OA13049A - Dèrivès de 2-acylamino-4-phénylthiazole, leur préparation et leur application en thérapeutique. - Google Patents
Dèrivès de 2-acylamino-4-phénylthiazole, leur préparation et leur application en thérapeutique. Download PDFInfo
- Publication number
- OA13049A OA13049A OA1200500305A OA1200500305A OA13049A OA 13049 A OA13049 A OA 13049A OA 1200500305 A OA1200500305 A OA 1200500305A OA 1200500305 A OA1200500305 A OA 1200500305A OA 13049 A OA13049 A OA 13049A
- Authority
- OA
- OAPI
- Prior art keywords
- alk
- group
- formula
- alkyl
- compound
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims abstract description 75
- 230000001225 therapeutic effect Effects 0.000 title description 3
- 239000003814 drug Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 262
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 187
- -1 trifluoromethoxy, trifluoroethoxy Chemical group 0.000 claims description 131
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 23
- 239000002243 precursor Substances 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 239000002585 base Substances 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000005336 allyloxy group Chemical group 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 12
- 150000007513 acids Chemical class 0.000 claims description 11
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims description 10
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 9
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 8
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 7
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 6
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 6
- 102000019034 Chemokines Human genes 0.000 claims description 6
- 108010012236 Chemokines Proteins 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 125000004069 aziridinyl group Chemical group 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000005059 halophenyl group Chemical group 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- 125000006173 tetrahydropyranylmethyl group Chemical group 0.000 claims description 4
- 208000026935 allergic disease Diseases 0.000 claims description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 208000035143 Bacterial infection Diseases 0.000 claims description 2
- 101100007538 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cpc-1 gene Proteins 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 230000002491 angiogenic effect Effects 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 230000000495 immunoinflammatory effect Effects 0.000 claims description 2
- 125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 208000019622 heart disease Diseases 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 182
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 88
- 239000000243 solution Substances 0.000 description 75
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 71
- 239000000203 mixture Substances 0.000 description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- 239000002609 medium Substances 0.000 description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- 239000012074 organic phase Substances 0.000 description 41
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 32
- 239000007787 solid Substances 0.000 description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- 238000003756 stirring Methods 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- 239000008346 aqueous phase Substances 0.000 description 16
