CS228104B2 - Preparation of esters of nitric acid and n-/2-hydroxyethyl/nicotinamides - Google Patents

Preparation of esters of nitric acid and n-/2-hydroxyethyl/nicotinamides Download PDF

Info

Publication number: CS228104B2
Authority: CS; Czechoslovakia
Prior art keywords: compound; group; solvent; formula; compounds
Prior art date: 1976-04-02

Application number

CS772189A

Other languages

Czech (cs)

English (en)

Inventor

Hiroyuki Nagano

Takashi Mori

Sakae Takaku

Isao Matsunaga

Tatsuo Kujirai

Toshichika Ogasawara

Shigeru Sugano

Minoru Shindo

Original Assignee

Chugai Pharmaceutical Co Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1976-04-02

Filing date

1977-04-01

Publication date

1984-05-14

1977-04-01 Application filed by Chugai Pharmaceutical Co Ltd filed Critical Chugai Pharmaceutical Co Ltd

1978-11-20 Priority to CS787549A priority Critical patent/CS228111B2/cs

1984-05-14 Publication of CS228104B2 publication Critical patent/CS228104B2/cs

Links

229910017604 nitric acid Inorganic materials 0.000 title claims description 18
238000002360 preparation method Methods 0.000 title claims description 13
150000002148 esters Chemical class 0.000 title claims description 11
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 title description 7
235000005152 nicotinamide Nutrition 0.000 title description 3
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 title 1
150000005480 nicotinamides Chemical class 0.000 title 1
-1 nicotinic acid amide nitric acid ester Chemical class 0.000 claims abstract description 33
150000001875 compounds Chemical class 0.000 claims description 176
238000000034 method Methods 0.000 claims description 38
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 31
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 30
230000008569 process Effects 0.000 claims description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 27
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 26
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 25
239000002904 solvent Substances 0.000 claims description 23
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 22
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 13
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
238000006243 chemical reaction Methods 0.000 claims description 11
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 claims description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
239000002253 acid Substances 0.000 claims description 9
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 8
CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical compound C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 claims description 8
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 7
150000001408 amides Chemical class 0.000 claims description 7
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 7
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 6
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
230000007935 neutral effect Effects 0.000 claims description 6
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 6
238000010992 reflux Methods 0.000 claims description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
229920000388 Polyphosphate Polymers 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
SJZLOWYUGKIWAK-UHFFFAOYSA-N n-(2-hydroxyethyl)pyridine-3-carboxamide Chemical compound OCCNC(=O)C1=CC=CN=C1 SJZLOWYUGKIWAK-UHFFFAOYSA-N 0.000 claims description 5
239000001205 polyphosphate Substances 0.000 claims description 5
235000011176 polyphosphates Nutrition 0.000 claims description 5
229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
239000012442 inert solvent Substances 0.000 claims description 4
150000007529 inorganic bases Chemical class 0.000 claims description 4
239000003960 organic solvent Substances 0.000 claims description 4
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 4
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
125000003277 amino group Chemical group 0.000 claims description 3
229910000019 calcium carbonate Inorganic materials 0.000 claims description 3
NLYBDFDXNDOSQY-UHFFFAOYSA-N chloro(methoxy)phosphinous acid Chemical compound COP(O)Cl NLYBDFDXNDOSQY-UHFFFAOYSA-N 0.000 claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
150000004820 halides Chemical class 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
UHAAFJWANJYDIS-UHFFFAOYSA-N n,n'-diethylmethanediimine Chemical compound CCN=C=NCC UHAAFJWANJYDIS-UHFFFAOYSA-N 0.000 claims description 3
235000011056 potassium acetate Nutrition 0.000 claims description 3
239000001632 sodium acetate Substances 0.000 claims description 3
235000017281 sodium acetate Nutrition 0.000 claims description 3
229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
235000011121 sodium hydroxide Nutrition 0.000 claims description 3
239000008096 xylene Substances 0.000 claims description 3
239000012736 aqueous medium Substances 0.000 claims description 2
VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 2
239000001639 calcium acetate Substances 0.000 claims description 2
