US3652650A - Guanidino fatty acid esters and their production - Google Patents
Guanidino fatty acid esters and their production Download PDFInfo
- Publication number
- US3652650A US3652650A US769815A US3652650DA US3652650A US 3652650 A US3652650 A US 3652650A US 769815 A US769815 A US 769815A US 3652650D A US3652650D A US 3652650DA US 3652650 A US3652650 A US 3652650A
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- US
- United States
- Prior art keywords
- guanidino
- acid esters
- fatty acid
- production
- guanidino fatty
- 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
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- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
Definitions
- This invention relates to novel w-guanidino fatty acid esters and their production.
- the fatty acids as used in the present invention are those fatty acids having 4 to 6 carbon atoms.
- the ester of such fatty acid is an alkyl, aryl or arylalkyl ester wherein the arylalkyl is a benzyl group which may have or may not have in the aromatic ring such substituent as, for example, a methylol, methoxy, halogen, carboxyl or nitro group.
- guanidino fatty acid esters of the present invention a guanidino fatty acid is esterified according to the following reaction formula with an alcohol which will give the desired ester mentioned above:
- n is an integer of 3 to 5 and R is an alkyl, aryl or arylalkyl group having 1 to 7 carbon atoms and which may be substituted as mentioned above.
- the guanidino fatty acid esters of the present invention are basic and therefore are preferable to be separated after converting the same in a salt with an acid which can form a salt with a guanidino base.
- acids are inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid or carbonic acid, and organic acids such as oxalic acid, tartaric acid or p-tosyl sulfonic acid.
- the w-guanidino fatty acid esters of the present invention are novel compounds and have action to strongly inhibit the hydrolysis of alginine ester by kallikrein as shown in the drawing which shows inhibitory effects of guanidino acid esters on hydrolysis of methyl Nu-tosyl-L-arginate by plasma kallikrein.
- the compounds are therefore useful for a medicine as an antikallikrein agent.
- the guanidino acid esters of the invention also inhibit the hydrolysis of casein by plasmin. Therefore, the esters are also useful as antiplasmin agents.
- guanidino fatty acid esters of the invention may be in a suitable from such as capsule, emulsion, powder, injection and tablet.
- n is the integer 4 or 5
- R is benzyl or cal-boxybenzyl
- X is an acid which is capable of forming a 1.
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- Health & Medical Sciences (AREA)
- Emergency Medicine (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)
Abstract
W-GUANIDINO FATTY ACID ESTERS OF THE FORMULA
H2N-C(=NH)-NH-(CH2)N-COO-RX
WHERE N IS AN INTEGER OF FROM 3 TO 5 INCLUSIVE AND R IS AN ALKYL, ARYL OR ARYLALKYL GROUP IN WHICH THE AROMATIC MAY OR MAY NOT BE SUBSTITUTED.
H2N-C(=NH)-NH-(CH2)N-COO-RX
WHERE N IS AN INTEGER OF FROM 3 TO 5 INCLUSIVE AND R IS AN ALKYL, ARYL OR ARYLALKYL GROUP IN WHICH THE AROMATIC MAY OR MAY NOT BE SUBSTITUTED.
Description
March 28, 1972 PERCENT INHIBITION SETSURO FUJII 3,652,650
GUANIDINO FATTY ACID ESTERS AND THEIR PRODUCTION Filed Oct. 23, 1968 I l o 2 4 s CONCENTRATION OF INHIBITOR (m M) INVENTGR SETSURO FUJII ATTORNEYS United States Patent US. Cl. 260-482 R 2 Claims ABSTRACT OF THE DISCLOSURE w-Guanidino fatty acid esters of the formula wherein n is an integer of from 3 to 5 inclusive and R is an alkyl, aryl or arylalkyl group in which the aromatic may or may not be substituted.
This invention relates to novel w-guanidino fatty acid esters and their production.
The fatty acids as used in the present invention are those fatty acids having 4 to 6 carbon atoms. The ester of such fatty acid is an alkyl, aryl or arylalkyl ester wherein the arylalkyl is a benzyl group which may have or may not have in the aromatic ring such substituent as, for example, a methylol, methoxy, halogen, carboxyl or nitro group.
In order to obtain the guanidino fatty acid esters of the present invention, a guanidino fatty acid is esterified according to the following reaction formula with an alcohol which will give the desired ester mentioned above:
wherein n is an integer of 3 to 5 and R is an alkyl, aryl or arylalkyl group having 1 to 7 carbon atoms and which may be substituted as mentioned above.
The guanidino fatty acid esters of the present invention are basic and therefore are preferable to be separated after converting the same in a salt with an acid which can form a salt with a guanidino base. Examples of such acids are inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid or carbonic acid, and organic acids such as oxalic acid, tartaric acid or p-tosyl sulfonic acid.
