DE3617976C2 - - Google Patents
Info
- Publication number
- DE3617976C2 DE3617976C2 DE3617976A DE3617976A DE3617976C2 DE 3617976 C2 DE3617976 C2 DE 3617976C2 DE 3617976 A DE3617976 A DE 3617976A DE 3617976 A DE3617976 A DE 3617976A DE 3617976 C2 DE3617976 C2 DE 3617976C2
- Authority
- DE
- Germany
- Prior art keywords
- compound
- formula
- defined above
- methyl
- ethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 claims description 56
- 230000000694 effects Effects 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 229960000581 salicylamide Drugs 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 229920006395 saturated elastomer Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 230000002792 vascular Effects 0.000 claims description 2
- 229940127217 antithrombotic drug Drugs 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 238000007395 thrombosis prophylaxis Methods 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 210000001772 blood platelet Anatomy 0.000 description 17
- 239000000126 substance Substances 0.000 description 17
- 229940125904 compound 1 Drugs 0.000 description 14
- 230000002776 aggregation Effects 0.000 description 13
- 238000004220 aggregation Methods 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- 238000002329 infrared spectrum Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 208000007536 Thrombosis Diseases 0.000 description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 229940126062 Compound A Drugs 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 5
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 102000008186 Collagen Human genes 0.000 description 4
- 108010035532 Collagen Proteins 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 229920001436 collagen Polymers 0.000 description 4
- -1 cyclic alkyl radical Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 208000009144 Pure autonomic failure Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 210000000709 aorta Anatomy 0.000 description 3
- DMSMPAJRVJJAGA-UHFFFAOYSA-N benzo[d]isothiazol-3-one Chemical compound C1=CC=C2C(=O)NSC2=C1 DMSMPAJRVJJAGA-UHFFFAOYSA-N 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 0.000 description 3
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 3
- 229960001597 nifedipine Drugs 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 2
- 229930182837 (R)-adrenaline Natural products 0.000 description 2
- 206010003178 Arterial thrombosis Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 208000005189 Embolism Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 238000004617 QSAR study Methods 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 238000009739 binding Methods 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 210000003298 dental enamel Anatomy 0.000 description 2
- WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 229960005139 epinephrine Drugs 0.000 description 2
- YPMPTULBFPFSEQ-PLNGDYQASA-N ethyl (z)-3-aminobut-2-enoate Chemical compound CCOC(=O)\C=C(\C)N YPMPTULBFPFSEQ-PLNGDYQASA-N 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000009931 harmful effect Effects 0.000 description 2
- 231100000086 high toxicity Toxicity 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000000297 inotrophic effect Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 230000010118 platelet activation Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000036387 respiratory rate Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- CHHASAIQKXOAOX-UHFFFAOYSA-N 1-(2,2-dimethylpropoxy)-2,2-dimethylpropane Chemical compound CC(C)(C)COCC(C)(C)C CHHASAIQKXOAOX-UHFFFAOYSA-N 0.000 description 1
- CJWAPCSQEWUZAE-UHFFFAOYSA-N 2-(2-hydroxyethyl)-1,1-dioxo-1,2-benzothiazol-3-one Chemical compound C1=CC=C2S(=O)(=O)N(CCO)C(=O)C2=C1 CJWAPCSQEWUZAE-UHFFFAOYSA-N 0.000 description 1
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- CDVAIHNNWWJFJW-UHFFFAOYSA-N 3,5-diethoxycarbonyl-1,4-dihydrocollidine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C CDVAIHNNWWJFJW-UHFFFAOYSA-N 0.000 description 1