- 239000002244 precipitate Substances 0.000 description 16
- 239000012429 reaction media Substances 0.000 description 16
- 239000011734 sodium Substances 0.000 description 16
- 239000011780 sodium chloride Substances 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 14
- 239000012047 saturated solution Substances 0.000 description 14
- 238000001704 evaporation Methods 0.000 description 13
- 230000008020 evaporation Effects 0.000 description 13
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 11
- 229910052708 sodium Inorganic materials 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 10
- 235000017550 sodium carbonate Nutrition 0.000 description 10
- 229910000029 sodium carbonate Inorganic materials 0.000 description 10
- 230000009471 action Effects 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 239000000377 silicon dioxide Substances 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 238000010908 decantation Methods 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 8
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
- GMAACCYBQHHVDO-UHFFFAOYSA-N 4-(2-hydroxyethoxy)-n-[4-(2-methoxy-5-propoxyphenyl)-1,3-thiazol-2-yl]benzamide Chemical compound CCCOC1=CC=C(OC)C(C=2N=C(NC(=O)C=3C=CC(OCCO)=CC=3)SC=2)=C1 GMAACCYBQHHVDO-UHFFFAOYSA-N 0.000 description 7
- 238000012512 characterization method Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 229950003476 aminothiazole Drugs 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- ZDMUWEXQZFRIMB-UHFFFAOYSA-N n-[4-(2-methoxy-5-propoxyphenyl)-1,3-thiazol-2-yl]-4-(2-oxoethoxy)benzamide Chemical compound CCCOC1=CC=C(OC)C(C=2N=C(NC(=O)C=3C=CC(OCC=O)=CC=3)SC=2)=C1 ZDMUWEXQZFRIMB-UHFFFAOYSA-N 0.000 description 6
- KYJVJOGYKLXLPL-UHFFFAOYSA-N n-[4-(5-butyl-2-methoxyphenyl)-1,3-thiazol-2-yl]-4-(2-chloroethyl)benzamide Chemical compound CCCCC1=CC=C(OC)C(C=2N=C(NC(=O)C=3C=CC(CCCl)=CC=3)SC=2)=C1 KYJVJOGYKLXLPL-UHFFFAOYSA-N 0.000 description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- 230000007170 pathology Effects 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 4
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 235000010233 benzoic acid Nutrition 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 102000004497 CCR2 Receptors Human genes 0.000 description 3
- 108010017312 CCR2 Receptors Proteins 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 150000008062 acetophenones Chemical class 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 150000004677 hydrates Chemical class 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
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- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
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- 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 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- OYAYJSSZNWHFQH-UHFFFAOYSA-N 1-methoxy-4-(1,1,2,2,2-pentafluoroethyl)benzene Chemical compound COC1=CC=C(C(F)(F)C(F)(F)F)C=C1 OYAYJSSZNWHFQH-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- UFMBOFGKHIXOTA-UHFFFAOYSA-N 2-methylterephthalic acid Chemical compound CC1=CC(C(O)=O)=CC=C1C(O)=O UFMBOFGKHIXOTA-UHFFFAOYSA-N 0.000 description 2
- NWLFUZQESWFKGV-UHFFFAOYSA-N 4-(2,2-diethoxyethoxy)benzoic acid Chemical compound CCOC(OCC)COC1=CC=C(C(O)=O)C=C1 NWLFUZQESWFKGV-UHFFFAOYSA-N 0.000 description 2
