IL155202A - Baryl compounds as serine protease inhibitors - Google Patents
Baryl compounds as serine protease inhibitorsInfo
- Publication number
- IL155202A IL155202A IL155202A IL15520203A IL155202A IL 155202 A IL155202 A IL 155202A IL 155202 A IL155202 A IL 155202A IL 15520203 A IL15520203 A IL 15520203A IL 155202 A IL155202 A IL 155202A
- Authority
- IL
- Israel
- Prior art keywords
- mmol
- reaction mixture
- group
- alkyl
- vacuo
- Prior art date
Links
- -1 Biaryl compounds Chemical class 0.000 title claims abstract description 104
- 239000003001 serine protease inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 86
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
- 150000003839 salts Chemical class 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 1
- 108090000190 Thrombin Proteins 0.000 abstract description 16
- 229960004072 thrombin Drugs 0.000 abstract description 16
- 108090000631 Trypsin Proteins 0.000 abstract description 9
- 102000004142 Trypsin Human genes 0.000 abstract description 9
- 239000012588 trypsin Substances 0.000 abstract description 9
- 108010074860 Factor Xa Proteins 0.000 abstract description 8
- 239000003146 anticoagulant agent Substances 0.000 abstract description 8
- 239000003112 inhibitor Substances 0.000 abstract description 5
- 206010053567 Coagulopathies Diseases 0.000 abstract description 3
- 108010036927 trypsin-like serine protease Proteins 0.000 abstract description 3
- 108010054265 Factor VIIa Proteins 0.000 abstract 1
- 229940012414 factor viia Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 121
- 239000011541 reaction mixture Substances 0.000 description 110
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
- 239000000243 solution Substances 0.000 description 74
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- 238000006243 chemical reaction Methods 0.000 description 64
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 61
- 239000012044 organic layer Substances 0.000 description 59
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 54
- 239000000203 mixture Substances 0.000 description 54
- 238000003818 flash chromatography Methods 0.000 description 48
- 239000000047 product Substances 0.000 description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 41
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- 239000012267 brine Substances 0.000 description 37
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
- 239000007787 solid Substances 0.000 description 36
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 34
- 229920006395 saturated elastomer Polymers 0.000 description 34
- 239000002253 acid Substances 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- 150000001299 aldehydes Chemical class 0.000 description 27
- 150000001412 amines Chemical class 0.000 description 27
- 238000002425 crystallisation Methods 0.000 description 25
- 230000008025 crystallization Effects 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- 125000003118 aryl group Chemical group 0.000 description 22
- 239000010410 layer Substances 0.000 description 22
- 125000004122 cyclic group Chemical group 0.000 description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- 125000005842 heteroatom Chemical group 0.000 description 19
- 238000000746 purification Methods 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 235000019441 ethanol Nutrition 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 125000004429 atom Chemical group 0.000 description 16
- 238000001914 filtration Methods 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- 108010000499 Thromboplastin Proteins 0.000 description 15
- 102000002262 Thromboplastin Human genes 0.000 description 15
- 150000002148 esters Chemical class 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- 150000001408 amides Chemical class 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 238000004440 column chromatography Methods 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- 125000000623 heterocyclic group Chemical group 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 125000002619 bicyclic group Chemical group 0.000 description 12
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 12
- 230000015271 coagulation Effects 0.000 description 12
- 238000005345 coagulation Methods 0.000 description 12
- 230000008878 coupling Effects 0.000 description 12
- 238000010168 coupling process Methods 0.000 description 12
- 238000005859 coupling reaction Methods 0.000 description 12
- 102000012479 Serine Proteases Human genes 0.000 description 11
- 108010022999 Serine Proteases Proteins 0.000 description 11
- 125000002877 alkyl aryl group Chemical group 0.000 description 11
- 150000001409 amidines Chemical class 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 125000003710 aryl alkyl group Chemical group 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 125000003342 alkenyl group Chemical group 0.000 description 9
- 125000000753 cycloalkyl group Chemical group 0.000 description 9
- 239000000651 prodrug Substances 0.000 description 9
