ZA200509706B - New P2X, receptor antagonists and their use - Google Patents
New P2X, receptor antagonists and their use Download PDFInfo
- Publication number
- ZA200509706B ZA200509706B ZA200509706A ZA200509706A ZA200509706B ZA 200509706 B ZA200509706 B ZA 200509706B ZA 200509706 A ZA200509706 A ZA 200509706A ZA 200509706 A ZA200509706 A ZA 200509706A ZA 200509706 B ZA200509706 B ZA 200509706B
- Authority
- ZA
- South Africa
- Prior art keywords
- chloro
- quinolinyl
- formula
- amino
- cyclohexaneacetamide
- Prior art date
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- 239000002464 receptor antagonist Substances 0.000 title description 3
- 229940044551 receptor antagonist Drugs 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 143
- 125000000217 alkyl group Chemical group 0.000 claims description 85
- 125000001424 substituent group Chemical group 0.000 claims description 80
- 229910052736 halogen Inorganic materials 0.000 claims description 78
- 150000002367 halogens Chemical class 0.000 claims description 78
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 75
- -1 nitro, cyano, amino Chemical group 0.000 claims description 65
- 125000000623 heterocyclic group Chemical group 0.000 claims description 63
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 229910052757 nitrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 29
- 239000000651 prodrug Substances 0.000 claims description 26
- 229940002612 prodrug Drugs 0.000 claims description 26
- 239000012453 solvate Substances 0.000 claims description 26
- 125000002837 carbocyclic group Chemical group 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 19
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 19
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 19
- 229910052794 bromium Inorganic materials 0.000 claims description 19
- 239000011630 iodine Substances 0.000 claims description 19
- 229910052740 iodine Inorganic materials 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 229910052721 tungsten Inorganic materials 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 11
- 125000003466 9 membered carbocyclic group Chemical group 0.000 claims description 10
- 239000005864 Sulphur Chemical group 0.000 claims description 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- 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 7
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 6
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- DKLQJNUJPSHYQG-UHFFFAOYSA-N 2-cyclohexylacetamide Chemical compound NC(=O)CC1CCCCC1 DKLQJNUJPSHYQG-UHFFFAOYSA-N 0.000 claims description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 4
- 150000001336 alkenes Chemical class 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 229910003002 lithium salt Inorganic materials 0.000 claims description 4
- 159000000002 lithium salts Chemical class 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
- 125000003627 8 membered carbocyclic group Chemical group 0.000 claims description 3
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 claims description 3
- VVHZEOFICMARAV-UHFFFAOYSA-N chlorosulfonylcarbamic acid Chemical compound OC(=O)NS(Cl)(=O)=O VVHZEOFICMARAV-UHFFFAOYSA-N 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 claims description 3
- XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 claims description 3
- 238000005984 hydrogenation reaction Methods 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000006268 reductive amination reaction Methods 0.000 claims description 3
- 239000000377 silicon dioxide Substances 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- LAZJEWURFXJBBQ-UHFFFAOYSA-N 1-[6-chloro-5-(2-cyclohexylethylcarbamoyl)quinolin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=CC=C(C(C(=O)NCCC2CCCCC2)=C(Cl)C=C2)C2=N1 LAZJEWURFXJBBQ-UHFFFAOYSA-N 0.000 claims description 2
- YWDUKXODAYJOPI-UHFFFAOYSA-N 2-(1-methylcyclohexyl)-n-quinolin-5-ylacetamide Chemical compound C=1C=CC2=NC=CC=C2C=1NC(=O)CC1(C)CCCCC1 YWDUKXODAYJOPI-UHFFFAOYSA-N 0.000 claims description 2
- JMCBXQUHXRJEAX-UHFFFAOYSA-N 2-(4-methylcyclohexyl)-n-quinolin-5-ylacetamide Chemical compound C1CC(C)CCC1CC(=O)NC1=CC=CC2=NC=CC=C12 JMCBXQUHXRJEAX-UHFFFAOYSA-N 0.000 claims description 2
- FFWDPNGSQDVFFQ-QCUBGVIVSA-N 2-[(3r)-3-aminopyrrolidin-1-yl]-6-chloro-n-(cyclohexylmethyl)quinoline-5-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1[C@H](N)CCN1C1=CC=C(C(C(=O)NCC2CCCCC2)=C(Cl)C=C2)C2=N1 FFWDPNGSQDVFFQ-QCUBGVIVSA-N 0.000 claims description 2
- BXZQJVRXGKJLHF-INIZCTEOSA-N 2-[(3s)-3-aminopiperidin-1-yl]-6-chloro-n-(cyclohexylmethyl)quinoline-5-carboxamide Chemical compound C1[C@@H](N)CCCN1C1=CC=C(C(C(=O)NCC2CCCCC2)=C(Cl)C=C2)C2=N1 BXZQJVRXGKJLHF-INIZCTEOSA-N 0.000 claims description 2
- CGNJXSPAKKCIDK-UHFFFAOYSA-N 2-[[6-chloro-5-[(2-cyclohexylacetyl)amino]quinolin-2-yl]amino]acetic acid Chemical compound ClC=1C=CC2=NC(NCC(=O)O)=CC=C2C=1NC(=O)CC1CCCCC1 CGNJXSPAKKCIDK-UHFFFAOYSA-N 0.000 claims description 2
- LOLYXDBESWAMRB-UHFFFAOYSA-N 2-cyclohexyl-n-(6-methyl-2-piperazin-1-ylquinolin-5-yl)acetamide Chemical compound CC1=CC=C2N=C(N3CCNCC3)C=CC2=C1NC(=O)CC1CCCCC1 LOLYXDBESWAMRB-UHFFFAOYSA-N 0.000 claims description 2
- LRYRZOCEUYUPAX-UHFFFAOYSA-N 2-cyclohexyl-n-quinolin-5-ylacetamide Chemical compound C=1C=CC2=NC=CC=C2C=1NC(=O)CC1CCCCC1 LRYRZOCEUYUPAX-UHFFFAOYSA-N 0.000 claims description 2
- XKUVYIHVWJZCMC-UHFFFAOYSA-N 3-cyclopentyl-n-quinolin-5-ylpropanamide Chemical compound C=1C=CC2=NC=CC=C2C=1NC(=O)CCC1CCCC1 XKUVYIHVWJZCMC-UHFFFAOYSA-N 0.000 claims description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 2
- SBQUTMVHNXUXGR-UHFFFAOYSA-N 4-[6-chloro-5-[(2-cyclohexylacetyl)amino]quinolin-2-yl]butanoic acid Chemical compound ClC=1C=CC2=NC(CCCC(=O)O)=CC=C2C=1NC(=O)CC1CCCCC1 SBQUTMVHNXUXGR-UHFFFAOYSA-N 0.000 claims description 2
- WERKFQSBRPCCJG-UHFFFAOYSA-N 6-chloro-n-(cyclohexylmethyl)-2-(3-hydroxyazetidin-1-yl)quinoline-5-carboxamide Chemical compound C1C(O)CN1C1=CC=C(C(C(=O)NCC2CCCCC2)=C(Cl)C=C2)C2=N1 WERKFQSBRPCCJG-UHFFFAOYSA-N 0.000 claims description 2
- PDIUYOQEVHQOHR-LMOVPXPDSA-N 6-chloro-n-(cyclohexylmethyl)-2-[(3s)-3-(2-hydroxyethylamino)pyrrolidin-1-yl]quinoline-5-carboxamide;hydrochloride Chemical compound Cl.C1[C@@H](NCCO)CCN1C1=CC=C(C(C(=O)NCC2CCCCC2)=C(Cl)C=C2)C2=N1 PDIUYOQEVHQOHR-LMOVPXPDSA-N 0.000 claims description 2
