RU2347778C2 - Новые антагонисты р2х7 рецепторов, способ их получения, фармацевтическая композиция, способ лечения и применение на их основе - Google Patents
Новые антагонисты р2х7 рецепторов, способ их получения, фармацевтическая композиция, способ лечения и применение на их основе Download PDFInfo
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- RU2347778C2 RU2347778C2 RU2005136130/04A RU2005136130A RU2347778C2 RU 2347778 C2 RU2347778 C2 RU 2347778C2 RU 2005136130/04 A RU2005136130/04 A RU 2005136130/04A RU 2005136130 A RU2005136130 A RU 2005136130A RU 2347778 C2 RU2347778 C2 RU 2347778C2
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- chloro
- quinolinyl
- amino
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- 238000000034 method Methods 0.000 title claims abstract 5
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract 4
- 102100037602 P2X purinoceptor 7 Human genes 0.000 title abstract 2
- 101710189965 P2X purinoceptor 7 Proteins 0.000 title abstract 2
- 239000002464 receptor antagonist Substances 0.000 title abstract 2
- 229940044551 receptor antagonist Drugs 0.000 title abstract 2
- 239000005557 antagonist Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 45
- 229910052736 halogen Inorganic materials 0.000 claims abstract 26
- 150000002367 halogens Chemical class 0.000 claims abstract 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 23
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 14
- 239000001257 hydrogen Substances 0.000 claims abstract 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract 12
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract 11
- 150000003839 salts Chemical class 0.000 claims abstract 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 8
- 239000012453 solvate Substances 0.000 claims abstract 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract 4
- 239000001301 oxygen Substances 0.000 claims abstract 4
- 229910052717 sulfur Inorganic materials 0.000 claims abstract 4
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims abstract 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract 3
- 229910052799 carbon Inorganic materials 0.000 claims abstract 3
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract 3
- 125000005842 heteroatom Chemical group 0.000 claims abstract 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims abstract 2
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims abstract 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract 2
- 125000003118 aryl group Chemical group 0.000 claims abstract 2
- -1 C 1 -C 6 alkyl Chemical group 0.000 claims 15
- 125000001424 substituent group Chemical group 0.000 claims 15
- 125000000217 alkyl group Chemical group 0.000 claims 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 10
- 230000003993 interaction Effects 0.000 claims 8
- 125000003545 alkoxy group Chemical group 0.000 claims 5
- 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 5
- 150000002431 hydrogen Chemical class 0.000 claims 5
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 4
- 238000006243 chemical reaction Methods 0.000 claims 4
- DKLQJNUJPSHYQG-UHFFFAOYSA-N 2-cyclohexylacetamide Chemical compound NC(=O)CC1CCCCC1 DKLQJNUJPSHYQG-UHFFFAOYSA-N 0.000 claims 3
- 125000002837 carbocyclic group Chemical group 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 2
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 150000001336 alkenes Chemical class 0.000 claims 2
- 125000002947 alkylene group Chemical group 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 229910003002 lithium salt Inorganic materials 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims 2
- TVMULIJSTDEVPC-GOSISDBHSA-N (2r)-1-[6-chloro-5-(cyclohexylmethylcarbamoyl)quinolin-2-yl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCN1C1=CC=C(C(C(=O)NCC2CCCCC2)=C(Cl)C=C2)C2=N1 TVMULIJSTDEVPC-GOSISDBHSA-N 0.000 claims 1