- 229940002612 prodrug Drugs 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- 101100097467 Arabidopsis thaliana SYD gene Proteins 0.000 description 8
- 101100495925 Schizosaccharomyces pombe (strain 972 / ATCC 24843) chr3 gene Proteins 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 239000012300 argon atmosphere Substances 0.000 description 8
- 230000023555 blood coagulation Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 230000037361 pathway Effects 0.000 description 8
- 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 description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 150000002009 diols Chemical class 0.000 description 7
- 229960002897 heparin Drugs 0.000 description 7
- 229920000669 heparin Polymers 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 125000000547 substituted alkyl group Chemical group 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
- 208000032843 Hemorrhage Diseases 0.000 description 6
- 208000007536 Thrombosis Diseases 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 125000005002 aryl methyl group Chemical group 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 6
- 230000006624 extrinsic pathway Effects 0.000 description 6
- 125000001475 halogen functional group Chemical group 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 6
- 150000002825 nitriles Chemical class 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 125000003107 substituted aryl group Chemical group 0.000 description 6
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
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- 229910052717 sulfur Inorganic materials 0.000 description 5
- 229920002554 vinyl polymer Polymers 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
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- 108010073385 Fibrin Proteins 0.000 description 4
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- 102000008946 Fibrinogen Human genes 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
- 102000035195 Peptidases Human genes 0.000 description 4
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- 229910020008 S(O) Inorganic materials 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
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- 125000003282 alkyl amino group Chemical group 0.000 description 4
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- 150000001499 aryl bromides Chemical class 0.000 description 4
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- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
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- 229910052760 oxygen Inorganic materials 0.000 description 4
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
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- 238000006911 enzymatic reaction Methods 0.000 description 3
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- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 description 3
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- 229910000489 osmium tetroxide Inorganic materials 0.000 description 3
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- 239000012279 sodium borohydride Substances 0.000 description 3
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- 230000001225 therapeutic effect Effects 0.000 description 3
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- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
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- WCNFFKHKJLERFM-UHFFFAOYSA-N thiomorpholinyl sulfone group Chemical group N1(CCSCC1)S(=O)(=O)N1CCSCC1 WCNFFKHKJLERFM-UHFFFAOYSA-N 0.000 description 1
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- WMSCYGTVHFMKNS-UHFFFAOYSA-N tributyl(methyl)stannane Chemical class CCCC[Sn](C)(CCCC)CCCC WMSCYGTVHFMKNS-UHFFFAOYSA-N 0.000 description 1
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- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
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- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
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- A61K31/19—Carboxylic acids, e.g. valproic acid
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/38—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to acyclic carbon atoms and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/53—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
- C07C233/54—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/84—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/57—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/12—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines
- C07C259/18—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines having carbon atoms of hydroxamidine groups bound to carbon atoms of six-membered aromatic rings
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- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/12—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines
- C07C259/20—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines with at least one nitrogen atom of hydroxamidine groups bound to another nitrogen atom
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- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/62—Compounds containing any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylcarbamates
- C07C271/64—Y being a hydrogen or a carbon atom, e.g. benzoylcarbamates
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
- C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
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- C07D—HETEROCYCLIC COMPOUNDS
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- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Furan Compounds (AREA)
- Pyridine Compounds (AREA)
- Pyrane Compounds (AREA)
- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Applications Claiming Priority (2)
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US28173501P | 2001-04-06 | 2001-04-06 | |
PCT/US2001/032582 WO2002034711A1 (en) | 2000-10-20 | 2001-10-22 | Biaryl compounds as serine protease inhibitors |
Publications (1)
Publication Number | Publication Date |
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IL155202A true IL155202A (en) | 2013-05-30 |
Family
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Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
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IL155202A IL155202A (en) | 2001-04-06 | 2003-04-02 | Baryl compounds as serine protease inhibitors |
IL222773A IL222773B (en) | 2001-04-06 | 2012-10-30 | Biaryl compounds, pharmaceutical preparations containing them, use of such compounds for the manufacture of drugs and in vitro methods and devices using such compounds |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
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IL222773A IL222773B (en) | 2001-04-06 | 2012-10-30 | Biaryl compounds, pharmaceutical preparations containing them, use of such compounds for the manufacture of drugs and in vitro methods and devices using such compounds |
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US (2) | US6699994B1 (de) |
EP (1) | EP1383731B1 (de) |
JP (1) | JP4342178B2 (de) |
AT (1) | ATE438615T1 (de) |
CY (1) | CY1110527T1 (de) |
DE (1) | DE60139510D1 (de) |
ES (1) | ES2332090T3 (de) |
IL (2) | IL155202A (de) |
PT (1) | PT1383731E (de) |
RU (1) | RU2003132706A (de) |
Families Citing this family (45)
Publication number | Priority date | Publication date | Assignee | Title |
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ATE438615T1 (de) * | 2001-04-06 | 2009-08-15 | Biocryst Pharm Inc | Biarylverbindungen als serinproteaseinhibitoren |
GB0124939D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124934D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124931D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124933D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124938D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124936D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
GB0124941D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
NZ533865A (en) * | 2002-02-12 | 2006-02-24 | Smithkline Beecham Corp | Nicotinamide derivates useful as p38 inhibitors |
GB0217757D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Novel compounds |
EP1594845A4 (de) * | 2003-02-11 | 2008-05-21 | Bristol Myers Squibb Co | Als serinproteaseinhibitoren geeignete benzolacetamidverbindungen |
WO2004072101A2 (en) * | 2003-02-11 | 2004-08-26 | Bristol-Myers Squibb Company | Phenylglycine derivatives useful as serine protease inhibitors |
GB0308185D0 (en) * | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
US7273886B2 (en) * | 2003-05-20 | 2007-09-25 | Genentech, Inc. | Benzofuran inhibitors of factor VIIa |
EP1628954A2 (de) * | 2003-05-20 | 2006-03-01 | Genentech, Inc. | Acylsulfamidinhibitoren von faktor viia |
GB0402143D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
US20080051416A1 (en) * | 2004-10-05 | 2008-02-28 | Smithkline Beecham Corporation | Novel Compounds |
PE20061117A1 (es) * | 2005-01-10 | 2006-10-13 | Bristol Myers Squibb Co | DERIVADOS DE FENILGLICINAMIDA COMO INHIBIDORES DEL FACTOR VIIa |
AU2006214247C1 (en) | 2005-02-16 | 2012-11-08 | Anacor Pharmaceuticals, Llc | Boron-containing small molecules |
DE602006015431D1 (de) * | 2005-02-16 | 2010-08-26 | Astrazeneca Ab | Chemische verbindungen |
US20060257337A1 (en) * | 2005-04-28 | 2006-11-16 | David Sherris | Compositions and methods to treat skin diseases characterized by cellular proliferation and angiogenesis |
USRE46558E1 (en) | 2005-04-28 | 2017-09-26 | Paloma Pharmaceuticals, Inc. | Compositions and methods to treat diseases characterized by cellular proliferation and angiogenesis |
GB0512429D0 (en) * | 2005-06-17 | 2005-07-27 | Smithkline Beecham Corp | Novel compound |
WO2007002313A2 (en) * | 2005-06-24 | 2007-01-04 | Bristol-Myers Squibb Company | Phenylglycinamide and pyridylglycinamide derivatives useful as anticoagulants |
WO2007072041A1 (en) * | 2005-12-23 | 2007-06-28 | Astex Therapeutics Limited | Therapeutic compounds |
