GB1397647A - Thiophene derivatives - Google Patents
Thiophene derivativesInfo
- Publication number
- GB1397647A GB1397647A GB3609572A GB3609572A GB1397647A GB 1397647 A GB1397647 A GB 1397647A GB 3609572 A GB3609572 A GB 3609572A GB 3609572 A GB3609572 A GB 3609572A GB 1397647 A GB1397647 A GB 1397647A
- Authority
- GB
- United Kingdom
- Prior art keywords
- alkyl
- compound
- alkoxy
- give
- phenyl
- 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
-
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/32—Oxygen atoms
Abstract
1397647 Thiophen derivatives SANDOZ Ltd 2 Aug 1972 [6 Aug 1971 (10)] 36095/72 Heading C2C Novel compounds I and salts thereof in which R 1 is H or 1-4 C alkyl; R 2 is OH, 1-4 C alkoxy, 3-6 C cycloalkoxy, 3-6 C cycloalkyl-1-4 C alkoxy, NH 2 , 1-4 C alkylamino or di-(1-4 C alkyl) amino; or R 1 and R 2 together form a single band; R 3 is H, Cl, or 1-4 C alkyl or if R 1 is H or if R 1 and R 2 are together a single bond then R 3 may be OH, or if R 1 is 1-4 C alkyl then R 3 may be 1-4 C alkoxy; R 4 is H, Cl, Br or 1-4 C alkyl or if R 1 is H or if R 1 and R 2 are together a single bond then R 4 may be OH, or if R 1 is 1-4 C alkyl then R 4 may be 1-4 C alkoxy, or if R 3 is H, then R 4 may be F or CF 3 ; R 5 is H or 1-4 C alkyl and R 6 is H or CH 3 ; are prepared by (i) solvolysing -CN to -COR<SP>1</SP> 2 (R<SP>1</SP> 2 is OH, NH 2 , alkoxy, cycloalkoxy or cycloalkyl-alkoxy) in a compound II (in which R<SP>AT</SP> is H or alkyl; R<SP>1</SP> 3 is H, Cl or alkyl or if R<SP>1</SP> 1 is H, R<SP>1</SP> 3 may be OH or if R<SP>1</SP> 1 is alkyl, R<SP>1</SP> 3 may be alkoxy; R<SP>1</SP> 4 is H, Cl, Br or alkyl or if R<SP>1</SP> 1 is H, R<SP>1</SP> 4 may be OH or if R<SP>1</SP> 1 is alkyl, R<SP>1</SP> 4 may be alkoxy or if R<SP>1</SP> 3 is H, R<SP>1</SP> 4 may be F or CF 3 ) to give a compound Ia (ii) hydrolysing a compound Ic (in which R<SP>11</SP> 2 is alkoxy, cycloalkoxy or cycloalkyl-alkoxy) to give a compound Ib (iii) esterifying a compound Ib to give a compound Ic; (iv) reacting a compound Ie (in which R<SP>IV</SP> 2 is OH, alkoxy, cycloalkoxy, cycloalkyl-alkoxy, NH 2 , or mono- or di-alkylamino) with a compound R<SP>1</SP> 5 X (in which R<SP>1</SP> 5 is alkyl and X is iodo, Cl, Br, R<SP>1</SP> 5 SO 2 or an organic sulphonate group) to give a compound Id (in which R<SP>11</SP> 1 is alkyl, R<SP>111</SP> 2 is as R<SP>IV</SP> 2 , R<SP>11</SP> 3 is H, Cl, alkyl or alkoxy; and R<SP>11</SP> 4 is H, Cl, Br, alkyl or alkoxy or if R<SP>11</SP> 3 is H, R<SP>11</SP> 4 may be F or CF 3 ); (v) reacting an acid Ib or a reactive derivative thereof with a compound HR<SP>v</SP> 2 (in which R<SP>V</SP> 2 is NH 2 or mono or dialkylamino) to give a compound If (vi) splitting the ether groups in a compound Ih to give a compound Ig (in which R<SP>111</SP> 3 is H, Cl, alkyl or OH and R<SP>111</SP> 4 is H @ Cl, Br, alkyl or OH or if R<SP>111</SP> 3 is H, R<SP>111</SP> 4 may be F or CF 3 ) ; or (vii) cyclizing a compound Ij to give a compound Ii 4 - Methoxy - 5 - phenyl - 3 - thiophene - carboxylic acid ethyl ester is prepared by reaction of the corresponding 4-hydroxy compound with NaH and CH 3 I. On reduction of the 4 methoxy compound with LiAlH 4 4-methoxy-5-phenyl-3- thenyl alcohol is produced. This may be reacted with SOCl 2 to give 4-methoxy-5-phenyl-3-thenyl chloride which may then be reacted with NaCN to give 4-methoxy-5-phenyl-3-thiophene-acetonitrile. Compounds similar to the above intermediates but in which the phenyl moiety is substituted by F, Cl, CH 3 or OCH 3 are prepared similarly. Ethyl 5-(3-chlorophenyl)-4-hydroxy-3-thiophene carboxylate is prepared by reaction of ethyl #- mercaptopropionate with ethyl α-bromo-3- chlorophenylacetate to give ethyl α-[2-(carbethoxy)ethylthio]-3-chlorophenyl acetate, reaction of this with sodium ethylate to give ethyl 5-(3- chlorophenyl)-tetrahydro-4-oxo-3-thiophene carboxylate and reaction of this with H 2 O 2 . Compounds similar to these intermediates but in which the phenyl moiety is unsubstituted or substituted, not by Cl, but by CF 3 , CH 3 , two Cl atoms, F, two OCH 3 groups &c, are prepared similarly. 4-Hydroxy-5-phenyl-3-thiophene-acetonitrile is prepared by reaction of 4-methoxy-5-phenyl-3- thiophene-acetonitrile with sodium ethylate mercaptide solution. Compounds in which the phenyl moiety is substituted by F, Cl, CH 3 &c. are prepared similarly. 2 - (4 - methoxy - 5 - phenyl - 3 - thienyl)- propionyl chloride is prepared by reaction of the appropriate acid with SOCl 2 . Pharmaceutical compositions having antiphlogistic properties and arthritis-inhibiting effect comprise a compound I or a suitable salt together with a carrier or diluent.
Applications Claiming Priority (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH1162171 | 1971-08-06 | ||
CH1161771A CH553203A (en) | 1971-08-06 | 1971-08-06 | 4-Alkoxy or hydroxy-5-phenyl-3-thienylalkano-ic acids - antiphlogistics |
CH1162471 | 1971-08-06 | ||
CH1162571 | 1971-08-06 | ||
CH1162071 | 1971-08-06 | ||
CH1161971 | 1971-08-06 | ||
CH1161871 | 1971-08-06 | ||
CH1162671 | 1971-08-06 | ||
CH1162271 | 1971-08-06 | ||
CH1162371 | 1971-08-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1397647A true GB1397647A (en) | 1975-06-11 |
Family
ID=27579081
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB3609572A Expired GB1397647A (en) | 1971-08-06 | 1972-08-02 | Thiophene derivatives |
Country Status (6)
Country | Link |
---|---|
JP (1) | JPS4826755A (en) |
BE (1) | BE787235A (en) |
DD (1) | DD99999A5 (en) |
GB (1) | GB1397647A (en) |
HU (1) | HU166152B (en) |
IL (1) | IL40051A0 (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2143234A (en) * | 1983-07-06 | 1985-02-06 | Shinogi Seiyaku Kabushiki Kais | (oxoheterocyclic carbonamido) cephem carboxylic acid derivatives |
US4820719A (en) * | 1985-04-19 | 1989-04-11 | Smithkline Beckman Corporation | Leukotriene antagonists |
US4939279A (en) * | 1985-04-19 | 1990-07-03 | Smithkline Beecham Corporation | Leukotriene antagonists |