- BMFALMJIQQDOOB-GMUIIQOCSA-N (2r)-1-[6-chloro-5-[(2-cyclohexylacetyl)amino]quinolin-2-yl]pyrrolidine-2-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)[C@H]1CCCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 BMFALMJIQQDOOB-GMUIIQOCSA-N 0.000 claims 1
- 125000006833 (C1-C5) alkylene group Chemical group 0.000 claims 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 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 1
- 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
- HRNIZLQBNHWDFW-UHFFFAOYSA-N 1-[6-chloro-5-(3-cyclopentylpropanoylamino)quinolin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=CC=C(C(NC(=O)CCC2CCCC2)=C(Cl)C=C2)C2=N1 HRNIZLQBNHWDFW-UHFFFAOYSA-N 0.000 claims 1
- XBOFTQJEMSYMKJ-UHFFFAOYSA-N 1-[6-chloro-5-[(2-cyclohexylacetyl)amino]quinolin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 XBOFTQJEMSYMKJ-UHFFFAOYSA-N 0.000 claims 1
- GNEVIDVAWKJYKC-UHFFFAOYSA-N 1-[6-chloro-5-[[2-(1-methylcyclohexyl)acetyl]amino]quinolin-2-yl]piperidine-4-carboxylic acid Chemical compound ClC=1C=CC2=NC(N3CCC(CC3)C(O)=O)=CC=C2C=1NC(=O)CC1(C)CCCCC1 GNEVIDVAWKJYKC-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- VXAWLBWKTFEBSJ-HNNXBMFYSA-N 2-[(3s)-3-aminopyrrolidin-1-yl]-6-chloro-n-(cyclohexylmethyl)quinoline-5-carboxamide Chemical compound C1[C@@H](N)CCN1C1=CC=C(C(C(=O)NCC2CCCCC2)=C(Cl)C=C2)C2=N1 VXAWLBWKTFEBSJ-HNNXBMFYSA-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
- WEUBAJVWGFSILC-INIZCTEOSA-N 2-[[(3s)-1-[6-chloro-5-[(2-cyclohexylacetyl)amino]quinolin-2-yl]pyrrolidin-3-yl]amino]acetic acid Chemical compound C1[C@@H](NCC(=O)O)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 WEUBAJVWGFSILC-INIZCTEOSA-N 0.000 claims 1
- 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 1
- 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 1
- IGEPROFODVNDRQ-QGZVFWFLSA-N 2-cyclohexyl-n-[2-[(3r)-3-hydroxypyrrolidin-1-yl]-6-methylquinolin-5-yl]acetamide Chemical compound CC1=CC=C2N=C(N3C[C@H](O)CC3)C=CC2=C1NC(=O)CC1CCCCC1 IGEPROFODVNDRQ-QGZVFWFLSA-N 0.000 claims 1
- QMPADMPYERKXEO-IBGZPJMESA-N 2-cyclohexyl-n-[2-[(3s)-3-(2-hydroxyethylamino)pyrrolidin-1-yl]-6-methylquinolin-5-yl]acetamide Chemical compound CC1=CC=C2N=C(N3C[C@H](CC3)NCCO)C=CC2=C1NC(=O)CC1CCCCC1 QMPADMPYERKXEO-IBGZPJMESA-N 0.000 claims 1
- HMYATMMCBWBOPQ-UHFFFAOYSA-N 2-cyclohexyl-n-[2-[3-(ethylamino)propyl]-6-methylquinolin-5-yl]acetamide;dihydrochloride Chemical compound Cl.Cl.CC=1C=CC2=NC(CCCNCC)=CC=C2C=1NC(=O)CC1CCCCC1 HMYATMMCBWBOPQ-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- MMKADPLXDTZCRK-KRWDZBQOSA-N 3-[[(3s)-1-[6-chloro-5-[(2-cyclohexylacetyl)amino]quinolin-2-yl]pyrrolidin-3-yl]amino]propanoic acid Chemical compound C1[C@@H](NCCC(=O)O)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 MMKADPLXDTZCRK-KRWDZBQOSA-N 0.000 claims 1
- TUBWIQXECXBPBM-UHFFFAOYSA-N 3-[[1-[6-chloro-5-(cyclohexylmethylcarbamoyl)quinolin-2-yl]azetidin-3-yl]amino]propanoic acid Chemical compound C1C(NCCC(=O)O)CN1C1=CC=C(C(C(=O)NCC2CCCCC2)=C(Cl)C=C2)C2=N1 TUBWIQXECXBPBM-UHFFFAOYSA-N 0.000 claims 1
- FKGXQEAGVZPHTC-UHFFFAOYSA-N 3-[[6-chloro-5-[(2-cyclohexylacetyl)amino]quinolin-2-yl]amino]propanoic acid Chemical compound ClC=1C=CC2=NC(NCCC(=O)O)=CC=C2C=1NC(=O)CC1CCCCC1 FKGXQEAGVZPHTC-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 1
- AMOCREBSAGYMHP-UHFFFAOYSA-N 4-[[6-chloro-5-[(2-cyclohexylacetyl)amino]quinolin-2-yl]amino]butanoic acid Chemical compound ClC=1C=CC2=NC(NCCCC(=O)O)=CC=C2C=1NC(=O)CC1CCCCC1 AMOCREBSAGYMHP-UHFFFAOYSA-N 0.000 claims 1
- TUYAVNVLAMLEHT-UHFFFAOYSA-N 5-[6-chloro-5-[(2-cyclohexylacetyl)amino]quinolin-2-yl]pentanoic acid Chemical compound ClC=1C=CC2=NC(CCCCC(=O)O)=CC=C2C=1NC(=O)CC1CCCCC1 TUYAVNVLAMLEHT-UHFFFAOYSA-N 0.000 claims 1