235000011092 calcium acetate Nutrition 0.000 claims description 2
229960005147 calcium acetate Drugs 0.000 claims description 2
235000010216 calcium carbonate Nutrition 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims description 2
235000011181 potassium carbonates Nutrition 0.000 claims description 2
235000017550 sodium carbonate Nutrition 0.000 claims description 2
239000007858 starting material Substances 0.000 claims description 2
BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 claims description 2
AHZOHFYNIDGBKN-UHFFFAOYSA-N chloro(ethoxy)phosphinic acid Chemical compound CCOP(O)(Cl)=O AHZOHFYNIDGBKN-UHFFFAOYSA-N 0.000 claims 1
150000003839 salts Chemical class 0.000 abstract 1
230000000694 effects Effects 0.000 description 56
230000017531 blood circulation Effects 0.000 description 40
239000000243 solution Substances 0.000 description 31
230000008859 change Effects 0.000 description 29
238000001990 intravenous administration Methods 0.000 description 28
238000002474 experimental method Methods 0.000 description 27
239000000006 Nitroglycerin Substances 0.000 description 24
229960003711 glyceryl trinitrate Drugs 0.000 description 24
SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 23
230000036772 blood pressure Effects 0.000 description 20
239000000203 mixture Substances 0.000 description 17
230000009885 systemic effect Effects 0.000 description 15
230000000747 cardiac effect Effects 0.000 description 12
230000008602 contraction Effects 0.000 description 12
210000004351 coronary vessel Anatomy 0.000 description 12
229910052757 nitrogen Inorganic materials 0.000 description 11
239000003826 tablet Substances 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 10
229910001424 calcium ion Inorganic materials 0.000 description 10
229910052799 carbon Inorganic materials 0.000 description 10
230000002401 inhibitory effect Effects 0.000 description 10
230000002829 reductive effect Effects 0.000 description 10
102000008186 Collagen Human genes 0.000 description 9
108010035532 Collagen Proteins 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
229920001436 collagen Polymers 0.000 description 9
229910052739 hydrogen Inorganic materials 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 8
XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 8
241000282472 Canis lupus familiaris Species 0.000 description 8
230000000052 comparative effect Effects 0.000 description 8
239000007924 injection Substances 0.000 description 8
238000002347 injection Methods 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
230000002861 ventricular Effects 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
239000002775 capsule Substances 0.000 description 7
239000008187 granular material Substances 0.000 description 7
238000002329 infrared spectrum Methods 0.000 description 7
238000002844 melting Methods 0.000 description 7
230000008018 melting Effects 0.000 description 7
238000003756 stirring Methods 0.000 description 7
206010002383 Angina Pectoris Diseases 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
230000009471 action Effects 0.000 description 6
239000013078 crystal Substances 0.000 description 6
239000003814 drug Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
239000004615 ingredient Substances 0.000 description 6
239000010410 layer Substances 0.000 description 6
210000003205 muscle Anatomy 0.000 description 6
239000002504 physiological saline solution Substances 0.000 description 6
239000000047 product Substances 0.000 description 6
239000000523 sample Substances 0.000 description 6
UZGLOGCJCWBBIV-UHFFFAOYSA-N 3-(chloromethyl)pyridin-1-ium;chloride Chemical compound Cl.ClCC1=CC=CN=C1 UZGLOGCJCWBBIV-UHFFFAOYSA-N 0.000 description 5
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 5
229910002651 NO3 Inorganic materials 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
231100000673 dose–response relationship Toxicity 0.000 description 5
239000000284 extract Substances 0.000 description 5
230000000302 ischemic effect Effects 0.000 description 5
239000008101 lactose Substances 0.000 description 5
230000000737 periodic effect Effects 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
241000700199 Cavia porcellus Species 0.000 description 4
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 4
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
230000015271 coagulation Effects 0.000 description 4
238000005345 coagulation Methods 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
229940079593 drug Drugs 0.000 description 4
230000005284 excitation Effects 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
208000031225 myocardial ischemia Diseases 0.000 description 4
210000002445 nipple Anatomy 0.000 description 4
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 4
229960001412 pentobarbital Drugs 0.000 description 4
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
229910001414 potassium ion Inorganic materials 0.000 description 4
239000000843 powder Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 3