US4954513A (en) * | 1988-12-23 | 1990-09-04 | Smithkline Beecham Corporation | Leukotriene antagonists |
US5143931A (en) * | 1982-06-24 | 1992-09-01 | Smithkline Beecham Corporation | Leukotriene antagonists containing tetrazolyl groups |
US5314918A (en) * | 1987-06-24 | 1994-05-24 | Smithkline Beecham Corporation | Leukotriene antagonists |
CN101959875A (en) * | 2008-02-29 | 2011-01-26 | 日产化学工业株式会社 | Process for production of thiophene compound and intermediate thereof |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2936295A (en) * | 1994-07-13 | 1996-02-16 | Taisho Pharmaceutical Co., Ltd. | Thiopheneacetic acid derivative |
-
0
- BE BE787235D patent/BE787235A/en unknown
-
1972
- 1972-07-20 DD DD164559A patent/DD99999A5/xx unknown
- 1972-08-02 GB GB3609572A patent/GB1397647A/en not_active Expired
- 1972-08-04 JP JP47078703A patent/JPS4826755A/ja active Pending
- 1972-08-04 HU HUSA2385A patent/HU166152B/hu unknown
- 1972-08-04 IL IL40051A patent/IL40051A0/en unknown
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5143931A (en) * | 1982-06-24 | 1992-09-01 | Smithkline Beecham Corporation | Leukotriene antagonists containing tetrazolyl groups |
GB2143234A (en) * | 1983-07-06 | 1985-02-06 | Shinogi Seiyaku Kabushiki Kais | (oxoheterocyclic carbonamido) cephem carboxylic acid derivatives |
US4820719A (en) * | 1985-04-19 | 1989-04-11 | Smithkline Beckman Corporation | Leukotriene antagonists |
US4874792A (en) * | 1985-04-19 | 1989-10-17 | Smithkline Beckman Corporation | Thiophenyl Alkanoic acids useful as leukotriene antagonists |
US4939279A (en) * | 1985-04-19 | 1990-07-03 | Smithkline Beecham Corporation | Leukotriene antagonists |
US5314918A (en) * | 1987-06-24 | 1994-05-24 | Smithkline Beecham Corporation | Leukotriene antagonists |
US4954513A (en) * | 1988-12-23 | 1990-09-04 | Smithkline Beecham Corporation | Leukotriene antagonists |
CN101959875A (en) * | 2008-02-29 | 2011-01-26 | 日产化学工业株式会社 | Process for production of thiophene compound and intermediate thereof |
CN101959875B (en) * | 2008-02-29 | 2013-10-16 | 日产化学工业株式会社 | Process for production of thiophene compound and intermediate thereof |
RU2495877C2 (en) * | 2008-02-29 | 2013-10-20 | Ниссан Кемикал Индастриз, Лтд. | Method of producing thiophene derivative and intermediate product thereof |
CN103360290A (en) * | 2008-02-29 | 2013-10-23 | 日产化学工业株式会社 | Process for producing thiophene compound and intermediate thereof |
CN103435593B (en) * | 2008-02-29 | 2015-01-28 | 日产化学工业株式会社 | Process for production of thiophene compound and intermediate thereof |
CN103360290B (en) * | 2008-02-29 | 2015-04-01 | 日产化学工业株式会社 | Process for producing thiophene compound and intermediate thereof |
Also Published As
Publication number | Publication date |
---|---|
JPS4826755A (en) | 1973-04-09 |
HU166152B (en) | 1975-01-28 |
IL40051A0 (en) | 1972-10-29 |
DD99999A5 (en) | 1973-09-05 |
BE787235A (en) | 1973-02-05 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PS | Patent sealed [section 19, patents act 1949] | ||
PLNP | Patent lapsed through nonpayment of renewal fees |