MXPA04007606A - Arilamidas de acido pirazolcarboxilico fusionadas substituidas y compuestos relacionados. - Google Patents
Arilamidas de acido pirazolcarboxilico fusionadas substituidas y compuestos relacionados.Info
- Publication number
- MXPA04007606A MXPA04007606A MXPA04007606A MXPA04007606A MXPA04007606A MX PA04007606 A MXPA04007606 A MX PA04007606A MX PA04007606 A MXPA04007606 A MX PA04007606A MX PA04007606 A MXPA04007606 A MX PA04007606A MX PA04007606 A MXPA04007606 A MX PA04007606A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- compound
- hydrogen
- amino
- cycloalkyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 304
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 title abstract description 10
- 102000027484 GABAA receptors Human genes 0.000 claims abstract description 55
- 108091008681 GABAA receptors Proteins 0.000 claims abstract description 55
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- 102000005962 receptors Human genes 0.000 claims abstract description 20
- 108020003175 receptors Proteins 0.000 claims abstract description 20
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 13
- 230000036506 anxiety Effects 0.000 claims abstract description 11
- 208000019116 sleep disease Diseases 0.000 claims abstract description 9
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 6
- 230000015654 memory Effects 0.000 claims abstract 3
- 125000000217 alkyl group Chemical group 0.000 claims description 301
- 229910052739 hydrogen Inorganic materials 0.000 claims description 242
- 239000001257 hydrogen Substances 0.000 claims description 241
- -1 cyano, nitro, amino Chemical group 0.000 claims description 145
- 229910052736 halogen Inorganic materials 0.000 claims description 95
- 150000002367 halogens Chemical class 0.000 claims description 95
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 82
- 125000003545 alkoxy group Chemical group 0.000 claims description 82
- 150000003839 salts Chemical class 0.000 claims description 69
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 65
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 59
- 125000000623 heterocyclic group Chemical group 0.000 claims description 51
- 229910052760 oxygen Inorganic materials 0.000 claims description 49
- 239000001301 oxygen Substances 0.000 claims description 46
- 125000003282 alkyl amino group Chemical group 0.000 claims description 45
- 125000004432 carbon atom Chemical group C* 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 44
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 43
- 125000002837 carbocyclic group Chemical group 0.000 claims description 41
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 33
- YMEHWISYYMKMFO-WOMRJYOTSA-N methyl N-[(12E,15S)-15-[(4S)-4-(3-chlorophenyl)-2-oxopiperidin-1-yl]-9-oxo-8,17,19-triazatricyclo[14.2.1.02,7]nonadeca-1(18),2(7),3,5,12,16-hexaen-5-yl]carbamate Chemical group COC(=O)Nc1ccc2-c3cnc([nH]3)[C@H](C\C=C\CCC(=O)Nc2c1)N1CC[C@@H](CC1=O)c1cccc(Cl)c1 YMEHWISYYMKMFO-WOMRJYOTSA-N 0.000 claims description 33
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 26
- 125000004076 pyridyl group Chemical group 0.000 claims description 26
- 229910052717 sulfur Inorganic materials 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 22
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 125000001188 haloalkyl group Chemical group 0.000 claims description 21
- 230000000694 effects Effects 0.000 claims description 20
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 19
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 19
- 239000011593 sulfur Substances 0.000 claims description 19
- 125000001544 thienyl group Chemical group 0.000 claims description 19
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 18
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 18
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 17
- 125000000304 alkynyl group Chemical group 0.000 claims description 16
- 210000004027 cell Anatomy 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000002883 imidazolyl group Chemical group 0.000 claims description 16
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 230000027455 binding Effects 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000006413 ring segment Chemical group 0.000 claims description 13
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000003386 piperidinyl group Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 11
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 10
- 125000002971 oxazolyl group Chemical group 0.000 claims description 10
