GB2098989A - Lysine salts - Google Patents
Lysine salts Download PDFInfo
- Publication number
- GB2098989A GB2098989A GB8214547A GB8214547A GB2098989A GB 2098989 A GB2098989 A GB 2098989A GB 8214547 A GB8214547 A GB 8214547A GB 8214547 A GB8214547 A GB 8214547A GB 2098989 A GB2098989 A GB 2098989A
- Authority
- GB
- United Kingdom
- Prior art keywords
- lysine
- pyrrole
- dimethyl
- water
- acetic acid
- 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.)
- Granted
Links
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims abstract description 31
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000004472 Lysine Substances 0.000 claims abstract description 16
- 235000019766 L-Lysine Nutrition 0.000 claims abstract description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000000202 analgesic effect Effects 0.000 claims abstract description 7
- ZXVNMYWKKDOREA-UHFFFAOYSA-N zomepirac Chemical compound C1=C(CC(O)=O)N(C)C(C(=O)C=2C=CC(Cl)=CC=2)=C1C ZXVNMYWKKDOREA-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002253 acid Substances 0.000 claims abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 8
- 208000002193 Pain Diseases 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 3
- 208000000094 Chronic Pain Diseases 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 208000005298 acute pain Diseases 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- 230000003211 malignant effect Effects 0.000 claims description 2
- 230000009826 neoplastic cell growth Effects 0.000 claims description 2
- 238000012829 orthopaedic surgery Methods 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 235000018977 lysine Nutrition 0.000 abstract description 3
- 241000700159 Rattus Species 0.000 description 9
- 238000013019 agitation Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 208000025865 Ulcer Diseases 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 231100000397 ulcer Toxicity 0.000 description 5
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- -1 L-lysine O Chemical class 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 206010000090 Abdominal rigidity Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000978776 Senegalia senegal Species 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000001767 cationic compounds Chemical class 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002682 general surgery Methods 0.000 description 1
- 229910001411 inorganic cation Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001562 ulcerogenic effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01S—RADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
- G01S3/00—Direction-finders for determining the direction from which infrasonic, sonic, ultrasonic, or electromagnetic waves, or particle emission, not having a directional significance, are being received
- G01S3/78—Direction-finders for determining the direction from which infrasonic, sonic, ultrasonic, or electromagnetic waves, or particle emission, not having a directional significance, are being received using electromagnetic waves other than radio waves
- G01S3/782—Systems for determining direction or deviation from predetermined direction
- G01S3/783—Systems for determining direction or deviation from predetermined direction using amplitude comparison of signals derived from static detectors or detector systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Electromagnetism (AREA)
- General Physics & Mathematics (AREA)
- Radar, Positioning & Navigation (AREA)
- Remote Sensing (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (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)
- Pyrrole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Photometry And Measurement Of Optical Pulse Characteristics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Salts of L'lysine or DL-lysine with 5-(p-chlorobenzoyl)-1 ,4-dimethyl- pyrrole-2-acetic acid, having the formula (A): <IMAGE> in which I is the said acid and II represents L-lysine or DL-lysine are prepared by reacting equimolecular quantities of L-lysine or DL-lysine with 5-(p- chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetic acid in the presence of water or water and alcohol at temperatures between 0 DEG C and 100 DEG C. They have analgesic activity and can be incorporated into pharmaceutical compositions.
Description
SPECIFICATION
Soluble compounds having analgesic activity
This invention relates to salts of 5-(p-chlorobenzoyl)-1 ,4-dimethyl-pyrrole-2-acetic acid (I) with the basic aminoacid lysine (II) having the structural formula (A), and a method of preparing same.
The lysine may be either L-lysine or DL-lysine.
According to the present invention there is provided salts of L-lysine or DL-lysine with 5-(pchlorobenzoyl)-1 ,4-dimethyl-pyrrole-2-acetic acid, having the formula (A):
in which I is the said acid and II represents L-lysine or DL-lysine.