- SHGCFVXNZKPHLW-UHFFFAOYSA-N 6-chloro-n-(cyclohexylmethyl)-2-[3-(2h-tetrazol-5-yl)azetidin-1-yl]quinoline-5-carboxamide Chemical compound ClC1=CC=C2N=C(N3CC(C3)C=3NN=NN=3)C=CC2=C1C(=O)NCC1CCCCC1 SHGCFVXNZKPHLW-UHFFFAOYSA-N 0.000 claims description 2
- ITRDTWBRIGTAOE-UHFFFAOYSA-N 6-chloro-n-(cyclohexylmethyl)quinoline-5-carboxamide Chemical compound ClC1=CC=C2N=CC=CC2=C1C(=O)NCC1CCCCC1 ITRDTWBRIGTAOE-UHFFFAOYSA-N 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 235000004279 alanine Nutrition 0.000 claims description 2
- 150000001345 alkine derivatives Chemical class 0.000 claims description 2
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 claims description 2
- FHUQHJJFACHEEQ-UHFFFAOYSA-N n-(6-chloro-2-piperazin-1-ylquinolin-5-yl)-2-[4-(trifluoromethyl)cyclohexyl]acetamide Chemical compound C1CC(C(F)(F)F)CCC1CC(=O)NC1=C(Cl)C=CC2=NC(N3CCNCC3)=CC=C12 FHUQHJJFACHEEQ-UHFFFAOYSA-N 0.000 claims description 2
- QRYSLFHTCYIURU-UHFFFAOYSA-N n-(6-chloro-2-piperazin-1-ylquinolin-5-yl)-2-cyclohexylacetamide;dihydrochloride Chemical compound Cl.Cl.ClC1=CC=C2N=C(N3CCNCC3)C=CC2=C1NC(=O)CC1CCCCC1 QRYSLFHTCYIURU-UHFFFAOYSA-N 0.000 claims description 2
- HKWKCXVXBWBQGR-UHFFFAOYSA-N n-(6-chloro-2-piperazin-1-ylquinolin-5-yl)-3-cyclohexylpropanamide Chemical compound ClC1=CC=C2N=C(N3CCNCC3)C=CC2=C1NC(=O)CCC1CCCCC1 HKWKCXVXBWBQGR-UHFFFAOYSA-N 0.000 claims description 2
- ZUSATBXYFWGVHJ-UHFFFAOYSA-N n-[2-(4-aminopiperidin-1-yl)-6-chloroquinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1CC(N)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 ZUSATBXYFWGVHJ-UHFFFAOYSA-N 0.000 claims description 2
- PBOHJDQKIYZTLV-OAHLLOKOSA-N n-[2-[(3r)-3-aminopyrrolidin-1-yl]-6-chloroquinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1[C@H](N)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 PBOHJDQKIYZTLV-OAHLLOKOSA-N 0.000 claims description 2
- LBNXHBRGPSEPFS-UHFFFAOYSA-N n-[2-[3-(butylamino)propyl]-6-chloroquinolin-5-yl]-2-cyclohexylacetamide;dihydrochloride Chemical compound Cl.Cl.ClC=1C=CC2=NC(CCCNCCCC)=CC=C2C=1NC(=O)CC1CCCCC1 LBNXHBRGPSEPFS-UHFFFAOYSA-N 0.000 claims description 2
- CCGNJOBSXTXZHH-UHFFFAOYSA-N n-[6-chloro-2-(4-cyanopiperidin-1-yl)quinolin-5-yl]-2-cyclohexylacetamide Chemical compound ClC1=CC=C2N=C(N3CCC(CC3)C#N)C=CC2=C1NC(=O)CC1CCCCC1 CCGNJOBSXTXZHH-UHFFFAOYSA-N 0.000 claims description 2
- OJPMEGWECRDTPY-UHFFFAOYSA-N n-[6-chloro-2-(piperidin-4-ylmethyl)quinolin-5-yl]-2-cyclohexylacetamide;dihydrochloride Chemical compound Cl.Cl.C1=CC2=C(NC(=O)CC3CCCCC3)C(Cl)=CC=C2N=C1CC1CCNCC1 OJPMEGWECRDTPY-UHFFFAOYSA-N 0.000 claims description 2
- SSGJRDKQKWGZRZ-QGZVFWFLSA-N n-[6-chloro-2-[(3r)-3-(2-hydroxyethylamino)pyrrolidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1[C@H](NCCO)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 SSGJRDKQKWGZRZ-QGZVFWFLSA-N 0.000 claims description 2
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- UDOBIIWJZTYDSM-UHFFFAOYSA-N n-[6-chloro-2-[2-(methylaminomethyl)pyrrolidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound CNCC1CCCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 UDOBIIWJZTYDSM-UHFFFAOYSA-N 0.000 claims description 2
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 2
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- 239000002671 adjuvant Substances 0.000 claims 2