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- 210000003169 central nervous system Anatomy 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 8
- 125000001425 triazolyl group Chemical group 0.000 claims description 8
- 125000002393 azetidinyl group Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 238000000211 autoradiogram Methods 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 238000000338 in vitro Methods 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 6
- 210000001519 tissue Anatomy 0.000 claims description 6
- 230000006735 deficit Effects 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 230000002708 enhancing effect Effects 0.000 claims description 5
- 238000001727 in vivo Methods 0.000 claims description 5
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 5
- BXPYWQDDRUVEMW-UHFFFAOYSA-N 6-[3-(diethylamino)propoxy]pyridin-3-amine Chemical group CCN(CC)CCCOC1=CC=C(N)C=N1 BXPYWQDDRUVEMW-UHFFFAOYSA-N 0.000 claims description 4
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 4
- 206010012289 Dementia Diseases 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 4
- 230000007831 electrophysiology Effects 0.000 claims description 4
- 238000002001 electrophysiology Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000019491 signal transduction Effects 0.000 claims description 4
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- 230000004075 alteration Effects 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 3
- HGLFWLLFPGIKOT-UHFFFAOYSA-N azulene-1-carboxylic acid Chemical compound C1=CC=CC=C2C(C(=O)O)=CC=C21 HGLFWLLFPGIKOT-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 239000012530 fluid Substances 0.000 claims description 3
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 230000006403 short-term memory Effects 0.000 claims description 3
- 125000004306 triazinyl group Chemical group 0.000 claims description 3
- MDTUWBLTRPRXBX-UHFFFAOYSA-N 1,2,4-triazol-3-one Chemical compound O=C1N=CN=N1 MDTUWBLTRPRXBX-UHFFFAOYSA-N 0.000 claims description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical group NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 claims description 2
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 238000001514 detection method Methods 0.000 claims description 2
- 230000002285 radioactive effect Effects 0.000 claims description 2
- 125000000565 sulfonamide group Chemical group 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 23
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 15
- 208000020685 sleep-wake disease Diseases 0.000 claims 3
- 208000013403 hyperactivity Diseases 0.000 claims 2
- BHXVYTQDWMQVBI-UHFFFAOYSA-N 1h-indazole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=NNC2=C1 BHXVYTQDWMQVBI-UHFFFAOYSA-N 0.000 claims 1
- 101100408921 Arabidopsis thaliana CRR2 gene Proteins 0.000 claims 1
- 230000006399 behavior Effects 0.000 claims 1
- 210000001124 body fluid Anatomy 0.000 claims 1
- 239000010839 body fluid Substances 0.000 claims 1
- 210000004958 brain cell Anatomy 0.000 claims 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims 1
- 239000004744 fabric Substances 0.000 claims 1
- 230000003834 intracellular effect Effects 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 210000002569 neuron Anatomy 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 229940049706 benzodiazepine Drugs 0.000 abstract description 24
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 abstract description 20
- 239000000523 sample Substances 0.000 abstract description 16
- 239000000556 agonist Substances 0.000 abstract description 13
- 229940079593 drug Drugs 0.000 abstract description 12
- 238000003786 synthesis reaction Methods 0.000 abstract description 9
- 230000015572 biosynthetic process Effects 0.000 abstract description 7
- 239000005557 antagonist Substances 0.000 abstract description 6
- 210000004556 brain Anatomy 0.000 abstract description 5
- 239000000651 prodrug Substances 0.000 abstract description 5
- 229940002612 prodrug Drugs 0.000 abstract description 5
- 239000000543 intermediate Substances 0.000 abstract description 4
- RCTBACSGXPVNOF-UHFFFAOYSA-N 5,6,7,8-tetrahydropyrazolo[2,3]cyclohepta[2,4-b]pyridine-10-carboxylic acid Chemical compound C1CCC2=CC=CN=C2C2=C1NN=C2C(=O)O RCTBACSGXPVNOF-UHFFFAOYSA-N 0.000 abstract description 3
- 206010015037 epilepsy Diseases 0.000 abstract description 3
- 230000004807 localization Effects 0.000 abstract description 3
- SSPQZSGBPQJKGU-UHFFFAOYSA-N 6,7-dihydro-5h-pyrazolo[3,4-h]quinoline-9-carboxylic acid Chemical compound C1CC2=CC=CN=C2C2=C1NN=C2C(=O)O SSPQZSGBPQJKGU-UHFFFAOYSA-N 0.000 abstract description 2
