SK18499A3 - Substituted pyrimidine derivatives and their pharmaceutical use - Google Patents

Substituted pyrimidine derivatives and their pharmaceutical use Download PDF

Info

Publication number: SK18499A3
Authority: SK; Slovakia
Prior art keywords: group; dichloromethane; solution; alkyl; piperazine
Prior art date: 1996-08-14

Application number

SK184-99A

Other languages

English (en)

Slovak (sk)

Inventor

George R Brown

Nicholas J Newcombe

Elaine S E Stokes

David Waterson

Original Assignee

Zeneca Ltd

Priority date (The priority date 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 date listed.)

1996-08-14

Filing date

1997-07-25

Publication date

1999-07-12

1996-08-14 Priority claimed from GBGB9617060.0A external-priority patent/GB9617060D0/en

1997-02-14 Priority claimed from GBGB9703027.4A external-priority patent/GB9703027D0/en

1997-07-25 Application filed by Zeneca Ltd filed Critical Zeneca Ltd

1999-07-12 Publication of SK18499A3 publication Critical patent/SK18499A3/sk

Links

229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
150000003230 pyrimidines Chemical class 0.000 title description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 63
238000000034 method Methods 0.000 claims abstract description 53
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 19
230000002401 inhibitory effect Effects 0.000 claims abstract description 14
108010059597 Lanosterol synthase Proteins 0.000 claims abstract description 11
201000010099 disease Diseases 0.000 claims abstract description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
238000002360 preparation method Methods 0.000 claims abstract description 8
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
-1 amino, methyl Chemical group 0.000 claims description 104
150000001875 compounds Chemical class 0.000 claims description 95
125000000217 alkyl group Chemical group 0.000 claims description 47
125000004432 carbon atom Chemical group C* 0.000 claims description 45
125000001424 substituent group Chemical group 0.000 claims description 44
229910052736 halogen Inorganic materials 0.000 claims description 34
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
125000005843 halogen group Chemical group 0.000 claims description 26
229910052757 nitrogen Inorganic materials 0.000 claims description 26
150000003839 salts Chemical class 0.000 claims description 22
150000002367 halogens Chemical class 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 14
125000003545 alkoxy group Chemical group 0.000 claims description 11
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
241001465754 Metazoa Species 0.000 claims description 7
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 5
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 4
125000005236 alkanoylamino group Chemical group 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
125000001624 naphthyl group Chemical group 0.000 claims description 4
125000003884 phenylalkyl group Chemical group 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
MCPRJPAHDHAHBK-UHFFFAOYSA-N [4-(4-bromophenyl)sulfonylpiperazin-1-yl]-[4-(6-methylpyrimidin-4-yl)piperazin-1-yl]methanone Chemical compound C1=NC(C)=CC(N2CCN(CC2)C(=O)N2CCN(CC2)S(=O)(=O)C=2C=CC(Br)=CC=2)=N1 MCPRJPAHDHAHBK-UHFFFAOYSA-N 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
210000004369 blood Anatomy 0.000 claims description 3
239000008280 blood Substances 0.000 claims description 3
229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
125000001072 heteroaryl group Chemical group 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
239000011593 sulfur Chemical group 0.000 claims description 3
125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 2
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 2
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
238000013160 medical therapy Methods 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 1
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
125000005530 alkylenedioxy group Chemical group 0.000 claims 1
235000012000 cholesterol Nutrition 0.000 abstract description 23
230000015572 biosynthetic process Effects 0.000 abstract description 18
201000001320 Atherosclerosis Diseases 0.000 abstract description 6
210000002381 plasma Anatomy 0.000 abstract description 6
208000035150 Hypercholesterolemia Diseases 0.000 abstract description 5
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 453
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 191
239000000243 solution Substances 0.000 description 147
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 141
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 131
238000005481 NMR spectroscopy Methods 0.000 description 113
239000007787 solid Substances 0.000 description 89
239000000203 mixture Substances 0.000 description 86
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
235000019439 ethyl acetate Nutrition 0.000 description 64
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
239000011541 reaction mixture Substances 0.000 description 46
239000002904 solvent Substances 0.000 description 44
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
230000002829 reductive effect Effects 0.000 description 37
238000006243 chemical reaction Methods 0.000 description 32
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
239000006260 foam Substances 0.000 description 29
239000011734 sodium Substances 0.000 description 28
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 28
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
239000007858 starting material Substances 0.000 description 26
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 25
239000003921 oil Substances 0.000 description 25
239000012267 brine Substances 0.000 description 24
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 23
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
229920006395 saturated elastomer Polymers 0.000 description 23
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
238000010992 reflux Methods 0.000 description 21
238000004587 chromatography analysis Methods 0.000 description 19
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 17
239000002253 acid Substances 0.000 description 17
239000000725 suspension Substances 0.000 description 17
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
238000001704 evaporation Methods 0.000 description 15
230000008020 evaporation Effects 0.000 description 15
239000012074 organic phase Substances 0.000 description 14
125000006239 protecting group Chemical group 0.000 description 14
239000000047 product Substances 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
229910000041 hydrogen chloride Inorganic materials 0.000 description 12
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
239000000377 silicon dioxide Substances 0.000 description 11
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 11
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
150000001412 amines Chemical class 0.000 description 10
239000002585 base Substances 0.000 description 10
235000017557 sodium bicarbonate Nutrition 0.000 description 10
229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
101710095468 Cyclase Proteins 0.000 description 9
125000002252 acyl group Chemical group 0.000 description 9
239000000908 ammonium hydroxide Substances 0.000 description 9
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
239000003826 tablet Substances 0.000 description 9
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
JIABXBYOURNKRZ-UHFFFAOYSA-N 1-(4-bromophenyl)sulfonylpiperazine Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)N1CCNCC1 JIABXBYOURNKRZ-UHFFFAOYSA-N 0.000 description 8
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 8
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 8
WDTVJRYCMIZPMX-UHFFFAOYSA-N 4-chloro-2-methylpyrimidine Chemical compound CC1=NC=CC(Cl)=N1 WDTVJRYCMIZPMX-UHFFFAOYSA-N 0.000 description 8
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
229910052786 argon Inorganic materials 0.000 description 8
238000002451 electron ionisation mass spectrometry Methods 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
239000000284 extract Substances 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
230000005764 inhibitory process Effects 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
238000001953 recrystallisation Methods 0.000 description 8
XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
239000003480 eluent Substances 0.000 description 7
238000001914 filtration Methods 0.000 description 7
239000007789 gas Substances 0.000 description 7
238000000746 purification Methods 0.000 description 7
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
238000012360 testing method Methods 0.000 description 7
KMMHZIBWCXYAAH-UHFFFAOYSA-N 4-bromobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(Br)C=C1 KMMHZIBWCXYAAH-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 6
239000003112 inhibitor Substances 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
BQPPJGMMIYJVBR-UHFFFAOYSA-N (10S)-3c-Acetoxy-4.4.10r.13c.14t-pentamethyl-17c-((R)-1.5-dimethyl-hexen-(4)-yl)-(5tH)-Delta8-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products CC12CCC(OC(C)=O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C BQPPJGMMIYJVBR-UHFFFAOYSA-N 0.000 description 5