- KEMBKBIOSMRWAA-UHFFFAOYSA-N 4-(2-methoxy-5-propoxyphenyl)-1,3-thiazol-2-amine Chemical compound CCCOC1=CC=C(OC)C(C=2N=C(N)SC=2)=C1 KEMBKBIOSMRWAA-UHFFFAOYSA-N 0.000 description 2
- ACNPMHHSEMHUGY-UHFFFAOYSA-N 4-(5-butyl-2-methoxyphenyl)-1,3-thiazol-2-amine Chemical compound CCCCC1=CC=C(OC)C(C=2N=C(N)SC=2)=C1 ACNPMHHSEMHUGY-UHFFFAOYSA-N 0.000 description 2
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- YWIAOILQRZTIOF-UHFFFAOYSA-N n-[4-(5-hexyl-2-methoxyphenyl)-1,3-thiazol-2-yl]-4-[4-(oxan-4-ylamino)piperidine-1-carbonyl]benzamide Chemical compound CCCCCCC1=CC=C(OC)C(C=2N=C(NC(=O)C=3C=CC(=CC=3)C(=O)N3CCC(CC3)NC3CCOCC3)SC=2)=C1 YWIAOILQRZTIOF-UHFFFAOYSA-N 0.000 description 1
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- 230000036961 partial effect Effects 0.000 description 1
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- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
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- 230000000704 physical effect Effects 0.000 description 1
- AHGFDQXBCIASJK-UHFFFAOYSA-M potassium;2,2,3,3,3-pentafluoropropanoate Chemical compound [K+].[O-]C(=O)C(F)(F)C(F)(F)F AHGFDQXBCIASJK-UHFFFAOYSA-M 0.000 description 1
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- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
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- 230000002829 reductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
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- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
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- MHSKRLJMQQNJNC-UHFFFAOYSA-N terephthalamide Chemical compound NC(=O)C1=CC=C(C(N)=O)C=C1 MHSKRLJMQQNJNC-UHFFFAOYSA-N 0.000 description 1
- CMIBWIAICVBURI-ZETCQYMHSA-N tert-butyl (3s)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](N)C1 CMIBWIAICVBURI-ZETCQYMHSA-N 0.000 description 1
- DQQJBEAXSOOCPG-SSDOTTSWSA-N tert-butyl n-[(3r)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCNC1 DQQJBEAXSOOCPG-SSDOTTSWSA-N 0.000 description 1
- RESRQUHKDRAWIN-UHFFFAOYSA-N tert-butyl n-[1-(1-benzylpiperidin-4-yl)pyrrolidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CCN1C1CCN(CC=2C=CC=CC=2)CC1 RESRQUHKDRAWIN-UHFFFAOYSA-N 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
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Classifications
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US12479816B2 (en) | 2019-02-08 | 2025-11-25 | University of Pittsburgh—of the Commonwealth System of Higher Education | 20-HETE formation inhibitors |
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| JO2676B1 (en) * | 2004-04-06 | 2012-06-17 | جانسين فارماسوتيكا ان. في | Derivatives of second-aza-spiro- (5,4) -dikan and their use as antihistamines |
| JO2527B1 (en) * | 2004-04-06 | 2010-03-17 | شركة جانسين فارماسوتيكا ان. في | Derivatives of second-aza-Spiro- (5,5) -andecan and their use as antihistamines |
| FR2872813B1 (fr) | 2004-07-09 | 2007-01-19 | Sanofi Synthelabo | Derives de 2-carbamide-4-phenylthiazole, leur preparation et leur application en therapeutique |
| GB0421908D0 (en) * | 2004-10-01 | 2004-11-03 | Angeletti P Ist Richerche Bio | New uses |
| FR2876692B1 (fr) * | 2004-10-19 | 2007-02-23 | Sanofi Aventis Sa | Derives de 2-amido-4-phenylthiazole, leur preparation et leur application en therapeutique |
| EP1833807A1 (en) * | 2005-01-05 | 2007-09-19 | Rigel Pharmaceuticals, Inc. | Ubiquitin ligase inhibitors |
| CN101137657B (zh) | 2005-03-08 | 2011-02-02 | 詹森药业有限公司 | 作为神经激肽(nk1)拮抗剂的二氮杂-螺-[4.4]-壬烷衍生物 |