- BEONNPCLUJPLLU-UHFFFAOYSA-N 5-ethoxycarbonyl-2,4,6-trimethyl-1,4-dihydropyridine-3-carboxylic acid Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C BEONNPCLUJPLLU-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 101100296182 Caenorhabditis elegans paf-2 gene Proteins 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 108010003541 Platelet Activating Factor Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- WRYNUJYAXVDTCB-UHFFFAOYSA-M acetyloxymercury Chemical compound CC(=O)O[Hg] WRYNUJYAXVDTCB-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000001994 activation Methods 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 230000006502 antiplatelets effects Effects 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000019568 aromas Nutrition 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 150000003938 benzyl alcohols Chemical class 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000002213 calciumantagonistic effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 150000001983 dialkylethers Chemical class 0.000 description 1
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- MGIYRDNGCNKGJU-UHFFFAOYSA-N isothiazolinone Chemical compound O=C1C=CSN1 MGIYRDNGCNKGJU-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 208000014173 thrombophilia due to thrombin defect Diseases 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (12)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19863617976 DE3617976A1 (de) | 1986-05-28 | 1986-05-28 | 1,4-dihydropyridin, verfahren zu dessen herstellung und dessen verwendung in antithrombotischen medikamenten |
| EP87107008A EP0253092B1 (en) | 1986-05-28 | 1987-05-14 | 1,4-dihydropyridines, processes for their preparation and their use as antithrombotic drugs |
| ES8701462A ES2004141A6 (es) | 1986-05-28 | 1987-05-18 | Un procedimiento de preparacion de nuevas 1,4-dihidropiridinas |
| US07/051,852 US4782069A (en) | 1986-05-28 | 1987-05-18 | 1,4-Dihydropiridines and their use as antithrombotic drugs |
| MX6578A MX163341A (es) | 1986-05-28 | 1987-05-21 | N procedimiento para la preparacion de nuevas 1,4 dihidropiridinas,utiles como medicamentos antibioticos |
| GR870824A GR870824B (en) | 1986-05-28 | 1987-05-25 | Process for the preparation of new 1,4 - dihydropyridines useful as antithrombotic drugs |
| CA000537913A CA1311481C (en) | 1986-05-28 | 1987-05-25 | 1,4-dihydropyridines, to their obtention processes and to their use asantithrombotic drugs |
| ZA873778A ZA873778B (en) | 1986-05-28 | 1987-05-26 | 1,4-dihydropyridines,to their obtention processes and to their use as antithrombotic drugs |
| AR87307647A AR243185A1 (es) | 1986-05-28 | 1987-05-26 | Procedimiento de preparacion de nuevas 1,4-dihidropiridinas utiles como medicamentos antitromboticos. |
| PT84959A PT84959B (pt) | 1986-05-28 | 1987-05-27 | Processo para a preparacao de novas 1,4-dihidropiridinas |
| AT0135687A AT395011B (de) | 1986-05-28 | 1987-05-27 | Verfahren zur herstellung von neuen 1,4-dihydropyridinen |
| JP62133243A JPS62289578A (ja) | 1986-05-28 | 1987-05-28 | １，４−ジヒドロピリジン化合物 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19863617976 DE3617976A1 (de) | 1986-05-28 | 1986-05-28 | 1,4-dihydropyridin, verfahren zu dessen herstellung und dessen verwendung in antithrombotischen medikamenten |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3617976A1 DE3617976A1 (de) | 1988-01-14 |
| DE3617976C2 true DE3617976C2 (en, 2012) | 1989-05-03 |
Family
ID=6301807
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19863617976 Granted DE3617976A1 (de) | 1986-05-28 | 1986-05-28 | 1,4-dihydropyridin, verfahren zu dessen herstellung und dessen verwendung in antithrombotischen medikamenten |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US4782069A (en, 2012) |
| EP (1) | EP0253092B1 (en, 2012) |
| JP (1) | JPS62289578A (en, 2012) |
| AR (1) | AR243185A1 (en, 2012) |
| AT (1) | AT395011B (en, 2012) |
| CA (1) | CA1311481C (en, 2012) |
| DE (1) | DE3617976A1 (en, 2012) |
| ES (1) | ES2004141A6 (en, 2012) |
| GR (1) | GR870824B (en, 2012) |
| MX (1) | MX163341A (en, 2012) |
| PT (1) | PT84959B (en, 2012) |
| ZA (1) | ZA873778B (en, 2012) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4003541C1 (en, 2012) * | 1990-02-06 | 1991-08-08 | Alter S.A., Madrid, Es |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5306818A (en) * | 1990-11-01 | 1994-04-26 | Sterling Winthrop Inc. | Tetrahydro 2-saccharinylmerthyl aryl carboxylates |
| AU642537B2 (en) * | 1990-11-01 | 1993-10-21 | Sanofi | 2-saccharinylmethyl aryl carboxylates useful as proteolytic enzyme inhibitors and compositions and method of use thereof |