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- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims 2
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- COJCWDWLMDYPQG-UHFFFAOYSA-N 1-[6-chloro-5-(3-cyclohexylpropanoylamino)quinolin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=CC=C(C(NC(=O)CCC2CCCCC2)=C(Cl)C=C2)C2=N1 COJCWDWLMDYPQG-UHFFFAOYSA-N 0.000 claims 1
- WCQYXQNUWCHDCK-INIZCTEOSA-N 2-[(3s)-3-aminopyrrolidin-1-yl]-n-(cyclohexylmethyl)quinoline-5-carboxamide Chemical compound C1[C@@H](N)CCN1C1=CC=C(C(=CC=C2)C(=O)NCC3CCCCC3)C2=N1 WCQYXQNUWCHDCK-INIZCTEOSA-N 0.000 claims 1
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- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
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- 101710189969 P2X purinoceptor 5 Proteins 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000004849 alkoxymethyl group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
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- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
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- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- USVZFSNDGFNNJT-UHFFFAOYSA-N cyclopenta-1,4-dien-1-yl(diphenyl)phosphane (2,3-dichlorocyclopenta-1,4-dien-1-yl)-diphenylphosphane iron(2+) Chemical compound [Fe++].c1cc[c-](c1)P(c1ccccc1)c1ccccc1.Clc1c(cc[c-]1Cl)P(c1ccccc1)c1ccccc1 USVZFSNDGFNNJT-UHFFFAOYSA-N 0.000 description 1
- JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 210000003584 mesangial cell Anatomy 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
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- 230000002025 microglial effect Effects 0.000 description 1
- WBGPDYJIPNTOIB-UHFFFAOYSA-N n,n-dibenzylethanamine Chemical compound C=1C=CC=CC=1CN(CC)CC1=CC=CC=C1 WBGPDYJIPNTOIB-UHFFFAOYSA-N 0.000 description 1
- RJRJLSPEPQNVSG-UHFFFAOYSA-N n-(2-amino-6-chloroquinolin-5-yl)-2-cyclohexylacetamide Chemical compound ClC=1C=CC2=NC(N)=CC=C2C=1NC(=O)CC1CCCCC1 RJRJLSPEPQNVSG-UHFFFAOYSA-N 0.000 description 1
- UITBUVBGYFIFAV-UHFFFAOYSA-N n-(6-chloro-2-piperazin-1-ylquinolin-5-yl)-1-cyclohexylcyclopropane-1-carboxamide Chemical compound ClC1=CC=C2N=C(N3CCNCC3)C=CC2=C1NC(=O)C1(C2CCCCC2)CC1 UITBUVBGYFIFAV-UHFFFAOYSA-N 0.000 description 1
- FPEROWRTMNZXLW-UHFFFAOYSA-N n-(cyclohexylmethyl)-6-methylquinoline-5-carboxamide Chemical compound CC1=CC=C2N=CC=CC2=C1C(=O)NCC1CCCCC1 FPEROWRTMNZXLW-UHFFFAOYSA-N 0.000 description 1
- YYCSRFBSHWKXKH-UHFFFAOYSA-N n-[6-chloro-2-(4-methylpiperazin-1-yl)quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1CN(C)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 YYCSRFBSHWKXKH-UHFFFAOYSA-N 0.000 description 1
- CKAOBTYBKVOEIT-HOTGVXAUSA-N n-[6-chloro-2-[(1s,4s)-2,5-diazabicyclo[2.2.1]heptan-2-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C([C@]1(NC[C@]2([H])C1)[H])N2C(N=C1C=CC=2Cl)=CC=C1C=2NC(=O)CC1CCCCC1 CKAOBTYBKVOEIT-HOTGVXAUSA-N 0.000 description 1
- SNALAXOTTURDHK-OAHLLOKOSA-N n-[6-chloro-2-[[(3r)-pyrrolidin-3-yl]amino]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1=CC2=C(NC(=O)CC3CCCCC3)C(Cl)=CC=C2N=C1N[C@@H]1CCNC1 SNALAXOTTURDHK-OAHLLOKOSA-N 0.000 description 1
