WO2005033089A1 - Salt of 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid with n, n-dimethyl-imidodicarbonimidic diamide - Google Patents
Salt of 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid with n, n-dimethyl-imidodicarbonimidic diamide Download PDFInfo
- Publication number
- WO2005033089A1 WO2005033089A1 PCT/IN2003/000329 IN0300329W WO2005033089A1 WO 2005033089 A1 WO2005033089 A1 WO 2005033089A1 IN 0300329 W IN0300329 W IN 0300329W WO 2005033089 A1 WO2005033089 A1 WO 2005033089A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- methyl
- isobenzofuranyl
- dihydro
- oxo
- methoxy
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Definitions
- 6-(l,3 ⁇ dihydro-4-hydroxy-6-methoxy-7-methyl-3- oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid, sodium salt or its 2-ethyl morphoiino derivative is used as immunosuppressants.
- 6- (l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5- isobenzofuranyl)-4-methyl-4-hexenoic acid is generally administered as a sodium salt or 2-ethyl morphoiino derivative so that active free acid is made available for absorption.
- Antihyperglycemic agents are used for treatment of diabetes.
- N, N- dimethyl- imidodicarbonimidic diamide is used for treatment of Non-insulin dependent diabetes mellitus (NIDDM).
- N, N-dimethyl- imidodicarbonimidic diamide is generally administered a HCI salt.
- the present inventions discloses a novel compound of formula I which can be simultaneously used as an immunosuppressant and antihyperglycemic agent for the treatment of diabetic nephropathy.
- SUMMARY OF THE INVENTION The present invention discloses a novel compound of formula I. The compound can be simultaneously used as an immunosuppressant and antihyperglycemic agent for the treatment of diabetic nephropathy.
- FORMULA I The important embodiment of the invention is that the compound of formula I, wherein the two drug molecules form a mutual salt which can be called X N, N-dimethyl- imidodicarbonimidic diamide salt of 6-(l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3- oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid.
- the invention discloses the compound of formula I, wherein the 6-(l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5- isobenzofuranyl)-4-methyl-4-hexenoic acid is an immunosuppressive drug and N, N-dimethyl- imidodicarbonimidic diamide is an antihyperglycemic drug.
- the compound of formula I is formed when the two compounds are treated with each other under suitable conditions to form a non-covalent bond between the carboxylic group of 6- (l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5- isobenzofuranyl)-4-methyl-4-hexenoic acid and nitrogen of N, N- dimethyl- imidodicarbonimidic diamide.
- the non- covalent bond thus formed is an ionic bond between 6-(l,3- dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)- 4-methyl-4-hexenoic acid and N, N-dimethyl- imidodicarbonimidic diamide.
- the compound of formula I is a mutual salt of 6-(l,3- dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)- 4-methyl-4-hexenoic acid and N, N-dimethyl- imidodicarbonimidic diamide.
- compound of formula I retain the free acid form of 6-(l,3-dihydro- 4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl- 4-hexenoic acid.
- Compound of formula I have the extra advantage of delivering the free acid form of 6-( ⁇ ,3-dihydro-4-hydroxy-6- methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid without employing any metal cation. Unlike prior art, compound of formula I delivers N, N- dimethyl- imidodicarbonimidic diamide free-base without employing any other acid salt like hydrochloride salt.
- the following non-limiting examples illustrate the inventors' preferred method for preparing the compound of the invention.
- reaction mixture was chilled (10-15° C) and filtered to afford the mutual salt of 6-(l,3-dihydro-4-hydroxy-6- methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic5 acid and N, N-dimethyl- imidodicarbonimidic diamide.
- Example 2 To a solution of 6-(l,3-dihydro-4-hydroxy-6-methoxy-7- methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid (10 g, 0.03 mol) in isobutyl acetate (75 ml), N, N-dimethyl-o imidodicarbonimidic diamide free base (4.0 g, 0.03 mol) was added and stirred.
- reaction mixture was chilled (10-15° C) and filtered o afford the mutual salt of 6-(l,3-dihydro-4-hydroxy-6-methoxy-7- methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid and N, N-dimethyl- imidodicarbonimidic diamide.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2003272083A AU2003272083A1 (en) | 2003-10-07 | 2003-10-07 | Salt of 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid with n, n-dimethyl-imidodicarbonimidic diamide |
PCT/IN2003/000329 WO2005033089A1 (en) | 2003-10-07 | 2003-10-07 | Salt of 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid with n, n-dimethyl-imidodicarbonimidic diamide |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/IN2003/000329 WO2005033089A1 (en) | 2003-10-07 | 2003-10-07 | Salt of 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid with n, n-dimethyl-imidodicarbonimidic diamide |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2005033089A1 true WO2005033089A1 (en) | 2005-04-14 |
Family
ID=34401267
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IN2003/000329 WO2005033089A1 (en) | 2003-10-07 | 2003-10-07 | Salt of 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid with n, n-dimethyl-imidodicarbonimidic diamide |
Country Status (2)
Country | Link |
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AU (1) | AU2003272083A1 (en) |
WO (1) | WO2005033089A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008003637A2 (en) * | 2006-07-05 | 2008-01-10 | Dsm Ip Assets B.V. | Isolation and use of amine salts of mycophenolic acid |
US7683188B2 (en) | 2004-04-26 | 2010-03-23 | TEVA Gyógyszergyár Zártkōrūen Mūkōdō Részvénytársaság | Process for preparation of mycophenolic acid and ester derivatives thereof |
WO2010146604A2 (en) | 2009-06-18 | 2010-12-23 | Exemed Pharmaceuticals | Processes for preparing metformin hydrochloride |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4948793A (en) * | 1987-01-30 | 1990-08-14 | Syntex (U.S.A.) Inc. | Treatment of autoimmune diseases with the morpholinoethyl ester of mycophenolic acid, and derivatives thereof |
WO2003011273A1 (en) * | 2001-07-31 | 2003-02-13 | The Governement Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Metformin in the treatment of hyperglycemic conditions |
-
2003
- 2003-10-07 AU AU2003272083A patent/AU2003272083A1/en not_active Abandoned
- 2003-10-07 WO PCT/IN2003/000329 patent/WO2005033089A1/en active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4948793A (en) * | 1987-01-30 | 1990-08-14 | Syntex (U.S.A.) Inc. | Treatment of autoimmune diseases with the morpholinoethyl ester of mycophenolic acid, and derivatives thereof |
WO2003011273A1 (en) * | 2001-07-31 | 2003-02-13 | The Governement Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Metformin in the treatment of hyperglycemic conditions |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7683188B2 (en) | 2004-04-26 | 2010-03-23 | TEVA Gyógyszergyár Zártkōrūen Mūkōdō Részvénytársaság | Process for preparation of mycophenolic acid and ester derivatives thereof |
WO2008003637A2 (en) * | 2006-07-05 | 2008-01-10 | Dsm Ip Assets B.V. | Isolation and use of amine salts of mycophenolic acid |
WO2008003637A3 (en) * | 2006-07-05 | 2008-05-08 | Dsm Ip Assets Bv | Isolation and use of amine salts of mycophenolic acid |
WO2010146604A2 (en) | 2009-06-18 | 2010-12-23 | Exemed Pharmaceuticals | Processes for preparing metformin hydrochloride |
Also Published As
Publication number | Publication date |
---|---|
AU2003272083A1 (en) | 2005-04-21 |
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