- MCVGJRDAAGBEET-UHFFFAOYSA-N 6-chloro-n-(2-cyclohexylethyl)-2-[4-(2h-tetrazol-5-yl)piperidin-1-yl]quinoline-5-carboxamide Chemical compound ClC1=CC=C2N=C(N3CCC(CC3)C=3NN=NN=3)C=CC2=C1C(=O)NCCC1CCCCC1 MCVGJRDAAGBEET-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- MQKVMEWBUZSJSR-INIZCTEOSA-N 6-chloro-n-(cyclohexylmethyl)-2-[(3s)-3-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)pyrrolidin-1-yl]quinoline-5-carboxamide Chemical compound ClC1=CC=C2N=C(N3C[C@H](CC3)N3S(NC(=O)C3)(=O)=O)C=CC2=C1C(=O)NCC1CCCCC1 MQKVMEWBUZSJSR-INIZCTEOSA-N 0.000 claims 1
- QDSFDCFUXNLBAL-FERBBOLQSA-N 6-chloro-n-(cyclohexylmethyl)-2-[(3s)-3-(2-hydroxyethylamino)piperidin-1-yl]quinoline-5-carboxamide;hydrochloride Chemical compound Cl.C1[C@@H](NCCO)CCCN1C1=CC=C(C(C(=O)NCC2CCCCC2)=C(Cl)C=C2)C2=N1 QDSFDCFUXNLBAL-FERBBOLQSA-N 0.000 claims 1
- 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 1
- BNWCJQPAWYXSHF-UHFFFAOYSA-N 6-chloro-n-(cyclohexylmethyl)-2-[3-(2-hydroxyethylamino)azetidin-1-yl]quinoline-5-carboxamide Chemical compound C1C(NCCO)CN1C1=CC=C(C(C(=O)NCC2CCCCC2)=C(Cl)C=C2)C2=N1 BNWCJQPAWYXSHF-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- HZTMPCGNFBDTIF-UHFFFAOYSA-N 6-chloro-n-(cyclohexylmethyl)-2-[4-(2h-tetrazol-5-yl)piperidin-1-yl]quinoline-5-carboxamide Chemical compound ClC1=CC=C2N=C(N3CCC(CC3)C=3NN=NN=3)C=CC2=C1C(=O)NCC1CCCCC1 HZTMPCGNFBDTIF-UHFFFAOYSA-N 0.000 claims 1
- HGWOWPOGQIKDSA-UHFFFAOYSA-N 6-chloro-n-(cyclohexylmethyl)-2-[methyl-[2-(methylamino)ethyl]amino]quinoline-5-carboxamide;dihydrochloride Chemical compound Cl.Cl.ClC=1C=CC2=NC(N(C)CCNC)=CC=C2C=1C(=O)NCC1CCCCC1 HGWOWPOGQIKDSA-UHFFFAOYSA-N 0.000 claims 1
- BFSRZKKESPDGJM-UHFFFAOYSA-N 6-chloro-n-(cyclohexylmethyl)-2-[methyl-[3-(methylamino)propyl]amino]quinoline-5-carboxamide;dihydrochloride Chemical compound Cl.Cl.ClC=1C=CC2=NC(N(C)CCCNC)=CC=C2C=1C(=O)NCC1CCCCC1 BFSRZKKESPDGJM-UHFFFAOYSA-N 0.000 claims 1
- JNBFCCUTLQSSLF-UHFFFAOYSA-N 6-chloro-n-(cyclohexylmethyl)-2-methylquinoline-5-carboxamide;hydrochloride Chemical compound Cl.ClC=1C=CC2=NC(C)=CC=C2C=1C(=O)NCC1CCCCC1 JNBFCCUTLQSSLF-UHFFFAOYSA-N 0.000 claims 1
- QRXFMYKYBQZYCN-UHFFFAOYSA-N 6-chloro-n-(cyclohexylmethyl)-2-piperazin-1-ylquinoline-5-carboxamide;dihydrochloride Chemical compound Cl.Cl.ClC1=CC=C2N=C(N3CCNCC3)C=CC2=C1C(=O)NCC1CCCCC1 QRXFMYKYBQZYCN-UHFFFAOYSA-N 0.000 claims 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- YMGZIABWYOANAM-SQKCAUCHSA-N OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C1[C@@H](N)CCN1C1=CC=C(C(C(=O)NCCC2CCCCC2)=C(Cl)C=C2)C2=N1 Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C1[C@@H](N)CCN1C1=CC=C(C(C(=O)NCCC2CCCCC2)=C(Cl)C=C2)C2=N1 YMGZIABWYOANAM-SQKCAUCHSA-N 0.000 claims 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
- NYPVSAWWXOUUCJ-LMOVPXPDSA-N acetic acid;2-[(3s)-3-aminopyrrolidin-1-yl]-n-(cyclohexylmethyl)-6-methylquinoline-5-carboxamide Chemical compound CC(O)=O.CC1=CC=C2N=C(N3C[C@@H](N)CC3)C=CC2=C1C(=O)NCC1CCCCC1 NYPVSAWWXOUUCJ-LMOVPXPDSA-N 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 230000003042 antagnostic effect Effects 0.000 claims 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 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 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 claims 1
- XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 claims 1
- 238000005984 hydrogenation reaction Methods 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 159000000002 lithium salts Chemical class 0.000 claims 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 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 claims 1
- 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 1
- 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 1
- 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 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 claims 1
