanate Drugs 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000011535 reaction buffer Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- HXKKHQJGJAFBHI-GSVOUGTGSA-N (2R)-1-aminopropan-2-ol Chemical compound C[C@@H](O)CN HXKKHQJGJAFBHI-GSVOUGTGSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- IKSNDOVDVVPSMA-UHFFFAOYSA-N 1-(bromomethyl)-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(CBr)C=C1 IKSNDOVDVVPSMA-UHFFFAOYSA-N 0.000 description 1
- HGKPAXHJTMHWAH-UHFFFAOYSA-N 1-(bromomethyl)-4-methylsulfonylbenzene Chemical compound CS(=O)(=O)C1=CC=C(CBr)C=C1 HGKPAXHJTMHWAH-UHFFFAOYSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- FNVOFDGAASRDQY-UHFFFAOYSA-N 3-amino-2,2-dimethylpropan-1-ol Chemical compound NCC(C)(C)CO FNVOFDGAASRDQY-UHFFFAOYSA-N 0.000 description 1
- RSKMURXZNFKYLF-UHFFFAOYSA-N 3-anilino-5-methyl-1,2-dihydropyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=2C(=O)N(C)C(=O)NC=2NN=C1NC1=CC=CC=C1 RSKMURXZNFKYLF-UHFFFAOYSA-N 0.000 description 1
- PMZCEKCDRDKGAO-UHFFFAOYSA-N 3-anilino-7-[(4-methoxyphenyl)methyl]-5-methyl-2h-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N(C)C(=O)C2=C1NN=C2NC1=CC=CC=C1 PMZCEKCDRDKGAO-UHFFFAOYSA-N 0.000 description 1
- SUVOQOOBXAPWRL-UHFFFAOYSA-N 3-benzyl-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(CC=3C=CC=CC=3)N(CC=3C=CC(=CC=3)C=3C=CC=CC=3)N=C21 SUVOQOOBXAPWRL-UHFFFAOYSA-N 0.000 description 1
- MOVSRIIBGRAUAF-UHFFFAOYSA-N 4-(bromomethyl)-2-fluoro-1-(trifluoromethyl)benzene Chemical compound FC1=CC(CBr)=CC=C1C(F)(F)F MOVSRIIBGRAUAF-UHFFFAOYSA-N 0.000 description 1
- KCYKKBNXHITUOU-UHFFFAOYSA-N 4-(thiadiazol-4-yl)benzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CSN=N1 KCYKKBNXHITUOU-UHFFFAOYSA-N 0.000 description 1
- DGHQOPZIGDRUIT-UHFFFAOYSA-N 4-[4-(bromomethyl)phenyl]thiadiazole Chemical compound C1=CC(CBr)=CC=C1C1=CSN=N1 DGHQOPZIGDRUIT-UHFFFAOYSA-N 0.000 description 1
- IRQUWHXXVJARBK-UHFFFAOYSA-N 5-(bromomethyl)-2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(CBr)C=N1 IRQUWHXXVJARBK-UHFFFAOYSA-N 0.000 description 1
- MNXHQSSGIULDQB-UHFFFAOYSA-N 5-anilino-8,12,12-trimethyl-4-[(4-phenylphenyl)methyl]-1,3,4,8,10-pentazatricyclo[7.4.0.02,6]trideca-2,5,9-trien-7-one Chemical compound N12CC(C)(C)CN=C2N(C)C(=O)C(=C2NC=3C=CC=CC=3)C1=NN2CC(C=C1)=CC=C1C1=CC=CC=C1 MNXHQSSGIULDQB-UHFFFAOYSA-N 0.000 description 1
- RVBOYHSNRVMXDX-UHFFFAOYSA-N 6-[(1-hydroxy-2-methylpropan-2-yl)amino]-5-methyl-2-[(4-phenylphenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=C2C(=O)N(C)C(NC(C)(C)CO)=NC2=NN1CC(C=C1)=CC=C1C1=CC=CC=C1 RVBOYHSNRVMXDX-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102000004631 Calcineurin Human genes 0.000 description 1
- 108010042955 Calcineurin Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000004657 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Human genes 0.000 description 1
- 108010003721 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- 101710095468 Cyclase Proteins 0.000 description 1
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 1
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 1
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
- 101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000010909 Monoamine Oxidase Human genes 0.000 description 1
- 108010062431 Monoamine oxidase Proteins 0.000 description 1
- 101000909851 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) cAMP/cGMP dual specificity phosphodiesterase Rv0805 Proteins 0.000 description 1
- XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methylthiourea Natural products CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 description 1
- QAADZYUXQLUXFX-UHFFFAOYSA-N N-phenylmethylthioformamide Natural products S=CNCC1=CC=CC=C1 QAADZYUXQLUXFX-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 101150098694 PDE5A gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229940121836 Phosphodiesterase 1 inhibitor Drugs 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 108010037572 Type 1 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 1
- 102000010856 Type 1 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 1
- RYULULVJWLRDQH-UHFFFAOYSA-N [4-(bromomethyl)phenyl]-phenylmethanone Chemical compound C1=CC(CBr)=CC=C1C(=O)C1=CC=CC=C1 RYULULVJWLRDQH-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 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 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229960004205 carbidopa Drugs 0.000 description 1
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 description 1
- 239000003543 catechol methyltransferase inhibitor Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000013530 defoamer Substances 0.000 description 1
- 210000001947 dentate gyrus Anatomy 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000000510 dopamine 1 receptor stimulating agent Substances 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 230000008923 dopaminergic innervation Effects 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 235000013928 guanylic acid Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000011141 high resolution liquid chromatography Methods 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000037041 intracellular level Effects 0.000 description 1
- 230000006662 intracellular pathway Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- VHWYCFISAQVCCP-UHFFFAOYSA-N methoxymethanol Chemical compound COCO VHWYCFISAQVCCP-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- XGEGHDBEHXKFPX-NJFSPNSNSA-N methylurea Chemical compound [14CH3]NC(N)=O XGEGHDBEHXKFPX-NJFSPNSNSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000001706 olfactory mucosa Anatomy 0.000 description 1
- 210000002475 olfactory pathway Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUYQIJQHYDZUDF-UHFFFAOYSA-N pyrazolo[3,4-d]pyrimidin-4-one Chemical class O=C1N=CN=C2N=NC=C12 IUYQIJQHYDZUDF-UHFFFAOYSA-N 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000011894 semi-preparative HPLC Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic 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
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Addiction (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Psychology (AREA)
- Reproductive Health (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Gynecology & Obstetrics (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Otolaryngology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US68771505P | 2005-06-06 | 2005-06-06 | |
| US687715P | 2005-06-06 | ||
| PCT/US2006/022066 WO2006133261A2 (en) | 2005-06-06 | 2006-06-06 | Organic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2645371T3 true ES2645371T3 (es) | 2017-12-05 |
Family
ID=37499079
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06772397.3T Active ES2645371T3 (es) | 2005-06-06 | 2006-06-06 | Compuestos orgánicos |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US8273750B2 (enExample) |