WAFNMNCIAQAQJU-UHFFFAOYSA-N 2-aminoethanol;nitric acid Chemical compound NCCO.O[N+]([O-])=O WAFNMNCIAQAQJU-UHFFFAOYSA-N 0.000 description 3
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
229930195725 Mannitol Natural products 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
230000002776 aggregation Effects 0.000 description 3
238000004220 aggregation Methods 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000011575 calcium Substances 0.000 description 3
229910052791 calcium Inorganic materials 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000012153 distilled water Substances 0.000 description 3
229940039009 isoproterenol Drugs 0.000 description 3
239000000594 mannitol Substances 0.000 description 3
235000010355 mannitol Nutrition 0.000 description 3
230000028161 membrane depolarization Effects 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
230000002035 prolonged effect Effects 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
230000002269 spontaneous effect Effects 0.000 description 3
208000010110 spontaneous platelet aggregation Diseases 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000012085 test solution Substances 0.000 description 3
238000005303 weighing Methods 0.000 description 3
OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 2
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 2
ZDHKVKPZQKYREU-UHFFFAOYSA-N 4-(chloromethyl)pyridine;hydron;chloride Chemical compound Cl.ClCC1=CC=NC=C1 ZDHKVKPZQKYREU-UHFFFAOYSA-N 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
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 description 2
229910004679 ONO2 Inorganic materials 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 2
WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 2
241000244155 Taenia Species 0.000 description 2
150000008065 acid anhydrides Chemical class 0.000 description 2
230000002411 adverse Effects 0.000 description 2
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239000004004 anti-anginal agent Substances 0.000 description 2
239000003146 anticoagulant agent Substances 0.000 description 2
210000001367 artery Anatomy 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
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TXHWYSOQHNMOOU-UHFFFAOYSA-N chloro(diethoxy)phosphane Chemical compound CCOP(Cl)OCC TXHWYSOQHNMOOU-UHFFFAOYSA-N 0.000 description 2
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201000010099 disease Diseases 0.000 description 2
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IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
210000005240 left ventricle Anatomy 0.000 description 2
239000007788 liquid Substances 0.000 description 2
238000005259 measurement Methods 0.000 description 2
239000011259 mixed solution Substances 0.000 description 2
QVPWDPDVDVVXIB-UHFFFAOYSA-N n-(2-hydroxyethyl)pyridine-4-carboxamide Chemical compound OCCNC(=O)C1=CC=NC=C1 QVPWDPDVDVVXIB-UHFFFAOYSA-N 0.000 description 2
JVHPKYBRJQNPAT-UHFFFAOYSA-N n-cyclohexyl-2,2-diphenylethenimine Chemical compound C1CCCCC1N=C=C(C=1C=CC=CC=1)C1=CC=CC=C1 JVHPKYBRJQNPAT-UHFFFAOYSA-N 0.000 description 2
239000011570 nicotinamide Substances 0.000 description 2
229960003966 nicotinamide Drugs 0.000 description 2
235000001968 nicotinic acid Nutrition 0.000 description 2
239000011664 nicotinic acid Substances 0.000 description 2
229960003512 nicotinic acid Drugs 0.000 description 2
125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
210000005259 peripheral blood Anatomy 0.000 description 2
239000011886 peripheral blood Substances 0.000 description 2
239000000810 peripheral vasodilating agent Substances 0.000 description 2
229960002116 peripheral vasodilator Drugs 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
230000008327 renal blood flow Effects 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000006190 sub-lingual tablet Substances 0.000 description 2
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
230000000304 vasodilatating effect Effects 0.000 description 2
HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 description 1
XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 1
CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 description 1
CEZQWBVHIJYRGO-UHFFFAOYSA-N 3-(pyridin-3-ylmethoxy)propane-1,2-diol Chemical compound OCC(O)COCC1=CC=CN=C1 CEZQWBVHIJYRGO-UHFFFAOYSA-N 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
KQIGMPWTAHJUMN-UHFFFAOYSA-N 3-aminopropane-1,2-diol Chemical compound NCC(O)CO KQIGMPWTAHJUMN-UHFFFAOYSA-N 0.000 description 1
DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
JMTQQUKUAVWKCR-UHFFFAOYSA-O CC[NH2+]CC(O[N+]([O-])=O)O[N+]([O-])=O.[O-][N+]([O-])=O.OC(C1=CN=CC=C1)=O Chemical compound CC[NH2+]CC(O[N+]([O-])=O)O[N+]([O-])=O.[O-][N+]([O-])=O.OC(C1=CN=CC=C1)=O JMTQQUKUAVWKCR-UHFFFAOYSA-O 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
PBPJEZZOQYDOQC-UHFFFAOYSA-N Cl.C(C1=CN=CC=C1)(=O)NCCCO Chemical compound Cl.C(C1=CN=CC=C1)(=O)NCCCO PBPJEZZOQYDOQC-UHFFFAOYSA-N 0.000 description 1
UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 1