- BSVLCHROLUEOFQ-UHFFFAOYSA-N n-[2-(3-aminopropyl)-6-chloroquinolin-5-yl]-2-cyclohexylacetamide Chemical compound ClC=1C=CC2=NC(CCCN)=CC=C2C=1NC(=O)CC1CCCCC1 BSVLCHROLUEOFQ-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 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 1
- VPZCTISEGWGAGR-INIZCTEOSA-N n-[2-[(3s)-3-aminopiperidin-1-yl]-6-chloroquinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1[C@@H](N)CCCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 VPZCTISEGWGAGR-INIZCTEOSA-N 0.000 claims 1
- PBOHJDQKIYZTLV-HNNXBMFYSA-N n-[2-[(3s)-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-HNNXBMFYSA-N 0.000 claims 1
- SSSYLNXVGHSRTI-HNNXBMFYSA-N n-[2-[(3s)-3-aminopyrrolidin-1-yl]-6-chloroquinolin-5-yl]-3-cyclopentylpropanamide Chemical compound C1[C@@H](N)CCN1C1=CC=C(C(NC(=O)CCC2CCCC2)=C(Cl)C=C2)C2=N1 SSSYLNXVGHSRTI-HNNXBMFYSA-N 0.000 claims 1
- 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 1
- ZFAFZEKFUZECHO-UHFFFAOYSA-N n-[6-chloro-2-(1,4-diazepan-1-yl)quinolin-5-yl]-2-cyclohexylacetamide Chemical compound ClC1=CC=C2N=C(N3CCNCCC3)C=CC2=C1NC(=O)CC1CCCCC1 ZFAFZEKFUZECHO-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 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 1
- PBEDBKAWEURFHD-MRXNPFEDSA-N n-[6-chloro-2-[(3r)-3-(methylamino)pyrrolidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1[C@H](NC)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 PBEDBKAWEURFHD-MRXNPFEDSA-N 0.000 claims 1
- DPIIJQKGZMTTPT-MRXNPFEDSA-N n-[6-chloro-2-[(3r)-3-hydroxypiperidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1[C@H](O)CCCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 DPIIJQKGZMTTPT-MRXNPFEDSA-N 0.000 claims 1
- DBDLZCQFOAKMKS-OAHLLOKOSA-N n-[6-chloro-2-[(3r)-3-hydroxypyrrolidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1[C@H](O)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 DBDLZCQFOAKMKS-OAHLLOKOSA-N 0.000 claims 1
- PBKPJRQLMKKLID-SFHVURJKSA-N n-[6-chloro-2-[(3s)-3-(2-hydroxyethylamino)piperidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1[C@@H](NCCO)CCCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 PBKPJRQLMKKLID-SFHVURJKSA-N 0.000 claims 1
- SSGJRDKQKWGZRZ-KRWDZBQOSA-N n-[6-chloro-2-[(3s)-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-KRWDZBQOSA-N 0.000 claims 1
- JUACMWWRYOYMLG-SFHVURJKSA-N n-[6-chloro-2-[(3s)-3-(2-hydroxyethylamino)pyrrolidin-1-yl]quinolin-5-yl]-3-cyclohexylpropanamide Chemical compound C1[C@@H](NCCO)CCN1C1=CC=C(C(NC(=O)CCC2CCCCC2)=C(Cl)C=C2)C2=N1 JUACMWWRYOYMLG-SFHVURJKSA-N 0.000 claims 1
- OKTMKOLMOZCGDA-KRWDZBQOSA-N n-[6-chloro-2-[(3s)-3-(2-hydroxyethylamino)pyrrolidin-1-yl]quinolin-5-yl]-3-cyclopentylpropanamide Chemical compound C1[C@@H](NCCO)CCN1C1=CC=C(C(NC(=O)CCC2CCCC2)=C(Cl)C=C2)C2=N1 OKTMKOLMOZCGDA-KRWDZBQOSA-N 0.000 claims 1
- AYTDZQRUUXBCDM-KRWDZBQOSA-N n-[6-chloro-2-[(3s)-3-(2-hydroxyethylsulfonyl)pyrrolidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1[C@@H](S(=O)(=O)CCO)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 AYTDZQRUUXBCDM-KRWDZBQOSA-N 0.000 claims 1
- PBEDBKAWEURFHD-INIZCTEOSA-N n-[6-chloro-2-[(3s)-3-(methylamino)pyrrolidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1[C@@H](NC)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 PBEDBKAWEURFHD-INIZCTEOSA-N 0.000 claims 1
- WJTRVFGZKUYWNY-INIZCTEOSA-N n-[6-chloro-2-[(3s)-3-(methylsulfonylcarbamoylamino)pyrrolidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1[C@@H](NC(=O)NS(=O)(=O)C)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 WJTRVFGZKUYWNY-INIZCTEOSA-N 0.000 claims 1
- NWUGSDWMBLQVLY-KRWDZBQOSA-N n-[6-chloro-2-[(3s)-3-[2-(2h-tetrazol-5-yl)ethylamino]pyrrolidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound ClC1=CC=C2N=C(N3C[C@H](CC3)NCCC3=NNN=N3)C=CC2=C1NC(=O)CC1CCCCC1 NWUGSDWMBLQVLY-KRWDZBQOSA-N 0.000 claims 1