| BRPI0608910A2 (pt) * | 2005-05-09 | 2010-02-17 | Achillion Pharmaceuticals Inc | uso de um composto da fórmula ou um sal ou hidrato farmaceuticamente aceitável desse, composto ou sal ou hidrato do mesmo, composição farmacêutica e composição farmacêutica embalada |
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| US8067415B2 (en) | 2005-11-01 | 2011-11-29 | Millennium Pharmaceuticals, Inc. | Compounds useful as antagonists of CCR2 |
| WO2007053498A1 (en) * | 2005-11-01 | 2007-05-10 | Millennium Pharmaceuticals, Inc. | Compounds useful as antagonists of ccr2 |
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| EP2059515A2 (en) * | 2006-04-12 | 2009-05-20 | Pfizer Limited | Pyrrolidine derivatives as modulators of chemokine ccr5 receptors |
| RU2303597C1 (ru) * | 2006-05-12 | 2007-07-27 | Иващенко Андрей Александрович | Фармацевтическая композиция, способы ее получения и применения |
| CN101096363B (zh) | 2006-06-27 | 2011-05-11 | 中国人民解放军军事医学科学院毒物药物研究所 | 2,4,5-三取代噻唑类化合物、其制备方法、药物组合物及其制药用途 |
| US20080076120A1 (en) * | 2006-09-14 | 2008-03-27 | Millennium Pharmaceuticals, Inc. | Methods for the identification, evaluation and treatment of patients having CC-Chemokine receptor 2 (CCR-2) mediated disorders |
| WO2008060621A2 (en) | 2006-11-17 | 2008-05-22 | Abbott Laboratories | Aminopyrrolidines as chemokine receptor antagonists |
| SI2118099T1 (sl) * | 2007-02-13 | 2011-11-30 | Ab Science | Postopek za sintezo 2-aminotiazolnih spojin kot kinaznih inhibitorjev |
| WO2008124000A2 (en) * | 2007-04-02 | 2008-10-16 | Ligand Pharmaceuticals Incorporated | Thiazole derivatives as androgen receptor modulator compounds |
| CA2687931C (en) | 2007-05-31 | 2016-05-24 | Boehringer Ingelheim International Gmbh | Ccr2 receptor antagonists and uses thereof |
| JP5164181B2 (ja) * | 2007-07-31 | 2013-03-13 | 塩野義製薬株式会社 | トロンボポエチン受容体アゴニスト作用を有する光学活性な化合物を含有する医薬組成物およびその中間体 |
| CN103724328B (zh) | 2008-12-19 | 2015-10-14 | 贝林格尔.英格海姆国际有限公司 | 作为ccr2受体拮抗剂用于治疗炎症、哮喘和copd的环状嘧啶-4-甲酰胺 |
| PL2513093T3 (pl) | 2009-12-17 | 2015-03-31 | Centrexion Therapeutics Corp | Nowi antagoniści receptora CCR2 i ich zastosowanie |
| WO2011115998A2 (en) | 2010-03-17 | 2011-09-22 | Taivex Therapeutics Inc. | Modulators of hec1 activity and methods therefor |
| JP2013526507A (ja) | 2010-05-12 | 2013-06-24 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規ccr2受容体アンタゴニスト、その製造方法及び薬物としてのその使用 |
| EP2569295B1 (en) | 2010-05-12 | 2014-11-19 | Boehringer Ingelheim International GmbH | New ccr2 receptor antagonists, method for producing the same, and use thereof as medicaments |
| US8841313B2 (en) | 2010-05-17 | 2014-09-23 | Boehringer Ingelheim International Gmbh | CCR2 antagonists and uses thereof |
| JP5636094B2 (ja) | 2010-05-25 | 2014-12-03 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ccr2受容体アンタゴニスト |
| EP2576538B1 (en) | 2010-06-01 | 2015-10-28 | Boehringer Ingelheim International GmbH | New CCR2 antagonists |
| WO2013010839A1 (en) | 2011-07-15 | 2013-01-24 | Boehringer Ingelheim International Gmbh | Novel and selective ccr2 antagonists |
| CN103086859B (zh) * | 2011-11-08 | 2015-11-11 | 清华大学 | 2,4-二羟基-5,6-取代-1-卤代苯衍生物、其合成方法及其应用 |
| US11071736B2 (en) | 2011-11-21 | 2021-07-27 | Taivex Therapeutics Corporation | Modulators of HEC1 activity and methods therefor |
| AU2016287584B2 (en) | 2015-07-02 | 2020-03-26 | Centrexion Therapeutics Corporation | (4-((3R,4R)-3-methoxytetrahydro-pyran-4-ylamino)piperidin-1-yl)(5-methyl-6-(((2R,6S)-6-(p-tolyl)tetrahydro-2H-pyran-2-yl)methylamino)pyrimidin-4yl)methanone citrate |