ASMQGLCHMVWBQR-UHFFFAOYSA-N Diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-N 0.000 description 1
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
241000700159 Rattus Species 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
229910021607 Silver chloride Inorganic materials 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
208000005392 Spasm Diseases 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
GARZYBXJFUZLBW-UHFFFAOYSA-N [N+](=O)(O)[O-].[N+](=O)(O)[O-].C(C1=CN=CC=C1)(=O)N Chemical compound [N+](=O)(O)[O-].[N+](=O)(O)[O-].C(C1=CN=CC=C1)(=O)N GARZYBXJFUZLBW-UHFFFAOYSA-N 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000007059 acute toxicity Effects 0.000 description 1
231100000403 acute toxicity Toxicity 0.000 description 1
UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
229950006790 adenosine phosphate Drugs 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
KZTZJUQNSSLNAG-UHFFFAOYSA-N aminoethyl nitrate Chemical compound NCCO[N+]([O-])=O KZTZJUQNSSLNAG-UHFFFAOYSA-N 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
239000003416 antiarrhythmic agent Substances 0.000 description 1
229940127219 anticoagulant drug Drugs 0.000 description 1
229940127088 antihypertensive drug Drugs 0.000 description 1
210000000709 aorta Anatomy 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
235000015278 beef Nutrition 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
YTFJQDNGSQJFNA-UHFFFAOYSA-N benzyl dihydrogen phosphate Chemical compound OP(O)(=O)OCC1=CC=CC=C1 YTFJQDNGSQJFNA-UHFFFAOYSA-N 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
210000005242 cardiac chamber Anatomy 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
239000002872 contrast media Substances 0.000 description 1
238000009402 cross-breeding Methods 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
230000000916 dilatatory effect Effects 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
239000011363 dried mixture Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000003480 eluent Substances 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000002964 excitative effect Effects 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
210000001105 femoral artery Anatomy 0.000 description 1
239000000835 fiber Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000011521 glass Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
210000002837 heart atrium Anatomy 0.000 description 1
230000010247 heart contraction Effects 0.000 description 1
230000006872 improvement Effects 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
230000001788 irregular Effects 0.000 description 1
230000007794 irritation Effects 0.000 description 1
229940102253 isopropanolamine Drugs 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
230000005923 long-lasting effect Effects 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
238000000691 measurement method Methods 0.000 description 1
230000004660 morphological change Effects 0.000 description 1
230000004118 muscle contraction Effects 0.000 description 1
SJXULIRYGQTEJK-UHFFFAOYSA-N n'-(2-morpholin-4-ylethyl)methanediimine Chemical compound N=C=NCCN1CCOCC1 SJXULIRYGQTEJK-UHFFFAOYSA-N 0.000 description 1
SIUMVFGIULAFNI-UHFFFAOYSA-N n-(2-hydroxyethyl)pyridine-2-carboxamide Chemical compound OCCNC(=O)C1=CC=CC=N1 SIUMVFGIULAFNI-UHFFFAOYSA-N 0.000 description 1
NBDWZSMXICVNGC-UHFFFAOYSA-N n-(2-hydroxypropyl)pyridine-3-carboxamide Chemical compound CC(O)CNC(=O)C1=CC=CN=C1 NBDWZSMXICVNGC-UHFFFAOYSA-N 0.000 description 1
SFIFCSGSHPDRCQ-UHFFFAOYSA-N n-(2-hydroxypropyl)pyridine-3-carboxamide;hydrochloride Chemical compound Cl.CC(O)CNC(=O)C1=CC=CN=C1 SFIFCSGSHPDRCQ-UHFFFAOYSA-N 0.000 description 1
LFLZOWIFJOBEPN-UHFFFAOYSA-N nitrate, nitrate Chemical compound O[N+]([O-])=O.O[N+]([O-])=O LFLZOWIFJOBEPN-UHFFFAOYSA-N 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
230000010412 perfusion Effects 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
238000009832 plasma treatment Methods 0.000 description 1
210000004623 platelet-rich plasma Anatomy 0.000 description 1
230000010287 polarization Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000035485 pulse pressure Effects 0.000 description 1
ATBIAJXSKNPHEI-UHFFFAOYSA-N pyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1 ATBIAJXSKNPHEI-UHFFFAOYSA-N 0.000 description 1
UDHZYEWSTDYKCZ-UHFFFAOYSA-N pyridine-4-carboxamide;hydrochloride Chemical compound Cl.NC(=O)C1=CC=NC=C1 UDHZYEWSTDYKCZ-UHFFFAOYSA-N 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
210000002254 renal artery Anatomy 0.000 description 1
229940124550 renal vasodilator Drugs 0.000 description 1
239000013049 sediment Substances 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
229940005605 valeric acid Drugs 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- 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
- A61P9/08—Vasodilators for multiple indications
- 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
- 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
- A61P9/12—Antihypertensives

