UA80820C2 - N-substituted tricyclic 3-aminopyrazoles as pdfg receptor inhibitors - Google Patents

N-substituted tricyclic 3-aminopyrazoles as pdfg receptor inhibitors Download PDF

Info

Publication number: UA80820C2
Authority: UA; Ukraine
Prior art keywords: alkyl; group; oalkyl; mnalkyl; halogenated
Prior art date: 2002-05-15

Application number

UA20041109391A

Other languages

English (en)

Ukrainian (uk)

Inventor

Chi Yung Ho

Original Assignee

Janssen Pharmaceutica Nv

Priority date (The priority date 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 date listed.)

2002-05-15

Filing date

2003-05-13

Publication date

2007-11-12

2003-05-13 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

2007-11-12 Publication of UA80820C2 publication Critical patent/UA80820C2/uk

Links

JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 title abstract description 5
108091006082 receptor inhibitors Proteins 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 586
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
125000000217 alkyl group Chemical group 0.000 claims description 1855
-1 -OH Chemical group 0.000 claims description 358
125000003545 alkoxy group Chemical group 0.000 claims description 294
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 260
125000003118 aryl group Chemical group 0.000 claims description 249
150000002367 halogens Chemical class 0.000 claims description 220
229910052736 halogen Inorganic materials 0.000 claims description 218
125000000753 cycloalkyl group Chemical group 0.000 claims description 186
125000001072 heteroaryl group Chemical group 0.000 claims description 184
125000004001 thioalkyl group Chemical group 0.000 claims description 169
125000003342 alkenyl group Chemical group 0.000 claims description 136
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 128
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 110
125000003282 alkyl amino group Chemical group 0.000 claims description 106
125000004663 dialkyl amino group Chemical group 0.000 claims description 104
150000002825 nitriles Chemical class 0.000 claims description 97
125000001424 substituent group Chemical group 0.000 claims description 93
125000004093 cyano group Chemical group *C#N 0.000 claims description 91
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 91
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 88
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 83
125000004149 thio group Chemical group *S* 0.000 claims description 75
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 52
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 41
230000027455 binding Effects 0.000 claims description 33
230000003287 optical effect Effects 0.000 claims description 32
150000003839 salts Chemical class 0.000 claims description 32
125000001153 fluoro group Chemical group F* 0.000 claims description 30
229910052739 hydrogen Inorganic materials 0.000 claims description 27
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 26
125000001309 chloro group Chemical group Cl* 0.000 claims description 24
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 claims description 23
125000004414 alkyl thio group Chemical group 0.000 claims description 20
125000004043 oxo group Chemical group O=* 0.000 claims description 20
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
229910052796 boron Inorganic materials 0.000 claims description 16
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 15
125000005647 linker group Chemical group 0.000 claims description 15
125000003277 amino group Chemical group 0.000 claims description 14
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 14
125000002757 morpholinyl group Chemical group 0.000 claims description 14
125000003386 piperidinyl group Chemical group 0.000 claims description 13
239000003937 drug carrier Substances 0.000 claims description 10
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
150000002431 hydrogen Chemical class 0.000 claims description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
229910052794 bromium Inorganic materials 0.000 claims description 5
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 4
125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 3
125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 3
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 3
125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
239000000460 chlorine Substances 0.000 claims description 3
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 3
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
125000004743 1-methylethoxycarbonyl group Chemical group CC(C)OC(=O)* 0.000 claims description 2
125000006508 2,6-difluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C(F)=C1[H])C([H])([H])* 0.000 claims description 2
125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 claims description 2
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 claims description 2
125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims 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 claims description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 claims description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
125000005055 alkyl alkoxy group Chemical group 0.000 claims description 2
125000002431 aminoalkoxy group Chemical group 0.000 claims description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 2
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical group CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 claims description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims 8
229910052801 chlorine Inorganic materials 0.000 claims 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 3
RHDYQUZYHZWTCI-UHFFFAOYSA-N 1-methoxy-4-phenylbenzene Chemical compound C1=CC(OC)=CC=C1C1=CC=CC=C1 RHDYQUZYHZWTCI-UHFFFAOYSA-N 0.000 claims 1
VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 claims 1
125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 1
125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims 1
125000001137 3-hydroxypropoxy group Chemical group [H]OC([H])([H])C([H])([H])C([H])([H])O* 0.000 claims 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
