LT4912B - Arilo ir heterociklilo pakaitus turintys pirimidino dariniai kaip antikoaguliantai - Google Patents

Arilo ir heterociklilo pakaitus turintys pirimidino dariniai kaip antikoaguliantai Download PDF

Info

Publication number: LT4912B
Authority: LT; Lithuania
Prior art keywords: oxy; compounds; benzyloxy; formula; methylimidazolin
Prior art date: 1998-12-04

Application number

LT2001061A

Other languages

English (en)

Lithuanian (lt)

Other versions

LT2001061A (en

Inventor

D. David Davey

B. Gary Phillips

Original Assignee

Berlex Laboratories,Inc.

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.)

1998-12-04

Filing date

2001-06-12

Publication date

2002-04-25

2001-06-12 Application filed by Berlex Laboratories,Inc. filed Critical Berlex Laboratories,Inc.

2001-12-27 Publication of LT2001061A publication Critical patent/LT2001061A/xx

2002-04-25 Publication of LT4912B publication Critical patent/LT4912B/lt

Links

125000003118 aryl group Chemical group 0.000 title claims abstract description 65
239000003146 anticoagulant agent Substances 0.000 title abstract description 11
229940127219 anticoagulant drug Drugs 0.000 title abstract description 11
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title abstract description 3
150000003230 pyrimidines Chemical class 0.000 title abstract description 3
125000000623 heterocyclic group Chemical group 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 219
-1 1-methylimidazolin-2-yl Chemical group 0.000 claims description 181
125000000217 alkyl group Chemical group 0.000 claims description 64
125000003710 aryl alkyl group Chemical group 0.000 claims description 44
125000004663 dialkyl amino group Chemical group 0.000 claims description 41
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 41
108010074860 Factor Xa Proteins 0.000 claims description 39
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 39
150000003839 salts Chemical class 0.000 claims description 38
125000003545 alkoxy group Chemical group 0.000 claims description 37
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 36
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 33
229910052736 halogen Inorganic materials 0.000 claims description 33
125000001188 haloalkyl group Chemical group 0.000 claims description 32
150000002367 halogens Chemical class 0.000 claims description 31
108090000190 Thrombin Proteins 0.000 claims description 23
229960004072 thrombin Drugs 0.000 claims description 23
238000003556 assay Methods 0.000 claims description 22
239000001257 hydrogen Substances 0.000 claims description 21
229910052739 hydrogen Inorganic materials 0.000 claims description 21
238000000034 method Methods 0.000 claims description 21
238000012360 testing method Methods 0.000 claims description 20
239000000243 solution Substances 0.000 claims description 19
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
238000006243 chemical reaction Methods 0.000 claims description 16
239000000203 mixture Substances 0.000 claims description 16
239000003112 inhibitor Substances 0.000 claims description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
125000001424 substituent group Chemical group 0.000 claims description 12
108010000499 Thromboplastin Proteins 0.000 claims description 11
102000002262 Thromboplastin Human genes 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 11
230000000694 effects Effects 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 10
102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 9
108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 9
239000008194 pharmaceutical composition Substances 0.000 claims description 9
229960000187 tissue plasminogen activator Drugs 0.000 claims description 9
102000004190 Enzymes Human genes 0.000 claims description 8
108090000790 Enzymes Proteins 0.000 claims description 8
229940088598 enzyme Drugs 0.000 claims description 8
238000011282 treatment Methods 0.000 claims description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
229910052757 nitrogen Inorganic materials 0.000 claims description 7
239000011734 sodium Substances 0.000 claims description 7
239000007787 solid Substances 0.000 claims description 7
WKTCFPZPRJPZID-UHFFFAOYSA-N 4-hydroxy-3-[6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-2-phenylpyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C(N)=N)O)C=2)C=2C=CC=CC=2)=C1 WKTCFPZPRJPZID-UHFFFAOYSA-N 0.000 claims description 6
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
239000002775 capsule Substances 0.000 claims description 6
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
235000019359 magnesium stearate Nutrition 0.000 claims description 6
229910052708 sodium Inorganic materials 0.000 claims description 6
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 claims description 5
239000008101 lactose Substances 0.000 claims description 5
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
239000011780 sodium chloride Substances 0.000 claims description 5
239000000758 substrate Substances 0.000 claims description 5
229920002472 Starch Polymers 0.000 claims description 4
PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims description 4
230000015572 biosynthetic process Effects 0.000 claims description 4
238000000338 in vitro Methods 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
150000007530 organic bases Chemical class 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
239000008107 starch Substances 0.000 claims description 4