| EP (1) | EP1888534B1 (enExample) |
| JP (3) | JP5084725B2 (enExample) |
| KR (2) | KR20140022114A (enExample) |
| CN (2) | CN101248050B (enExample) |
| AU (1) | AU2006255028B2 (enExample) |
| BR (1) | BRPI0611095B8 (enExample) |
| CA (1) | CA2611312C (enExample) |
| ES (1) | ES2645371T3 (enExample) |
| WO (1) | WO2006133261A2 (enExample) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2459161A1 (en) | 2001-08-31 | 2003-03-13 | The Rockefeller University | Phosphodiesterase activity and regulation of phosphodiesterase 1b-mediated signaling in brain |
| CN101248050B (zh) | 2005-06-06 | 2013-07-17 | 武田药品工业株式会社 | 有机化合物 |
| EP1919287A4 (en) * | 2005-08-23 | 2010-04-28 | Intra Cellular Therapies Inc | ORGANIC COMPOUNDS FOR TREATING A REDUCED DOPAMINE RECEPTOR SIGNALING ACTIVITY |
| KR20090042227A (ko) | 2006-06-06 | 2009-04-29 | 인트라-셀룰라 써래피스, 인코퍼레이티드. | 유기 화합물 |
| WO2008063505A1 (en) * | 2006-11-13 | 2008-05-29 | 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 |
| AU2012204137B2 (en) * | 2007-12-06 | 2015-06-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| WO2009075784A1 (en) * | 2007-12-06 | 2009-06-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US20120070443A1 (en) * | 2008-12-02 | 2012-03-22 | University Of Utah Research Foundation | Pde1 as a target therapeutic in heart disease |
| EP2358204B1 (en) * | 2008-12-06 | 2015-08-05 | Intra-Cellular Therapies, Inc. | 4,5,7,8-tetrahydro-4-oxo-2H-imidazo[1,2-a]pyrrolo[3,4-e]pyrimidine compounds as PDE1 inhibitors. |
| EP2367429B1 (en) * | 2008-12-06 | 2017-06-07 | Intra-Cellular Therapies, Inc. | Organic compounds |
| KR20110098731A (ko) | 2008-12-06 | 2011-09-01 | 인트라-셀룰라 써래피스, 인코퍼레이티드. | 유기 화합물 |
| CN102223799A (zh) | 2008-12-06 | 2011-10-19 | 细胞内治疗公司 | 有机化合物 |
| CN102232077A (zh) | 2008-12-06 | 2011-11-02 | 细胞内治疗公司 | 有机化合物 |
| WO2010065147A1 (en) * | 2008-12-06 | 2010-06-10 | Intra-Cellular Therapies, Inc. | Organic compounds |
| EP2400970A4 (en) * | 2009-02-25 | 2012-07-18 | Intra Cellular Therapies Inc | PDE-1-HEMMER FOR EYE DRESSING |
| US9468637B2 (en) | 2009-05-13 | 2016-10-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| WO2011016861A2 (en) | 2009-08-05 | 2011-02-10 | Intra-Cellular Therapies, Inc. | Novel regulatory proteins and inhibitors |
| JP2013507360A (ja) * | 2009-10-08 | 2013-03-04 | イントラ−セルラー・セラピーズ・インコーポレイテッド | ホスホジエステラーゼ１−標的トレーサーおよび方法 |
| WO2011153135A1 (en) | 2010-05-31 | 2011-12-08 | Intra-Cellular Therapies, Inc. | Organic compounds |
| TW201206937A (en) | 2010-05-31 | 2012-02-16 | Intra Cellular Therapies Inc | Organic compounds |
| JP5911854B2 (ja) * | 2010-05-31 | 2016-04-27 | 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 |
| JP5879336B2 (ja) | 2010-05-31 | 2016-03-08 | 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 |
| US10561656B2 (en) | 2011-06-10 | 2020-02-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| MX2014012374A (es) * | 2012-04-14 | 2015-04-17 | Intra Cellular Therapies Inc | Compuestos organicos. |
| 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 |
| CN103012287B (zh) * | 2012-12-24 | 2015-06-17 | 济南圣泉唐和唐生物科技有限公司 | 6-氯-3-甲基脲嘧啶的制备方法 |
| US9801882B2 (en) | 2013-02-17 | 2017-10-31 | Intra-Cellular Therapies, Inc. | Phosphodiesterase-1 inhibitors and their use in treatment of cardiovascular diseases |
| ES2836129T3 (es) * | 2013-03-15 | 2021-06-24 | Intra Cellular Therapies Inc | Compuestos orgánicos |