The salt obtained by using L-lysine will hereinafter be called L-(A) and the salt obtained with DLlysine will be called DL-(A). Compounds of the invention have excellent analgesic activity, as shown by phenylquinone writhing tests. In these tests, no substantial differences in activity were observed between the salt obtained with L-lysine and the salt obtained with DL-lysine. The acute toxicities of L (A) and DL-(A) in the mouse and the rat was also similar.
The compounds according to the invention are much more soluble in water than salts of (1) with inorganic cations. This, together with the near-neutral pH of the aqueous solutions, enables the compounds to be used in preparations for parenteral use.
The compounds according to the invention can be used in human therapy for the treatment of acute or chronic pain resulting from malignant neoplasia, oral surgery, osteoarthritis, headache of various origin, or general or orthopaedic surgery. The proposed forms of administration are oral, parenteral and rectal. For oral administration tablets, pills or capsules containing a quantity of (A) between 50 mg and 800 mg may be used. The estimated dose is 1-6 tablets, pills or capsules in 24 hours.
For parenteral administration, pre-packed solutions or vials containing compound (a) in
lyophilised form accompanied by vials of solvent excipient may be provided. The proposed amount of compound (A) in each vial is between 50 mg and 500 mg. The estimated dose is 1-3 vials per 24 hours.
For rectal administration suppositories containing between 100 mg and 1000 mg of compound (A) may be used. The estimated dose is 1-5 suppositories in 24 hours.
The analgesic activity of the compound (A) was studied in the phenylquinone writhing test, by the method described by Hendershot and Forsaith in J. Pharmacol. Exp. Therap, 123, 237 (1959). Male
COBS CD-1 mice, unfed for 3 hours, were orally given the compound under test 30 minutes before endoperitoneal injection of 0.25 ml of a 0.02% solution of phenylquinone in ethanol: water (5:95). Five minutes after injection of phenylquinone, the abdominal spasms (writhing) of each animal were counted for 1 5 minutes. Groups of 10 animals were used for each tested dose. The analgesic activity of the compound under examination, expressed as the EDso (the dose which reduces the number of abdominal contractions by 50% compared with the non-treated animals) was 0.72 mg/kg for L-(A) and 0.77 mg/kg for DL-(A).The oral LD50 for both compounds was above 1 g/kg for both the rat and the mouse.
The above-described high analgesic activity of compounds L-(A) and DL-(A) is accompanied by the complete absence of ulcerogenic activity. Male COBS CD (SD) rats weighing 1 60-200 g and unfed since the preceding evening were slightly anaesthetised with ether after which the pylorus was ligated. They were given drinking water after the operation.
Two hours later the rats were orally given L-(A), DL-(A), the sodium salt of I and aspirin in equimolecular doses, suspended in 5% gum arabic.
After an hour the rats were sacrificed and their stomachs were examined for the presence of ulcers.
The number of rats having ulcers and the average number of ulcers per rat were measured as follows:
% of rats Number of
with ulcers ulcers per rat
121 mg/kg of L-lysine O 0 1 21 mg/kg of DL-lysine O 0
97 mg/kg of sodium salt of 1 60 14
50 mg/kg of aspirin 100 34
This invention also provides a method of preparing compounds of formula (A), comprising reacting equimolecular quantities of I and II in the presence of water or water and alcohol, at a temperature of from 00 to 1 OO"C. The resulting salt may be isolated by concentration or cooling the solution or by the addition of a non-solvent.
The following examples illustrate the method according to the invention.
Example I
29.2 kg of 5-(p-chlorobenzoyl)-1 ,4-dimethyl-pyrrole-2-acetic acid were added at intervals over one hour to an aqueous solution of 50% L-lysine containing 14.6 kg L-lysine, heated to a temperature between 400C and 550C and continuously and efficiently stirred.
Agitation and heating were continued until a clear, yellow solution was obtained. After filtering, the solution was cooled to room temperature and 90 litres of acetone were added with slow agitation.
The mixture was cooled to 2-50C and left to stand at this temperature for 2 hours. The precipitate was collected by filtration, washed with 10 litres of acetone and then with 10 litres of ethyl ether. It was dried in a vacuum chamber at a temperature not above 400 C. The product was an ivory-white crystalline powder, melting with decomposition at 21 8-2200C. By a similar procedure DL-(A) melting at 205-2070C was obtained by using DL-lysine.
Example 2
35 kg distilled water and 10 kg ethanol were added to a 50% aqueous solution of L-lysine containing 7.3 kg of L-lysine. The mixture was heated to 45-500C and 14.6 kg of 5-(p chlornbenzoyl)-1 ,4-dimethyl-pyrrole-2-acetic acid were added in portions, with efficient agitation.
Agitation and heating were continued until the mixture dissolved. The resulting solution was filtered and concentrated to dryness in vacuo in a rotating evaporator. The yellowish residue obtained was dissolved in 120 kg absolute ethanol, the material being suspended with violent agitation. The mixture was cooled, with continued agitation, to 00C and 1 5 kg ethanol were added and the mixture was left to stand at 00C, for 8 hours. It was filtered and washed with 6 kg of ethanol and dried in a vacuum chamber at a temperature not above 450C.
Claims (5)
1. Salts of L-lysine or DL-lysine with 5-(p-chlorobenzoyl)-1 ,4-dimethyl-pyrrole-2-acetic acid, having the formula (A):
in which I is the said acid and il represents L-lysine or DL-lysine.
2. A method of preparing the compounds claimed in claim 1, comprising reacting equimolecular quantities of L-lysine or DL-iysine with 5-(p-chlorobenzoyl)-1 ,4-dimethyl-pyrrole-2-acetic acid in the presence of water or water and alcohol at temperatures between OOC and 1 000C.
3. A method as claimed in claim 2 in which the salt is isolated either by concentration or cooling the solution or by addition of a non-solvent.
4. Salts of formula (A) whenever prepared by the method claimed in claim 2 or 3.
5. A pharmaceutical composition having analgesic activity and suitable for treating acute or chronic pain resulting from malignant neoplasia, general, oral or orthopaedic surgery, osteoarthritis or headache of various origin comprising a compound claimed in claim 1 or claim 4 and a pharmaceutical vehicle.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT21949/81A IT1137229B (en) | 1981-05-26 | 1981-05-26 | ANALGESIC ACTIVITY SOLUBLE COMPOUND |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2098989A true GB2098989A (en) | 1982-12-01 |
| GB2098989B GB2098989B (en) | 1984-10-10 |
Family
ID=11189271
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8214547A Expired GB2098989B (en) | 1981-05-26 | 1982-05-19 | Lysine salts |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS57200359A (en) |
| KR (1) | KR860000292B1 (en) |
| BE (1) | BE893039A (en) |
| CA (1) | CA1171421A (en) |
| DE (1) | DE3219605A1 (en) |
| ES (1) | ES8302653A1 (en) |
| FR (1) | FR2506766A1 (en) |
| GB (1) | GB2098989B (en) |
| IT (1) | IT1137229B (en) |
| PT (1) | PT74949B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4568690A (en) * | 1983-07-29 | 1986-02-04 | Medosan Industrie Biochimide Riunite S.P.A. | 1-Methyl-5-p-methylbenzoylpyrrole-2-acetamidoacetanilides with antiinflammatory, analgesic, antipyretic and anti-platelet aggregant activity |