- KJEQZROLBVKHDP-MRXNPFEDSA-N n-[6-chloro-2-[(3s)-3-cyanopyrrolidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound ClC1=CC=C2N=C(N3C[C@H](CC3)C#N)C=CC2=C1NC(=O)CC1CCCCC1 KJEQZROLBVKHDP-MRXNPFEDSA-N 0.000 claims 1
- DBDLZCQFOAKMKS-HNNXBMFYSA-N n-[6-chloro-2-[(3s)-3-hydroxypyrrolidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1[C@@H](O)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 DBDLZCQFOAKMKS-HNNXBMFYSA-N 0.000 claims 1
- 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 1
- PBKPJRQLMKKLID-UHFFFAOYSA-N n-[6-chloro-2-[3-(2-hydroxyethylamino)piperidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1C(NCCO)CCCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 PBKPJRQLMKKLID-UHFFFAOYSA-N 0.000 claims 1
- ROCWOKQZSYZAGT-UHFFFAOYSA-N n-[6-chloro-2-[3-(3-hydroxypropylamino)propyl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound ClC=1C=CC2=NC(CCCNCCCO)=CC=C2C=1NC(=O)CC1CCCCC1 ROCWOKQZSYZAGT-UHFFFAOYSA-N 0.000 claims 1
- LQICGJQRDNOPLQ-UHFFFAOYSA-N n-[6-chloro-2-[3-(ethylamino)propyl]quinolin-5-yl]-2-cyclohexylacetamide;dihydrochloride Chemical compound Cl.Cl.ClC=1C=CC2=NC(CCCNCC)=CC=C2C=1NC(=O)CC1CCCCC1 LQICGJQRDNOPLQ-UHFFFAOYSA-N 0.000 claims 1
- XUNCXAHCYPVFRD-UHFFFAOYSA-N n-[6-chloro-2-[3-(methylamino)piperidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1C(NC)CCCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 XUNCXAHCYPVFRD-UHFFFAOYSA-N 0.000 claims 1
- QRVKHPFYCNVPEK-UHFFFAOYSA-N n-[6-chloro-2-[4-(5-oxo-1h-1,2,4-triazol-4-yl)piperidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound ClC1=CC=C2N=C(N3CCC(CC3)N3C(NN=C3)=O)C=CC2=C1NC(=O)CC1CCCCC1 QRVKHPFYCNVPEK-UHFFFAOYSA-N 0.000 claims 1
- KUOLYXYVTHYRCG-UHFFFAOYSA-N n-[6-chloro-2-[4-(5-oxo-2h-1,2,4-oxadiazol-3-yl)piperidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound ClC1=CC=C2N=C(N3CCC(CC3)C=3NC(=O)ON=3)C=CC2=C1NC(=O)CC1CCCCC1 KUOLYXYVTHYRCG-UHFFFAOYSA-N 0.000 claims 1
- CXLOCOFXFDRSHQ-UHFFFAOYSA-N n-[6-chloro-2-[4-(5-oxo-2h-1,2,4-thiadiazol-3-yl)piperidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound ClC1=CC=C2N=C(N3CCC(CC3)C=3NC(=O)SN=3)C=CC2=C1NC(=O)CC1CCCCC1 CXLOCOFXFDRSHQ-UHFFFAOYSA-N 0.000 claims 1
- PSFKHFPINHIZLB-UHFFFAOYSA-N n-[6-chloro-2-[4-(trifluoromethylsulfonylamino)piperidin-1-yl]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound C1CC(NS(=O)(=O)C(F)(F)F)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 PSFKHFPINHIZLB-UHFFFAOYSA-N 0.000 claims 1
- DOOMNKPIFUBAGG-CQSZACIVSA-N n-[6-chloro-2-[[(2r)-2,3-dihydroxypropyl]amino]quinolin-5-yl]-2-cyclohexylacetamide Chemical compound ClC=1C=CC2=NC(NC[C@@H](O)CO)=CC=C2C=1NC(=O)CC1CCCCC1 DOOMNKPIFUBAGG-CQSZACIVSA-N 0.000 claims 1
- MFCFJCUMQRCZJC-QCUBGVIVSA-N n-[6-chloro-2-[[(3r)-pyrrolidin-3-yl]amino]quinolin-5-yl]-2-cyclohexylacetamide;dihydrochloride Chemical compound Cl.Cl.C1=CC2=C(NC(=O)CC3CCCCC3)C(Cl)=CC=C2N=C1N[C@@H]1CCNC1 MFCFJCUMQRCZJC-QCUBGVIVSA-N 0.000 claims 1
- LVHLPXKHPJIGGF-UHFFFAOYSA-N n-[6-chloro-2-[methyl-[3-(methylamino)propyl]amino]quinolin-5-yl]-1-cyclohexylcyclopropane-1-carboxamide;hydrochloride Chemical compound Cl.ClC=1C=CC2=NC(N(C)CCCNC)=CC=C2C=1NC(=O)C1(C2CCCCC2)CC1 LVHLPXKHPJIGGF-UHFFFAOYSA-N 0.000 claims 1
- SZUGUXBIMOODHB-UHFFFAOYSA-N n-[6-chloro-2-[methyl-[3-(methylamino)propyl]amino]quinolin-5-yl]-3-cyclohexylpropanamide Chemical compound ClC=1C=CC2=NC(N(C)CCCNC)=CC=C2C=1NC(=O)CCC1CCCCC1 SZUGUXBIMOODHB-UHFFFAOYSA-N 0.000 claims 1
- 201000008482 osteoarthritis Diseases 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
- 239000000651 prodrug Substances 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 claims 1
- 229960002429 proline Drugs 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 238000006268 reductive amination reaction Methods 0.000 claims 1
- 235000012239 silicon dioxide Nutrition 0.000 claims 1