- 125000004708 n-butylthio group Chemical group C(CCC)S* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 125000005633 phthalidyl group Chemical group 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical compound C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- GYGSVGGRZHTGTP-UHFFFAOYSA-N tert-butyl n-[1-[6-chloro-5-[(2-cyclohexylacetyl)amino]quinolin-2-yl]pyrrolidin-3-yl]-n-(2-hydroxyethyl)carbamate Chemical compound C1C(N(CCO)C(=O)OC(C)(C)C)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 GYGSVGGRZHTGTP-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D401/02—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 two hetero rings
- C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D401/02—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 two hetero rings
- C07D401/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- 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
- C07D487/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0312609.1A GB0312609D0 (en) | 2003-06-02 | 2003-06-02 | Novel compounds |
| SE0301700A SE0301700D0 (sv) | 2003-06-02 | 2003-06-10 | Novel compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200509706B true ZA200509706B (en) | 2006-12-27 |
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| ZA200509706A ZA200509706B (en) | 2003-06-02 | 2005-11-30 | New P2X, receptor antagonists and their use |
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| EP (1) | EP1633717B1 (ja) |
| JP (1) | JP4682128B2 (ja) |
| KR (1) | KR101244971B1 (ja) |
| CN (1) | CN1832925B (ja) |
| AR (1) | AR045691A1 (ja) |
| AT (1) | ATE446953T1 (ja) |
| AU (1) | AU2004242626B2 (ja) |
| BR (1) | BRPI0410933A (ja) |
| CA (1) | CA2526884C (ja) |
| CO (1) | CO5700720A2 (ja) |
| DE (1) | DE602004023840D1 (ja) |
| ES (1) | ES2333721T3 (ja) |
| GB (1) | GB0312609D0 (ja) |
| HK (1) | HK1085736A1 (ja) |
| IS (1) | IS8190A (ja) |
| MX (1) | MXPA05012883A (ja) |
| NO (1) | NO20060001L (ja) |
| RU (1) | RU2347778C2 (ja) |
| SA (1) | SA04250155B1 (ja) |
| SE (1) | SE0301700D0 (ja) |
| TW (1) | TW200508214A (ja) |
| UA (1) | UA83659C2 (ja) |
| UY (1) | UY28342A1 (ja) |
| WO (1) | WO2004106305A1 (ja) |
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| GB0312609D0 (en) | 2003-06-02 | 2003-07-09 | Astrazeneca Ab | Novel compounds |
| US7141596B2 (en) | 2003-10-08 | 2006-11-28 | Incyte Corporation | Inhibitors of proteins that bind phosphorylated molecules |
| JP2008513426A (ja) * | 2004-09-20 | 2008-05-01 | バイオリポックス エービー | 炎症の治療に有用なピラゾール化合物 |
| BRPI0606437A (pt) * | 2005-01-06 | 2008-03-11 | Astrazeneca Ab | composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, uso de um composto, e, método de tratamento de um distúrbio de agregação de plaqueta |
| US7297700B2 (en) * | 2005-03-24 | 2007-11-20 | Renovis, Inc. | Bicycloheteroaryl compounds as P2X7 modulators and uses thereof |
| WO2006110516A1 (en) * | 2005-04-11 | 2006-10-19 | Abbott Laboratories | Acylhydrazide p2x7 antagonists and uses thereof |
| KR20080039405A (ko) * | 2005-07-13 | 2008-05-07 | 아스트라제네카 아베 | 신규한 피리딘 유사체 |
| KR20080036125A (ko) * | 2005-08-01 | 2008-04-24 | 페노믹스 코포레이션 | 헤테로시클릭 보론산 및 그의 유도체의 제조 방법 |
| US7547782B2 (en) | 2005-09-30 | 2009-06-16 | Bristol-Myers Squibb Company | Met kinase inhibitors |