235000019698 starch Nutrition 0.000 claims description 4
239000000725 suspension Substances 0.000 claims description 4
108010094028 Prothrombin Proteins 0.000 claims description 3
102100027378 Prothrombin Human genes 0.000 claims description 3
230000004913 activation Effects 0.000 claims description 3
239000000443 aerosol Substances 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims description 3
150000007529 inorganic bases Chemical class 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
239000000843 powder Substances 0.000 claims description 3
229940039716 prothrombin Drugs 0.000 claims description 3
229910052717 sulfur Inorganic materials 0.000 claims description 3
125000004434 sulfur atom Chemical group 0.000 claims description 3
239000000829 suppository Substances 0.000 claims description 3
238000003786 synthesis reaction Methods 0.000 claims description 3
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
239000000872 buffer Substances 0.000 claims description 2
239000003153 chemical reaction reagent Substances 0.000 claims description 2
239000000460 chlorine Substances 0.000 claims description 2
229920000669 heparin Polymers 0.000 claims description 2
229960002897 heparin Drugs 0.000 claims description 2
239000007788 liquid Substances 0.000 claims description 2
230000008569 process Effects 0.000 claims description 2
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
238000011160 research Methods 0.000 claims description 2
229920006395 saturated elastomer Polymers 0.000 claims description 2
239000011593 sulfur Substances 0.000 claims description 2
238000002360 preparation method Methods 0.000 claims 21
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 16
239000011541 reaction mixture Substances 0.000 claims 13
235000002639 sodium chloride Nutrition 0.000 claims 13
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 12
239000011550 stock solution Substances 0.000 claims 12
239000004615 ingredient Substances 0.000 claims 11
239000000543 intermediate Substances 0.000 claims 11
239000002904 solvent Substances 0.000 claims 11
239000012224 working solution Substances 0.000 claims 11
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 9
239000012131 assay buffer Substances 0.000 claims 8
239000002244 precipitate Substances 0.000 claims 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 6
238000003756 stirring Methods 0.000 claims 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 4
238000010790 dilution Methods 0.000 claims 4
239000012895 dilution Substances 0.000 claims 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims 4
229940068918 polyethylene glycol 400 Drugs 0.000 claims 4
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims 4
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims 4
229940068968 polysorbate 80 Drugs 0.000 claims 4
229920000053 polysorbate 80 Polymers 0.000 claims 4
229960004063 propylene glycol Drugs 0.000 claims 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
239000002585 base Substances 0.000 claims 3
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 3
238000001704 evaporation Methods 0.000 claims 3
230000008020 evaporation Effects 0.000 claims 3
238000002955 isolation Methods 0.000 claims 3
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims 3
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 claims 2
PXDXIYWVZWQHON-UHFFFAOYSA-N 3-(6-chloro-2-phenylpyrimidin-4-yl)oxy-4-phenylmethoxybenzonitrile Chemical compound N=1C(C=2C=CC=CC=2)=NC(Cl)=CC=1OC1=CC(C#N)=CC=C1OCC1=CC=CC=C1 PXDXIYWVZWQHON-UHFFFAOYSA-N 0.000 claims 2
WTDXDRUHQKVYKO-UHFFFAOYSA-N 4-hydroxy-2-phenyl-1h-pyrimidin-6-one Chemical compound OC1=CC(=O)NC(C=2C=CC=CC=2)=N1 WTDXDRUHQKVYKO-UHFFFAOYSA-N 0.000 claims 2
UDAOJHAASAWVIQ-UHFFFAOYSA-N 4-phenylmethoxybenzonitrile Chemical compound C1=CC(C#N)=CC=C1OCC1=CC=CC=C1 UDAOJHAASAWVIQ-UHFFFAOYSA-N 0.000 claims 2
XEKNACRTWJHOCE-UHFFFAOYSA-N 6-Phenyl-2-thiouracil Chemical compound O=C1NC(S)=NC(C=2C=CC=CC=2)=C1 XEKNACRTWJHOCE-UHFFFAOYSA-N 0.000 claims 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims 2
101710178035 Chorismate synthase 2 Proteins 0.000 claims 2
101710152694 Cysteine synthase 2 Proteins 0.000 claims 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
NRFQZTCQAYEXEE-UHFFFAOYSA-N Fenclorim Chemical compound ClC1=CC(Cl)=NC(C=2C=CC=CC=2)=N1 NRFQZTCQAYEXEE-UHFFFAOYSA-N 0.000 claims 2
229910052783 alkali metal Inorganic materials 0.000 claims 2
150000001340 alkali metals Chemical class 0.000 claims 2
125000003277 amino group Chemical group 0.000 claims 2
125000002102 aryl alkyloxo group Chemical group 0.000 claims 2
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims 2
229910000024 caesium carbonate Inorganic materials 0.000 claims 2
235000011089 carbon dioxide Nutrition 0.000 claims 2
GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 claims 2
238000000605 extraction Methods 0.000 claims 2
238000003818 flash chromatography Methods 0.000 claims 2
239000012458 free base Substances 0.000 claims 2
238000004128 high performance liquid chromatography Methods 0.000 claims 2
229910052751 metal Inorganic materials 0.000 claims 2
239000002184 metal Substances 0.000 claims 2
239000003921 oil Substances 0.000 claims 2
235000019198 oils Nutrition 0.000 claims 2
239000002798 polar solvent Substances 0.000 claims 2
229940093429 polyethylene glycol 6000 Drugs 0.000 claims 2
238000010992 reflux Methods 0.000 claims 2
238000013207 serial dilution Methods 0.000 claims 2
238000004809 thin layer chromatography Methods 0.000 claims 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims 2
