GB2113676A - m-Hydroxyphenyl substituted compounds - Google Patents
m-Hydroxyphenyl substituted compounds Download PDFInfo
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- GB2113676A GB2113676A GB08232536A GB8232536A GB2113676A GB 2113676 A GB2113676 A GB 2113676A GB 08232536 A GB08232536 A GB 08232536A GB 8232536 A GB8232536 A GB 8232536A GB 2113676 A GB2113676 A GB 2113676A
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- hydrogen
- alkyl
- compound
- oxocyclohex
- general formula
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/08—Oxygen atoms
- C07D223/10—Oxygen atoms attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
Abstract
m-Hydroxyphenyl substituted compounds of formula <IMAGE> where R is an organic radical and R<1> is hydrogen or an organic radical are prepared by dehydrohalogenating a compound of formula <IMAGE> (where X is chlorine or bromine, and R and R<1> have the above meanings). Preferred novel starting materials of formula (II) are of the formula <IMAGE> (where R<1> and X are as above, n is 2, 3 or 4, R<2> is hydrogen or lower alkyl and R<3> is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl(lower)alkyl or aryl(lower)alkyl).
Description
SPECIFICATION m-Hydroxyphenyl substituted compounds
This invention relates to m-hydroxyphenyl substituted compounds, to their preparation and to intermediates used in their preparation.
Many m-hydroxyphenyl substituted compounds are known and are useful particularly as pharmaceuticals.
For example analgesic 3-hydroxyphenyl-hexahydroazepines such as meptazinol are disclosed in U.K. Patent
Specification No. 1,285,025. Profadol and related pyrrolidines are described in J. Med. Chem. 1965,8,316 and Belgian Patent Specification No. 850,777 while myfadol and related piperidines area described in J. Med.
Chem., 1965,8, 313. We have now found a novel process for preparing m-hydroxyphenyl substituted compounds. The process can be used in the preparation of pharmacologically active compounds such as those mentioned above.
According to the invention there is provided a process for preparing m-hydroxyphenyl substituted compounds of the general formula
where R is an organic radical and R1 is hydrogen or an organic radical, which process comprises dehydrohalogenating a compound of the general formula
(where R is an organic radical, R1 is hydrogen or an organic radical and Xis chlorine or bromine) in the presence of a strong nucleophilic acid catalyst.
The organic radical Rand also R1 when it is an organic radical, may be an aliphatic, aromatic or heterocyciic radical. The radicals may contain substituents, including functional groups. Some substituents may be modified under the conditions of the reaction so that the organic radical R or R1 in the starting material may be different from the organic radical R or R1 in the product.
Preferably R1 is hydrogen. When R is a heterocyclic radical it can be, for example, a monocyclic or bicyclic heterocyclic radical containing one or more hetero atoms. The hetero atoms or atoms may be, for example, oxygen, sulphur or nitrogen. Examples of heterocyclic radicals include pyrrolidine, piperidine and hexahydroazepine radicals, particularly those of the formula (III)
where n is 2,3 or 4 (preferably 4), R2 is hydrogen or lower alkyl and R3 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl(lower)alkyl or aryl(lower)alkyl. The term "lower" as used herein means that the radical referred to contains 1 to 6 carbon atoms. The radical preferably contains 1 to 4 carbon atoms. For example, a lower alkyl radical is preferably methyl, ethyl, propyl or butyl.Examples of lower alkenyl and lower alkynyl radicals are allyl, propargyl, 3,3-dimethyiallyl and 1-methyl-2-prnpynyl. An example of cycloalkyl(lower)alkyl is cyclopropylmethyl. Examples of aryl(lower)aikyl are phenethyl or benzyl in which the phenyl group may be substituted by one or more substituents such as halogen, alkoxy, trifluoromethyl or other substituents common in medicinal chemistry.
Compounds of general formula II in which X has the meaning given above, R1 has the meaning given above (preferably hydrogen) and the radical R has formula (III) are novel compounds and are provided by the invention.