241001516584 Andrya Species 0.000 claims 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
125000002102 aryl alkyloxo group Chemical group 0.000 claims 1
239000011737 fluorine Substances 0.000 claims 1
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims 1
238000000034 method Methods 0.000 abstract description 203
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 27
206010028980 Neoplasm Diseases 0.000 abstract description 16
230000002062 proliferating effect Effects 0.000 abstract description 14
239000003112 inhibitor Substances 0.000 abstract description 10
238000002360 preparation method Methods 0.000 abstract description 7
108091008606 PDGF receptors Proteins 0.000 abstract description 3
102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 abstract description 3
102000001253 Protein Kinase Human genes 0.000 abstract description 3
108060006633 protein kinase Proteins 0.000 abstract description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 77
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 76
239000000543 intermediate Substances 0.000 description 64
239000000203 mixture Substances 0.000 description 62
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 52
238000006243 chemical reaction Methods 0.000 description 43
239000011541 reaction mixture Substances 0.000 description 43
230000015572 biosynthetic process Effects 0.000 description 37
125000004432 carbon atom Chemical group C* 0.000 description 37
239000002904 solvent Substances 0.000 description 37
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 32
241000282414 Homo sapiens Species 0.000 description 29
229910052799 carbon Inorganic materials 0.000 description 28
235000019439 ethyl acetate Nutrition 0.000 description 27
229960000583 acetic acid Drugs 0.000 description 25
229910052740 iodine Inorganic materials 0.000 description 25
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
230000008569 process Effects 0.000 description 23
239000000243 solution Substances 0.000 description 23
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
150000001721 carbon Chemical group 0.000 description 22
239000012267 brine Substances 0.000 description 21
210000004027 cell Anatomy 0.000 description 21
208000035475 disorder Diseases 0.000 description 21
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
239000007787 solid Substances 0.000 description 21
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
238000005481 NMR spectroscopy Methods 0.000 description 20
239000002585 base Substances 0.000 description 20
239000002253 acid Substances 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 18
239000000010 aprotic solvent Substances 0.000 description 16
238000004821 distillation Methods 0.000 description 16
230000007958 sleep Effects 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
239000003960 organic solvent Substances 0.000 description 15
239000013058 crude material Substances 0.000 description 14
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 14
239000012071 phase Substances 0.000 description 13
238000003756 stirring Methods 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
238000010898 silica gel chromatography Methods 0.000 description 12
229910052938 sodium sulfate Inorganic materials 0.000 description 12
235000011152 sodium sulphate Nutrition 0.000 description 12
108091000080 Phosphotransferase Proteins 0.000 description 11
238000004440 column chromatography Methods 0.000 description 11
102000020233 phosphotransferase Human genes 0.000 description 11
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
125000004076 pyridyl group Chemical group 0.000 description 11
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 11
238000011282 treatment Methods 0.000 description 11
IHMQOBPGHZFGLC-UHFFFAOYSA-N 5,6-dimethoxy-2,3-dihydroinden-1-one Chemical compound C1=C(OC)C(OC)=CC2=C1C(=O)CC2 IHMQOBPGHZFGLC-UHFFFAOYSA-N 0.000 description 10
230000000694 effects Effects 0.000 description 10
238000004128 high performance liquid chromatography Methods 0.000 description 10
125000002883 imidazolyl group Chemical group 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 9
241000220317 Rosa Species 0.000 description 9
150000001412 amines Chemical class 0.000 description 9
125000005843 halogen group Chemical group 0.000 description 9
230000002401 inhibitory effect Effects 0.000 description 9
125000000714 pyrimidinyl group Chemical group 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 8
125000003710 aryl alkyl group Chemical group 0.000 description 8
229940126543 compound 14 Drugs 0.000 description 8
238000004108 freeze drying Methods 0.000 description 8
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
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102000005962 receptors Human genes 0.000 description 8
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WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 8
238000003786 synthesis reaction Methods 0.000 description 8
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 7
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
125000002619 bicyclic group Chemical group 0.000 description 7
125000005842 heteroatom Chemical group 0.000 description 7
NJCBOMBOMCXCRM-UHFFFAOYSA-N lithium;trimethyl(trimethylsilyl)silane Chemical compound [Li].C[Si](C)(C)[Si](C)(C)C NJCBOMBOMCXCRM-UHFFFAOYSA-N 0.000 description 7
229910052760 oxygen Inorganic materials 0.000 description 7
239000011734 sodium Substances 0.000 description 7
239000012312 sodium hydride Substances 0.000 description 7
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229910052727 yttrium Inorganic materials 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
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125000000842 isoxazolyl group Chemical group 0.000 description 6
239000010410 layer Substances 0.000 description 6
QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
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NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 5
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 5
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 5
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Classifications