229960003766 thrombin (human) Drugs 0.000 claims 2
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims 1
OXEDXHIBHVMDST-UHFFFAOYSA-N 12Z-octadecenoic acid Natural products CCCCCC=CCCCCCCCCCCC(O)=O OXEDXHIBHVMDST-UHFFFAOYSA-N 0.000 claims 1
LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 claims 1
DQXNTSXKIUZJJS-UHFFFAOYSA-N 2,4-dichloro-5-methylpyrimidine Chemical compound CC1=CN=C(Cl)N=C1Cl DQXNTSXKIUZJJS-UHFFFAOYSA-N 0.000 claims 1
XMPXHBKLXQCONZ-UHFFFAOYSA-N 2,4-dichloro-6-(1-ethylpiperidin-4-yl)pyrimidine Chemical compound C1CN(CC)CCC1C1=CC(Cl)=NC(Cl)=N1 XMPXHBKLXQCONZ-UHFFFAOYSA-N 0.000 claims 1
FRIYSTDNVKUKLX-UHFFFAOYSA-N 2,4-dichloro-6-(3-chlorophenyl)pyrimidine Chemical compound ClC1=CC=CC(C=2N=C(Cl)N=C(Cl)C=2)=C1 FRIYSTDNVKUKLX-UHFFFAOYSA-N 0.000 claims 1
IWZHZHVKIBONRZ-UHFFFAOYSA-N 2,4-dichloro-6-(4,5-dihydro-1h-imidazol-2-yl)pyrimidine Chemical compound ClC1=NC(Cl)=CC(C=2NCCN=2)=N1 IWZHZHVKIBONRZ-UHFFFAOYSA-N 0.000 claims 1
QYHGNJWTEXUEGF-UHFFFAOYSA-N 2,4-dichloro-6-(4-methoxyphenyl)pyrimidine Chemical compound C1=CC(OC)=CC=C1C1=CC(Cl)=NC(Cl)=N1 QYHGNJWTEXUEGF-UHFFFAOYSA-N 0.000 claims 1
JMMNAMVVOXSZHE-UHFFFAOYSA-N 2,4-dichloro-6-(4-methylphenyl)pyrimidine Chemical compound C1=CC(C)=CC=C1C1=CC(Cl)=NC(Cl)=N1 JMMNAMVVOXSZHE-UHFFFAOYSA-N 0.000 claims 1
CSFBBYXBXMIWOV-UHFFFAOYSA-N 2,4-dichloro-6-(4-phenylmethoxyphenyl)pyrimidine Chemical compound ClC1=NC(Cl)=CC(C=2C=CC(OCC=3C=CC=CC=3)=CC=2)=N1 CSFBBYXBXMIWOV-UHFFFAOYSA-N 0.000 claims 1
KTLYHIYQPLADGF-UHFFFAOYSA-N 2,4-dichloro-6-(4-phenylphenyl)pyrimidine Chemical compound ClC1=NC(Cl)=CC(C=2C=CC(=CC=2)C=2C=CC=CC=2)=N1 KTLYHIYQPLADGF-UHFFFAOYSA-N 0.000 claims 1
VRNSMZDBMUSIFT-UHFFFAOYSA-N 2,4-dichloro-6-phenylpyrimidine Chemical compound ClC1=NC(Cl)=CC(C=2C=CC=CC=2)=N1 VRNSMZDBMUSIFT-UHFFFAOYSA-N 0.000 claims 1
VONHTGNOEMMNQQ-UHFFFAOYSA-N 2,4-dichloro-6-pyridin-2-ylpyrimidine Chemical compound ClC1=NC(Cl)=CC(C=2N=CC=CC=2)=N1 VONHTGNOEMMNQQ-UHFFFAOYSA-N 0.000 claims 1
BLBKOHVKWYHLCJ-UHFFFAOYSA-N 2-(1-ethylpiperidin-4-yl)-4-hydroxy-1h-pyrimidin-6-one Chemical compound C1CN(CC)CCC1C1=NC(O)=CC(O)=N1 BLBKOHVKWYHLCJ-UHFFFAOYSA-N 0.000 claims 1
UVJGNCMMQOWOMD-UHFFFAOYSA-N 2-(3-chlorophenyl)-4-hydroxy-1h-pyrimidin-6-one Chemical compound OC1=CC(O)=NC(C=2C=C(Cl)C=CC=2)=N1 UVJGNCMMQOWOMD-UHFFFAOYSA-N 0.000 claims 1
DZOPLVRMPIZJRH-UHFFFAOYSA-N 2-(4,5-dihydro-1h-imidazol-2-yl)-4-hydroxy-1h-pyrimidin-6-one Chemical compound OC1=CC(O)=NC(C=2NCCN=2)=N1 DZOPLVRMPIZJRH-UHFFFAOYSA-N 0.000 claims 1
VKFMPPVTIUHPPG-UHFFFAOYSA-N 2-[4-(dimethylamino)phenyl]-4-hydroxy-1h-pyrimidin-6-one Chemical compound C1=CC(N(C)C)=CC=C1C1=NC(O)=CC(O)=N1 VKFMPPVTIUHPPG-UHFFFAOYSA-N 0.000 claims 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims 1
OBZBNMGJXZKUJO-UHFFFAOYSA-N 3-(1-methyl-4,5-dihydroimidazol-2-yl)phenol Chemical compound CN1CCN=C1C1=CC=CC(O)=C1 OBZBNMGJXZKUJO-UHFFFAOYSA-N 0.000 claims 1
PGBCBIRMLXFBOL-UHFFFAOYSA-N 3-(2-chloro-6-phenylpyrimidin-4-yl)oxy-4-phenylmethoxybenzonitrile Chemical compound C=1C(C=2C=CC=CC=2)=NC(Cl)=NC=1OC1=CC(C#N)=CC=C1OCC1=CC=CC=C1 PGBCBIRMLXFBOL-UHFFFAOYSA-N 0.000 claims 1
GKFZMLRATULORQ-UHFFFAOYSA-N 3-(4-chloro-6-phenylpyrimidin-2-yl)oxy-4-phenylmethoxybenzonitrile Chemical compound N=1C(Cl)=CC(C=2C=CC=CC=2)=NC=1OC1=CC(C#N)=CC=C1OCC1=CC=CC=C1 GKFZMLRATULORQ-UHFFFAOYSA-N 0.000 claims 1
HHZMBDOWMIXEIG-UHFFFAOYSA-N 3-[2-(3-chlorophenyl)-6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-hydroxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C(N)=N)O)C=2)C=2C=C(Cl)C=CC=2)=C1 HHZMBDOWMIXEIG-UHFFFAOYSA-N 0.000 claims 1
VGUXCQQNHSZEOF-UHFFFAOYSA-N 3-[2-(3-chlorophenyl)-6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)C=2)C=2C=C(Cl)C=CC=2)=C1 VGUXCQQNHSZEOF-UHFFFAOYSA-N 0.000 claims 1
VDDNPIWAJYOFBL-UHFFFAOYSA-N 3-[2-(4,5-dihydro-1H-imidazol-2-yl)-6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-hydroxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C(N)=N)O)C=2)C=2NCCN=2)=C1 VDDNPIWAJYOFBL-UHFFFAOYSA-N 0.000 claims 1
YRHVNQHCTOCBAL-UHFFFAOYSA-N 3-[2-(4,5-dihydro-1h-imidazol-2-yl)-6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)C=2)C=2NCCN=2)=C1 YRHVNQHCTOCBAL-UHFFFAOYSA-N 0.000 claims 1
CSTXQEZZLJTXSO-UHFFFAOYSA-N 3-[2-(4-methoxyphenyl)-6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound C1=CC(OC)=CC=C1C1=NC(OC=2C=C(C=CC=2)C=2N(CCN=2)C)=CC(OC=2C(=CC=C(C=2)C#N)OCC=2C=CC=CC=2)=N1 CSTXQEZZLJTXSO-UHFFFAOYSA-N 0.000 claims 1
RWWZFWLBEXDIGX-UHFFFAOYSA-N 3-[2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-6-(4-methylphenyl)pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)N=2)C=2C=CC(C)=CC=2)=C1 RWWZFWLBEXDIGX-UHFFFAOYSA-N 0.000 claims 1
VOCUDJALLSTPQL-UHFFFAOYSA-N 3-[2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-6-(4-phenylmethoxyphenyl)pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)N=2)C=2C=CC(OCC=3C=CC=CC=3)=CC=2)=C1 VOCUDJALLSTPQL-UHFFFAOYSA-N 0.000 claims 1
YQFRCIKONRQZRF-UHFFFAOYSA-N 3-[2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-6-(4-phenylphenyl)pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)N=2)C=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 YQFRCIKONRQZRF-UHFFFAOYSA-N 0.000 claims 1
KTYJIALZSZVMRS-UHFFFAOYSA-N 3-[2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-6-phenylpyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)N=2)C=2C=CC=CC=2)=C1 KTYJIALZSZVMRS-UHFFFAOYSA-N 0.000 claims 1