- FFRVYBLGEPTAIP-UHFFFAOYSA-N 1,4,5,6-tetrahydropyrazolo[3,4-e]indazole-8-carboxylic acid Chemical compound C1CC2=CNN=C2C2=C1NN=C2C(=O)O FFRVYBLGEPTAIP-UHFFFAOYSA-N 0.000 abstract 1
- YWTLNUUWJFOGPI-UHFFFAOYSA-N 6,7-dihydro-5h-pyrazolo[3,4-h]quinazoline-9-carboxylic acid Chemical compound C1CC2=CN=CN=C2C2=C1NN=C2C(=O)O YWTLNUUWJFOGPI-UHFFFAOYSA-N 0.000 abstract 1
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 138
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 52
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 208000035475 disorder Diseases 0.000 description 15
- 229910002092 carbon dioxide Inorganic materials 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 13
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 13
- 239000002904 solvent Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 231100000252 nontoxic Toxicity 0.000 description 9
- 230000003000 nontoxic effect Effects 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- 101150041968 CDC13 gene Proteins 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 7
- 230000009471 action Effects 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 229910052722 tritium Inorganic materials 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- RRLMPLDPCKRASL-ONEGZZNKSA-N (e)-3-(dimethylamino)prop-2-enal Chemical compound CN(C)\C=C\C=O RRLMPLDPCKRASL-ONEGZZNKSA-N 0.000 description 4
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
- 239000005695 Ammonium acetate Substances 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 235000019257 ammonium acetate Nutrition 0.000 description 4
- 229940043376 ammonium acetate Drugs 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- 208000015114 central nervous system disease Diseases 0.000 description 4
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- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 4
- 210000000287 oocyte Anatomy 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 238000000159 protein binding assay Methods 0.000 description 4
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- 239000000375 suspending agent Substances 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
- RBCXINQNJWBBOV-UHFFFAOYSA-N 4-oxo-1,5,6,7-tetrahydroindazole-3-carboxylic acid Chemical compound C1CCC(=O)C2=C1NN=C2C(=O)O RBCXINQNJWBBOV-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000028698 Cognitive impairment Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 3
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 3
- 235000019483 Peanut oil Nutrition 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
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- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
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- 238000001953 recrystallisation Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 208000025874 separation anxiety disease Diseases 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000003567 signal transduction assay Methods 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 201000001716 specific phobia Diseases 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
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- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61P25/20—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
- A61P25/28—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35531402P | 2002-02-07 | 2002-02-07 | |
| PCT/US2003/003872 WO2003066634A1 (en) | 2002-02-07 | 2003-02-07 | Substituted fused pyrazolecarboxylic acid arylamides and related compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA04007606A true MXPA04007606A (es) | 2004-11-10 |
Family
ID=27734501
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA04007606A MXPA04007606A (es) | 2002-02-07 | 2003-02-07 | Arilamidas de acido pirazolcarboxilico fusionadas substituidas y compuestos relacionados. |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6852730B2 (https=) |
| EP (1) | EP1472252A1 (https=) |
| JP (1) | JP2005525333A (https=) |
| AU (1) | AU2003212979A1 (https=) |
| BR (1) | BR0307504A (https=) |
| CA (1) | CA2486446A1 (https=) |
| MX (1) | MXPA04007606A (https=) |
| WO (1) | WO2003066634A1 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8513238B2 (en) | 2010-05-10 | 2013-08-20 | Hoffmann-La Roche Inc. | Heteroaryl-cyclohexyl-tetraazabenzo[E]azulenes |
| US20150374705A1 (en) | 2012-02-14 | 2015-12-31 | Shanghai Institues for Biological Sciences | Substances for treatment or relief of pain |