The w-guanidino fatty acid esters of the present invention are novel compounds and have action to strongly inhibit the hydrolysis of alginine ester by kallikrein as shown in the drawing which shows inhibitory effects of guanidino acid esters on hydrolysis of methyl Nu-tosyl-L-arginate by plasma kallikrein. The compounds are therefore useful for a medicine as an antikallikrein agent. Further, the guanidino acid esters of the invention also inhibit the hydrolysis of casein by plasmin. Therefore, the esters are also useful as antiplasmin agents.
The effects of the guanidino fatty acid esters on dogs with experimental pancreatitis were tested by the method of Elliott, D. W. (Ann. Surg. 146,669 1957). Thus, each of amyl e-guanidinovalerate and benzyl e-guanidinocaproate was intravenously injected in an amount of 5 mg./ kg. bodyweight before the operation, and infused in an amount of mg./animal after the operation. The results are as follows:
Effects of guanidino acid esters in dogs with experimental pancreatitis.
1 Percent, 24 hours after operation. 2 Units, 24 hours after operation.
Further the inhibitory effects the guanidino acid esters of the invention on the hydrolysis of methyl Na-tosyl L-arginate by plasma kallikrein and on caseinolysis by plasmin are as follows:
Inhibition of Inhibition of hydrolysis, percent 1 caseinolysis, percent 1 Hexyl 5-guanidino valerate 33. 2 63.0 72. 0 85. 0 Arnyl 5-guanidino valerate 38. 0 2 62.0 71. 0 75. 3 Benzyl rS-guanidino 35. 8 53. 7 2 70. 4 44. 2 54. 0 Benzyl t-guanidino caproate 65. 3 83.0 34. 3 40. 5 p-Carboxybenzyl 6- guanidino valerate 37. 1 37. 1 73. 4 94. 7 97. 2 p-Carboxybenzyl 5- guanidino caproate- 35. 7 39. 9 66.0 79.8 91. 5
1 Concentration of inhibitors, millimoles. Z 5 millimoles.
In the administration of the guanidino fatty acid esters of the invention to human being they may be in a suitable from such as capsule, emulsion, powder, injection and tablet.
HzN
PHYSICAL PROPERTIES OF Analysis, percent Calculated Found M C. Formula Number 0H2o a 2 1 84-86 CroHzzNgOzCl 84-85 OIIHQANQOZO].
116-118 ciaHar a s HCl 54.09 8.01 10.51 53.85 7.78 10.47 SOaH 05-100 C11H23N3O5 100-107 CizHzs a s 71-72 C2QH35N305S 55.88 8.31 9.71 -55.92 8.21 9.78 SO H 120-123 C22H2gN3O1S 55.29 6.48 8.54 55.10 6.10 8.76 -SO H.
What I claim is: wherein n is the integer 4 or 5, R is benzyl or cal-boxybenzyl, and X is an acid which is capable of forming a 1. A compound of the formula salt with the guanidino base.
\ ONH-(CH2)..COOR References Cited FOREIGN PATENTS 1963 Japan 260 wherein n is the integer 4 or 5 and R is benzyi 0r 3,320,564 carboxybenzyl.
2. Alcompound of the formula 40 JAMES A. PAT'IEN, Primary Examiner P. I. KILLOS, Assistant Examiner
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6869267 | 1967-10-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3652650A true US3652650A (en) | 1972-03-28 |
Family
ID=13381049
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US769815A Expired - Lifetime US3652650A (en) | 1967-10-24 | 1968-10-23 | Guanidino fatty acid esters and their production |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US3652650A (en) |
| BE (1) | BE722519A (en) |
| CH (1) | CH510645A (en) |
| FR (2) | FR1601127A (en) |
| SE (1) | SE352076B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6388122B1 (en) | 1996-04-10 | 2002-05-14 | Ono Pharmaceutical Co., Ltd. | Tryptase inhibitor and novel guanidino derivatives |
-
1968
- 1968-10-18 SE SE14146/68A patent/SE352076B/xx unknown
- 1968-10-18 BE BE722519D patent/BE722519A/xx unknown
- 1968-10-23 FR FR1601127D patent/FR1601127A/fr not_active Expired
- 1968-10-23 US US769815A patent/US3652650A/en not_active Expired - Lifetime
- 1968-10-23 CH CH1583368A patent/CH510645A/en not_active IP Right Cessation
-
1969
- 1969-01-22 FR FR183226A patent/FR8272M/fr not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6388122B1 (en) | 1996-04-10 | 2002-05-14 | Ono Pharmaceutical Co., Ltd. | Tryptase inhibitor and novel guanidino derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| FR1601127A (en) | 1970-08-10 |
| BE722519A (en) | 1969-04-18 |
| SE352076B (en) | 1972-12-18 |
| FR8272M (en) | 1970-10-26 |
| CH510645A (en) | 1971-07-31 |
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