CHGIKSSZNBCNDW-UHFFFAOYSA-N (3beta,5alpha)-4,4-Dimethylcholesta-8,24-dien-3-ol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21 CHGIKSSZNBCNDW-UHFFFAOYSA-N 0.000 description 5
XYTLYKGXLMKYMV-UHFFFAOYSA-N 14alpha-methylzymosterol Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C XYTLYKGXLMKYMV-UHFFFAOYSA-N 0.000 description 5
FPTJELQXIUUCEY-UHFFFAOYSA-N 3beta-Hydroxy-lanostan Natural products C1CC2C(C)(C)C(O)CCC2(C)C2C1C1(C)CCC(C(C)CCCC(C)C)C1(C)CC2 FPTJELQXIUUCEY-UHFFFAOYSA-N 0.000 description 5
AWQASGVMXFSQQI-UHFFFAOYSA-N 4-o-tert-butyl 1-o-(4-nitrophenyl) piperazine-1,4-dicarboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(=O)OC1=CC=C([N+]([O-])=O)C=C1 AWQASGVMXFSQQI-UHFFFAOYSA-N 0.000 description 5
BKLIAINBCQPSOV-UHFFFAOYSA-N Gluanol Natural products CC(C)CC=CC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(O)C(C)(C)C4CC3 BKLIAINBCQPSOV-UHFFFAOYSA-N 0.000 description 5
LOPKHWOTGJIQLC-UHFFFAOYSA-N Lanosterol Natural products CC(CCC=C(C)C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 LOPKHWOTGJIQLC-UHFFFAOYSA-N 0.000 description 5
CAHGCLMLTWQZNJ-UHFFFAOYSA-N Nerifoliol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C CAHGCLMLTWQZNJ-UHFFFAOYSA-N 0.000 description 5
235000019270 ammonium chloride Nutrition 0.000 description 5
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
ONCCWDRMOZMNSM-FBCQKBJTSA-N compound Z Chemical compound N1=C2C(=O)NC(N)=NC2=NC=C1C(=O)[C@H]1OP(O)(=O)OC[C@H]1O ONCCWDRMOZMNSM-FBCQKBJTSA-N 0.000 description 5
239000006071 cream Substances 0.000 description 5
QBSJHOGDIUQWTH-UHFFFAOYSA-N dihydrolanosterol Natural products CC(C)CCCC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 QBSJHOGDIUQWTH-UHFFFAOYSA-N 0.000 description 5
238000010828 elution Methods 0.000 description 5
238000003818 flash chromatography Methods 0.000 description 5
CAHGCLMLTWQZNJ-RGEKOYMOSA-N lanosterol Chemical compound C([C@]12C)C[C@@H](O)C(C)(C)[C@H]1CCC1=C2CC[C@]2(C)[C@H]([C@H](CCC=C(C)C)C)CC[C@@]21C CAHGCLMLTWQZNJ-RGEKOYMOSA-N 0.000 description 5
229940058690 lanosterol Drugs 0.000 description 5
210000001589 microsome Anatomy 0.000 description 5
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
230000009467 reduction Effects 0.000 description 5
238000010898 silica gel chromatography Methods 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
239000012258 stirred mixture Substances 0.000 description 5
OZDCZHDOIBUGAJ-UHFFFAOYSA-N 4-(trifluoromethyl)benzenesulfonyl chloride Chemical compound FC(F)(F)C1=CC=C(S(Cl)(=O)=O)C=C1 OZDCZHDOIBUGAJ-UHFFFAOYSA-N 0.000 description 4
GSXFOGXQLRLSKK-UHFFFAOYSA-N 4-chloro-2,6-dimethylpyrimidine Chemical compound CC1=CC(Cl)=NC(C)=N1 GSXFOGXQLRLSKK-UHFFFAOYSA-N 0.000 description 4
ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
YBYWWDRYZSZRFR-UHFFFAOYSA-N [1-(6-chloropyrimidin-4-yl)piperidin-4-yl]-[4-[4-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]methanone Chemical compound C1=CC(C(F)(F)F)=CC=C1S(=O)(=O)N1CCN(C(=O)C2CCN(CC2)C=2N=CN=C(Cl)C=2)CC1 YBYWWDRYZSZRFR-UHFFFAOYSA-N 0.000 description 4
150000001340 alkali metals Chemical class 0.000 description 4
125000000304 alkynyl group Chemical group 0.000 description 4
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
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LJXIIBRDOUBZAC-UHFFFAOYSA-N tert-butyl 4-(4-pyrimidin-4-ylpiperazine-1-carbonyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(=O)N1CCN(C=2N=CN=CC=2)CC1 LJXIIBRDOUBZAC-UHFFFAOYSA-N 0.000 description 1
LDBPMZYHUNVDAX-UHFFFAOYSA-N tert-butyl 4-[1-(4-bromophenyl)sulfonylpiperidine-4-carbonyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(=O)C1CCN(S(=O)(=O)C=2C=CC(Br)=CC=2)CC1 LDBPMZYHUNVDAX-UHFFFAOYSA-N 0.000 description 1
KHOKGXFIKYERKI-UHFFFAOYSA-N tert-butyl 4-[1-(4-bromophenyl)sulfonylpiperidine-4-carbonyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(=O)C1CCN(S(=O)(=O)C=2C=CC(Br)=CC=2)CC1 KHOKGXFIKYERKI-UHFFFAOYSA-N 0.000 description 1
ORBYTRVMSCIQAB-UHFFFAOYSA-N tert-butyl 4-[4-(4-bromophenyl)sulfonylpiperazine-1-carbonyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(=O)N1CCN(S(=O)(=O)C=2C=CC(Br)=CC=2)CC1 ORBYTRVMSCIQAB-UHFFFAOYSA-N 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
NLOUTGCXBXLQIA-UHFFFAOYSA-N trichloro phosphate Chemical compound ClOP(=O)(OCl)OCl NLOUTGCXBXLQIA-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
- 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
- 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
- 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
- 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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms 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

