GB970440A - Anti-inflammatory compositions comprising steroids and indole derivatives - Google Patents
Anti-inflammatory compositions comprising steroids and indole derivativesInfo
- Publication number
- GB970440A GB970440A GB29735/62A GB2973562A GB970440A GB 970440 A GB970440 A GB 970440A GB 29735/62 A GB29735/62 A GB 29735/62A GB 2973562 A GB2973562 A GB 2973562A GB 970440 A GB970440 A GB 970440A
- Authority
- GB
- United Kingdom
- Prior art keywords
- methyl
- indolyl
- methoxy
- ethyl
- propionate
- 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
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—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
- C07D209/22—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 with an aralkyl radical attached to the ring nitrogen atom
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—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
- C07D209/26—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 with an acyl radical attached to the ring nitrogen atom
- C07D209/28—1-(4-Chlorobenzoyl)-2-methyl-indolyl-3-acetic acid, substituted in position 5 by an oxygen or nitrogen atom; Esters thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical 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)
- Indole Compounds (AREA)
Abstract
a -(2-Methyl-5-lower alkoxy-3-indolyl)-lower fatty acid derivatives and the corresponding 5-lower alkyl compounds of the general formula <FORM:0970440/C1/1> wherein A represents -CH2- or <FORM:0970440/C1/2> , R is a hydrogen atom or a methyl radical, R2 is a C1-5 alkyl or C1-5 alkoxy radical, Y is a hydrogen atom, a C1-5 alkyl radical or an equivalent of a metal, and R1 is a hydrogen, chlorine, bromine or fluorine atom or a C1-5 alkyl, mercapto, methylmercapto, methoxy, hydroxy, cyano, trifluoromethyl, nitro, acyl or amino radical, and, when R1 is a chlorine, bromine or fluorine atom, one or more such atoms are attached to the ring, may be prepared by reacting an aralkyl or aroyl halide with the sodium derivative of an a -(2-methyl-5-substituted-3-indolyl)-lower aliphatic acid ester of the general formula <FORM:0970440/C1/3> (where R is a hydrogen atom or a methyl radical, R2 is a C1-5 alkyl or alkoxy radical and Y is a C1-5 alkyl radical and, if desired, converting the resulting ester into the free acid or a salt thereof. Specific examples relating to the preparation of such compounds and intermediates are as follows: (A) Ethyl-a -(2-methyl-5-methoxy-3-indolyl)-propionate; Ethyl-a -(2,5-dimethyl-3-indolyl)-propionate and the corresponding acetates are prepared by reacting the appropriately substituted phenylhydrazine with ethyl-a -methyl-laevulinate or ethyl laevulinate. They may be saponified to the corresponding free acids by treatment with sodium hydroxide. (B) a -(1-p-Chlorobenzyl-2-methyl-5-methoxy-3-indolyl)-propionic acid is prepared by reacting ethyl-a -(2-methyl-5-methoxy-3-indolyl)-propionate with p-chlorobenzyl chloride in the presence of sodium hydride to give ethyl-a -(1-p-chlorobenzyl -2-methyl-5-methoxy-3-indolyl)-propionate which is saponified to the free acid. The corresponding acetic acid derivative is similarly prepared from its acetate ester and from ethyl-a -(2,5-dimethyl-3-indolyl)-propionate there may be similarly obtained ethyl-a -(1-p-chlorobenzyl-2,5-dimethyl-3-indolyl)-propionate and the free acid. (C) a -(1-p-Methylthiobenzyl-2-methyl-5-methoxy -3-indolyl)-propionic acid is prepared by reacting thioanisole with chloromethyl methyl ether to give p-methylthiobenzyl chloride which is reacted with ethyl-a -(2-methyl-5-methoxy-3-indolyl)-propionate to give ethyl a -(1-p-methylthiobenzyl-2-methyl-5-methoxy-3-indolyl)-propionate which may be saponified to the free acid which may be converted to the sodium or aluminium salts. The corresponding (1-p-methylthiobenzyl-2-methyl-5-methoxy-3-indolyl)-acetate and the free acid may be similarly prepared from ethyl (2-methyl-5-methoxy-3-indolyl)-acetate. (D) a -(2-Methyl-5-methoxy-3-indolyl)-propionic anhydride is prepared by treating 2-methyl-5-methoxy-3-indolyl-a -propionic acid with dicyclohexylcarbodiimide and is converted to t-butyl a -(2-methyl-5-methoxy-3-indolyl)-propionate by treatment with t-butyl alcohol and zinc chloride. Treatment of this t-butyl ester with p-methylthiobenzoyl chloride or p-chlorobenzoyl chloride yields t-butyl a -(1-p-methylthiobenzoyl-2-methyl-5-methoxy-3-indolyl)-propionate or the corresponding 1-p-chlorobenzoyl compound both of which may be converted to the free acids by heating to 215 DEG C. under nitrogen. By similar reactions and commencing with 2-methyl-5-methoxy-3-indolyl acetic acid, there are produced (a) 2-methyl-5-methoxy-3-indolyl acetic anhydride, (b) t-butyl 2-methyl-5-methoxy-3-indolyl acetate, (c) t-butyl (1 - p - chlorobenzoyl - 2 - methyl -5- methoxy-3-indolyl)-acetate and, (d) the corresponding free acid. Racemic forms of compounds produced as above may be resolved by the method described in Specification 957,990.ALSO:Pharmaceutical anti-inflammatory compositions comprise an anti-inflammatory steroid compound and a compound of the general formula <FORM:0970440/A5-A6/1> wherein A is > CH2 or > C = O, R is a hydrogen atom of a methyl radical, Y is a hydrogen atom or a methyl radical, Y is a hydrogen atom or a lower (C1-5) alkyl radical or a metal (e.g. Na, K, Al, Mg), R2 is a C1-5 alkyl or C1-5 alkoxy radical and R1 is a hydrogen, chlorine, fluorine or bromine atom or a C1-5 alkyl, mercapto, methyl mercapto, methoxy, hydroxy, cyano, trifluoromethyl, nitro, acyl or amino radical. When R1 is halogen, one or more such atoms may be attached to the benzene ring. Specified steroids are cortisone, hydrocortisone, prednisone, prednisolone, dexamethasone, triamcinolone, D 6-dexamethasone, 6a -methyl prednisolone, 6a -fluoro dexamethasone, 16b -methyl-9a -fluoro-prednisolone and 9a -chloro-16a -methyl prednisolone. They may be in forms suitable for oral, parenteral and topical application, e.g. a tablet, capsule, syrup, elixir, cream, ointmennt, jelly, sterile and non-sterile solutions and suspensions which may comprise conventional pharmaceutical excipients. Specification 957,990 is referred to.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13109361A | 1961-08-14 | 1961-08-14 |
Publications (1)
Publication Number | Publication Date |
---|---|
GB970440A true GB970440A (en) | 1964-09-23 |
Family
ID=22447849
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB29735/62A Expired GB970440A (en) | 1961-08-14 | 1962-08-02 | Anti-inflammatory compositions comprising steroids and indole derivatives |
Country Status (3)
Country | Link |
---|---|
CY (1) | CY319A (en) |
FR (1) | FR2354M (en) |
GB (1) | GB970440A (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991006537A2 (en) * | 1989-10-27 | 1991-05-16 | American Home Products Corporation | Substituted indole-, indene-, pyranoindole- and tetrahydrocarbazole- alkanoic acid derivatives as inhibitors of pla2 and lipoxygenase |
WO1996037468A1 (en) * | 1995-05-22 | 1996-11-28 | Merck Frosst Canada Inc. | N-benzyl-3-indoleacetic acids as cyclooxygenase-2-inhibitors and antiinflammatory drugs |
WO2004073685A1 (en) * | 2003-02-20 | 2004-09-02 | Constant Research & Development Limited | Dexamethasone-containing formulations for oral administration as well the process for manufacturing required therefor |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5707981A (en) * | 1994-07-28 | 1998-01-13 | Psorial, L.L.C. | Synergistic pharmaceutical compositions |
-
1962
- 1962-08-02 GB GB29735/62A patent/GB970440A/en not_active Expired
- 1962-08-13 FR FR906853A patent/FR2354M/en active Active
-
1965
- 1965-10-01 CY CY31965A patent/CY319A/en unknown
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991006537A2 (en) * | 1989-10-27 | 1991-05-16 | American Home Products Corporation | Substituted indole-, indene-, pyranoindole- and tetrahydrocarbazole- alkanoic acid derivatives as inhibitors of pla2 and lipoxygenase |
WO1991006537A3 (en) * | 1989-10-27 | 1991-10-17 | American Home Prod | Substituted indole-, indene-, pyranoindole- and tetrahydrocarbazole- alkanoic acid derivatives as inhibitors of pla2 and lipoxygenase |
WO1996037468A1 (en) * | 1995-05-22 | 1996-11-28 | Merck Frosst Canada Inc. | N-benzyl-3-indoleacetic acids as cyclooxygenase-2-inhibitors and antiinflammatory drugs |
WO2004073685A1 (en) * | 2003-02-20 | 2004-09-02 | Constant Research & Development Limited | Dexamethasone-containing formulations for oral administration as well the process for manufacturing required therefor |
Also Published As
Publication number | Publication date |
---|---|
FR2354M (en) | 1964-02-24 |
CY319A (en) | 1965-10-01 |
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