AU2006255028B2 - Organic compounds - Google Patents
Organic compounds Download PDFInfo
- Publication number
- AU2006255028B2 AU2006255028B2 AU2006255028A AU2006255028A AU2006255028B2 AU 2006255028 B2 AU2006255028 B2 AU 2006255028B2 AU 2006255028 A AU2006255028 A AU 2006255028A AU 2006255028 A AU2006255028 A AU 2006255028A AU 2006255028 B2 AU2006255028 B2 AU 2006255028B2
- Authority
- AU
- Australia
- Prior art keywords
- formula
- pyrazolo
- pyrimidin
- imidazo
- halogen
- 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
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- 150000002894 organic compounds Chemical class 0.000 title description 2
- 150000003839 salts Chemical group 0.000 claims abstract description 42
- 238000000034 method Methods 0.000 claims abstract description 33
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 16
- TZYQTWHRLVDYPL-UHFFFAOYSA-N 5h-pyrimidin-4-one Chemical class O=C1CC=NC=N1 TZYQTWHRLVDYPL-UHFFFAOYSA-N 0.000 claims abstract description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 9
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 9
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical class O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 142
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- -1 hydroxy, carboxy Chemical group 0.000 claims description 41
- 229910052736 halogen Inorganic materials 0.000 claims description 40
- 150000002367 halogens Chemical class 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 37
- 125000001072 heteroaryl group Chemical group 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 23
- 125000004076 pyridyl group Chemical group 0.000 claims description 23
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 22
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000001188 haloalkyl group Chemical group 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 14
- 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
- 201000010099 disease Diseases 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
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 208000018737 Parkinson disease Diseases 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 230000019491 signal transduction Effects 0.000 claims description 6
- 208000028698 Cognitive impairment Diseases 0.000 claims description 5
- 125000001769 aryl amino group Chemical group 0.000 claims description 5
- 208000010877 cognitive disease Diseases 0.000 claims description 5
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 4
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 4
- 206010038743 Restlessness Diseases 0.000 claims description 4
- 125000004390 alkyl sulfonyl 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
- 229940079593 drug Drugs 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
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 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 description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 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
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
- 208000006011 Stroke 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
- 206010013663 drug dependence Diseases 0.000 claims description 2
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 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
- 208000011117 substance-related 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
- RDTIPFRJCLQNJL-LJQANCHMSA-N (11R)-5-anilino-8,11-dimethyl-4-[(4-phenylphenyl)methyl]-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,5,9-trien-7-one Chemical compound C([C@H](N=1)C)N2C=1N(C)C(=O)C(=C1NC=3C=CC=CC=3)C2=NN1CC(C=C1)=CC=C1C1=CC=CC=C1 RDTIPFRJCLQNJL-LJQANCHMSA-N 0.000 claims 1
- VFCNKEMDWFEMIT-LJQANCHMSA-N (12R)-5-anilino-8,12-dimethyl-4-[(4-phenylphenyl)methyl]-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,5,9-trien-7-one Chemical compound C([C@H]1C)N=C(N(C(=O)C2=C3NC=4C=CC=CC=4)C)N1C2=NN3CC(C=C1)=CC=C1C1=CC=CC=C1 VFCNKEMDWFEMIT-LJQANCHMSA-N 0.000 claims 1
- 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 claims 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 claims 1
- 125000004663 dialkyl amino group Chemical group 0.000 claims 1
- 208000020685 sleep-wake disease Diseases 0.000 claims 1
- 239000000651 prodrug Chemical group 0.000 abstract description 6
- 229940002612 prodrug Drugs 0.000 abstract description 6
- 239000003112 inhibitor Substances 0.000 abstract description 4
- 230000008569 process Effects 0.000 abstract description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000000543 intermediate Substances 0.000 description 29
- 239000000243 solution Substances 0.000 description 28
- 239000002904 solvent Substances 0.000 description 22
- 239000000047 product Substances 0.000 description 21
- 238000001308 synthesis method Methods 0.000 description 20
- 239000007787 solid Substances 0.000 description 19
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 18
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 18
- 239000011541 reaction mixture Substances 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
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 17
- 239000000203 mixture Substances 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
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 11
- 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 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 9
- 125000004512 1,2,3-thiadiazol-4-yl group Chemical group S1N=NC(=C1)* 0.000 description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- 102100024318 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B Human genes 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 101001117099 Homo sapiens Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B Proteins 0.000 description 8
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 8
- 108010010677 Phosphodiesterase I Proteins 0.000 description 8
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 229940125890 compound Ia Drugs 0.000 description 7
- 229960003638 dopamine Drugs 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- PQMCFTMVQORYJC-PHDIDXHHSA-N (1r,2r)-2-aminocyclohexan-1-ol Chemical compound N[C@@H]1CCCC[C@H]1O PQMCFTMVQORYJC-PHDIDXHHSA-N 0.000 description 6
- JFFOUICIRBXFRC-RFZPGFLSSA-N (1r,2r)-2-aminocyclopentan-1-ol Chemical compound N[C@@H]1CCC[C@H]1O JFFOUICIRBXFRC-RFZPGFLSSA-N 0.000 description 6
- 229940058020 2-amino-2-methyl-1-propanol Drugs 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 229960001866 silicon dioxide Drugs 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
- 101100243082 Caenorhabditis elegans pde-1 gene Proteins 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
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- 208000035475 disorder Diseases 0.000 description 5
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- 238000001819 mass spectrum Methods 0.000 description 5
- 210000001577 neostriatum Anatomy 0.000 description 5
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 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
- FCLQGHNSQXFQEG-UHFFFAOYSA-N 2-[4-(bromomethyl)phenyl]pyridine Chemical compound C1=CC(CBr)=CC=C1C1=CC=CC=N1 FCLQGHNSQXFQEG-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- 102000004076 Dopamine D1 Receptors Human genes 0.000 description 4
- 108090000511 Dopamine D1 Receptors Proteins 0.000 description 4
- 101100520660 Drosophila melanogaster Poc1 gene Proteins 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
- 101100520662 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PBA1 gene Proteins 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
- 150000001414 amino alcohols Chemical class 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
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- 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
- 230000001965 increasing effect Effects 0.000 description 4
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
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- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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 3
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- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 3
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 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
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- PCCNIENXBRUYFK-UHFFFAOYSA-O azanium;cerium(4+);pentanitrate Chemical compound [NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O PCCNIENXBRUYFK-UHFFFAOYSA-O 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 238000002875 fluorescence polarization Methods 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
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- 125000001424 substituent group Chemical group 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
- 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
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Landscapes
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| US68771505P | 2005-06-06 | 2005-06-06 | |
| US60/687,715 | 2005-06-06 | ||
| PCT/US2006/022066 WO2006133261A2 (en) | 2005-06-06 | 2006-06-06 | Organic compounds |
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| AU2006255028A1 AU2006255028A1 (en) | 2006-12-14 |
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| 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 |
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| AU2012204137B2 (en) * | 2007-12-06 | 2015-06-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
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| US20120070443A1 (en) * | 2008-12-02 | 2012-03-22 | University Of Utah Research Foundation | Pde1 as a target therapeutic in heart disease |
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| 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 |
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| 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 |
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