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Enzymes And Modification Thereof (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Plural Heterocyclic Compounds (AREA)

SK184-99A 1996-08-14 1997-07-25 Substituted pyrimidine derivatives and their pharmaceutical use SK18499A3 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GBGB9617060.0A GB9617060D0 (en)	1996-08-14	1996-08-14	Chemical compounds
GBGB9703027.4A GB9703027D0 (en)	1997-02-14	1997-02-14	Chemical compounds
PCT/GB1997/002029 WO1998006705A1 (en)	1996-08-14	1997-07-25	Substituted pyrimidine derivatives and their pharmaceutical use

Publications (1)

Publication Number	Publication Date
SK18499A3 true SK18499A3 (en)	1999-07-12

Family

ID=26309870

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK184-99A SK18499A3 (en)	1996-08-14	1997-07-25	Substituted pyrimidine derivatives and their pharmaceutical use

Country Status (18)

Country	Link
US (1)	US6093718A (de)
EP (1)	EP0925286B1 (de)
JP (1)	JP2000516602A (de)
KR (1)	KR20000029984A (de)
CN (1)	CN1228087A (de)
AT (1)	ATE230399T1 (de)
AU (1)	AU3701797A (de)
BG (1)	BG103190A (de)
BR (1)	BR9711135A (de)
CA (1)	CA2260872A1 (de)
CZ (1)	CZ45699A3 (de)
DE (1)	DE69718177T2 (de)
IL (1)	IL128428A0 (de)
NO (1)	NO990663L (de)
PL (1)	PL331599A1 (de)
SK (1)	SK18499A3 (de)
TR (1)	TR199900303T2 (de)
WO (1)	WO1998006705A1 (de)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL115420A0 (en)	1994-09-26	1995-12-31	Zeneca Ltd	Aminoheterocyclic derivatives
EP0880501A1 (de)	1996-02-02	1998-12-02	Zeneca Limited	Heterocyclische verbindungen verwendbar als pharmazeutische mittel
GB9602166D0 (en) *	1996-02-02	1996-04-03	Zeneca Ltd	Aminoheterocyclic derivatives
US6093718A (en) *	1996-08-14	2000-07-25	Zeneca Limited	Substituted pyrimidine derivatives and their pharmaceutical use
UA56197C2 (uk)	1996-11-08	2003-05-15	Зенека Лімітед	Гетероциклічні похідні
AU5999698A (en)	1997-02-13	1998-09-08	Zeneca Limited	Heterocyclic compounds useful as oxido-squalene cyclase inhibitors
DE69815509T2 (de)	1997-02-13	2004-05-13	Astrazeneca Ab	Heterozyklische verbindungen die als oxido-squalen-zyklase-inhibitoren anwendung finden
US7115632B1 (en)	1999-05-12	2006-10-03	G. D. Searle & Co.	Sulfonyl aryl or heteroaryl hydroxamic acid compounds
US6794511B2 (en)	1997-03-04	2004-09-21	G. D. Searle	Sulfonyl aryl or heteroaryl hydroxamic acid compounds
US6696449B2 (en)	1997-03-04	2004-02-24	Pharmacia Corporation	Sulfonyl aryl hydroxamates and their use as matrix metalloprotease inhibitors
GB9715892D0 (en) *	1997-07-29	1997-10-01	Zeneca Ltd	Heterocyclic compounds
GB9715895D0 (en)	1997-07-29	1997-10-01	Zeneca Ltd	Heterocyclic compounds
US6525042B1 (en) *	1997-09-30	2003-02-25	Daiichi Pharmaceutical Co., Ltd.	Sulfonyl derivatives
DE69934093T2 (de) *	1998-01-27	2007-06-21	Aventis Pharmaceuticals Inc.	SUBSTITUIERTE OXOAZAHETEROCYCLYL FAKTOR Xa HEMMER
CA2340100A1 (en) *	1998-08-11	2000-02-24	Daiichi Pharmaceutical Co., Ltd.	Novel sulfonyl derivatives
GB9902989D0 (en)	1999-02-11	1999-03-31	Zeneca Ltd	Heterocyclic derivatives
EP1177173A1 (de) *	1999-05-12	2002-02-06	G.D. Searle & Co.	Hydroxamsäurederivate als inhibitoren von matrix-metalloproteinasen
TWI290136B (en)	2000-04-05	2007-11-21	Daiichi Seiyaku Co	Ethylenediamine derivatives
WO2003000657A1 (en)	2001-06-20	2003-01-03	Daiichi Pharmaceutical Co., Ltd.	Diamine derivatives
EP1441728A2 (de) *	2001-11-01	2004-08-04	Vertex Pharmaceuticals Incorporated	Modulatoren der cholesterol biosynthese
MXPA05011352A (es) *	2003-04-23	2005-11-28	Glaxo Group Ltd	Derivados de piperazina y su uso para el tratamiento de enfermedades neurologicas y psiquiatricas.