| US5378720A (en) * | 1991-12-19 | 1995-01-03 | Sterling Winthrop Inc. | Saccharin derivative proteolytic enzyme inhibitors |
| AU668694B2 (en) * | 1991-12-19 | 1996-05-16 | Sanofi-Synthelabo | Saccharin derivative proteolytic enzyme inhibitors |
| AU653279B2 (en) * | 1991-12-30 | 1994-09-22 | Sanofi | Novel 2-saccharinylmethyl heterocyclic carboxylates useful as proteolytic enzyme inhibitors and compositions and method of use thereof |
| TW226016B (en, 2012) * | 1991-12-30 | 1994-07-01 | Sterling Winthrop Inc | |
| WO1995014018A1 (es) * | 1993-11-19 | 1995-05-26 | Laboratorios Alter, S.A. | Nuevos derivados de 1,4-dihidropiridina, procedimiento para su fabricacion y uso como agentes terapeuticos |
| EP0771560A1 (en) * | 1995-08-25 | 1997-05-07 | Laboratorios Alter, S.A. | Use of 2- N-(1,2-benzoisothiazolyl-3(2H)one-1,1-dioxide ethyl 5-ethoxycarbonyl-2,4,6-trimethyl-1,4-dihydropiridine-3-carboxylate in the treatment of vascular disorders |
| JP2022538674A (ja) | 2019-07-01 | 2022-09-05 | トニックス ファーマ リミテッド | 抗ｃｄ１５４抗体およびその使用 |
| AU2022205313A1 (en) | 2021-01-06 | 2023-07-20 | Tonix Pharma Limited | Methods of inducing immune tolerance with modified anti-cd154 antibodies |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ182325A (en) * | 1975-11-18 | 1979-03-16 | Beecham Group Ltd | 2-substituted-1,2-benzisothiazol-3-ones |
| EP0000254B1 (en) * | 1977-06-20 | 1981-06-10 | Beecham Group Plc | Antithrombotic 2-(gamma-(1-piperidinyl)propyl)1,2-benzisothiazol 3-one, its pharmaceutically acceptable acid addition salts, their preparation and their compositions |
| US4656181A (en) * | 1982-11-24 | 1987-04-07 | Cermol S.A. | Esters of 1,4-dihydropyridines, processes for the preparation of the new esters, and medicaments containing the same |
| AU561213B2 (en) * | 1983-06-02 | 1987-04-30 | Teijin Limited | 1, 4-dihydropyridine derivative |
| JPS60120861A (ja) * | 1983-12-02 | 1985-06-28 | Otsuka Pharmaceut Co Ltd | ジヒドロピリジン誘導体 |
| DE3420784A1 (de) * | 1984-06-04 | 1985-12-05 | Bayer Ag, 5090 Leverkusen | 3-nitro-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung in arzneimitteln |
| JPS6143165A (ja) * | 1984-08-07 | 1986-03-01 | Otsuka Pharmaceut Co Ltd | ジヒドロピリジン誘導体の製造法 |
| GR851819B (en, 2012) * | 1984-08-17 | 1985-11-26 | Wyeth John & Brother Ltd | |
| US4757071A (en) * | 1984-12-14 | 1988-07-12 | Nisshin Flour Milling Co., Ltd. | 1,4-dihydropyridine derivatives, and pharmaceutical compositions containing same, useful for treating cardiovascular diseases |
-
1986
- 1986-05-28 DE DE19863617976 patent/DE3617976A1/de active Granted
-
1987
- 1987-05-14 EP EP87107008A patent/EP0253092B1/en not_active Expired - Lifetime
- 1987-05-18 ES ES8701462A patent/ES2004141A6/es not_active Expired
- 1987-05-18 US US07/051,852 patent/US4782069A/en not_active Expired - Fee Related
- 1987-05-21 MX MX6578A patent/MX163341A/es unknown
- 1987-05-25 CA CA000537913A patent/CA1311481C/en not_active Expired - Lifetime
- 1987-05-25 GR GR870824A patent/GR870824B/el unknown
- 1987-05-26 ZA ZA873778A patent/ZA873778B/xx unknown
- 1987-05-26 AR AR87307647A patent/AR243185A1/es active
- 1987-05-27 AT AT0135687A patent/AT395011B/de not_active IP Right Cessation
- 1987-05-27 PT PT84959A patent/PT84959B/pt not_active IP Right Cessation
- 1987-05-28 JP JP62133243A patent/JPS62289578A/ja active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4003541C1 (en, 2012) * | 1990-02-06 | 1991-08-08 | Alter S.A., Madrid, Es |
Also Published As
| Publication number | Publication date |
|---|---|
| CA1311481C (en) | 1992-12-15 |
| PT84959B (pt) | 1990-02-08 |
| ES2004141A6 (es) | 1988-12-01 |
| US4782069A (en) | 1988-11-01 |
| GR870824B (en) | 1987-09-30 |
| AT395011B (de) | 1992-08-25 |
| ATA135687A (de) | 1992-01-15 |
| EP0253092A1 (en) | 1988-01-20 |
| JPH0411547B2 (en, 2012) | 1992-02-28 |
| DE3617976A1 (de) | 1988-01-14 |
| AR243185A1 (es) | 1993-07-30 |
| EP0253092B1 (en) | 1991-09-25 |
| ZA873778B (en) | 1987-11-20 |
| MX163341A (es) | 1992-04-24 |
| PT84959A (en) | 1987-06-01 |
| JPS62289578A (ja) | 1987-12-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OP8 | Request for examination as to paragraph 44 patent law | ||
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |