DE1695613A1 - Verfahren zur Herstellung von neuen Nicotinsaeurederivaten - Google Patents
Verfahren zur Herstellung von neuen NicotinsaeurederivatenInfo
- Publication number
- DE1695613A1 DE1695613A1 DE19671695613 DE1695613A DE1695613A1 DE 1695613 A1 DE1695613 A1 DE 1695613A1 DE 19671695613 DE19671695613 DE 19671695613 DE 1695613 A DE1695613 A DE 1695613A DE 1695613 A1 DE1695613 A1 DE 1695613A1
- Authority
- DE
- Germany
- Prior art keywords
- nicotinic acid
- methyl
- dinicotinate
- esculetin
- effect
- 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.)
- Pending
Links
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 title claims description 46
- 238000000034 method Methods 0.000 title claims description 18
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 229960003512 nicotinic acid Drugs 0.000 claims description 18
- 235000001968 nicotinic acid Nutrition 0.000 claims description 18
- 239000011664 nicotinic acid Substances 0.000 claims description 18
- KVOJTUXGYQVLAJ-UHFFFAOYSA-N 6,7-dihydroxy-4-methylcoumarin Chemical compound C1=C(O)C(O)=CC2=C1OC(=O)C=C2C KVOJTUXGYQVLAJ-UHFFFAOYSA-N 0.000 claims description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 239000012024 dehydrating agents Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims 1
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- VPODXHOUBDCEHN-UHFFFAOYSA-N pyridine-3-carbonyl pyridine-3-carboxylate Chemical class C=1C=CN=CC=1C(=O)OC(=O)C1=CC=CN=C1 VPODXHOUBDCEHN-UHFFFAOYSA-N 0.000 claims 1
- 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 14
- 230000000694 effects Effects 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000000725 suspension Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 230000000055 hyoplipidemic effect Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- 150000003626 triacylglycerols Chemical class 0.000 description 5
- 230000000304 vasodilatating effect Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 244000215068 Acacia senegal Species 0.000 description 4
- 229920000084 Gum arabic Polymers 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 239000000205 acacia gum Substances 0.000 description 4
- 235000010489 acacia gum Nutrition 0.000 description 4
- 210000005069 ears Anatomy 0.000 description 4
- -1 methyl-- Chemical class 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000003071 vasodilator agent Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229940124549 vasodilator Drugs 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- ZZKDGABMFBCSRP-UHFFFAOYSA-N 3-ethyl-2-methylpyridine Chemical compound CCC1=CC=CN=C1C ZZKDGABMFBCSRP-UHFFFAOYSA-N 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- XBLVHTDFJBKJLG-UHFFFAOYSA-N Ethyl nicotinate Chemical compound CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QNHQEUFMIKRNTB-UHFFFAOYSA-N aesculetin Natural products C1CC(=O)OC2=C1C=C(O)C(O)=C2 QNHQEUFMIKRNTB-UHFFFAOYSA-N 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000008119 colloidal silica Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000000871 hypocholesterolemic effect Effects 0.000 description 2
- 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 2
- 239000008101 lactose Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- ATBIAJXSKNPHEI-UHFFFAOYSA-N pyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1 ATBIAJXSKNPHEI-UHFFFAOYSA-N 0.000 description 2
- 229940100486 rice starch Drugs 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 229940100445 wheat starch Drugs 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010052895 Coronary artery insufficiency Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010029400 Nicotinic acid deficiency Diseases 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000002141 Pellagra Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000678 effect on lipid Effects 0.000 description 1
- ILEDWLMCKZNDJK-UHFFFAOYSA-N esculetin Chemical compound C1=CC(=O)OC2=C1C=C(O)C(O)=C2 ILEDWLMCKZNDJK-UHFFFAOYSA-N 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940064982 ethylnicotinate Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003516 hyperlipidaemic effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000003212 lipotrophic effect Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000810 peripheral vasodilating agent Substances 0.000 description 1
- 229960002116 peripheral vasodilator Drugs 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- RQAITHJHUFFEIV-UHFFFAOYSA-N thurfyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1CCCO1 RQAITHJHUFFEIV-UHFFFAOYSA-N 0.000 description 1
- 229950006036 thurfyl nicotinate Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000001457 vasomotor Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (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)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR47667A FR5383M (enrdf_load_stackoverflow) | 1966-01-28 | 1966-01-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1695613A1 true DE1695613A1 (de) | 1971-07-01 |
Family
ID=8600035
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19671695613 Pending DE1695613A1 (de) | 1966-01-28 | 1967-01-27 | Verfahren zur Herstellung von neuen Nicotinsaeurederivaten |
Country Status (11)
| Country | Link |
|---|---|
| AT (1) | AT263007B (enrdf_load_stackoverflow) |
| BE (1) | BE693043A (enrdf_load_stackoverflow) |
| CH (1) | CH471813A (enrdf_load_stackoverflow) |
| DE (1) | DE1695613A1 (enrdf_load_stackoverflow) |
| DK (1) | DK113429B (enrdf_load_stackoverflow) |
| ES (1) | ES336131A1 (enrdf_load_stackoverflow) |
| FR (1) | FR5383M (enrdf_load_stackoverflow) |
| GB (1) | GB1158676A (enrdf_load_stackoverflow) |
| IL (1) | IL27346A (enrdf_load_stackoverflow) |
| NL (1) | NL6701301A (enrdf_load_stackoverflow) |
| SE (1) | SE304010B (enrdf_load_stackoverflow) |
-
1966
- 1966-01-28 FR FR47667A patent/FR5383M/fr not_active Expired
-
1967
- 1967-01-23 BE BE693043D patent/BE693043A/xx unknown
- 1967-01-24 CH CH98967A patent/CH471813A/fr not_active IP Right Cessation
- 1967-01-26 SE SE119567A patent/SE304010B/xx unknown
- 1967-01-26 GB GB399267A patent/GB1158676A/en not_active Expired
- 1967-01-26 DK DK45567A patent/DK113429B/da unknown
- 1967-01-27 NL NL6701301A patent/NL6701301A/xx unknown
- 1967-01-27 ES ES336131A patent/ES336131A1/es not_active Expired
- 1967-01-27 DE DE19671695613 patent/DE1695613A1/de active Pending
- 1967-01-27 IL IL2734667A patent/IL27346A/en unknown
- 1967-01-30 AT AT86167A patent/AT263007B/de active
Also Published As
| Publication number | Publication date |
|---|---|
| CH471813A (fr) | 1969-04-30 |
| IL27346A (en) | 1971-02-25 |
| BE693043A (enrdf_load_stackoverflow) | 1967-07-24 |
| DK113429B (da) | 1969-03-24 |
| AT263007B (de) | 1968-07-10 |
| FR5383M (enrdf_load_stackoverflow) | 1967-09-18 |
| NL6701301A (enrdf_load_stackoverflow) | 1967-07-31 |
| ES336131A1 (es) | 1968-04-01 |
| SE304010B (enrdf_load_stackoverflow) | 1968-09-16 |
| GB1158676A (en) | 1969-07-16 |
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