| EP2968338B1 (en) | 2013-03-15 | 2019-01-09 | Intra-Cellular Therapies, Inc. | Pde1 inhibitors for use in the treatment and/or prevention of cns injuries, and pns diseases, disorders or injuries |
| EP3010509B1 (en) * | 2013-06-21 | 2021-07-28 | Intra-Cellular Therapies, Inc. | Free base crystals |
| JP6696904B2 (ja) * | 2014-01-08 | 2020-05-20 | 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． | 製剤および医薬組成物 |
| US9884872B2 (en) | 2014-06-20 | 2018-02-06 | Intra-Cellular Therapies, Inc. | Organic compounds |
| ES2745819T3 (es) * | 2014-08-07 | 2020-03-03 | Intra Cellular Therapies Inc | Derivados de imidazo[1,2-a]-pirazolo[4,3-e]-pirimidin-4-ona con actividad inhibidora de la PDE1 |
| US10005789B2 (en) | 2014-08-07 | 2018-06-26 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US9546175B2 (en) | 2014-08-07 | 2017-01-17 | Intra-Cellular Therapies, Inc. | Organic compounds |
| WO2016022825A1 (en) * | 2014-08-07 | 2016-02-11 | 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 |
| 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) |
| HK1243935A1 (zh) | 2014-12-06 | 2018-07-27 | Intra-Cellular Therapies, Inc. | 有机化合物 |
| HK1243936A1 (zh) | 2014-12-06 | 2018-07-27 | Intra-Cellular Therapies, Inc. | 有机化合物 |
| WO2016191935A1 (en) * | 2015-05-29 | 2016-12-08 | Merck Sharp & Dohme Corp. | 6-alkyl dihydropyrazolopyrimidinone compounds as pde2 inhibitors |
| WO2016192083A1 (en) * | 2015-06-04 | 2016-12-08 | Merck Sharp & Dohme Corp. | Dihydropyrazolopyrimidinone compounds as pde2 inhibitors |
| 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 |
| JP6996074B2 (ja) * | 2016-06-28 | 2022-01-17 | 住友ゴム工業株式会社 | ゴム組成物およびタイヤ |
| JP7134168B6 (ja) | 2016-09-12 | 2024-02-02 | 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 |
| AU2017388054B2 (en) | 2016-12-28 | 2022-03-24 | Dart Neuroscience, Llc | Substituted pyrazolopyrimidinone compounds as PDE2 inhibitors |
| CN109422749B (zh) * | 2017-08-21 | 2023-01-24 | 重庆医药工业研究院有限责任公司 | 一种抑制单羧酸转运蛋白的嘧啶二酮衍生物 |
| CA3120971A1 (en) | 2017-11-27 | 2019-05-31 | Dart Neuroscience, Llc | Substituted furanopyrimidine compounds as pde1 inhibitors |
| EP3746081A4 (en) | 2018-01-31 | 2021-10-27 | Intra-Cellular Therapies, Inc. | Novel uses |
| CN112189013A (zh) | 2018-05-25 | 2021-01-05 | 细胞内治疗公司 | 有机化合物 |
| WO2020146384A1 (en) * | 2019-01-07 | 2020-07-16 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US11628171B2 (en) | 2019-03-13 | 2023-04-18 | Children's Medical Center Corporation | Method for treating brain or nerve injury |
| EP4413980A3 (en) | 2019-09-03 | 2024-10-30 | Intra-Cellular Therapies, Inc. | Novel compounds |
| US20230355625A1 (en) * | 2019-11-27 | 2023-11-09 | Intra-Cellular Therapies, Inc. | Methods of treatment |
| US12435093B2 (en) | 2020-05-06 | 2025-10-07 | Intra-Cellular Therapies, Inc. | Free base crystals |
| US12364695B2 (en) | 2020-06-02 | 2025-07-22 | Intra-Cellular Therapies, Inc. | Methods of treating inflammatory disease |
| JP2023535224A (ja) * | 2020-07-26 | 2023-08-16 | 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 |
Family Cites Families (73)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6032638B2 (ja) | 1976-09-01 | 1985-07-29 | 武田薬品工業株式会社 | ３−アミノピラゾロ〔３，４−ｄ〕ピリミジン誘導体 |
| EP0077372A1 (de) | 1981-04-22 | 1983-04-27 | Byk Gulden Lomberg Chemische Fabrik GmbH | NEUE PYRAZOLO(3,4-d)PYRIMIDINE, VERFAHREN ZU DEREN HERSTELLUNG UND SIE ENTHALTENDE ARZNEIMITTEL |