EP1976536A4 (de) | 2005-12-30 | 2011-03-02 | Anacor Pharmaceuticals Inc | Borhaltige kleine moleküle |
MX335993B (es) * | 2005-12-30 | 2016-01-07 | Anacor Pharmaceuticals Inc | Moleculas pequeñas que contienen boro. |
JP2009528273A (ja) * | 2006-01-25 | 2009-08-06 | シンタ ファーマシューティカルズ コーポレーション | 炎症および免疫関連使用用の置換ビアリール化合物 |
BRPI0708318A2 (pt) * | 2006-02-28 | 2011-05-24 | Paloma Pharmaceuticals Inc | composições e uso de compostos para tratar doenças caracterizadas por proliferação celular e angiogênese |
US8084614B2 (en) | 2007-04-06 | 2011-12-27 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
AR065947A1 (es) | 2007-04-06 | 2009-07-15 | Neurocrine Biosciences Inc | Antagonistas de los receptores de la hormona liberadora de gonadodropina (gnrh) |
MX2010010431A (es) * | 2008-03-25 | 2010-11-25 | Paloma Pharmaceuticals Inc | Metodos para tratar desordenes fibroticos. |
US9221765B2 (en) * | 2009-06-10 | 2015-12-29 | North Carolina State University | Inhibition and dispersion of bacterial biofilms with benzimidazole derivatives |
WO2012112791A1 (en) | 2011-02-16 | 2012-08-23 | Paloma Pharmaceuticals, Inc. | Radiation countermeasure agents |
US8980823B2 (en) | 2012-03-07 | 2015-03-17 | Shaker A. Mousa | Formulations of Factor VIIa inhibitors and utility |
EP3016646A4 (de) * | 2013-07-05 | 2017-03-01 | Shaker A. Mousa | Neuartige formulierungen von faktor-viia-hemmern und verwendung davon |
CA2959026C (en) * | 2014-08-22 | 2023-10-24 | Biocryst Pharmaceuticals, Inc. | Compositions and uses of amidine derivatives |
WO2016029216A2 (en) | 2014-08-22 | 2016-02-25 | Biocryst Pharmaceuticals, Inc. | Method for producing amidine derivatives |
WO2017035263A1 (en) * | 2015-08-24 | 2017-03-02 | Biocryst Pharmaceuticals, Inc. | Compositions comprising a plasma kallikrein inhibitor |
US11447506B2 (en) | 2016-05-09 | 2022-09-20 | Anacor Pharmaceuticals, Inc. | Crystal forms of crisaborole in free form and preparation method and use thereof |
ES2942285T3 (es) * | 2016-10-31 | 2023-05-31 | Biocryst Pharm Inc | Profármacos de inhibidores de la calicreína |
UY37806A (es) | 2017-07-11 | 2020-01-31 | Vertex Pharma | Carboxamidas como moduladores de los canales de sodio |
US20200115389A1 (en) | 2018-09-18 | 2020-04-16 | Nikang Therapeutics, Inc. | Fused tricyclic ring derivatives as src homology-2 phosphatase inhibitors |
TWI794742B (zh) | 2020-02-18 | 2023-03-01 | 美商基利科學股份有限公司 | 抗病毒化合物 |
US11697666B2 (en) | 2021-04-16 | 2023-07-11 | Gilead Sciences, Inc. | Methods of preparing carbanucleosides using amides |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0919840B1 (de) * | 1997-02-14 | 2008-04-23 | Nippon Telegraph and Telephone Corporation | Optischer wellenleiterschaltkreis und ein diesen enthaltendes optisches wellenleitermodul |
FR2770307B1 (fr) * | 1997-10-27 | 1999-11-26 | Commissariat Energie Atomique | Dispositif a reseau de phase ou phasar et procede de fabrication de celui-ci |
US5905824A (en) * | 1997-12-09 | 1999-05-18 | Delisle; Vincent | Temperature compensated insensitive optical multiplexor/demultiplexor |
KR20010082515A (ko) * | 1998-02-17 | 2001-08-30 | 우에노 도시오 | 아미디노 유도체 및 그 유도체를 유효 성분으로서함유하는 약제 |
JP3434489B2 (ja) * | 1999-09-24 | 2003-08-11 | 古河電気工業株式会社 | アレイ導波路型回折格子 |
ATE438615T1 (de) * | 2001-04-06 | 2009-08-15 | Biocryst Pharm Inc | Biarylverbindungen als serinproteaseinhibitoren |
-
2001
- 2001-10-22 AT AT01981772T patent/ATE438615T1/de active
- 2001-10-22 EP EP01981772A patent/EP1383731B1/de not_active Expired - Lifetime
- 2001-10-22 PT PT01981772T patent/PT1383731E/pt unknown
- 2001-10-22 ES ES01981772T patent/ES2332090T3/es not_active Expired - Lifetime
- 2001-10-22 JP JP2002537705A patent/JP4342178B2/ja not_active Expired - Lifetime
- 2001-10-22 RU RU2003132706/04A patent/RU2003132706A/ru unknown
- 2001-10-22 DE DE60139510T patent/DE60139510D1/de not_active Expired - Lifetime
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2002
- 2002-04-23 US US10/127,460 patent/US6699994B1/en not_active Expired - Lifetime
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2003
- 2003-04-02 IL IL155202A patent/IL155202A/en active IP Right Grant
- 2003-12-18 US US10/738,027 patent/US6936719B2/en not_active Expired - Lifetime
-
2009
- 2009-11-04 CY CY20091101140T patent/CY1110527T1/el unknown
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- 2012-10-30 IL IL222773A patent/IL222773B/en active IP Right Grant
Also Published As
Publication number | Publication date |
---|---|
US6936719B2 (en) | 2005-08-30 |
JP2004523481A (ja) | 2004-08-05 |
EP1383731A4 (de) | 2005-09-28 |
RU2003132706A (ru) | 2005-04-20 |
CY1110527T1 (el) | 2015-04-29 |
DE60139510D1 (de) | 2009-09-17 |
JP4342178B2 (ja) | 2009-10-14 |
US20040162281A1 (en) | 2004-08-19 |
US6699994B1 (en) | 2004-03-02 |
IL222773B (en) | 2018-02-28 |
IL222773A0 (en) | 2012-12-31 |
PT1383731E (pt) | 2009-11-03 |
EP1383731B1 (de) | 2009-08-05 |
ATE438615T1 (de) | 2009-08-15 |
EP1383731A1 (de) | 2004-01-28 |
ES2332090T3 (es) | 2010-01-26 |
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