US3641129A - Antifibrinolytic compounds - Google Patents
Antifibrinolytic compounds Download PDFInfo
- Publication number
- US3641129A US3641129A US834139A US3641129DA US3641129A US 3641129 A US3641129 A US 3641129A US 834139 A US834139 A US 834139A US 3641129D A US3641129D A US 3641129DA US 3641129 A US3641129 A US 3641129A
- Authority
- US
- United States
- Prior art keywords
- compound
- acid
- octane
- antifibrinolytic
- pharmaceutically acceptable
- 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 - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title abstract description 22
- 230000001567 anti-fibrinolytic effect Effects 0.000 title abstract description 6
- 150000003839 salts Chemical class 0.000 abstract description 8
- QNWUEDPDEBVNJB-UHFFFAOYSA-N 2-[4-(aminomethyl)-1-bicyclo[2.2.2]octanyl]acetic acid Chemical compound NCC12CCC(CC1)(CC2)CC(=O)O QNWUEDPDEBVNJB-UHFFFAOYSA-N 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- -1 aminomethyl bicyclic carboxylic acid Chemical class 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 7
- 229960002684 aminocaproic acid Drugs 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 108010088842 Fibrinolysin Proteins 0.000 description 6
- 102000013566 Plasminogen Human genes 0.000 description 5
- 108010051456 Plasminogen Proteins 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000003480 fibrinolytic effect Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229940012957 plasmin Drugs 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 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 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- GYDJEQRTZSCIOI-UHFFFAOYSA-N Tranexamic acid Chemical compound NCC1CCC(C(O)=O)CC1 GYDJEQRTZSCIOI-UHFFFAOYSA-N 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 239000000504 antifibrinolytic agent Substances 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 239000003527 fibrinolytic agent Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- QCTBMLYLENLHLA-UHFFFAOYSA-N aminomethylbenzoic acid Chemical compound NCC1=CC=C(C(O)=O)C=C1 QCTBMLYLENLHLA-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- BUVHVMMJPCTDSQ-UHFFFAOYSA-N 1-(aminomethyl)bicyclo[2.2.2]octane-4-carboxylic acid;hydrochloride Chemical compound Cl.C1CC2(C(O)=O)CCC1(CN)CC2 BUVHVMMJPCTDSQ-UHFFFAOYSA-N 0.000 description 1
- ONXKUOTWYIGFMY-UHFFFAOYSA-N 1-cyanobicyclo[2.2.2]octane-4-carboxylic acid Chemical compound C1CC2(C#N)CCC1(C(=O)O)CC2 ONXKUOTWYIGFMY-UHFFFAOYSA-N 0.000 description 1
- ZOICSFZIPOIPFR-UHFFFAOYSA-N 4-(benzamidomethyl)bicyclo[2.2.2]octane-1-carboxylic acid Chemical compound C(C1=CC=CC=C1)(=O)NCC12CCC(CC1)(CC2)C(=O)O ZOICSFZIPOIPFR-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 229960003375 aminomethylbenzoic acid Drugs 0.000 description 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- XXTZHYXQVWRADW-UHFFFAOYSA-N diazomethanone Chemical compound [N]N=C=O XXTZHYXQVWRADW-UHFFFAOYSA-N 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 229940001501 fibrinolysin Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 208000007106 menorrhagia Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 230000036515 potency Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000002700 urine Anatomy 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
Definitions
- This invention relates to a new antifibrinolytic compound and to a method of counteracting certain hemorrhagic conditions and other disorders resulting from a pathological fibrinolytic state in patients. More specifically, this invention relates to a new compound of the structure n ucu lu coon and the pharmaceutically acceptable salts thereof. More specifically, it relates to the prevention or treatment of a pathological fibrinolytic state in patients by the oral administration of from 1 to 20 and preferably 2 to 8 mg./kg. of body weight per day of the above compounds for varying periods of treatment.
- fibrinolytic activity results from an overabundance of such activators.
- plasmin fibrinolysin
- activators in the blood and it would appear that excessive fibrinolytic activity results from an overabundance of such activators.
- fibrinolytic state When too much plasmin is present, the clotting system of the blood becomes unbalanced, viable clots cannot be maintained, and hemorrhage may result. This situation is known as a fibrinolytic state.
- Other enzyme systems i.e., the kallikreins, complement
- antifibrinolytic agents i.e. drugs which will inhibit the activation of plasminogen to form plasmin.
- antifibrinolytic agents are believed to interfere with the function of the activators of converting plasminogen to plasmin.
- the clinical uses of such drugs include their administration to persons undergoing various kinds of surgery (such as heartlung and prostate surgery), obstetrical hemorrhage problems, menorrhagia, and many other uses which have been suggested in the literature (e.g. see Nilssen, Acta Medicia Scand. Suppl. 448, volume 180, 1966).
- EACA epsilon aminocaproic acid
- AMCHA trans-4-aminomethylcyclohexane carboxylic acid
- PAMBA 4-aminomethylbenzoic acid
- the new compound of my invention has the general structure ll NCH E cn cooa
- the pharmaceutically acceptable salts of the compound also show antifibrinolytic activity.
- the present invention also provides a process of pre paring a compound of the structure which comprises hydrolyzing a compound of the structure wherein R is an organic radical containing of from 1 to about 10 carbon atoms.
- the hydrolysis is carried out under conventional conditions generally in the presence of an inorganic acid.
- the R groups are either lower al-kyl or benzyl.
- the compound is used in the method of this invention by either oral or intravenous administration, although the oral route is preferred.
- the esters and amides of this class compound are not themselves very active in vitro but the action of enzymes in vivo cause the slow liberation of the highly active amino acids, thus providing a prolonged availability of the drug in the body. This is important because of the tendency of these drugs to be swiftly eliminated in the urine.
- Such amides and esters are to be considered as being within the scope of the present invention since it is actually the present compound which produces the result within the body.
- the compound of this invention can be used in a composition comprising any pharmaceutically acceptable carrier, in the form of pills, tablets or capsules.
- pharmaceutically acceptable salts both of the amino group such as the hydrochloride, hydrobromide, sulfate, citrate, tartrate, etc.and of the carboxy group such as the alkali metal, alkaline earth metal, etc., salts
- the pharmaceutically acceptable salts are readily usable, especially in injectable compositions.
- EXAMPLE 1 (A) 4 aminomethylbicyclo [2.2.2]-octane-l-carboxylic acid hydrochloride salt To a solution of 2.80 g. (0.0156 mole) of 4-cyanobicyclo-[2.2.2]-octane-l-carboxylic acid (Roberts et a1. LACS 1953 75, 637) in 100 ml. ethanol is added 5.0 ml. 6 N hydrochloric acid and 500 mg. platinum oxide. During hydrogenation on a Parr apparatus at room temperature and 40 lbs/in. pressure, the theoretical quantity of hydrogen is absorbed during the first half hour. After 2 hours, the hydrogenation is stopped and the reaction mixture filtered through sintered glass to remove the platinum catalyst.
- This crude benzyl ester (3.35 g.) is saponified by stirring overnight in 12 ml. ethanol containing 4.3 ml. 2.0 N NAOH. Removal of the ethanol and acidification of the aqueous solution gives an oil which is extracted into ethyl acetate. The oil is purified by column chromatography on silica gel (benzen-ethyl acetate eluant) to give pure 4-benzamidomethylbicyclo- [2.2.2]-octane-l-acetic acid (700 mg. 23% yield). Because this material could not be obtained in crystalline form, it is hydrolyzed directly without further purification to the amino acid.
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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83413969A | 1969-06-17 | 1969-06-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3641129A true US3641129A (en) | 1972-02-08 |
Family
ID=25266215
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US834139A Expired - Lifetime US3641129A (en) | 1969-06-17 | 1969-06-17 | Antifibrinolytic compounds |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US3641129A (enrdf_load_stackoverflow) |
| BE (1) | BE752043A (enrdf_load_stackoverflow) |
| CH (1) | CH537365A (enrdf_load_stackoverflow) |
| DE (1) | DE2029807C3 (enrdf_load_stackoverflow) |
| FR (1) | FR2052979B1 (enrdf_load_stackoverflow) |
| GB (1) | GB1252540A (enrdf_load_stackoverflow) |
| IL (1) | IL34650A0 (enrdf_load_stackoverflow) |
| NL (1) | NL7007535A (enrdf_load_stackoverflow) |
| SE (1) | SE365505B (enrdf_load_stackoverflow) |
| ZA (1) | ZA704089B (enrdf_load_stackoverflow) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6020370A (en) * | 1996-03-14 | 2000-02-01 | Warner-Lambert Company | Bridged cyclic amino acids as pharmaceutical agents |
| US10202331B2 (en) | 2014-11-03 | 2019-02-12 | Thrombolytics, Llc | Antifibrinolytic compounds |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HN2000000224A (es) * | 1999-10-20 | 2001-04-11 | Warner Lambert Co | Aminoacidos biciclicos como agentes farmaceuticos |
-
1969
- 1969-06-17 US US834139A patent/US3641129A/en not_active Expired - Lifetime
-
1970
- 1970-05-25 NL NL7007535A patent/NL7007535A/xx not_active Application Discontinuation
- 1970-06-02 IL IL34650A patent/IL34650A0/xx unknown
- 1970-06-12 CH CH890570A patent/CH537365A/de not_active IP Right Cessation
- 1970-06-15 SE SE08264/70A patent/SE365505B/xx unknown
- 1970-06-15 GB GB1252540D patent/GB1252540A/en not_active Expired
- 1970-06-16 ZA ZA704089A patent/ZA704089B/xx unknown
- 1970-06-16 BE BE752043D patent/BE752043A/xx unknown
- 1970-06-16 DE DE2029807A patent/DE2029807C3/de not_active Expired
- 1970-06-16 FR FR7022080A patent/FR2052979B1/fr not_active Expired
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6020370A (en) * | 1996-03-14 | 2000-02-01 | Warner-Lambert Company | Bridged cyclic amino acids as pharmaceutical agents |
| US10202331B2 (en) | 2014-11-03 | 2019-02-12 | Thrombolytics, Llc | Antifibrinolytic compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| DE2029807B2 (de) | 1978-10-26 |
| SE365505B (enrdf_load_stackoverflow) | 1974-03-25 |
| NL7007535A (enrdf_load_stackoverflow) | 1970-12-21 |
| IL34650A0 (en) | 1970-08-19 |
| DE2029807C3 (de) | 1979-06-21 |
| ZA704089B (en) | 1972-01-26 |
| DE2029807A1 (de) | 1971-01-07 |
| BE752043A (fr) | 1970-12-16 |
| GB1252540A (enrdf_load_stackoverflow) | 1971-11-03 |
| FR2052979A1 (enrdf_load_stackoverflow) | 1971-04-16 |
| FR2052979B1 (enrdf_load_stackoverflow) | 1974-05-24 |
| CH537365A (de) | 1973-05-31 |
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