| US4469868A (en) | 1982-05-24 | 1984-09-04 | Warner-Lambert Company | Alkylimidazo[1,2-c]pyrazolo[3,4-e]pyrimidines |
| US4666908A (en) | 1985-04-05 | 1987-05-19 | Warner-Lambert Company | 5-Substituted pyrazolo[4,3-d]pyrimidine-7-ones and methods of use |
| KR920004437B1 (ko) | 1989-09-12 | 1992-06-05 | 삼성전자 주식회사 | 금전등록기의 거래선 관리방법 |
| NZ238609A (en) * | 1990-06-21 | 1993-12-23 | Schering Corp | Polycyclic guanine derivatives; preparation, pharmaceutical compositions, |
| US5202328A (en) | 1991-03-06 | 1993-04-13 | Merck & Co., Inc. | Substituted fused pyrimidinones |
| US5294612A (en) | 1992-03-30 | 1994-03-15 | Sterling Winthrop Inc. | 6-heterocyclyl pyrazolo [3,4-d]pyrimidin-4-ones and compositions and method of use thereof |
| CA2156918A1 (en) * | 1993-02-26 | 1994-09-01 | Deen Tulshian | 2-benzyl-polycyclic guanine derivatives and process for preparing them |
| GB9304919D0 (en) | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9315017D0 (en) | 1993-07-20 | 1993-09-01 | Glaxo Lab Sa | Chemical compounds |
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| US5824683A (en) * | 1995-11-28 | 1998-10-20 | Schering Corporation | 2'- 4'-halo- 1,1'-biphenyl!-4-yl!methyl!-5'-methyl-spiro cyclopentane-1,7' (8'H)- 3H! imidazo 2,1-b!purin!-4' (5'H)-ones |
| GB9526245D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9622363D0 (en) | 1996-10-28 | 1997-01-08 | Celltech Therapeutics Ltd | Chemical compounds |
| JP2001507349A (ja) | 1996-12-23 | 2001-06-05 | セルテック セラピューティックス リミテッド | 縮合多環式２−アミノピリミジン誘導体、それらの製造およびたんぱく質チロシンキナーゼ抑制因子としてのそれらの使用 |
| SE9701398D0 (sv) | 1997-04-15 | 1997-04-15 | Astra Pharma Prod | Novel compounds |
| IT1291372B1 (it) | 1997-05-21 | 1999-01-07 | Schering Plough S P A | Uso di analoghi eterociclici di 1,2,4-triazolo (1,5-c) pirimidine per la preparazione di medicamenti utili per il trattamento delle malattie |
| JP3391466B2 (ja) | 1997-06-13 | 2003-03-31 | アースロケア コーポレイション | 閉塞した体内管腔の再疎通のための電気外科のカテーテルシステム及びカテーテル |
| US6013621A (en) * | 1997-10-17 | 2000-01-11 | The Rockfeller University | Method of treating psychosis and/or hyperactivity |
| GB9722520D0 (en) | 1997-10-24 | 1997-12-24 | Pfizer Ltd | Compounds |
| ES2356886T3 (es) | 1998-03-31 | 2011-04-14 | Kyowa Hakko Kirin Co., Ltd. | Compuestos heterocíclicos nitrogenados. |
| US6133273A (en) | 1998-05-08 | 2000-10-17 | American Home Products Corporation | Pyrazolopyrimidine-2,4-dione sulfonamides |
| GB9907658D0 (en) | 1999-04-06 | 1999-05-26 | Zeneca Ltd | Chemical compounds |
| EP1194152A4 (en) | 1999-06-30 | 2002-11-06 | Merck & Co Inc | Links to SRC kinase inhibition |
| EP1206265B1 (en) | 1999-06-30 | 2003-11-12 | Merck & Co., Inc. | Src kinase inhibitor compounds |
| DE19931206A1 (de) * | 1999-07-07 | 2001-01-11 | Stief Christian | Arzneimittel zur Erhöhung des cAMP-Spiegels und deren Verwendung |
| ATE309241T1 (de) | 1999-09-10 | 2005-11-15 | Merck & Co Inc | Tyrosin kinase inhibitoren |
| AU7738100A (en) | 1999-09-30 | 2001-04-30 | Neurogen Corporation | Certain alkylene diamine-substituted pyrazolo(1,5,-a)-1,5-pyrimidines and pyrazolo(1,5-a)-1,3,5-triazines |
| JP2003511452A (ja) | 1999-10-11 | 2003-03-25 | ファイザー・インク | ホスホジエステラーゼ阻害剤としての５−（２−置換−５−ヘテロシクリルスルホニルピリド−３−イル）−ジヒドロピラゾロ［４，３−ｄ］ピリミジン−７−オン |
| TWI265925B (en) | 1999-10-11 | 2006-11-11 | Pfizer | Pyrazolo[4,3-d]pyrimidin-7-ones useful in inhibiting type 5 cyclic guanosine 3',5'-monophosphate phosphodiesterases(cGMP PDE5), process and intermediates for their preparation, their uses and composition comprising them |
| IL139073A0 (en) * | 1999-10-21 | 2001-11-25 | Pfizer | Treatment of neuropathy |
| MY125533A (en) | 1999-12-06 | 2006-08-30 | Bristol Myers Squibb Co | Heterocyclic dihydropyrimidine compounds |
| GB0004890D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| AU2001255849B8 (en) | 2000-04-19 | 2006-04-27 | Lilly Icos, Llc. | PDE-V inhibitors for treatment of Parkinson's Disease |
| US6693099B2 (en) | 2000-10-17 | 2004-02-17 | The Procter & Gamble Company | Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance |
| ES2241994T3 (es) | 2001-03-16 | 2005-11-01 | Pfizer Inc. | Compuestos pirazolo(4,3-d)pirimidinona como inhibidores de gmpc. |
| WO2002088079A2 (en) | 2001-05-01 | 2002-11-07 | Bristol-Myers Squibb Company | Dual inhibitors of pde 7 and pde 4 |
| SE0102315D0 (sv) | 2001-06-28 | 2001-06-28 | Astrazeneca Ab | Compounds |
| CN1315835C (zh) | 2001-08-28 | 2007-05-16 | 先灵公司 | 多环鸟嘌呤磷酸二酯酶v抑制剂 |
| CA2459161A1 (en) | 2001-08-31 | 2003-03-13 | The Rockefeller University | Phosphodiesterase activity and regulation of phosphodiesterase 1b-mediated signaling in brain |
| US6943171B2 (en) | 2001-11-09 | 2005-09-13 | Schering Corporation | Polycyclic guanine derivative phosphodiesterase V inhibitors |
| HRP20040850A2 (en) | 2002-02-15 | 2005-08-31 | Synovo Gmbh | Conjugates of biologically active compounds, methods for their preparation and use formulation and pharmaceutical applications thereof |
| US20050153372A1 (en) * | 2002-02-21 | 2005-07-14 | Paul Greengard | Compositions and method for regulation of calcium-dependent signaling in brain |
| GB0230045D0 (en) | 2002-12-23 | 2003-01-29 | Glaxo Group Ltd | Compounds |
| EP1613747A1 (en) | 2003-03-31 | 2006-01-11 | Pfizer Products Inc. | Crystal structure of 3 ,5 -cyclic nucleotide phosphodiesterase 1b (pde1b) and uses thereof |
| BRPI0409229A (pt) | 2003-04-01 | 2006-03-28 | Applied Research Systems | inibidores das fosfodiesterases na infertilidade |
| CN1878773A (zh) | 2003-09-05 | 2006-12-13 | 神经能质公司 | 作为crf1受体配位体的杂芳基稠合的吡啶,吡嗪及嘧啶 |
| CN101248050B (zh) | 2005-06-06 | 2013-07-17 | 武田药品工业株式会社 | 有机化合物 |
| EP1919287A4 (en) * | 2005-08-23 | 2010-04-28 | Intra Cellular Therapies Inc | ORGANIC COMPOUNDS FOR TREATING A REDUCED DOPAMINE RECEPTOR SIGNALING ACTIVITY |
| KR20090042227A (ko) | 2006-06-06 | 2009-04-29 | 인트라-셀룰라 써래피스, 인코퍼레이티드. | 유기 화합물 |
| US20070286890A1 (en) | 2006-06-07 | 2007-12-13 | John Garnett Walt | Eyelash applicator and method |
| WO2008063505A1 (en) | 2006-11-13 | 2008-05-29 | 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 |
| WO2009075784A1 (en) | 2007-12-06 | 2009-06-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| AU2008331833A1 (en) | 2007-12-06 | 2009-06-11 | Intra-Cellular Therapies, Inc | Organic compounds |
| JPWO2009107578A1 (ja) | 2008-02-25 | 2011-06-30 | 佐藤 謙治 | 音響装置 |
| CN102223799A (zh) | 2008-12-06 | 2011-10-19 | 细胞内治疗公司 | 有机化合物 |
| CN102232077A (zh) | 2008-12-06 | 2011-11-02 | 细胞内治疗公司 | 有机化合物 |
| KR20110098731A (ko) | 2008-12-06 | 2011-09-01 | 인트라-셀룰라 써래피스, 인코퍼레이티드. | 유기 화합물 |
| EP2358204B1 (en) | 2008-12-06 | 2015-08-05 | Intra-Cellular Therapies, Inc. | 4,5,7,8-tetrahydro-4-oxo-2H-imidazo[1,2-a]pyrrolo[3,4-e]pyrimidine compounds as PDE1 inhibitors. |
| WO2010065147A1 (en) | 2008-12-06 | 2010-06-10 | Intra-Cellular Therapies, Inc. | Organic compounds |