MASGFUYQRRDHKN-UHFFFAOYSA-N 3-[2-[4-(dimethylamino)phenyl]-6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-hydroxybenzenecarboximidamide Chemical compound C1=CC(N(C)C)=CC=C1C1=NC(OC=2C=C(C=CC=2)C=2N(CCN=2)C)=CC(OC=2C(=CC=C(C=2)C(N)=N)O)=N1 MASGFUYQRRDHKN-UHFFFAOYSA-N 0.000 claims 1
UKWQETMSAVGIKW-UHFFFAOYSA-N 3-[4-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-6-phenylpyrimidin-2-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)N=C(C=2)C=2C=CC=CC=2)=C1 UKWQETMSAVGIKW-UHFFFAOYSA-N 0.000 claims 1
LCHFFTJCFXVNLL-UHFFFAOYSA-N 3-[6-(1-ethylpiperidin-4-yl)-2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-hydroxybenzenecarboximidamide Chemical compound C1CN(CC)CCC1C1=CC(OC=2C(=CC=C(C=2)C(N)=N)O)=NC(OC=2C=C(C=CC=2)C=2N(CCN=2)C)=N1 LCHFFTJCFXVNLL-UHFFFAOYSA-N 0.000 claims 1
DDRGFXBPBMRWRJ-UHFFFAOYSA-N 3-[6-(3-chlorophenyl)-2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-hydroxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C(N)=N)O)N=2)C=2C=C(Cl)C=CC=2)=C1 DDRGFXBPBMRWRJ-UHFFFAOYSA-N 0.000 claims 1
ZOHYJRBGMHKCSZ-UHFFFAOYSA-N 3-[6-(3-chlorophenyl)-2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)N=2)C=2C=C(Cl)C=CC=2)=C1 ZOHYJRBGMHKCSZ-UHFFFAOYSA-N 0.000 claims 1
IKEUOMUHNLZMHI-UHFFFAOYSA-N 3-[6-(4,5-dihydro-1H-imidazol-2-yl)-2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-hydroxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C(N)=N)O)N=2)C=2NCCN=2)=C1 IKEUOMUHNLZMHI-UHFFFAOYSA-N 0.000 claims 1
BXLWPXNZNNCLGW-UHFFFAOYSA-N 3-[6-(4-aminophenyl)-2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-hydroxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C(N)=N)O)N=2)C=2C=CC(N)=CC=2)=C1 BXLWPXNZNNCLGW-UHFFFAOYSA-N 0.000 claims 1
FGPLDRZZDBJYRV-UHFFFAOYSA-N 3-[6-(4-methoxyphenyl)-2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound C1=CC(OC)=CC=C1C1=CC(OC=2C(=CC=C(C=2)C#N)OCC=2C=CC=CC=2)=NC(OC=2C=C(C=CC=2)C=2N(CCN=2)C)=N1 FGPLDRZZDBJYRV-UHFFFAOYSA-N 0.000 claims 1
XRRRRPNFIWOKFM-UHFFFAOYSA-N 3-[6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-2-(4-methylphenyl)pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)C=2)C=2C=CC(C)=CC=2)=C1 XRRRRPNFIWOKFM-UHFFFAOYSA-N 0.000 claims 1
KHEMOHXCAHRYEG-UHFFFAOYSA-N 3-[6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-2-(4-phenylmethoxyphenyl)pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)C=2)C=2C=CC(OCC=3C=CC=CC=3)=CC=2)=C1 KHEMOHXCAHRYEG-UHFFFAOYSA-N 0.000 claims 1
DOIAUALWQUVIRQ-UHFFFAOYSA-N 3-[6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-2-(4-phenylphenyl)pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)C=2)C=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 DOIAUALWQUVIRQ-UHFFFAOYSA-N 0.000 claims 1
XQOZEBHORYCVQM-UHFFFAOYSA-N 3-[6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-2-(piperidin-1-ylmethyl)pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(CN3CCCCC3)N=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)C=2)=C1 XQOZEBHORYCVQM-UHFFFAOYSA-N 0.000 claims 1
MGZHUHNZQOTIKG-UHFFFAOYSA-N 3-[6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-2-pyridin-2-ylpyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C#N)OCC=3C=CC=CC=3)C=2)C=2N=CC=CC=2)=C1 MGZHUHNZQOTIKG-UHFFFAOYSA-N 0.000 claims 1
ZWVMOQBPNNLIHW-UHFFFAOYSA-N 3-[6-[4-(dimethylamino)phenyl]-2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-hydroxybenzenecarboximidamide Chemical compound C1=CC(N(C)C)=CC=C1C1=CC(OC=2C(=CC=C(C=2)C(N)=N)O)=NC(OC=2C=C(C=CC=2)C=2N(CCN=2)C)=N1 ZWVMOQBPNNLIHW-UHFFFAOYSA-N 0.000 claims 1
PJYBUMISXDAPSM-UHFFFAOYSA-N 3-[6-[4-(dimethylamino)phenyl]-2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxy-4-phenylmethoxybenzonitrile Chemical compound C1=CC(N(C)C)=CC=C1C1=CC(OC=2C(=CC=C(C=2)C#N)OCC=2C=CC=CC=2)=NC(OC=2C=C(C=CC=2)C=2N(CCN=2)C)=N1 PJYBUMISXDAPSM-UHFFFAOYSA-N 0.000 claims 1
QNSMOBQYLIFMGD-UHFFFAOYSA-N 4,6-dichloro-2-(1-ethylpiperidin-4-yl)pyrimidine Chemical compound C1CN(CC)CCC1C1=NC(Cl)=CC(Cl)=N1 QNSMOBQYLIFMGD-UHFFFAOYSA-N 0.000 claims 1
CHAVUZHEVBYMBC-UHFFFAOYSA-N 4,6-dichloro-2-(3-chlorophenyl)pyrimidine Chemical compound ClC1=CC=CC(C=2N=C(Cl)C=C(Cl)N=2)=C1 CHAVUZHEVBYMBC-UHFFFAOYSA-N 0.000 claims 1
CTWQZYDKYPMPPM-UHFFFAOYSA-N 4,6-dichloro-2-(4,5-dihydro-1h-imidazol-2-yl)pyrimidine Chemical compound ClC1=CC(Cl)=NC(C=2NCCN=2)=N1 CTWQZYDKYPMPPM-UHFFFAOYSA-N 0.000 claims 1
CHLAKIWCDADMAD-UHFFFAOYSA-N 4,6-dichloro-2-(4-methoxyphenyl)pyrimidine Chemical compound C1=CC(OC)=CC=C1C1=NC(Cl)=CC(Cl)=N1 CHLAKIWCDADMAD-UHFFFAOYSA-N 0.000 claims 1
SPGOAFUOMCIVDB-UHFFFAOYSA-N 4,6-dichloro-2-(4-methylphenyl)pyrimidine Chemical compound C1=CC(C)=CC=C1C1=NC(Cl)=CC(Cl)=N1 SPGOAFUOMCIVDB-UHFFFAOYSA-N 0.000 claims 1
QJYOLAAXYGAUOF-UHFFFAOYSA-N 4,6-dichloro-2-(4-phenylmethoxyphenyl)pyrimidine Chemical compound ClC1=CC(Cl)=NC(C=2C=CC(OCC=3C=CC=CC=3)=CC=2)=N1 QJYOLAAXYGAUOF-UHFFFAOYSA-N 0.000 claims 1
XGLURXDMKXERQK-UHFFFAOYSA-N 4,6-dichloro-2-(4-phenylphenyl)pyrimidine Chemical compound ClC1=CC(Cl)=NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)=N1 XGLURXDMKXERQK-UHFFFAOYSA-N 0.000 claims 1
NBAPGMJZRHWJAA-UHFFFAOYSA-N 4,6-dichloro-2-pyridin-2-ylpyrimidine Chemical compound ClC1=CC(Cl)=NC(C=2N=CC=CC=2)=N1 NBAPGMJZRHWJAA-UHFFFAOYSA-N 0.000 claims 1
NHXDVQFYKDTXSO-UHFFFAOYSA-N 4,6-dichloro-5-methyl-2-piperidin-1-ylpyrimidine Chemical compound N1=C(Cl)C(C)=C(Cl)N=C1N1CCCCC1 NHXDVQFYKDTXSO-UHFFFAOYSA-N 0.000 claims 1
JAGGXQOSAWEEFI-UHFFFAOYSA-N 4-(2,4-dioxo-1h-pyrimidin-6-yl)benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=CC(O)=NC(O)=N1 JAGGXQOSAWEEFI-UHFFFAOYSA-N 0.000 claims 1
GVYSWDKKTHWGTK-UHFFFAOYSA-N 4-(2,6-dichloropyrimidin-4-yl)-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC(Cl)=NC(Cl)=N1 GVYSWDKKTHWGTK-UHFFFAOYSA-N 0.000 claims 1