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- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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UA20041109391A 2002-05-15 2003-05-13 N-substituted tricyclic 3-aminopyrazoles as pdfg receptor inhibitors UA80820C2 (en)

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Application Number	Priority Date	Filing Date	Title
US38073502P	2002-05-15	2002-05-15
PCT/US2003/015193 WO2003097609A1 (en)	2002-05-15	2003-05-13	N-substituted tricyclic 3-aminopyrazoles as pdfg receptor inhibitors

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US (2)	US7196110B2 (es)
EP (1)	EP1506175B1 (es)
JP (1)	JP2006502097A (es)
KR (1)	KR20040106554A (es)
CN (1)	CN100396670C (es)
AR (1)	AR040079A1 (es)
AT (1)	ATE427301T1 (es)
AU (1)	AU2003234567A1 (es)
BR (1)	BRPI0311179A2 (es)
CA (1)	CA2486097A1 (es)
CR (1)	CR7574A (es)
DE (1)	DE60326950D1 (es)
EA (1)	EA008770B1 (es)
ES (1)	ES2323952T3 (es)
HR (1)	HRP20041188A2 (es)
IL (1)	IL165197A0 (es)
MX (1)	MXPA04011320A (es)
MY (1)	MY138268A (es)
NO (1)	NO20045451L (es)
NZ (1)	NZ548796A (es)
PE (1)	PE20040758A1 (es)
PL (1)	PL374062A1 (es)
RS (1)	RS98804A (es)
SA (1)	SA03240431A (es)
TW (1)	TW200407311A (es)
UA (1)	UA80820C2 (es)
UY (1)	UY27811A1 (es)
WO (1)	WO2003097609A1 (es)
ZA (1)	ZA200410108B (es)

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- 2003-05-13 AU AU2003234567A patent/AU2003234567A1/en not_active Abandoned
- 2003-05-13 RS YU98804A patent/RS98804A/sr unknown
- 2003-05-13 JP JP2004505342A patent/JP2006502097A/ja not_active Withdrawn
- 2003-05-13 MX MXPA04011320A patent/MXPA04011320A/es active IP Right Grant
- 2003-05-13 HR HR20041188A patent/HRP20041188A2/xx not_active Application Discontinuation
- 2003-05-13 AT AT03728909T patent/ATE427301T1/de not_active IP Right Cessation
- 2003-05-13 EP EP03728909A patent/EP1506175B1/en not_active Expired - Lifetime
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- 2003-05-13 UA UA20041109391A patent/UA80820C2/uk unknown
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- 2003-05-13 PL PL03374062A patent/PL374062A1/xx not_active Application Discontinuation
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- 2003-05-13 CN CNB038164884A patent/CN100396670C/zh not_active Expired - Fee Related
- 2003-05-13 KR KR10-2004-7018454A patent/KR20040106554A/ko not_active Ceased
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- 2003-05-13 DE DE60326950T patent/DE60326950D1/de not_active Expired - Fee Related
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Also Published As

Publication number	Publication date
US20070142305A1 (en)	2007-06-21
CN100396670C (zh)	2008-06-25
EP1506175B1 (en)	2009-04-01
DE60326950D1 (de)	2009-05-14
BRPI0311179A2 (pt)	2016-06-21
IL165197A0 (en)	2005-12-18
US20040082639A1 (en)	2004-04-29
TW200407311A (en)	2004-05-16
CN1668601A (zh)	2005-09-14
PL374062A1 (en)	2005-09-19
UY27811A1 (es)	2003-10-31
EA008770B1 (ru)	2007-08-31
ZA200410108B (en)	2006-05-31
MXPA04011320A (es)	2005-08-16
NZ548796A (en)	2008-01-31
ES2323952T3 (es)	2009-07-28
PE20040758A1 (es)	2005-01-01
ATE427301T1 (de)	2009-04-15
CR7574A (es)	2008-09-10
MY138268A (en)	2009-05-29
EA200401378A1 (ru)	2005-06-30
WO2003097609A1 (en)	2003-11-27
AR040079A1 (es)	2005-03-16
SA03240431A (ar)	2005-12-03
CA2486097A1 (en)	2003-11-27
JP2006502097A (ja)	2006-01-19
US7196110B2 (en)	2007-03-27
KR20040106554A (ko)	2004-12-17
RS98804A (sr)	2006-10-27
EP1506175A1 (en)	2005-02-16
US7795440B2 (en)	2010-09-14
NO20045451L (no)	2005-02-09
HRP20041188A2 (hr)	2007-03-31
AU2003234567A1 (en)	2003-12-02

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