- 239000000377 silicon dioxide Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 239000011593 sulfur Chemical group 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 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 claims 1
- 125000003831 tetrazolyl group Chemical group 0.000 claims 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims 1
- 125000004665 trialkylsilyl group Chemical group 0.000 claims 1
- 239000011701 zinc Substances 0.000 claims 1
- 229910052725 zinc Inorganic materials 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 abstract 1
- 230000004071 biological effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
Classifications
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- 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
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- 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
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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
- A61P19/08—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
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- 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
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
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- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0312609.1A GB0312609D0 (en) | 2003-06-02 | 2003-06-02 | Novel compounds |
| GB0312609.1 | 2003-06-02 | ||
| SE0301700-1 | 2003-06-10 | ||
| SE0301700A SE0301700D0 (sv) | 2003-06-02 | 2003-06-10 | Novel compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2005136130A RU2005136130A (ru) | 2006-06-27 |
| RU2347778C2 true RU2347778C2 (ru) | 2009-02-27 |
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| RU2005136130/04A RU2347778C2 (ru) | 2003-06-02 | 2004-06-01 | Новые антагонисты р2х7 рецепторов, способ их получения, фармацевтическая композиция, способ лечения и применение на их основе |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US7408065B2 (https=) |
| EP (1) | EP1633717B1 (https=) |
| JP (1) | JP4682128B2 (https=) |
| KR (1) | KR101244971B1 (https=) |
| CN (1) | CN1832925B (https=) |
| AR (1) | AR045691A1 (https=) |
| AT (1) | ATE446953T1 (https=) |
| AU (1) | AU2004242626B2 (https=) |
| BR (1) | BRPI0410933A (https=) |
| CA (1) | CA2526884C (https=) |
| CO (1) | CO5700720A2 (https=) |
| DE (1) | DE602004023840D1 (https=) |
| ES (1) | ES2333721T3 (https=) |
| GB (1) | GB0312609D0 (https=) |
| IS (1) | IS8190A (https=) |
| MX (1) | MXPA05012883A (https=) |
| NO (1) | NO20060001L (https=) |
| RU (1) | RU2347778C2 (https=) |
| SA (1) | SA04250155B1 (https=) |
| SE (1) | SE0301700D0 (https=) |
| TW (1) | TW200508214A (https=) |
| UA (1) | UA83659C2 (https=) |
| UY (1) | UY28342A1 (https=) |
| WO (1) | WO2004106305A1 (https=) |
| ZA (1) | ZA200509706B (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2768865C2 (ru) * | 2017-05-03 | 2022-03-25 | Акссам С.П.А. | Гетероциклические антагонисты Р2Х7 |
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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 |
| EP1836189A1 (en) * | 2005-01-06 | 2007-09-26 | AstraZeneca AB | Novel pyridine compounds |
| 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 |
| RU2008101924A (ru) * | 2005-07-13 | 2009-08-20 | Астразенека Аб (Se) | Новые аналоги пиридина |
| CA2617310A1 (en) * | 2005-08-01 | 2007-02-08 | Phenomix Corporation | Methods of preparing hetercyclic boronic acids and derivatives thereof |
| 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 |
| ZA200803636B (en) * | 2005-10-31 | 2009-10-28 | Biolipox Ab | Triazole compounds as lipoxygenase inhibitors |
| 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 |
| 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 |
| BRPI0709596A2 (pt) | 2006-03-16 | 2011-07-19 | Renovis Inc | compostos bicicloeteroarila como moduladores de p2x7 e seus usos |
| 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 |
| WO2007109172A2 (en) * | 2006-03-16 | 2007-09-27 | Renovis, Inc. | Bicycloheteroaryl compounds as p2x7 modulators and uses thereof |
| WO2008013494A1 (en) * | 2006-07-27 | 2008-01-31 | Astrazeneca Ab | Quinoline derivatives as p2x7 receptor antagonist and their use in the treatment of rheumatoid arthritis, osteoarthritis, copd and ibd |
| MX2009003170A (es) * | 2006-09-28 | 2009-04-03 | Hoffmann La Roche | Derivados de quinolina con propiedades de union a 5-hidroxitriptamina (5-ht). |
| EA201300152A1 (ru) | 2006-11-27 | 2013-07-30 | Х. Лундбекк А/С | Гетероариламидные производные |
| AU2007329064C1 (en) | 2006-12-07 | 2013-01-17 | F. Hoffmann-La Roche Ag | 2-Aminoquinolines as 5-HT(5A) receptor antagonists |
| BRPI0809106A2 (pt) * | 2007-03-22 | 2014-08-26 | Astrazeneca Ab | Derivados de quinolina para o tratamento de doenças inflamatórias |
| BRPI0809567A2 (pt) * | 2007-04-10 | 2014-09-23 | Lundbeck & Co As H | Composto, composição farmacêutica, método para modular a atividade de um receptor de p2x7, para tratar uma condição responsiva à modulação do receptor de p2x7 em um paciente, para inibir a morte de células do gânglio retinal em um paciente, e para determinar a presença ou ausência do receptor de p2x7 em uma amostra, preparação farmacêutica acondiciaonada, e, uso de um composto |
| US8106073B2 (en) | 2007-11-30 | 2012-01-31 | Astrazeneca Ab | Quinoline derivatives 057 |
| WO2009108551A2 (en) * | 2008-02-25 | 2009-09-03 | H. Lundbeck A/S | Heteroaryl amide analogues |
| CN101959864A (zh) | 2008-03-07 | 2011-01-26 | 弗·哈夫曼-拉罗切有限公司 | 2-氨基喹啉衍生物 |
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| CA2722035C (en) * | 2008-04-22 | 2016-10-11 | Janssen Pharmaceutica Nv | Quinoline or isoquinoline substituted p2x7 antagonists |
| WO2010118921A1 (en) | 2009-04-14 | 2010-10-21 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| EP2435407B1 (en) * | 2009-05-29 | 2019-12-25 | RaQualia Pharma Inc. | Aryl substituted carboxamide derivatives as calcium or sodium channel blockers |
| EP2569281A1 (en) | 2010-05-14 | 2013-03-20 | Affectis Pharmaceuticals AG | Novel methods for the preparation of p2x7r antagonists |
| WO2012110190A1 (en) | 2011-02-17 | 2012-08-23 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| WO2012163456A1 (en) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| WO2012163792A1 (en) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| CN103687860B (zh) | 2011-07-22 | 2016-06-08 | 埃科特莱茵药品有限公司 | 作为p2x7受体拮抗剂的杂环酰胺衍生物 |
| EA024204B1 (ru) | 2012-01-20 | 2016-08-31 | Актелион Фармасьютиклз Лтд. | Производные гетероциклических амидов в качестве антагонистов p2xрецептора |
| AR093921A1 (es) | 2012-12-12 | 2015-06-24 | Actelion Pharmaceuticals Ltd | Derivados de indol carboxamida como antagonistas del receptor p2x7 |
| KR102232744B1 (ko) | 2012-12-18 | 2021-03-26 | 이도르시아 파마슈티컬스 리미티드 | Ｐ２ｘ７ 수용체 길항제로서의 인돌 카르복사미드 유도체 |
| ES2616883T3 (es) | 2013-01-22 | 2017-06-14 | Actelion Pharmaceuticals Ltd. | Derivados amida heterocíclicos como antagonistas del receptor P2X7 |
| KR102222220B1 (ko) | 2013-01-22 | 2021-03-03 | 이도르시아 파마슈티컬스 리미티드 | Ｐ2ｘ7 수용체 길항제로서의 헤테로시클릭 아미드 유도체 |
| ES2654288T3 (es) | 2013-03-14 | 2018-02-13 | Janssen Pharmaceutica, N.V. | Moduladores de P2X7 |
| TWI627174B (zh) | 2013-03-14 | 2018-06-21 | 比利時商健生藥品公司 | Ｐ２ｘ７調控劑 |
| TWI644671B (zh) | 2013-03-14 | 2018-12-21 | 比利時商健生藥品公司 | Ｐ２ｘ７調節劑 |
| WO2014152537A1 (en) | 2013-03-14 | 2014-09-25 | Janssen Pharmaceutica Nv | P2x7 modulators |
| WO2015187905A1 (en) * | 2014-06-05 | 2015-12-10 | Merck Patent Gmbh | Novel quinoline derivatives and their use in neurodegenerative diseases |
| CA2960968A1 (en) | 2014-09-12 | 2016-03-17 | Janssen Pharmaceutica Nv | P2x7 modulators |
| WO2016039983A1 (en) | 2014-09-12 | 2016-03-17 | Janssen Pharmaceutica Nv | P2x7 modulating n-acyl-triazolopyrazines |