POCZEOYOGVHKCX-UHFFFAOYSA-N 4-(2,6-dichloropyrimidin-4-yl)benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=CC(Cl)=NC(Cl)=N1 POCZEOYOGVHKCX-UHFFFAOYSA-N 0.000 claims 1
RIOOZRCQPYGYBB-UHFFFAOYSA-N 4-(4,6-dichloropyrimidin-2-yl)-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=NC(Cl)=CC(Cl)=N1 RIOOZRCQPYGYBB-UHFFFAOYSA-N 0.000 claims 1
REOCBOXYPSMJDE-UHFFFAOYSA-N 4-(4,6-dichloropyrimidin-2-yl)benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=NC(Cl)=CC(Cl)=N1 REOCBOXYPSMJDE-UHFFFAOYSA-N 0.000 claims 1
ZOHNSQBIEBIBOV-UHFFFAOYSA-N 4-(4-hydroxy-6-oxo-1h-pyrimidin-2-yl)benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=NC(O)=CC(O)=N1 ZOHNSQBIEBIBOV-UHFFFAOYSA-N 0.000 claims 1
OMQCIMRXTOGWRU-UHFFFAOYSA-N 4-hydroxy-2-(4-methoxyphenyl)-1h-pyrimidin-6-one Chemical compound C1=CC(OC)=CC=C1C1=NC(O)=CC(O)=N1 OMQCIMRXTOGWRU-UHFFFAOYSA-N 0.000 claims 1
ZLZAWYKBEGMPAU-UHFFFAOYSA-N 4-hydroxy-2-(4-methylphenyl)-1h-pyrimidin-6-one Chemical compound C1=CC(C)=CC=C1C1=NC(O)=CC(O)=N1 ZLZAWYKBEGMPAU-UHFFFAOYSA-N 0.000 claims 1
QVFBYDKVZBVENX-UHFFFAOYSA-N 4-hydroxy-2-(4-phenylmethoxyphenyl)-1h-pyrimidin-6-one Chemical compound OC1=CC(O)=NC(C=2C=CC(OCC=3C=CC=CC=3)=CC=2)=N1 QVFBYDKVZBVENX-UHFFFAOYSA-N 0.000 claims 1
KOICYDGKJZTJGD-UHFFFAOYSA-N 4-hydroxy-2-(4-phenylphenyl)-1h-pyrimidin-6-one Chemical compound OC1=CC(O)=NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)=N1 KOICYDGKJZTJGD-UHFFFAOYSA-N 0.000 claims 1
KYJMYKDNPYLJLR-UHFFFAOYSA-N 4-hydroxy-2-pyridin-2-yl-1h-pyrimidin-6-one Chemical compound OC1=CC(=O)NC(C=2N=CC=CC=2)=N1 KYJMYKDNPYLJLR-UHFFFAOYSA-N 0.000 claims 1
IKQBUSNVASDMDQ-UHFFFAOYSA-N 4-hydroxy-3-[2-(4-hydroxyphenyl)-6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C(N)=N)O)C=2)C=2C=CC(O)=CC=2)=C1 IKQBUSNVASDMDQ-UHFFFAOYSA-N 0.000 claims 1
SGRVBACDRQTAGA-UHFFFAOYSA-N 4-hydroxy-3-[2-(4-methoxyphenyl)-6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound C1=CC(OC)=CC=C1C1=NC(OC=2C=C(C=CC=2)C=2N(CCN=2)C)=CC(OC=2C(=CC=C(C=2)C(N)=N)O)=N1 SGRVBACDRQTAGA-UHFFFAOYSA-N 0.000 claims 1
IZBKXXINRDPPRF-UHFFFAOYSA-N 4-hydroxy-3-[2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-6-(4-methylphenyl)pyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C(N)=N)O)N=2)C=2C=CC(C)=CC=2)=C1 IZBKXXINRDPPRF-UHFFFAOYSA-N 0.000 claims 1
LKBGQENITJBCDD-UHFFFAOYSA-N 4-hydroxy-3-[2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-6-(4-phenylphenyl)pyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C(N)=N)O)N=2)C=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 LKBGQENITJBCDD-UHFFFAOYSA-N 0.000 claims 1
SPWZQUUYXGWMNZ-UHFFFAOYSA-N 4-hydroxy-3-[2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-6-(piperidin-1-ylmethyl)pyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(OC=3C(=CC=C(C=3)C(N)=N)O)C=C(CN3CCCCC3)N=2)=C1 SPWZQUUYXGWMNZ-UHFFFAOYSA-N 0.000 claims 1
BIGVQWJNBHKVKS-UHFFFAOYSA-N 4-hydroxy-3-[2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-6-piperidin-4-ylpyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C(N)=N)O)N=2)C2CCNCC2)=C1 BIGVQWJNBHKVKS-UHFFFAOYSA-N 0.000 claims 1
KKMNRWPPWQLHJX-UHFFFAOYSA-N 4-hydroxy-3-[2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-6-pyridin-2-ylpyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C(N)=N)O)N=2)C=2N=CC=CC=2)=C1 KKMNRWPPWQLHJX-UHFFFAOYSA-N 0.000 claims 1
PVIFUWCECRZEPD-UHFFFAOYSA-N 4-hydroxy-3-[2-[3-(methylamino)phenyl]-6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CNC1=CC=CC(C=2N=C(OC=3C(=CC=C(C=3)C(N)=N)O)C=C(OC=3C=C(C=CC=3)C=3N(CCN=3)C)N=2)=C1 PVIFUWCECRZEPD-UHFFFAOYSA-N 0.000 claims 1
TXUWQDJWMHKCLC-UHFFFAOYSA-N 4-hydroxy-3-[4-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-6-phenylpyrimidin-2-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(OC=3C(=CC=C(C=3)C(N)=N)O)N=C(C=2)C=2C=CC=CC=2)=C1 TXUWQDJWMHKCLC-UHFFFAOYSA-N 0.000 claims 1
UVOAVTVJOUQFOX-UHFFFAOYSA-N 4-hydroxy-3-[6-(4-hydroxyphenyl)-2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(C=C(OC=3C(=CC=C(C=3)C(N)=N)O)N=2)C=2C=CC(O)=CC=2)=C1 UVOAVTVJOUQFOX-UHFFFAOYSA-N 0.000 claims 1
WXZFFUKHAISVSP-UHFFFAOYSA-N 4-hydroxy-3-[6-(4-methoxyphenyl)-2-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound C1=CC(OC)=CC=C1C1=CC(OC=2C(=CC=C(C=2)C(N)=N)O)=NC(OC=2C=C(C=CC=2)C=2N(CCN=2)C)=N1 WXZFFUKHAISVSP-UHFFFAOYSA-N 0.000 claims 1
PFDMNOQBBIDBOF-UHFFFAOYSA-N 4-hydroxy-3-[6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-2-(4-methylphenyl)pyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C(N)=N)O)C=2)C=2C=CC(C)=CC=2)=C1 PFDMNOQBBIDBOF-UHFFFAOYSA-N 0.000 claims 1
LDMUSCQOTQDPKE-UHFFFAOYSA-N 4-hydroxy-3-[6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-2-(4-phenylphenyl)pyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C(N)=N)O)C=2)C=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 LDMUSCQOTQDPKE-UHFFFAOYSA-N 0.000 claims 1
GYMAYBJBBKTEOC-UHFFFAOYSA-N 4-hydroxy-3-[6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-2-(piperidin-1-ylmethyl)pyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(CN3CCCCC3)N=C(OC=3C(=CC=C(C=3)C(N)=N)O)C=2)=C1 GYMAYBJBBKTEOC-UHFFFAOYSA-N 0.000 claims 1
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VRGLHUHJRJXAMF-UHFFFAOYSA-N 4-hydroxy-3-[6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]-2-pyridin-2-ylpyrimidin-4-yl]oxybenzenecarboximidamide Chemical compound CN1CCN=C1C1=CC=CC(OC=2N=C(N=C(OC=3C(=CC=C(C=3)C(N)=N)O)C=2)C=2N=CC=CC=2)=C1 VRGLHUHJRJXAMF-UHFFFAOYSA-N 0.000 claims 1
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Classifications