| RU2015106013A (ru) * | 2012-08-10 | 2016-10-10 | Ф. Хоффманн-Ля Рош Аг | Соединения пиразолкарбоксамида, композиции и способы применения |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| WO2020168197A1 (en) | 2019-02-15 | 2020-08-20 | Incyte Corporation | Pyrrolo[2,3-d]pyrimidinone compounds as cdk2 inhibitors |
| WO2020180959A1 (en) | 2019-03-05 | 2020-09-10 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
| US11440914B2 (en) | 2019-05-01 | 2022-09-13 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| WO2020223558A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | Tricyclic amine compounds as cdk2 inhibitors |
| TW202115024A (zh) | 2019-08-14 | 2021-04-16 | 美商英塞特公司 | 作為cdk2 抑制劑之咪唑基嘧啶基胺化合物 |
| AU2020364007A1 (en) | 2019-10-11 | 2022-04-28 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5750702A (en) * | 1993-10-27 | 1998-05-12 | Neurogen Corporation | Certain pyrrolo pyridine-3-carboxamides; a new class of GABA brain receptor ligands |
| US5484944A (en) * | 1993-10-27 | 1996-01-16 | Neurogen Corporation | Certain fused pyrrolecarboxanilides and their use as GABA brain receptor ligands |
| US5804686A (en) * | 1996-01-19 | 1998-09-08 | Neurogen Corporation | fused pyrrolecarboxamides; a new class of GABA brain receptor ligands |
| US6211365B1 (en) * | 1996-01-19 | 2001-04-03 | Neurogen Corporation | Fused pyrrolecarboxamides; a new class of GABA brain receptor ligands |
| KR19990087585A (ko) * | 1996-03-08 | 1999-12-27 | 돈 리사 로얄 | 신경학적 활성제로서의 아졸로벤즈아제핀 유도체 |
| WO1997034870A1 (en) * | 1996-03-22 | 1997-09-25 | Neurogen Corporation | Certain fused pyrrolecarboxamides as gaba brain receptor ligands |
| US5723462A (en) * | 1996-04-26 | 1998-03-03 | Neurogen Corporation | Certain fused pyrrolecarboxamides a new class of GABA brain receptor ligands |
| IL135710A0 (en) | 1997-11-13 | 2001-05-20 | Pfizer Prod Inc | Method of synthesis of pyrrole amides |
| WO1999064425A1 (en) * | 1998-06-09 | 1999-12-16 | Neurogen Corporation | Substituted thienocycloalkylpyrazoles: dopamine receptor subtype specific ligands |
| GB9900222D0 (en) * | 1999-01-06 | 1999-02-24 | Merck Sharp & Dohme | Therapeutic compounds |
| GB9911803D0 (en) | 1999-05-20 | 1999-07-21 | Merck Sharp & Dohme | Therapeutic combination |
| GB9911804D0 (en) | 1999-05-20 | 1999-07-21 | Merck Sharp & Dohme | Therapeutic combination |
| OA12015A (en) | 1999-08-31 | 2006-04-19 | Neurogen Corp | Fused pyrrolecarboxamides: gaba brain receptor ligands. |
| GB9929685D0 (en) * | 1999-12-15 | 2000-02-09 | Merck Sharp & Dohme | Therapeutic agents |
| MXPA03001186A (es) * | 2000-08-07 | 2004-04-20 | Neurogen Corp | Compuestos heterociclicos como ligandos del receptor acido gamma aminobutirico (gabaa). |
| BR0113697A (pt) | 2000-09-06 | 2003-07-22 | Neurogen Corp | Composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, uso de um composto ou sal, embalagem e métodos para, para alterar a atividade transdutora de sinal dos receptores de gabaa, para tratar ansiedade, depressão, um distúrbio do sono, ou demência de alzheimer, para demonstrar a presença dos receptores de gabaa em células ou amostras de tecido e para preparar um composto |
| CA2419958A1 (en) | 2000-09-06 | 2002-03-14 | Neurogen Corporation | Substituted fused pyrroleimines and pyrazoleimines |
| EP1339681A1 (en) | 2000-12-04 | 2003-09-03 | Pfizer Products Inc. | Synthesis of fused pyrrolecarboxamides |
| US6861529B2 (en) | 2001-07-06 | 2005-03-01 | Pfizer Inc | Cycloalkypyrrole-3-carboxylic acid derivatives and heterocycloalkylpyrrole-3-carboxylic acid derivatives |
-
2003
- 2003-02-07 BR BR0307504-4A patent/BR0307504A/pt not_active Application Discontinuation
- 2003-02-07 WO PCT/US2003/003872 patent/WO2003066634A1/en not_active Ceased
- 2003-02-07 JP JP2003566007A patent/JP2005525333A/ja not_active Ceased
- 2003-02-07 EP EP03709023A patent/EP1472252A1/en not_active Withdrawn
- 2003-02-07 CA CA002486446A patent/CA2486446A1/en not_active Abandoned
- 2003-02-07 AU AU2003212979A patent/AU2003212979A1/en not_active Abandoned
- 2003-02-07 US US10/360,963 patent/US6852730B2/en not_active Expired - Fee Related
- 2003-02-07 MX MXPA04007606A patent/MXPA04007606A/es active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| BR0307504A (pt) | 2004-12-07 |
| WO2003066634A1 (en) | 2003-08-14 |
| EP1472252A1 (en) | 2004-11-03 |
| US6852730B2 (en) | 2005-02-08 |
| JP2005525333A (ja) | 2005-08-25 |
| CA2486446A1 (en) | 2003-08-14 |
| AU2003212979A1 (en) | 2003-09-02 |
| US20030216379A1 (en) | 2003-11-20 |
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| Date | Code | Title | Description |
|---|---|---|---|
| FG | Grant or registration |