AU2005259947A1 (en)	2004-06-28	2006-01-12	Hutta, Daniel A.	Hetero isonipecotic modulators of vanilloid VR1 receptor
WO2006040192A1 (en) *	2004-10-15	2006-04-20	Glaxo Group Limited	Pyrrolidine derivatives as histamine receptors ligands
US20090203676A1 (en) *	2005-06-30	2009-08-13	Oscar Barba	G-protein Coupled Receptor Agonists
TWI417095B (zh) *	2006-03-15	2013-12-01	Janssen Pharmaceuticals Inc	１，４-二取代之３-氰基-吡啶酮衍生物及其作為ｍＧｌｕＲ２-受體之正向異位性調節劑之用途
TW200900065A (en)	2007-03-07	2009-01-01	Janssen Pharmaceutica Nv	3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives
TW200845978A (en) *	2007-03-07	2008-12-01	Janssen Pharmaceutica Nv	3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives
CN103772299A (zh) *	2007-08-13	2014-05-07	霍夫曼-拉罗奇有限公司	新型哌嗪酰胺衍生物
KR20100080597A (ko) *	2007-09-14	2010-07-09	오르토-맥닐-얀센 파마슈티칼스 인코포레이티드	１,３-이치환된-４-페닐-1ｈ-피리딘-2-온
CA2696948C (en) *	2007-09-14	2013-04-30	Jose Maria Cid-Nunez	1',3'-disubstituted-4-phenyl-3,4,5,6-tetrahydro-2h,1'h-[1,4']bipyridinyl-2'-ones
KR20100065191A (ko)	2007-09-14	2010-06-15	오르토-맥닐-얀센 파마슈티칼스 인코포레이티드	１,３-이치환된 ４-(아릴-ｘ-페닐)-１ｈ-피리딘-２-온
EP2220083B1 (de) *	2007-11-14	2017-07-19	Janssen Pharmaceuticals, Inc.	Imidazo[1,2-a]-pyridin-derivate und ihre verwendung als positive allosterische modulatoren von mglur2-rezeptoren
WO2009079547A1 (en) *	2007-12-18	2009-06-25	Smithkline Beecham (Cork) Limited	Quinazoline anhydrate forms
CA2731897C (en) *	2008-08-06	2013-07-02	Pfizer Limited	Diazepine and diazocane compounds as mc4 agonists
CA2735764C (en)	2008-09-02	2016-06-14	Ortho-Mcneil-Janssen Pharmaceuticals, Inc.	3-azabicyclo[3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors
GB0818241D0 (en)	2008-10-06	2008-11-12	Cancer Res Technology	Compounds and their use
AU2009304293B2 (en)	2008-10-16	2012-04-26	Addex Pharma S.A.	Indole and benzomorpholine derivatives as modulators of metabotropic glutamate receptors
BRPI0921333A2 (pt)	2008-11-28	2015-12-29	Addex Pharmaceuticals Sa	derivados de indol e benzoxazina como moduladores de receptores de glutamato metabotrópicos
EA020671B1 (ru)	2009-05-12	2014-12-30	Янссен Фармасьютикалз, Инк.	ПРОИЗВОДНЫЕ 1,2,4-ТРИАЗОЛО[4,3-a]ПИРИДИНА И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ПОЛОЖИТЕЛЬНЫХ АЛЛОСТЕРИЧЕСКИХ МОДУЛЯТОРОВ РЕЦЕПТОРОВ mGluR2
NZ596078A (en)	2009-05-12	2013-06-28	Janssen Pharmaceuticals Inc	1,2,4-TRIAZOLO [4,3-a] PYRIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OR PREVENTION OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS
MY153913A (en)	2009-05-12	2015-04-15	Janssen Pharmaceuticals Inc	7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
CA2815002C (en)	2010-11-08	2019-10-22	Janssen Pharmaceuticals, Inc.	1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
CN103298810B (zh)	2010-11-08	2016-03-16	杨森制药公司	1,2,4-三唑并[4,3-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途
EP2643320B1 (de)	2010-11-08	2015-03-04	Janssen Pharmaceuticals, Inc.	1,2,4-triazolo[4,3-a]pyridinderivate und ihre verwendung als positiv allosterische modulatoren des mglur2 receptors
JO3368B1 (ar)	2013-06-04	2019-03-13	Janssen Pharmaceutica Nv	مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2
JO3367B1 (ar)	2013-09-06	2019-03-13	Janssen Pharmaceutica Nv	مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2
LT3431106T (lt)	2014-01-21	2021-02-10	Janssen Pharmaceutica Nv	Deriniai, apimantys 2 potipio metabotropinio glutamaterginio receptoriaus teigiamus alosterinius moduliatorius arba ortosterinius agonistus, ir jų panaudojimas
KR102414246B1 (ko)	2014-01-21	2022-06-27	얀센 파마슈티카 엔.브이.	대사 조절형 글루탐산 작동성 수용체 제2아형의 양성 알로스테릭 조절제 또는 오르토스테릭 작동제를 포함하는 조합 및 그 용도