- 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
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Hematology (AREA)
Oncology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Vascular Medicine (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Obesity (AREA)
Urology & Nephrology (AREA)
Communicable Diseases (AREA)
Pulmonology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Separation Of Suspended Particles By Flocculating Agents (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)

LT2001061A 1998-12-04 2001-06-12 Arilo ir heterociklilo pakaitus turintys pirimidino dariniai kaip antikoaguliantai LT4912B (lt)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US09/205,498 US6127376A (en)	1998-12-04	1998-12-04	Aryl and heterocyclyl substituted pyrimidine derivatives as anti-coagulants

Publications (2)

Publication Number	Publication Date
LT2001061A LT2001061A (en)	2001-12-27
LT4912B true LT4912B (lt)	2002-04-25

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Family Applications (1)

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LT2001061A LT4912B (lt)	1998-12-04	2001-06-12	Arilo ir heterociklilo pakaitus turintys pirimidino dariniai kaip antikoaguliantai

Country Status (26)

Country	Link
US (2)	US6127376A (no)
EP (1)	EP1135131A4 (no)
JP (1)	JP2002531506A (no)
KR (1)	KR20010093799A (no)
CN (1)	CN1329491A (no)
AU (1)	AU760370B2 (no)
BG (1)	BG105557A (no)
BR (1)	BR9915938A (no)
CA (1)	CA2354040A1 (no)
CZ (1)	CZ20011932A3 (no)
EE (1)	EE200100298A (no)
HR (1)	HRP20010499A2 (no)
HU (1)	HUP0104508A3 (no)
IL (2)	IL143347A0 (no)
LT (1)	LT4912B (no)
LV (1)	LV12783B (no)
MX (1)	MXPA01005656A (no)
NO (1)	NO20012701L (no)
NZ (1)	NZ512104A (no)
PL (1)	PL348034A1 (no)
RO (1)	RO120971B1 (no)
RU (1)	RU2001118466A (no)
SI (1)	SI20637A (no)
SK (1)	SK7632001A3 (no)
WO (1)	WO2000033844A1 (no)
ZA (1)	ZA200104235B (no)

Families Citing this family (45)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK0813525T3 (da)	1995-03-10	2004-02-16	Berlex Lab	Benzamidinderivater, deres fremstilling og anvendelse som antikoagulanter
US6686364B2 (en)	1997-12-08	2004-02-03	Berlex Laboratories, Inc.	Benzamidine derivatives and their use as anti-coagulants
US6262088B1 (en)	1998-11-19	2001-07-17	Berlex Laboratories, Inc.	Polyhydroxylated monocyclic N-heterocyclic derivatives as anti-coagulants
US6350761B1 (en)	1999-07-30	2002-02-26	Berlex Laboratories, Inc.	Benzenamine derivatives as anti-coagulants
US7122544B2 (en)	2000-12-06	2006-10-17	Signal Pharmaceuticals, Llc	Anilinopyrimidine derivatives as IKK inhibitors and compositions and methods related thereto
US7129242B2 (en)	2000-12-06	2006-10-31	Signal Pharmaceuticals, Llc	Anilinopyrimidine derivatives as JNK pathway inhibitors and compositions and methods related thereto
TWI329105B (en) *	2002-02-01	2010-08-21	Rigel Pharmaceuticals Inc	2,4-pyrimidinediamine compounds and their uses
CA2478338A1 (en)	2002-03-08	2003-09-18	Signal Pharmaceuticals, Inc.	Combination therapy for treating, preventing or managing proliferative disorders and cancers
GB0206215D0 (en)	2002-03-15	2002-05-01	Novartis Ag	Organic compounds
NZ537752A (en)	2002-07-29	2006-12-22	Rigel Pharmaceuticals Inc	Use of 2,4-pyrimidinediamine compounds in the preparation of medicaments for treating autoimmune diseases
EP1546116A1 (en) *	2002-08-08	2005-06-29	Amgen Inc.	Vanilloid receptor ligands and their use in treatments
DK1569912T3 (en)	2002-12-03	2015-06-29	Pharmacyclics Inc	2- (2-hydroxybiphenyl-3-yl) -1h-benzoimidazole-5-carboxamidine derivatives as factor VIIa inhibitors.
JP4886511B2 (ja) *	2003-07-30	2012-02-29	ライジェルファーマシューティカルズ，インコーポレイテッド	２，４−ピリミジンジアミン化合物による自己免疫疾患の治療または予防方法
US8455489B2 (en) *	2003-11-10	2013-06-04	Exelixis, Inc.	Substituted pyrimidine compositions and methods of use
DK1814878T3 (da)	2004-11-24	2012-05-07	Rigel Pharmaceuticals Inc	Spiro-2, 4-pyrimidindiamin-forbindelser og anvendelser deraf
KR101278397B1 (ko)	2005-01-19	2013-06-25	리겔 파마슈티칼스, 인크.	2,4-피리미딘디아민 화합물의 전구약물 및 이의 용도
CA2604551A1 (en) *	2005-05-03	2007-03-08	Rigel Pharmaceuticals, Inc.	Jak kinase inhibitors and their uses
RU2448097C2 (ru) *	2006-07-21	2012-04-20	Новартис Аг	Производные пиримидина и их применение в качестве пестицидов
US8138339B2 (en)	2008-04-16	2012-03-20	Portola Pharmaceuticals, Inc.	Inhibitors of protein kinases
ES2546502T3 (es)	2008-04-16	2015-09-24	Portola Pharmaceuticals, Inc.	2,6-Diamino-pirimidin-5-il-carboxamidas como inhibidores de syk o JAK quinasas
US9273077B2 (en)	2008-05-21	2016-03-01	Ariad Pharmaceuticals, Inc.	Phosphorus derivatives as kinase inhibitors
EA029131B1 (ru)	2008-05-21	2018-02-28	Ариад Фармасьютикалз, Инк.	Фосфорсодержащие производные в качестве ингибиторов киназы
US11351168B1 (en)	2008-06-27	2022-06-07	Celgene Car Llc	2,4-disubstituted pyrimidines useful as kinase inhibitors
US8338439B2 (en) *	2008-06-27	2012-12-25	Celgene Avilomics Research, Inc.	2,4-disubstituted pyrimidines useful as kinase inhibitors
DK2361248T3 (en)	2008-06-27	2019-01-14	Celgene Car Llc	Heteroberl compounds and uses thereof
WO2010093787A2 (en) *	2009-02-11	2010-08-19	Northwestern University	Aminopyridine dimer compounds, compositions and related methods for neuronal nitric oxide synthase inhibition
US8932842B2 (en)	2009-02-11	2015-01-13	Northwestern University	Aminopyridine dimer compounds, compositions and related methods for neuronal nitric oxide synthase inhibition
EP2440559B1 (en)	2009-05-05	2018-01-10	Dana-Farber Cancer Institute, Inc.	Egfr inhibitors and methods of treating disorders
KR20130099040A (ko)	2010-08-10	2013-09-05	셀진 아빌로믹스 리서치, 인코포레이티드	Ｂｔｋ 억제제의 베실레이트 염
EP2635285B1 (en)	2010-11-01	2017-05-03	Celgene Avilomics Research, Inc.	Heteroaryl compounds and uses thereof
JP5957460B2 (ja)	2010-11-01	2016-07-27	セルジーンアヴィロミクスリサーチ，インコーポレイテッド	複素環式化合物またはその使用
JP5957003B2 (ja)	2010-11-10	2016-07-27	セルジーンアヴィロミクスリサーチ，インコーポレイテッド	変異体選択的ｅｇｆｒ阻害剤およびその使用
CA2832504C (en)	2011-05-04	2019-10-01	Ariad Pharmaceuticals, Inc.	Compounds for inhibiting cell proliferation in egfr-driven cancers
AR088570A1 (es)	2011-10-28	2014-06-18	Celgene Avilomics Res Inc	Metodos para tratar una enfermedad o trastorno relacionado con la tirosina quinasa de bruton
CA2856301C (en)	2011-11-23	2020-10-06	Portola Pharmaceuticals, Inc.	Pyrazine kinase inhibitors
US9056839B2 (en)	2012-03-15	2015-06-16	Celgene Avilomics Research, Inc.	Solid forms of an epidermal growth factor receptor kinase inhibitor
DK2825042T3 (en)	2012-03-15	2018-11-26	Celgene Car Llc	SALTS OF THE CHINASE INHIBITOR OF THE EPIDERMAL GROWTH FACTOR RECEPTOR
AU2013204563B2 (en)	2012-05-05	2016-05-19	Takeda Pharmaceutical Company Limited	Compounds for inhibiting cell proliferation in EGFR-driven cancers
US9126950B2 (en)	2012-12-21	2015-09-08	Celgene Avilomics Research, Inc.	Heteroaryl compounds and uses thereof
MX2015009952A (es)	2013-02-08	2015-10-05	Celgene Avilomics Res Inc	Inhibidores de cinasas reguladas por señales extracelulares (erk) y sus usos.
US9611283B1 (en)	2013-04-10	2017-04-04	Ariad Pharmaceuticals, Inc.	Methods for inhibiting cell proliferation in ALK-driven cancers
US9492471B2 (en)	2013-08-27	2016-11-15	Celgene Avilomics Research, Inc.	Methods of treating a disease or disorder associated with Bruton'S Tyrosine Kinase
US9415049B2 (en)	2013-12-20	2016-08-16	Celgene Avilomics Research, Inc.	Heteroaryl compounds and uses thereof
EP3179858B1 (en)	2014-08-13	2019-05-15	Celgene Car Llc	Forms and compositions of an erk inhibitor
CN109897005B (zh) *	2019-04-12	2022-07-22	湖南省农业生物技术研究所	含取代苯氧基的苯基嘧啶类似物及其制备方法和应用