| TW200800911A (en) * | 2005-10-20 | 2008-01-01 | Biolipox Ab | Pyrazoles useful in the treatment of inflammation |
| EA200801108A1 (ru) * | 2005-10-31 | 2008-10-30 | Биолипокс Аб | Триазолы, пригодные для лечения воспалений |
| TW200732320A (en) * | 2005-10-31 | 2007-09-01 | Biolipox Ab | Pyrazoles useful in the treatment of inflammation |
| WO2007052000A1 (en) * | 2005-11-01 | 2007-05-10 | Biolipox Ab | Pyrazoles useful in the treatment of inflammation |
| US8007849B2 (en) | 2005-12-14 | 2011-08-30 | International Flavors & Fragrances Inc. | Unsaturated cyclic and acyclic carbamates exhibiting taste and flavor enhancement effect in flavor compositions |
| DK1937643T3 (en) * | 2006-03-16 | 2016-10-10 | Second Genome Inc | Bicycloheteroarylforbindelser som p2x7-modulatorer og anvendelser deraf |
| JP2009541205A (ja) * | 2006-03-16 | 2009-11-26 | レノビス， インコーポレイテッド | Ｐ２ｘ７調節因子としてのビシクロへテロアリール化合物およびその使用 |
| EP2001474B1 (en) * | 2006-03-16 | 2016-03-09 | Second Genome, Inc. | Bicycloheteroaryl compounds as p2x7 modulators and uses thereof |
| TWI464148B (zh) * | 2006-03-16 | 2014-12-11 | Evotec Us Inc | 作為ｐ２ｘ7調節劑之雙環雜芳基化合物與其用途 |
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2004
- 2004-01-06 UA UAA200510608A patent/UA83659C2/ru unknown
- 2004-05-27 TW TW093115168A patent/TW200508214A/zh unknown
- 2004-06-01 JP JP2006508566A patent/JP4682128B2/ja not_active Expired - Fee Related
- 2004-06-01 RU RU2005136130/04A patent/RU2347778C2/ru not_active IP Right Cessation
- 2004-06-01 KR KR1020057023022A patent/KR101244971B1/ko not_active IP Right Cessation
- 2004-06-01 AT AT04735697T patent/ATE446953T1/de not_active IP Right Cessation
- 2004-06-01 CN CN2004800222482A patent/CN1832925B/zh not_active Expired - Fee Related
- 2004-06-01 WO PCT/SE2004/000836 patent/WO2004106305A1/en active Application Filing
- 2004-06-01 CA CA2526884A patent/CA2526884C/en not_active Expired - Fee Related
- 2004-06-01 BR BRPI0410933-3A patent/BRPI0410933A/pt not_active IP Right Cessation
- 2004-06-01 DE DE602004023840T patent/DE602004023840D1/de not_active Expired - Lifetime
- 2004-06-01 AU AU2004242626A patent/AU2004242626B2/en not_active Ceased
- 2004-06-01 ES ES04735697T patent/ES2333721T3/es not_active Expired - Lifetime
- 2004-06-01 US US10/558,898 patent/US7408065B2/en not_active Expired - Fee Related
- 2004-06-01 MX MXPA05012883A patent/MXPA05012883A/es active IP Right Grant
- 2004-06-01 EP EP04735697A patent/EP1633717B1/en not_active Expired - Lifetime
- 2004-06-02 UY UY28342A patent/UY28342A1/es unknown
- 2004-06-02 AR ARP040101893A patent/AR045691A1/es unknown
- 2004-06-09 SA SA04250155A patent/SA04250155B1/ar unknown
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2005
- 2005-11-29 CO CO05120983A patent/CO5700720A2/es not_active Application Discontinuation
- 2005-11-30 ZA ZA200509706A patent/ZA200509706B/en unknown
- 2005-12-21 IS IS8190A patent/IS8190A/is unknown
-
2006
- 2006-01-02 NO NO20060001A patent/NO20060001L/no not_active Application Discontinuation
- 2006-05-20 HK HK06105844.1A patent/HK1085736A1/xx not_active IP Right Cessation
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2008
- 2008-05-02 US US12/114,126 patent/US20090143354A1/en not_active Abandoned
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