JP2006526617A5 - - Google Patents
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- JP2006526617A5 JP2006526617A5 JP2006508566A JP2006508566A JP2006526617A5 JP 2006526617 A5 JP2006526617 A5 JP 2006526617A5 JP 2006508566 A JP2006508566 A JP 2006508566A JP 2006508566 A JP2006508566 A JP 2006508566A JP 2006526617 A5 JP2006526617 A5 JP 2006526617A5
- Authority
- JP
- Japan
- Prior art keywords
- chloro
- quinolinyl
- formula
- amino
- cyclohexaneacetamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 150000001875 compounds Chemical group 0.000 claims description 78
- -1 nitro, cyano, amino Chemical group 0.000 claims description 42
- 229910052736 halogen Inorganic materials 0.000 claims description 38
- 150000002367 halogens Chemical group 0.000 claims description 38
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 31
- 125000000623 heterocyclic group Chemical group 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 25
- 239000012453 solvate Substances 0.000 claims description 21
- 239000000651 prodrug Substances 0.000 claims description 19
- 229940002612 prodrug Drugs 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 125000002837 carbocyclic group Chemical group 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 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 6
- 150000002148 esters Chemical class 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 125000003466 9 membered carbocyclic group Chemical group 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 201000008482 osteoarthritis Diseases 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 4
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 230000000414 obstructive effect Effects 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 208000023504 respiratory system disease Diseases 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 150000001721 carbon Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- 125000003627 8 membered carbocyclic group Chemical group 0.000 claims description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 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 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
- 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 description 2
- 238000006268 reductive amination reaction Methods 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 6
- 239000003814 drug Substances 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 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 4
- 125000002947 alkylene group Chemical group 0.000 claims 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 3
- 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
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims 2
- 150000001336 alkenes Chemical class 0.000 claims 2
- 229910003002 lithium salt Inorganic materials 0.000 claims 2
- 159000000002 lithium salts Chemical class 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
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 125000006552 (C3-C8) 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
- 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 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
- MGGFTDPLMXJORL-UHFFFAOYSA-N 2-[1-[6-chloro-5-(cyclohexylmethylcarbamoyl)quinolin-2-yl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C1=CC=C(C(C(=O)NCC2CCCCC2)=C(Cl)C=C2)C2=N1 MGGFTDPLMXJORL-UHFFFAOYSA-N 0.000 claims 1
- KMSLNTMWMNFOGN-UHFFFAOYSA-N 2-[1-[6-chloro-5-[(2-cyclohexylacetyl)amino]quinolin-2-yl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C1=CC=C(C(NC(=O)CC2CCCCC2)=C(Cl)C=C2)C2=N1 KMSLNTMWMNFOGN-UHFFFAOYSA-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
- 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
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 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 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
- 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