Citations (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0540051A1 (en)	1991-10-31	1993-05-05	Daiichi Pharmaceutical Co., Ltd.	Aromatic amidine derivatives and salts thereof
US5451700A (en)	1991-06-11	1995-09-19	Ciba-Geigy Corporation	Amidino compounds, their manufacture and methods of treatment
WO1996028427A1 (en)	1995-03-10	1996-09-19	Berlex Laboratories, Inc.	Benzamidine derivatives their preparation and their use as anti-coagulants
US5612363A (en)	1995-06-02	1997-03-18	Berlex Laboratories, Inc.	N,N-di(aryl) cyclic urea derivatives as anti-coagulants
US5633381A (en)	1994-07-05	1997-05-27	Berlex Laboratories, Inc.	(Z,Z), (Z,E) and (E,Z) isomers of substituted bis(phenylmethylene)cycloketones
WO1997021437A1 (en)	1995-12-08	1997-06-19	Berlex Laboratories, Inc.	Naphthyl-substituted benzimidazole derivatives as anticoagulants
WO1997029067A1 (en)	1996-02-12	1997-08-14	Berlex Laboratories, Inc.	Benzamidine derivatives substituted by amino acid and hydroxy acid derivatives and their use as anti-coagulants

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB824908A (en) *	1958-06-03	1959-12-09	May & Baker Ltd	Improvements in or relating to triazine derivatives
JPS5922697B2 (ja) *	1976-01-13	1984-05-28	エーザイ株式会社	ビス−（メタ−アミジノフエノキシ）−化合物
EP0518818A3 (en) *	1991-06-11	1993-04-28	Ciba-Geigy Ag	Arylethers, their manufacture and use as medicament
EP0627929B1 (en) *	1992-02-14	1998-09-30	Corvas International, Inc.	Inhibitors of thrombosis
DE4213919A1 (de) *	1992-04-28	1993-11-04	Thomae Gmbh Dr K	Cyclische iminoderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
IL106324A (en) *	1992-07-17	1998-09-24	Shell Int Research	Transformed pyrimidine compounds, their preparation and use as pesticides
AU675981B2 (en) *	1992-12-02	1997-02-27	Bristol-Myers Squibb Company	Guanidinyl-substituted heterocyclic thrombin inhibitors
ATE177752T1 (de) *	1992-12-15	1999-04-15	Corvas Int Inc	Neue inhibitoren von faktor xa
US5332822A (en) *	1992-12-24	1994-07-26	Bristol-Myers Squibb Company	Heteroaromatic and thioheteroaromatic substituted sulfonamide thrombin inhibitors
DE69419141D1 (de) *	1993-02-12	1999-07-22	Corvas Int Inc	Inhibitoren gegen thrombose
IL115420A0 (en) *	1994-09-26	1995-12-31	Zeneca Ltd	Aminoheterocyclic derivatives
US5691364A (en) *	1995-03-10	1997-11-25	Berlex Laboratories, Inc.	Benzamidine derivatives and their use as anti-coagulants
US5693641A (en) *	1996-08-16	1997-12-02	Berlex Laboratories Inc.	Bicyclic pyrimidine derivatives and their use as anti-coagulants
US5753635A (en) *	1996-08-16	1998-05-19	Berlex Laboratories, Inc.	Purine derivatives and their use as anti-coagulants
NZ334264A (en) *	1996-09-12	2000-08-25	Schering Ag	Benzamidine derivatives substituted by cyclic amino acid or cyclic hydroxy acid derivatives and their use as anti-coagulants
US6008234A (en)	1996-09-12	1999-12-28	Berlex Laboratories, Inc.	Benzamidine derivatives substituted by cyclic amino acid and cyclic hydroxy acid derivatives and their use as anti-coagulants
US6004985A (en) *	1996-10-09	1999-12-21	Berlex Laboratories, Inc.	Thio acid derived monocylic N-heterocyclics as anticoagulants
CA2293824A1 (en) *	1997-06-19	1998-12-23	Mimi Lifen Quan	(amidino)6-membered aromatics as factor xa inhibitors
IL135536A0 (en)	1997-12-19	2001-05-20	Schering Ag	Ortho-anthranilamide derivatives and pharmaceutical compositions containing the same