| US11028061B2 (en) * | 2015-07-27 | 2021-06-08 | Sanford Burnham Prebys Medical Discovery Institute | Modulators of myocyte lipid accumulation and insulin resistance and methods of use thereof |
| WO2019222393A1 (en) | 2018-05-15 | 2019-11-21 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Neuroprotective compositions and methods of using the same |
| WO2020086625A1 (en) * | 2018-10-22 | 2020-04-30 | The Regents Of The University Of California | Vaccine adjuvant |
| CN112004798A (zh) * | 2019-01-07 | 2020-11-27 | 江苏凯迪恩医药科技有限公司 | 一种苯甲酰胺类化合物、中间体、制备方法及应用 |
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| DE55034C (de) * | H. KRÜGER in Berlin N., Artilleriestrafse 23 | Zapfenverschlufs für chirurgische Instrumente | ||
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| US3458526A (en) * | 1966-09-26 | 1969-07-29 | Upjohn Co | Certain 2-amino-4,5-bis(p-methoxyphenyl)thiazoles |
| FR2296497A1 (fr) * | 1974-12-31 | 1976-07-30 | Asselin Robert | Perfectionnement apporte aux fixations de verres optiques sur supports en vue de leur usinage |
| DE2706269C3 (de) * | 1977-02-15 | 1979-08-02 | Th. Goldschmidt Ag, 4300 Essen | Verwendung von Aminderivaten zur Beeinflussung der Theologischen Eigenschaften von Bitumen und bituminösen Massen |
| FR2406634A1 (fr) * | 1977-10-19 | 1979-05-18 | Fabre Sa Pierre | Immunostimulants derives d'amino thiazoles |
| JPH0717589B2 (ja) * | 1990-01-22 | 1995-03-01 | ファイザー製薬株式会社 | 新規1,3―ジカルボニル化合物およびその組成物 |
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| AU2000092A (en) | 1991-06-21 | 1993-01-25 | Boehringer Mannheim Italia S.P.A. | 2-amino-4-aryl-thiazoles with antiasthmatic and anti-inflammatory activities on the respiratory tract |
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| CA2136999C (en) * | 1993-04-07 | 2004-05-11 | Takafumi Fujioka | Peripheral vasodilating agent containing piperidine derivative as active ingredient |
| DE4326344A1 (de) * | 1993-08-05 | 1995-02-09 | Thomae Gmbh Dr K | Carbonamide, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| US6331545B1 (en) * | 1998-12-18 | 2001-12-18 | Soo S. Ko | Heterocycyclic piperidines as modulators of chemokine receptor activity |
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| JP4083422B2 (ja) * | 2000-12-22 | 2008-04-30 | 石原産業株式会社 | アニリン誘導体またはその塩ならびにそれらを含有するサイトカイン産生抑制剤 |
| GB0104050D0 (en) * | 2001-02-19 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| GB0108876D0 (en) * | 2001-04-09 | 2001-05-30 | Novartis Ag | Organic Compounds |
| US20030055263A1 (en) * | 2001-07-11 | 2003-03-20 | Boehringer Ingelheim Pharma Kg | Carboxylic acid derivatives, medicaments comprising these compounds, their use and processes for their production |
| WO2003015778A1 (en) | 2001-08-17 | 2003-02-27 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| TW200403058A (en) | 2002-04-19 | 2004-03-01 | Bristol Myers Squibb Co | Heterocyclo inhibitors of potassium channel function |
| JP2004256429A (ja) * | 2003-02-26 | 2004-09-16 | Sankyo Co Ltd | イソキノリン誘導体 |
| FR2872813B1 (fr) | 2004-07-09 | 2007-01-19 | Sanofi Synthelabo | Derives de 2-carbamide-4-phenylthiazole, leur preparation et leur application en therapeutique |
| FR2876692B1 (fr) | 2004-10-19 | 2007-02-23 | Sanofi Aventis Sa | Derives de 2-amido-4-phenylthiazole, leur preparation et leur application en therapeutique |