| EP2367429B1 (en) | 2008-12-06 | 2017-06-07 | Intra-Cellular Therapies, Inc. | Organic compounds |
| EP2400970A4 (en) | 2009-02-25 | 2012-07-18 | Intra Cellular Therapies Inc | PDE-1-HEMMER FOR EYE DRESSING |
| US9468637B2 (en) | 2009-05-13 | 2016-10-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| JP2013507360A (ja) | 2009-10-08 | 2013-03-04 | イントラ−セルラー・セラピーズ・インコーポレイテッド | ホスホジエステラーゼ１−標的トレーサーおよび方法 |
| JP5911854B2 (ja) | 2010-05-31 | 2016-04-27 | 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 |
| JP5879336B2 (ja) | 2010-05-31 | 2016-03-08 | 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 |
| WO2011153135A1 (en) | 2010-05-31 | 2011-12-08 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US10561656B2 (en) | 2011-06-10 | 2020-02-18 | 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 |
| ES2836129T3 (es) | 2013-03-15 | 2021-06-24 | Intra Cellular Therapies Inc | Compuestos orgánicos |
-
2006
- 2006-06-06 CN CN2006800269736A patent/CN101248050B/zh active Active
- 2006-06-06 AU AU2006255028A patent/AU2006255028B2/en active Active
- 2006-06-06 EP EP06772397.3A patent/EP1888534B1/en active Active
- 2006-06-06 CN CN2013102507232A patent/CN103467471A/zh active Pending
- 2006-06-06 JP JP2008515858A patent/JP5084725B2/ja active Active
- 2006-06-06 WO PCT/US2006/022066 patent/WO2006133261A2/en not_active Ceased
- 2006-06-06 KR KR1020147002847A patent/KR20140022114A/ko not_active Ceased
- 2006-06-06 BR BRPI0611095A patent/BRPI0611095B8/pt active IP Right Grant
- 2006-06-06 US US11/916,761 patent/US8273750B2/en active Active
- 2006-06-06 ES ES06772397.3T patent/ES2645371T3/es active Active
- 2006-06-06 CA CA2611312A patent/CA2611312C/en active Active
-
2008
- 2008-01-03 KR KR1020087000132A patent/KR101478368B1/ko active Active
-
2012
- 2012-05-22 JP JP2012116786A patent/JP5649614B2/ja active Active
- 2012-07-18 US US13/552,381 patent/US9000001B2/en active Active
-
2014
- 2014-09-10 JP JP2014184489A patent/JP2015007121A/ja active Pending
-
2015
- 2015-03-27 US US14/671,531 patent/US9624230B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN103467471A (zh) | 2013-12-25 |
| CA2611312C (en) | 2013-12-03 |
| CA2611312A1 (en) | 2006-12-14 |
| EP1888534B1 (en) | 2017-07-26 |
| WO2006133261A3 (en) | 2007-06-21 |
| KR20140022114A (ko) | 2014-02-21 |
| AU2006255028B2 (en) | 2012-04-19 |
| AU2006255028A1 (en) | 2006-12-14 |
| BRPI0611095A2 (pt) | 2010-12-07 |
| US20130018063A1 (en) | 2013-01-17 |
| JP5084725B2 (ja) | 2012-11-28 |
| EP1888534A2 (en) | 2008-02-20 |
| JP2008545783A (ja) | 2008-12-18 |
| US20080188492A1 (en) | 2008-08-07 |
| BRPI0611095B8 (pt) | 2021-05-25 |
| CN101248050A (zh) | 2008-08-20 |
| JP2015007121A (ja) | 2015-01-15 |
| EP1888534A4 (en) | 2010-06-16 |
| KR101478368B1 (ko) | 2014-12-31 |
| JP5649614B2 (ja) | 2015-01-07 |
| KR20080028903A (ko) | 2008-04-02 |
| BRPI0611095B1 (pt) | 2021-02-02 |
| US20150197528A1 (en) | 2015-07-16 |
| CN101248050B (zh) | 2013-07-17 |
| US9000001B2 (en) | 2015-04-07 |
| WO2006133261A2 (en) | 2006-12-14 |
| US9624230B2 (en) | 2017-04-18 |
| JP2012180369A (ja) | 2012-09-20 |
| US8273750B2 (en) | 2012-09-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2645371T3 (es) | Compuestos orgánicos | |
| ES2436780T3 (es) | Compuestos orgánicos | |
| ES2411604T3 (es) | Compuestos orgánicos | |
| HK1113272B (en) | Organic compounds | |
| HK1113272A (en) | Organic compounds | |
| WO2021035157A1 (en) | Organic compounds | |
| MX2007015356A (en) | Organic compounds |