Family Cites Families (42)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AT340933B (de) *	1973-08-20	1978-01-10	Thomae Gmbh Dr K	Verfahren zur herstellung neuer pyrimidinderivate und ihrer saureadditionssalze
US4167567A (en) *	1978-05-05	1979-09-11	The Upjohn Company	Antihypertensive 4-aminoquinolines
US4231938A (en) *	1979-06-15	1980-11-04	Merck & Co., Inc.	Hypocholesteremic fermentation products and process of preparation
SE8203887D0 (sv) *	1982-06-23	1982-06-23	Kabivitrum Ab	Nya trombininhiberande foreningar
GB8601160D0 (en) *	1986-01-17	1986-02-19	Fujisawa Pharmaceutical Co	Heterocyclic compounds
GB8603120D0 (en) *	1986-02-07	1986-03-12	Pfizer Ltd	Anti-dysrhythmia agents
GB8609630D0 (en) *	1986-04-19	1986-05-21	Pfizer Ltd	Anti-arrhythmia agents
JPH0696575B2 (ja) *	1987-09-17	1994-11-30	三菱化成株式会社	４−アミノピリジン誘導体及びその酸付加塩
US4871721A (en) *	1988-01-11	1989-10-03	E. R. Squibb & Sons, Inc.	Phosphorus-containing squalene synthetase inhibitors
GB8817315D0 (en) *	1988-07-20	1988-08-24	Pfizer Ltd	Triazole antifungal agents
GB8819307D0 (en) *	1988-08-13	1988-09-14	Pfizer Ltd	Antiarrhythmic agents
DE3905364A1 (de) *	1989-02-22	1990-08-23	Hoechst Ag	Substituierte pyrimidin-derivate, verfahren zu ihrer herstellung und ihre verwendung als tool
IE64358B1 (en) *	1989-07-18	1995-07-26	Ici Plc	Diaryl ether heterocycles
JPH05503300A (ja) *	1990-11-15	1993-06-03	ペンタファルム　アクチェンゲゼルシャフト	メタ置換フェニルアラニン誘導体
EP0495750A3 (en) *	1991-01-14	1992-09-16	Ciba-Geigy Ag	Heterocyclic hydroxylamine
IT1245712B (it) *	1991-04-09	1994-10-14	Boehringer Mannheim Italia	Ammine eterocicliche utili terapia dell'asma e dell'infiammazione delle vie aeree
FR2676054B1 (fr) *	1991-05-03	1993-09-03	Sanofi Elf	Nouveaux composes n-alkylenepiperidino et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant.
WO1993000342A1 (en) *	1991-06-21	1993-01-07	Boehringer Mannheim Italia S.P.A.	2-amino-4-aryl-thiazoles with antiasthmatic and anti-inflammatory activities on the respiratory tract
WO1993006085A1 (en) *	1991-09-19	1993-04-01	Smithkline Beecham Corporation	Pyridine compounds for treating leukotriene-related diseases
PH31294A (en) *	1992-02-13	1998-07-06	Thomae Gmbh Dr K	Benzimidazolyl derivatives, pharmaceutical compositions containing these compounds and process for preparing them.
HU211995B (en) *	1992-06-30	1996-01-29	Gyogyszerkutato Intezet	Process to prepare novel benzoyl amino acid derivs. and pharmaceutical compns. contg.them
