JP2011504183A5 - - Google Patents
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- JP2011504183A5 JP2011504183A5 JP2010535068A JP2010535068A JP2011504183A5 JP 2011504183 A5 JP2011504183 A5 JP 2011504183A5 JP 2010535068 A JP2010535068 A JP 2010535068A JP 2010535068 A JP2010535068 A JP 2010535068A JP 2011504183 A5 JP2011504183 A5 JP 2011504183A5
- Authority
- JP
- Japan
- Prior art keywords
- group
- nhc
- alkyl
- amino acid
- amino
- 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.)
- Granted
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- -1 hydroxyethyl group Chemical group 0.000 claims description 22
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 150000001413 amino acids Chemical class 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 8
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 125000000539 amino acid group Chemical group 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- 125000004442 acylamino group Chemical group 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 4
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 4
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 claims description 4
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 3
- 125000000676 alkoxyimino group Chemical group 0.000 claims description 3
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 3
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 3
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 3
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 3
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 3
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 125000004984 dialkylaminoalkoxy group Chemical group 0.000 claims description 3
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000005936 piperidyl group Chemical group 0.000 claims description 3
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims description 3
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 2
- 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 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
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 125000001424 substituent group Chemical group 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 10
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 4
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229960001456 adenosine triphosphate Drugs 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 4
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 4
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- OSSMJQGXYASWSA-UHFFFAOYSA-N 2,2,2-trichloroethylphosphane Chemical compound PCC(Cl)(Cl)Cl OSSMJQGXYASWSA-UHFFFAOYSA-N 0.000 description 3
- 102000002281 Adenylate kinase Human genes 0.000 description 3
- 108020000543 Adenylate kinase Proteins 0.000 description 3
- 0 CC(C*)(*1)*=C(*)C2=C1[U]C(C)=*2 Chemical compound CC(C*)(*1)*=C(*)C2=C1[U]C(C)=*2 0.000 description 3
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 3
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 3
- 102000013009 Pyruvate Kinase Human genes 0.000 description 3
- 108020005115 Pyruvate Kinase Proteins 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 239000003039 volatile agent Substances 0.000 description 3
- 150000005749 2-halopyridines Chemical class 0.000 description 2
- 150000005695 2-halopyrimidines Chemical class 0.000 description 2
- XYVMOLOUBJBNBF-UHFFFAOYSA-N 3h-1,3-oxazol-2-one Chemical class OC1=NC=CO1 XYVMOLOUBJBNBF-UHFFFAOYSA-N 0.000 description 2
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- WZELXJBMMZFDDU-UHFFFAOYSA-N Imidazol-2-one Chemical class O=C1N=CC=N1 WZELXJBMMZFDDU-UHFFFAOYSA-N 0.000 description 2
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 125000002015 acyclic group Chemical group 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 2
- 235000013877 carbamide Nutrition 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 229930029653 phosphoenolpyruvate Natural products 0.000 description 2
- DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 description 2
- 150000003217 pyrazoles Chemical class 0.000 description 2