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyridine Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

CS772189A 1976-04-02 1977-04-01 Preparation of esters of nitric acid and n-/2-hydroxyethyl/nicotinamides CS228104B2 (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CS787549A CS228111B2 (cs)	1976-04-02	1978-11-20	Způsob přípravy esteru kyseliny dusičné a N-(2-hydroxyethylJ-nikotinamidu

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
JP51036101A JPS5817463B2 (ja)	1976-04-02	1976-04-02	ニコチン酸アミド誘導体

Publications (1)

Publication Number	Publication Date
CS228104B2 true CS228104B2 (en)	1984-05-14

Family

ID=12460366

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS772189A CS228104B2 (en)	1976-04-02	1977-04-01	Preparation of esters of nitric acid and n-/2-hydroxyethyl/nicotinamides

Country Status (5)

Country	Link
JP (1)	JPS5817463B2 (fr)
BE (1)	BE853144A (fr)
CS (1)	CS228104B2 (fr)
SU (2)	SU999965A3 (fr)
ZA (1)	ZA771976B (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS59192562U (ja) *	1983-06-07	1984-12-20	四国化成工業株式会社	支柱
JP2020100598A (ja)	2018-12-25	2020-07-02	公益財団法人応用生化学研究所	レンバチニブ誘導体、並びにそれを用いた医薬研究用組成物及び腫瘍治療剤

1976
- 1976-04-02 JP JP51036101A patent/JPS5817463B2/ja not_active Expired
1977
- 1977-03-31 ZA ZA00771976A patent/ZA771976B/xx unknown
- 1977-04-01 CS CS772189A patent/CS228104B2/cs unknown
- 1977-04-01 SU SU772467501A patent/SU999965A3/ru active
- 1977-04-01 BE BE2055790A patent/BE853144A/fr not_active IP Right Cessation
1978
- 1978-07-28 SU SU782640400A patent/SU942593A3/ru active

Also Published As

Publication number	Publication date
SU999965A3 (ru)	1983-02-23
BE853144A (fr)	1977-08-01
SU942593A3 (ru)	1982-07-07
JPS52122373A (en)	1977-10-14
ZA771976B (en)	1978-03-29
JPS5817463B2 (ja)	1983-04-07

Publication	Publication Date	Title
US4200640A (en)	1980-04-29	Nitric ester of N-(2-hydroxyethyl)nicotinamide and pharmaceutical use
DE2548886C2 (de)	1986-03-13	p-(p'-Guanidinobenzoyloxy)-phenylcarbonsäureester, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel
EP0539153B1 (fr)	1997-04-23	Dérivé d'acridine comme agent thérapeutique
SU1340583A3 (ru)	1987-09-23	Способ получени производных аминогуанидина или их кислотно-аудитивных солей
US4562196A (en)	1985-12-31	2,4-Diaminopyridine as a pharmacologic agent
CA1088944A (fr)	1980-11-04	Procede d'obtention d'ester nitrique de n-(2- hydroxyethyl) nicotinamide
JP3083544B2 (ja)	2000-09-04	心疾患を予防または治療する薬剤
US4011330A (en)	1977-03-08	Vincaminic acid amides
CS228104B2 (en)	1984-05-14	Preparation of esters of nitric acid and n-/2-hydroxyethyl/nicotinamides
US4017636A (en)	1977-04-12	Esters of γ-glutamyl amide of dopamine
JPH0140026B2 (fr)	1989-08-24
US4600710A (en)	1986-07-15	β-Adrenergic receptor agonist alkylaminoalkyl pyridinemethanol derivatives
EP0105458B1 (fr)	1989-11-23	Dérivés d'acide alpha-aryl-alpha-pyridylalkanoique, procédé pour leur préparation et composition pharmaceutique les contenant
EP3906969A1 (fr)	2021-11-10	Composé polyol antihypertenseur et dérivé de celui-ci
WO1994005290A1 (fr)	1994-03-17	Inhibiteur d'agregation plaquettaire
DE3825242A1 (de)	1989-02-09	Durch schwefelhaltige gruppen substituierte histidinylamino-verbindungen
US4128555A (en)	1978-12-05	3-Phenoxypyridine monosulfate and a method for its production
JPH0545585B2 (fr)	1993-07-09
SU1127529A3 (ru)	1984-11-30	Способ получени производных пиридина или их солей с фармацевтически приемлемой кислотой
US4438115A (en)	1984-03-20	Compositions and methods for treating diseases in circulatory organs
GB1562962A (en)	1980-03-19	Nicotinamide derivatives processes for producting the same and pharmaceutical compositions containing the same
EP0252422A2 (fr)	1988-01-13	Dérivés de pyridazinone et leur sels
JP5301441B2 (ja)	2013-09-25	新規ヒスチジン誘導体
US4855497A (en)	1989-08-08	Novel diamine derivatives
JP2007523926A (ja)	2007-08-23	心房収縮性の選択的増加及び心不全の治療のためのＫｖ１．５遮断剤