US5371091A (en) *	1992-08-31	1994-12-06	Bristol-Myers Squibb Company	Heteroaromatic amine thrombin inhibitors
FR2697252B1 (fr) *	1992-10-28	1994-12-09	Fournier Ind & Sante	Dérivés de 1,2,3,5,6,7,8,8a-octahydro-5,5,8a-triméthyl-(8abeta)-6-isoquinolineamine, leur procédé de préparation et leur utilisation en thérapeutique.
DE4243858A1 (de) *	1992-12-23	1994-06-30	Thomae Gmbh Dr K	Aminosäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
US5332822A (en) *	1992-12-24	1994-07-26	Bristol-Myers Squibb Company	Heteroaromatic and thioheteroaromatic substituted sulfonamide thrombin inhibitors
DE4302485A1 (de) *	1993-01-29	1994-08-04	Merck Patent Gmbh	Piperazinderivate
CZ245994A3 (en) *	1993-02-10	1995-10-18	Pentapharm Ag	Piperazides of substituted phenylalanine derivatives as thrombin inhibitors
DE4306506A1 (de) *	1993-03-03	1994-09-08	Boehringer Mannheim Gmbh	Neue 4-Alkylaminopyridine - Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel
TW257757B (de) *	1993-03-03	1995-09-21	Boehringer Mannheim Gmbh
DE4306873A1 (de) *	1993-03-05	1994-09-08	Boehringer Mannheim Gmbh	Neue 4-Aminopyridine-Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel
GB9406144D0 (en) *	1993-03-29	1994-05-18	Zeneca Ltd	Heterocyclic compounds
AU3107795A (en) *	1994-08-09	1996-03-07	Pentapharm Ag	Inhibitors of the benzamidine type
IL115420A0 (en) *	1994-09-26	1995-12-31	Zeneca Ltd	Aminoheterocyclic derivatives
CN1160403A (zh) *	1994-10-11	1997-09-24	武田药品工业株式会社	取代杂双环烷基胺和它们作为角鲨烯氧化物环化酶抑制剂的用途
IL117149A0 (en) *	1995-02-23	1996-06-18	Schering Corp	Muscarinic antagonists
IL117580A0 (en) *	1995-03-29	1996-07-23	Merck & Co Inc	Inhibitors of farnesyl-protein transferase and pharmaceutical compositions containing them
US5856326A (en) *	1995-03-29	1999-01-05	Merck & Co., Inc.	Inhibitors of farnesyl-protein transferase
GB9516709D0 (en) *	1995-08-15	1995-10-18	Zeneca Ltd	Medicament
EP0880501A1 (de) *	1996-02-02	1998-12-02	Zeneca Limited	Heterocyclische verbindungen verwendbar als pharmazeutische mittel
GB9602166D0 (en) *	1996-02-02	1996-04-03	Zeneca Ltd	Aminoheterocyclic derivatives
DE69717268T2 (de) *	1996-02-22	2003-09-04	Bristol-Myers Squibb Pharma Co., Wilmington	M-amidinophenyl-analoga als faktor-xa-inhibitoren
US6093718A (en) *	1996-08-14	2000-07-25	Zeneca Limited	Substituted pyrimidine derivatives and their pharmaceutical use