| CN106084068B (zh) * | 2016-06-16 | 2019-07-16 | 郑州大学第一附属医院 | 一组肠菌素-抗生素衍生物及其应用 |
| US11077100B2 (en) * | 2017-03-13 | 2021-08-03 | Raqualia Pharma Inc. | Tetrahydroquinoline derivatives as P2X7 receptor antagonists |
| WO2020065614A1 (en) | 2018-09-28 | 2020-04-02 | Janssen Pharmaceutica Nv | Monoacylglycerol lipase modulators |
| EP3856178B1 (en) | 2018-09-28 | 2026-03-11 | Janssen Pharmaceutica NV | Monoacylglycerol lipase modulators |
| MX2022003819A (es) | 2019-09-30 | 2022-05-11 | Janssen Pharmaceutica Nv | Ligandos de pet de mgl radiomarcados. |
| BR112022019077A2 (pt) | 2020-03-26 | 2022-12-27 | Janssen Pharmaceutica Nv | Moduladores da monoacilglicerol lipase |
| CN115305282A (zh) * | 2022-08-04 | 2022-11-08 | 烟台毓璜顶医院 | 一种用于AR-induced OD诊断和预后判别的靶点及治疗方法 |
| CN120574171A (zh) * | 2024-03-01 | 2025-09-02 | 武汉人福创新药物研发中心有限公司 | 含sf5类喹啉衍生物及其作为p2x7拮抗剂的用途 |
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| RU2214997C2 (ru) * | 1997-12-05 | 2003-10-27 | АСТРАЗЕНЕКА Ю Кей ЛИМИТЕД | Производные адамантана, способ их получения, фармацевтическая композиция и способ получения фармацевтической композиции |
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| SE0103836D0 (sv) | 2001-11-16 | 2001-11-16 | Astrazeneca Ab | Novel compounds |
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| SE0200920D0 (sv) | 2002-03-25 | 2002-03-25 | Astrazeneca Ab | Novel compounds |
| GB0312609D0 (en) | 2003-06-02 | 2003-07-09 | Astrazeneca Ab | Novel compounds |
| SE0302139D0 (sv) | 2003-07-28 | 2003-07-28 | Astrazeneca Ab | Novel compounds |
| SE0402925D0 (sv) | 2004-11-30 | 2004-11-30 | Astrazeneca Ab | Novel Compounds |
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- 2003-06-02 GB GBGB0312609.1A patent/GB0312609D0/en not_active Ceased
- 2003-06-10 SE SE0301700A patent/SE0301700D0/xx unknown
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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 AT AT04735697T patent/ATE446953T1/de not_active IP Right Cessation
- 2004-06-01 KR KR1020057023022A patent/KR101244971B1/ko not_active Expired - Fee Related
- 2004-06-01 AU AU2004242626A patent/AU2004242626B2/en not_active Ceased
- 2004-06-01 CA CA2526884A patent/CA2526884C/en not_active Expired - Fee Related
- 2004-06-01 JP JP2006508566A patent/JP4682128B2/ja not_active Expired - Fee Related
- 2004-06-01 ES ES04735697T patent/ES2333721T3/es not_active Expired - Lifetime
- 2004-06-01 CN CN2004800222482A patent/CN1832925B/zh not_active Expired - Fee Related
- 2004-06-01 BR BRPI0410933-3A patent/BRPI0410933A/pt not_active IP Right Cessation
- 2004-06-01 EP EP04735697A patent/EP1633717B1/en not_active Expired - Lifetime
- 2004-06-01 MX MXPA05012883A patent/MXPA05012883A/es active IP Right Grant
- 2004-06-01 RU RU2005136130/04A patent/RU2347778C2/ru not_active IP Right Cessation
- 2004-06-01 WO PCT/SE2004/000836 patent/WO2004106305A1/en not_active Ceased
- 2004-06-01 US US10/558,898 patent/US7408065B2/en not_active Expired - Fee Related
- 2004-06-01 DE DE602004023840T patent/DE602004023840D1/de not_active Expired - Lifetime
- 2004-06-02 AR ARP040101893A patent/AR045691A1/es unknown
- 2004-06-02 UY UY28342A patent/UY28342A1/es unknown
- 2004-06-09 SA SA04250155A patent/SA04250155B1/ar unknown
-
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
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2006
- 2006-01-02 NO NO20060001A patent/NO20060001L/no not_active Application Discontinuation
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2008
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2768865C2 (ru) * | 2017-05-03 | 2022-03-25 | Акссам С.П.А. | Гетероциклические антагонисты Р2Х7 |
| US11623919B2 (en) | 2017-05-03 | 2023-04-11 | Breye Therapeutics Aps | Heterocyclic P2X7 antagonists |
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