| US4578481A (en) * | 1982-02-26 | 1986-03-25 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Pyrrolacetic amides having antiinflammatory activity |
| US4873340A (en) * | 1986-05-29 | 1989-10-10 | Syntex (U.S.A.) Inc. | Process for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-A]pyrrole-1,1-dicarboxylates |
| US4988822A (en) * | 1986-05-29 | 1991-01-29 | Syntex (U.S.A.) Inc. | Intermediates for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo(1,2-A)pyrrole-1,1-dicarboxylates |
| US5017297A (en) * | 1988-08-17 | 1991-05-21 | Dow Corning Limited | Microemulsions for treating fibrous materials containing the reaction product of a silane and a siloxane |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3328401A1 (en) * | 1983-08-05 | 1985-02-21 | Merckle GmbH, 7902 Blaubeuren | INJECTABLE SOLUTION FOR TREATING INFLAMMATION |
| KR100898501B1 (en) * | 2007-09-03 | 2009-05-21 | 윤주평 | Solar tracking device using CDS device |
| KR101091936B1 (en) * | 2009-08-31 | 2011-12-08 | 에스디엔 주식회사 | Apparatus for detecting sunlight incident angle using pyranometer sensor |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4213905A (en) * | 1979-06-25 | 1980-07-22 | Mcneilab, Inc. | Preparation of 5-aroyl-1-loweralkylpyrrole-2-acetic acid salts |
-
1981
- 1981-05-26 IT IT21949/81A patent/IT1137229B/en active
-
1982
- 1982-04-30 BE BE0/207975A patent/BE893039A/en not_active IP Right Cessation
- 1982-05-19 GB GB8214547A patent/GB2098989B/en not_active Expired
- 1982-05-24 PT PT74949A patent/PT74949B/en unknown
- 1982-05-25 CA CA000403645A patent/CA1171421A/en not_active Expired
- 1982-05-25 ES ES512510A patent/ES8302653A1/en not_active Expired
- 1982-05-25 DE DE19823219605 patent/DE3219605A1/en not_active Withdrawn
- 1982-05-25 FR FR8209026A patent/FR2506766A1/en active Pending
- 1982-05-26 JP JP57089594A patent/JPS57200359A/en active Pending
- 1982-05-26 KR KR828202319A patent/KR860000292B1/en not_active Expired
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4578481A (en) * | 1982-02-26 | 1986-03-25 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Pyrrolacetic amides having antiinflammatory activity |
| US4882349A (en) * | 1982-02-26 | 1989-11-21 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A | Pyrrolacetic amides having antiinflammatory activity |
| US4568690A (en) * | 1983-07-29 | 1986-02-04 | Medosan Industrie Biochimide Riunite S.P.A. | 1-Methyl-5-p-methylbenzoylpyrrole-2-acetamidoacetanilides with antiinflammatory, analgesic, antipyretic and anti-platelet aggregant activity |
| US4873340A (en) * | 1986-05-29 | 1989-10-10 | Syntex (U.S.A.) Inc. | Process for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-A]pyrrole-1,1-dicarboxylates |
| US4988822A (en) * | 1986-05-29 | 1991-01-29 | Syntex (U.S.A.) Inc. | Intermediates for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo(1,2-A)pyrrole-1,1-dicarboxylates |
| US5017297A (en) * | 1988-08-17 | 1991-05-21 | Dow Corning Limited | Microemulsions for treating fibrous materials containing the reaction product of a silane and a siloxane |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57200359A (en) | 1982-12-08 |
| DE3219605A1 (en) | 1982-12-23 |
| ES512510A0 (en) | 1983-02-01 |
| CA1171421A (en) | 1984-07-24 |
| ES8302653A1 (en) | 1983-02-01 |
| KR830010067A (en) | 1983-12-26 |
| GB2098989B (en) | 1984-10-10 |
| PT74949A (en) | 1982-06-01 |
| BE893039A (en) | 1982-08-16 |
| FR2506766A1 (en) | 1982-12-03 |
| IT8121949A0 (en) | 1981-05-26 |
| KR860000292B1 (en) | 1986-03-26 |
| IT1137229B (en) | 1986-09-03 |
| PT74949B (en) | 1983-12-23 |
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