- UBLOLWQVDUZNEH-UHFFFAOYSA-N 6-chloro-n-(cyclohexylmethyl)-2-[3-(3-hydroxypropylamino)propyl]quinoline-5-carboxamide Chemical compound ClC=1C=CC2=NC(CCCNCCCO)=CC=C2C=1C(=O)NCC1CCCCC1 UBLOLWQVDUZNEH-UHFFFAOYSA-N 0.000 claims 1
- SXLFOLYKBHDXPJ-UHFFFAOYSA-N 6-chloro-n-(cyclohexylmethyl)-2-[4-(2h-tetrazol-5-yl)butyl]quinoline-5-carboxamide Chemical compound C1=CC2=C(C(=O)NCC3CCCCC3)C(Cl)=CC=C2N=C1CCCCC1=NN=NN1 SXLFOLYKBHDXPJ-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
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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 |
| CN102046240B (zh) | 2008-03-25 | 2014-06-25 | 阿费克蒂斯药品公司 | 新的p2x7r拮抗剂及其应用 |
| 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 |
| EP3398941A1 (en) * | 2017-05-03 | 2018-11-07 | AXXAM S.p.A. | Heterocyclic p2x7 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 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3352912A (en) | 1963-07-24 | 1967-11-14 | Du Pont | Adamantanes and tricyclo[4. 3. 1. 1 3.8] undecanes |
| US3471491A (en) | 1967-08-28 | 1969-10-07 | Squibb & Sons Inc | Adamantyl-s-triazines |
| US3464998A (en) | 1968-03-04 | 1969-09-02 | Searle & Co | Adamantyl esters and amides of pyridinecarboxylic acids |
| GB1274652A (en) | 1968-08-27 | 1972-05-17 | Lilly Industries Ltd | Adamantanyl-alkylamine derivatives and their preparation |
| US3741491A (en) * | 1971-11-29 | 1973-06-26 | Leesona Corp | Apparatus for winding yarn |
| IL53441A0 (en) | 1977-11-22 | 1978-01-31 | Teva Pharma | Methyladamantyl hydrazines their preparation and pharmaceutical compositions containing them |
| US4751292A (en) | 1985-07-02 | 1988-06-14 | The Plant Cell Research Institute, Inc. | Adamantyl purines |
| DE69216873T2 (de) | 1991-02-21 | 1997-08-21 | Sankyo Co | Benzolderivate zum Fördern der Produktion des Nervenwachstumsfaktors |
| PL181782B1 (pl) | 1993-08-10 | 2001-09-28 | Black James Foundation | Nowe zwiazki i sposób wytwarzania nowych zwiazków PL |
| DK0804419T3 (da) | 1994-05-27 | 2003-11-24 | Glaxosmithkline Spa | Quinolinderivater som tachykinin NK 3-receptor-antagonister |
| AR004735A1 (es) | 1995-11-24 | 1999-03-10 | Smithkline Beecham Spa | Quinoleina 4-amido sustituida, un procedimiento para su preparacion, una composicion farmaceutica que los contiene y el uso de los mismos para lapreparacion de un medicamento. |
| EP0952832B1 (en) | 1996-05-20 | 2008-08-27 | Darwin Discovery Limited | Quinoline carboxamides as tnf inhibitors and as pde-iv inhibitors |
| FR2761358B1 (fr) | 1997-03-27 | 1999-05-07 | Adir | Nouveaux composes de n-aryl piperidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| JP2001524468A (ja) | 1997-11-21 | 2001-12-04 | エヌピーエス ファーマシューティカルズ インコーポレーテッド | 中枢神経系疾患を治療するための代謝調節型グルタミン酸受容体アンタゴニスト |
| SE9704544D0 (sv) * | 1997-12-05 | 1997-12-05 | Astra Pharma Prod | Novel compounds |
| SE9704545D0 (sv) | 1997-12-05 | 1997-12-05 | Astra Pharma Prod | Novel compounds |
| CN1147483C (zh) | 1999-04-09 | 2004-04-28 | 阿斯特拉曾尼卡有限公司 | 金刚烷衍生物 |
| CN1361768A (zh) | 1999-06-02 | 2002-07-31 | Nps药物有限公司 | 代谢移变的谷氨酸盐受体拮抗剂和它们治疗中枢神经系统疾病的用途 |
| CA2389681C (en) * | 1999-11-26 | 2010-11-02 | Shionogi & Co., Ltd. | Npy y5 antagonist |
| GB0013737D0 (en) | 2000-06-07 | 2000-07-26 | Astrazeneca Ab | Novel compounds |
| US8058441B2 (en) | 2001-07-02 | 2011-11-15 | N.V. Organon | Tetrahydroquinoline derivatives |
| WO2003042190A1 (en) | 2001-11-12 | 2003-05-22 | Pfizer Products Inc. | N-alkyl-adamantyl derivatives as p2x7-receptor antagonists |
| SE0103836D0 (sv) | 2001-11-16 | 2001-11-16 | Astrazeneca Ab | Novel compounds |
| CA2468015A1 (en) | 2001-11-27 | 2003-06-05 | Merck & Co., Inc. | 2-aminoquinoline compounds |
| 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 |
-
2003
- 2003-06-02 GB GBGB0312609.1A patent/GB0312609D0/en not_active Ceased
- 2003-06-10 SE SE0301700A patent/SE0301700D0/xx unknown
-
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
-
2006
- 2006-01-02 NO NO20060001A patent/NO20060001L/no not_active Application Discontinuation
-
2008
- 2008-05-02 US US12/114,126 patent/US20090143354A1/en not_active Abandoned
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