1998
- 1998-12-04 US US09/205,498 patent/US6127376A/en not_active Expired - Fee Related
1999
- 1999-12-03 CZ CZ20011932A patent/CZ20011932A3/cs unknown
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- 1999-12-03 PL PL99348034A patent/PL348034A1/xx not_active Application Discontinuation
- 1999-12-03 WO PCT/US1999/028537 patent/WO2000033844A1/en not_active Ceased
- 1999-12-03 SK SK763-2001A patent/SK7632001A3/sk unknown
- 1999-12-03 CA CA002354040A patent/CA2354040A1/en not_active Abandoned
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- 2000-03-30 US US09/539,812 patent/US6372751B1/en not_active Expired - Fee Related
2001
- 2001-05-23 ZA ZA200104235A patent/ZA200104235B/en unknown
- 2001-05-24 IL IL143347A patent/IL143347A/en not_active IP Right Cessation
- 2001-06-01 NO NO20012701A patent/NO20012701L/no not_active Application Discontinuation
- 2001-06-01 BG BG105557A patent/BG105557A/xx unknown
- 2001-06-12 LT LT2001061A patent/LT4912B/lt not_active IP Right Cessation
- 2001-07-04 LV LVP-01-100A patent/LV12783B/xx unknown

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5451700A (en)	1991-06-11	1995-09-19	Ciba-Geigy Corporation	Amidino compounds, their manufacture and methods of treatment
EP0540051A1 (en)	1991-10-31	1993-05-05	Daiichi Pharmaceutical Co., Ltd.	Aromatic amidine derivatives and salts thereof
US5633381A (en)	1994-07-05	1997-05-27	Berlex Laboratories, Inc.	(Z,Z), (Z,E) and (E,Z) isomers of substituted bis(phenylmethylene)cycloketones
WO1996028427A1 (en)	1995-03-10	1996-09-19	Berlex Laboratories, Inc.	Benzamidine derivatives their preparation and their use as anti-coagulants
US5612363A (en)	1995-06-02	1997-03-18	Berlex Laboratories, Inc.	N,N-di(aryl) cyclic urea derivatives as anti-coagulants
WO1997021437A1 (en)	1995-12-08	1997-06-19	Berlex Laboratories, Inc.	Naphthyl-substituted benzimidazole derivatives as anticoagulants
WO1997029067A1 (en)	1996-02-12	1997-08-14	Berlex Laboratories, Inc.	Benzamidine derivatives substituted by amino acid and hydroxy acid derivatives and their use as anti-coagulants

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
D. BAGDY ET AL.: "Comparative studies in vitro and ex vivo on the anticoagulant effect of a reversible and an irreversible tripeptide inhibitor of thrombin", THROMBOSIS RESEARCH, 1992, pages 221 - 231, XP026465287, DOI: doi:10.1016/0049-3848(92)90141-V
E. W. DAVIE ET AL.: "The coagulation cascade: initiation, maintenance, and regulation", BIOCHEMISTRY, 1991, pages 10363 - 10370, XP000230645, DOI: doi:10.1021/bi00107a001
L WAXMAN ET AL.: "Tick anticoagulant peptide (TAP) is a novel inhibitor of blood coagulation factor Xa", SCIENCE, 1990, pages 593 - 596, XP002202494, DOI: doi:10.1126/science.2333510
RYOJI KIKUMOTO ET AL.: "Selective inhibition of thrombin by (2R,4R)-4-methyl-1-[N2-[1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl]-L-arginyl]-2-piperidinecarboxylic acid", BIOCHEMISTRY, 1984, pages 85 - 90, XP002049060, DOI: doi:10.1021/bi00296a014

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HUP0104508A2 (hu)	2002-05-29
MXPA01005656A (es)	2002-04-24
RU2001118466A (ru)	2003-04-20
WO2000033844A1 (en)	2000-06-15
NO20012701D0 (no)	2001-06-01
LT2001061A (en)	2001-12-27
HUP0104508A3 (en)	2002-07-29
IL143347A0 (en)	2002-04-21
AU3107500A (en)	2000-06-26
ZA200104235B (en)	2002-08-23
NO20012701L (no)	2001-07-25
CN1329491A (zh)	2002-01-02
US6372751B1 (en)	2002-04-16
JP2002531506A (ja)	2002-09-24
EP1135131A4 (en)	2002-01-02
LV12783B (en)	2002-10-20
KR20010093799A (ko)	2001-10-29
EE200100298A (et)	2002-12-16
SK7632001A3 (en)	2001-12-03
RO120971B1 (ro)	2006-10-30
PL348034A1 (en)	2002-05-06
BG105557A (en)	2001-12-29
AU760370B2 (en)	2003-05-15
NZ512104A (en)	2003-10-31
SI20637A (sl)	2002-02-28
HRP20010499A2 (en)	2003-04-30
CA2354040A1 (en)	2000-06-15
CZ20011932A3 (cs)	2001-10-17
LV12783A (en)	2002-01-20
IL143347A (en)	2006-12-10
EP1135131A1 (en)	2001-09-26
US6127376A (en)	2000-10-03
BR9915938A (pt)	2001-08-21

Publication	Publication Date	Title
LT4912B (lt)	2002-04-25	Arilo ir heterociklilo pakaitus turintys pirimidino dariniai kaip antikoaguliantai
EP0922045B1 (en)	2003-04-16	Bicyclic pyrimidine derivatives and their use as anti-coagulants
EP0929547B1 (en)	2002-11-27	Benzamidine derivatives substituted by cyclic amino acid or cycl ic hydroxy acid derivatives and their use as anti-coagulants
US6686367B2 (en)	2004-02-03	Polyhydroxylated monocyclic N-heterocyclic derivatives as anti-coagulants
US20100144771A1 (en)	2010-06-10	Novel Hydantoin Derivatives for the Treatment of Obstructive Airway Diseases
HUP9902308A2 (en)	2000-07-28	Anti-coagulant purine derivatives, medicaments containing them and method for producing them
LT4972B (lt)	2002-11-25	Benzenamine derivatives as anti-coagulants

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