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- SDEAGACSNFSZCU-UHFFFAOYSA-N (3-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1 SDEAGACSNFSZCU-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- KNVRBEGQERGQRP-UHFFFAOYSA-N 2-amino-n,n-dimethylacetamide Chemical compound CN(C)C(=O)CN KNVRBEGQERGQRP-UHFFFAOYSA-N 0.000 description 1
- NCRHNHLDQOEULF-UHFFFAOYSA-N 4-[[4-(3-chlorophenyl)-5-fluoro-1,3-benzothiazol-6-yl]methyl]-n-ethylpiperazine-1-carboxamide;hydrochloride Chemical compound Cl.C1CN(C(=O)NCC)CCN1CC(C(=C1C=2C=C(Cl)C=CC=2)F)=CC2=C1N=CS2 NCRHNHLDQOEULF-UHFFFAOYSA-N 0.000 description 1
- MZFPAWGWFDGCHP-UHFFFAOYSA-N 5-diphenylphosphanylpentyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 MZFPAWGWFDGCHP-UHFFFAOYSA-N 0.000 description 1
- UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 125000004945 acylaminoalkyl group Chemical group 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
- 229950006790 adenosine phosphate Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000001816 cooling Methods 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
- 239000013058 crude material Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- BWRFKYFRRMLPSG-UHFFFAOYSA-N n-[4-[[2-amino-4-(3-chlorophenyl)-1,3-benzoxazol-6-yl]methyl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1CC1=CC(C=2C=C(Cl)C=CC=2)=C(N=C(N)O2)C2=C1 BWRFKYFRRMLPSG-UHFFFAOYSA-N 0.000 description 1
- BLMFRGFZCXILJZ-UHFFFAOYSA-N n-[4-[[2-amino-4-(3-chlorophenyl)-5-fluoro-1,3-benzothiazol-6-yl]methyl]phenyl]methanesulfonamide;hydrochloride Chemical compound Cl.C1=CC(NS(=O)(=O)C)=CC=C1CC(C(=C1C=2C=C(Cl)C=CC=2)F)=CC2=C1N=C(N)S2 BLMFRGFZCXILJZ-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- DTBNBXWJWCWCIK-UHFFFAOYSA-K phosphonatoenolpyruvate Chemical compound [O-]C(=O)C(=C)OP([O-])([O-])=O DTBNBXWJWCWCIK-UHFFFAOYSA-K 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical group C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- QEBJJLIAUXUPDR-UHFFFAOYSA-N tert-butyl n-[4-bromo-6-(hydroxymethyl)-1,3-benzothiazol-2-yl]carbamate Chemical compound C1=C(CO)C=C2SC(NC(=O)OC(C)(C)C)=NC2=C1Br QEBJJLIAUXUPDR-UHFFFAOYSA-N 0.000 description 1
- IYAUGELUSAMAGF-UHFFFAOYSA-N tert-butyl n-[6-[(4-fluorophenyl)-hydroxymethyl]-4-[3-(trifluoromethyl)phenyl]-1,3-benzothiazol-2-yl]carbamate Chemical compound C1=C2SC(NC(=O)OC(C)(C)C)=NC2=C(C=2C=C(C=CC=2)C(F)(F)F)C=C1C(O)C1=CC=C(F)C=C1 IYAUGELUSAMAGF-UHFFFAOYSA-N 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US98955707P | 2007-11-21 | 2007-11-21 | |
| US60/989,557 | 2007-11-21 | ||
| PCT/US2008/084199 WO2009067604A1 (en) | 2007-11-21 | 2008-11-20 | Substituted benzoazole pde4 inhibitors for treating inflammatory, cardiovascular and cns disorders |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011504183A JP2011504183A (ja) | 2011-02-03 |
| JP2011504183A5 true JP2011504183A5 (https=) | 2013-04-04 |
| JP5529746B2 JP5529746B2 (ja) | 2014-06-25 |
Family
ID=40229764
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010535072A Expired - Fee Related JP5524853B2 (ja) | 2007-11-21 | 2008-11-20 | 肺疾患及び心臓血管疾患を治療するための置換されたベンゾアゾールｐｄｅ４阻害剤 |
| JP2010535068A Expired - Fee Related JP5529746B2 (ja) | 2007-11-21 | 2008-11-20 | 炎症性疾患、心臓血管疾患及び中枢神経系障害を治療するための置換されたベンゾアゾールｐｄｅ４阻害剤 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010535072A Expired - Fee Related JP5524853B2 (ja) | 2007-11-21 | 2008-11-20 | 肺疾患及び心臓血管疾患を治療するための置換されたベンゾアゾールｐｄｅ４阻害剤 |
Country Status (9)
| Country | Link |
|---|---|
| US (4) | US20090130076A1 (https=) |
| EP (2) | EP2225215A1 (https=) |
| JP (2) | JP5524853B2 (https=) |
| KR (2) | KR20100097711A (https=) |
| CN (2) | CN101918380B (https=) |
| AU (2) | AU2008326399C1 (https=) |
| CA (2) | CA2722591A1 (https=) |
| IL (3) | IL205884A0 (https=) |
| WO (2) | WO2009067618A1 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2533136Y2 (ja) | 1991-03-01 | 1997-04-23 | 株式会社アマダ | パンチプレス |
| US20090130076A1 (en) * | 2007-11-21 | 2009-05-21 | Decode Genetics Ehf | Substituted benzoazole pde4 inhibitors for treating pulmonary and cardiovascular disorders |