1997
- 1997-07-25 US US09/242,309 patent/US6093718A/en not_active Expired - Fee Related
- 1997-07-25 CZ CZ99456A patent/CZ45699A3/cs unknown
- 1997-07-25 CA CA002260872A patent/CA2260872A1/en not_active Abandoned
- 1997-07-25 IL IL12842897A patent/IL128428A0/xx unknown
- 1997-07-25 CN CN97197282A patent/CN1228087A/zh active Pending
- 1997-07-25 WO PCT/GB1997/002029 patent/WO1998006705A1/en not_active Ceased
- 1997-07-25 EP EP97933774A patent/EP0925286B1/de not_active Expired - Lifetime
- 1997-07-25 PL PL97331599A patent/PL331599A1/xx unknown
- 1997-07-25 AU AU37017/97A patent/AU3701797A/en not_active Abandoned
- 1997-07-25 KR KR1019997001247A patent/KR20000029984A/ko not_active Withdrawn
- 1997-07-25 BR BR9711135A patent/BR9711135A/pt not_active Application Discontinuation
- 1997-07-25 DE DE69718177T patent/DE69718177T2/de not_active Expired - Fee Related
- 1997-07-25 TR TR1999/00303T patent/TR199900303T2/xx unknown
- 1997-07-25 JP JP10509469A patent/JP2000516602A/ja not_active Ceased
- 1997-07-25 SK SK184-99A patent/SK18499A3/sk unknown
- 1997-07-25 AT AT97933774T patent/ATE230399T1/de not_active IP Right Cessation
1999
- 1999-02-12 NO NO990663A patent/NO990663L/no not_active Application Discontinuation
- 1999-02-22 BG BG103190A patent/BG103190A/xx unknown

Also Published As

Publication number	Publication date
CN1228087A (zh)	1999-09-08
BR9711135A (pt)	1999-08-17
PL331599A1 (en)	1999-08-02
EP0925286A1 (de)	1999-06-30
US6093718A (en)	2000-07-25
DE69718177T2 (de)	2003-10-23
CZ45699A3 (cs)	1999-05-12
JP2000516602A (ja)	2000-12-12
ATE230399T1 (de)	2003-01-15
CA2260872A1 (en)	1998-02-19
NO990663L (no)	1999-04-12
BG103190A (en)	1999-11-30
IL128428A0 (en)	2000-01-31
AU3701797A (en)	1998-03-06
KR20000029984A (ko)	2000-05-25
DE69718177D1 (de)	2003-02-06
NO990663D0 (no)	1999-02-12
WO1998006705A1 (en)	1998-02-19
EP0925286B1 (de)	2003-01-02
TR199900303T2 (xx)	1999-06-21

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