| FR2895989B1 (fr) | 2006-01-06 | 2010-04-30 | Sanofi Aventis | Derives de 2-carbamide-4-phenylthiazole, leur preparation et leur application en therapeutique |
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2003
- 2003-04-25 FR FR0305213A patent/FR2854158B1/fr not_active Expired - Fee Related
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2004
- 2004-04-22 OA OA1200500305A patent/OA13049A/fr unknown
- 2004-04-22 RS YUP-2005/0769A patent/RS20050769A/sr unknown
- 2004-04-22 EP EP04742558A patent/EP1656373B1/fr not_active Expired - Lifetime
- 2004-04-22 AU AU2004234101A patent/AU2004234101A1/en not_active Abandoned
- 2004-04-22 CN CNA2004800180511A patent/CN1826339A/zh active Pending
- 2004-04-22 MX MXPA05011522A patent/MXPA05011522A/es unknown
- 2004-04-22 WO PCT/FR2004/000981 patent/WO2004096798A2/fr not_active Ceased
- 2004-04-22 JP JP2006505808A patent/JP4839208B2/ja not_active Expired - Fee Related
- 2004-04-22 KR KR1020057020168A patent/KR20060006935A/ko not_active Ceased
- 2004-04-22 ZA ZA200508608A patent/ZA200508608B/en unknown
- 2004-04-22 BR BRPI0409716-5A patent/BRPI0409716A/pt not_active IP Right Cessation
- 2004-04-22 CA CA002521158A patent/CA2521158A1/fr not_active Abandoned
- 2004-04-22 RU RU2005136663/04A patent/RU2348630C2/ru not_active IP Right Cessation
- 2004-04-22 AT AT04742558T patent/ATE541843T1/de active
- 2004-04-23 AR ARP040101382A patent/AR044070A1/es unknown
- 2004-04-26 TW TW093111632A patent/TW200510325A/zh unknown
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2005
- 2005-10-06 TN TNP2005000254A patent/TNSN05254A1/en unknown
- 2005-10-11 CR CR8037A patent/CR8037A/es not_active Application Discontinuation
- 2005-10-19 US US11/253,998 patent/US7504511B2/en not_active Expired - Fee Related
- 2005-10-21 EC EC2005006111A patent/ECSP056111A/es unknown
- 2005-10-24 MA MA28569A patent/MA27769A1/fr unknown
- 2005-10-24 NO NO20054905A patent/NO20054905L/no not_active Application Discontinuation
- 2005-10-25 CO CO05108740A patent/CO5640106A2/es not_active Application Discontinuation
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12479816B2 (en) | 2019-02-08 | 2025-11-25 | University of Pittsburgh—of the Commonwealth System of Higher Education | 20-HETE formation inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1656373A2 (fr) | 2006-05-17 |
| ECSP056111A (es) | 2006-03-01 |
| WO2004096798A3 (fr) | 2006-01-26 |
| TW200510325A (en) | 2005-03-16 |
| RU2348630C2 (ru) | 2009-03-10 |
| US7777041B2 (en) | 2010-08-17 |
| JP2011126891A (ja) | 2011-06-30 |
| US20090156574A1 (en) | 2009-06-18 |
| CA2521158A1 (fr) | 2004-11-11 |
| CN1826339A (zh) | 2006-08-30 |
| KR20060006935A (ko) | 2006-01-20 |
| FR2854158A1 (fr) | 2004-10-29 |
| US20060135575A1 (en) | 2006-06-22 |
| FR2854158B1 (fr) | 2006-11-17 |
| WO2004096798A2 (fr) | 2004-11-11 |
| ATE541843T1 (de) | 2012-02-15 |
| RS20050769A (sr) | 2007-11-15 |
| NO20054905D0 (no) | 2005-10-24 |
| CR8037A (es) | 2008-07-29 |
| AR044070A1 (es) | 2005-08-24 |
| CO5640106A2 (es) | 2006-05-31 |
| US7504511B2 (en) | 2009-03-17 |
| ZA200508608B (en) | 2007-01-31 |
| JP4839208B2 (ja) | 2011-12-21 |
| JP2006524669A (ja) | 2006-11-02 |
| EP1656373B1 (fr) | 2012-01-18 |
| TNSN05254A1 (en) | 2007-07-10 |
| MA27769A1 (fr) | 2006-02-01 |
| AU2004234101A1 (en) | 2004-11-11 |
| MXPA05011522A (es) | 2006-01-23 |
| RU2005136663A (ru) | 2006-03-20 |
| BRPI0409716A (pt) | 2006-05-02 |
| NO20054905L (no) | 2006-01-25 |
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