| JP2011504505A (ja) * | 2007-11-21 | 2011-02-10 | デコード ジェネティクス イーエイチエフ | 肺および心血管障害を治療するためのビアリールｐｄｅ４抑制剤 |
| US8865723B2 (en) * | 2012-10-25 | 2014-10-21 | Tetra Discovery Partners Llc | Selective PDE4 B inhibition and improvement in cognition in subjects with brain injury |
| JP6282721B2 (ja) | 2013-03-14 | 2018-02-21 | ダート・ニューロサイエンス・（ケイマン）・リミテッド | Ｐｄｅ４阻害剤としての置換ピリジン及びピラジン化合物 |
| AU2016287463B2 (en) * | 2015-07-02 | 2020-07-02 | F. Hoffmann-La Roche Ag | Benzoxazepin oxazolidinone compounds and methods of use |
| WO2017089347A1 (en) | 2015-11-25 | 2017-06-01 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and pharmaceutical compositions for the treatment of braf inhibitor resistant melanomas |
| US12317744B2 (en) | 2016-07-07 | 2025-05-27 | Hodogaya Chemical Co., Ltd. | Compound having a fused-azole ring structure and organic electroluminescent element |
| CN109053623B (zh) * | 2018-08-27 | 2020-08-04 | 济南悟通生物科技有限公司 | 一种4-甲基-5-噻唑甲醛的制备方法 |
| EP3925958A1 (en) * | 2019-02-13 | 2021-12-22 | Hodogaya Chemical Co., Ltd. | Compound having benzazole ring structure, and organic electroluminescent device |
| GB202102088D0 (en) * | 2021-02-15 | 2021-03-31 | Mironid Ltd | Compounds and their use as pde4 activators |
| CN115215800B (zh) * | 2021-04-21 | 2023-07-18 | 赣江中药创新中心 | 一种二苯并环基-环胺基醚衍生物或盐及其制备方法和应用 |
| WO2025194063A1 (en) * | 2024-03-15 | 2025-09-18 | Board Of Trustees Of Northern Illinois University | Benzothiazole derivatives for treating diseases |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS579774A (en) * | 1980-06-23 | 1982-01-19 | Nippon Kayaku Co Ltd | Production of 2-aminobenzothiazole |
| US5665737B1 (en) * | 1994-10-12 | 1999-02-16 | Euro Celtique Sa | Substituted benzoxazoles |
| JP2002519423A (ja) * | 1998-07-06 | 2002-07-02 | ビイク グルデン ロンベルク ヒエーミツシエ フアブリーク ゲゼルシヤフト ミツト ベシユレンクテル ハフツング | Ｐｅｄ阻害作用を有する新規ベンゾオキサゾール |
| CN1489588A (zh) * | 2001-01-31 | 2004-04-14 | �Ʒ� | 用作pde4同功酶抑制剂的噻唑基,噁唑基,吡咯基,和咪唑基羧酸酰胺衍生物 |
| US7723336B2 (en) * | 2005-09-22 | 2010-05-25 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
| US20070078136A1 (en) * | 2005-09-22 | 2007-04-05 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
| TWI306217B (en) * | 2006-10-26 | 2009-02-11 | Siliconware Precision Industries Co Ltd | Insertion-type semiconductor device and fabrication method thereof |
| US20090130076A1 (en) * | 2007-11-21 | 2009-05-21 | Decode Genetics Ehf | Substituted benzoazole pde4 inhibitors for treating pulmonary and cardiovascular disorders |
-
2008
- 2008-11-20 US US12/275,164 patent/US20090130076A1/en not_active Abandoned
- 2008-11-20 AU AU2008326399A patent/AU2008326399C1/en not_active Ceased
- 2008-11-20 CN CN200880125182.8A patent/CN101918380B/zh not_active Expired - Fee Related
- 2008-11-20 WO PCT/US2008/084225 patent/WO2009067618A1/en not_active Ceased
- 2008-11-20 JP JP2010535072A patent/JP5524853B2/ja not_active Expired - Fee Related
- 2008-11-20 JP JP2010535068A patent/JP5529746B2/ja not_active Expired - Fee Related
- 2008-11-20 KR KR1020107013783A patent/KR20100097711A/ko not_active Ceased
- 2008-11-20 CN CN2008801251917A patent/CN101918381A/zh active Pending
- 2008-11-20 EP EP08853006A patent/EP2225215A1/en not_active Withdrawn
- 2008-11-20 US US12/275,165 patent/US8883833B2/en not_active Expired - Fee Related
- 2008-11-20 WO PCT/US2008/084199 patent/WO2009067604A1/en not_active Ceased
- 2008-11-20 AU AU2008326385A patent/AU2008326385B2/en not_active Ceased
- 2008-11-20 KR KR1020107013782A patent/KR20100090289A/ko not_active Ceased
- 2008-11-20 CA CA2722591A patent/CA2722591A1/en not_active Abandoned
- 2008-11-20 EP EP08853012A patent/EP2225216A1/en not_active Withdrawn
- 2008-11-20 CA CA2722586A patent/CA2722586A1/en not_active Abandoned
-
2010
- 2010-05-20 IL IL205884A patent/IL205884A0/en not_active IP Right Cessation
- 2010-05-20 IL IL205883A patent/IL205883A0/en unknown
-
2012
- 2012-04-24 US US13/454,487 patent/US20120207729A1/en not_active Abandoned
-
2014
- 2014-05-28 US US14/288,470 patent/US20140275553A1/en not_active Abandoned
-
2018
- 2018-09-19 IL IL261853A patent/IL261853A/en unknown
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