The compound of formula (I) in which R1 is hydrogen and R has the formula (III) (where R2 is lower alkyl and and R3 and n are as defined above) may be reduced e.g. with a hydride transfer agent, such as lithium aluminium hydride to a compound of formula (IV)
(where R4 is lower alkyl and n and R3 have the meanings given above). The compounds of general formula (IV) are useful as analgesics or as intermediates therefor as explained, for example, in the above mentioned refernnces. The compound of general formula (IV) in which R3 is methyl, n is 4 and R4 is ethyl is the analgesic, meptazinol. Compounds of formula I in which R has the formula (III) where R2 is hydrogen may be
C-alkylated to give corresponding compounds in which R2 is lower alkyl.Compounds of formula I or of formula (IV) in which R3 is hydrogen may be N-alkylated to give compounds in which R3 is lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl(lower)alkyl or aryi(lower)alkyl. The reduction, C-alkylation and N-alkylation processes are further described in, for example, U.K. Patent Specification No. 1,285,025 and European Patent
Application No. 0,003,253.
The process of the invention may also be used, for example, in the preparation of compounds of formula (I) in which R is a carboxymethyl radical or a derivative therefor such as -CH2COO(lower)alkyl and R1 is (lower)alkyl, phenyl or substituted phenyl such as chlorophenyl (the substituent R1 being meta to both the R group and the hydroxy group). Such compounds have anti-inflammatory activity or are useful as intermediates for anti-inflammatory compounds as disclosed by Tamura et al, J.Med.Chem. 1977,20, 709-714.
The process of the inventon may also be used in the preparation of a compound of formula (I) in which R is hydrogen and R is
i.e. a m-hydroxyphenyl substituted compound of formula formula
The compound is prepared by dehydrohalogenating a compound of general formula
where Xis chlorine or bromine (preferably bromine) by the process of the invention.
The product of general formula (VI) may be reduced with, for example, a hydride transfer agent (preferably borane-tetrahydrofuran complex) to give a 3-(1-prnpyl-3-piperidinyl)phenol of formula
The compound of general formula (VIII) and its pharmaceutically acceptable acid addition salts are known and stated to be selective dopamine autoreceptor agonists which can be used e.g. for the treatment of disease states associated with disturbances in central dopamine autoreceptortransmission.
The process of the invention may be carried out in a solvent such as methylene chloride, chloroform or acetic acid, e.g. under substantially an hydros conditions. The reaction may be carried out at ambient temperatures. The strong nucleophilic acid catalyst may be for example, hydrogen bromide or hydrogen chloride. The process has advantages over conventional processes of aromatisation since the starting materials are normally easily isolated, the process employs mild conditions and the process avoids the use of bromine which is difficult to handle on a large scale and which tends to result in overbrominated products.
The starting material, of formula (II) may be prepared by reacting a 2-halocyclohexenone derivative of general formula (IX)
where X and R1 are as defined above and Q is a hydrolysable protecting group such as lower alkoxy, benzyloxy or trialkyl-, triaryl- or triaralkyl-siloxy (e.g. trimethyl-silyloxy) with a nucleophilic reagent and subjecting the product to hydrolysis. For example, where R in formula (II) is a radical of formula (III) the nucleophilic reagent may be an anion or dianion of a lactam of general formula (X)
(where n and R2 are as defined above and R5 is hydrogen, lower alkyl, aryllower alkyl, or trialkyl-, triaryl or triaralkyl-silyl). The preparation and reactions of the anion or dianion of the lactam of formula (VI) is described in, for example, European Patent Application 0003253.When R is formula (II) has the formula (V), the nucleophilic reagent may be an anion (preferably the sodium, potassium, lithium or MgHal anion) of a lactam of general formula (XI)
The anion of the lactam may be prepared by reacting the lactam with e.g. lithium diisopropylamide.
The 2-halocyclohexanone derivatives of general formula (IX) are known or can be prepared by the process illustrated below
The halogenation step (Xl) to (XII) may be carried out by methods known in the art (by reaction with, e.g.
N-bromosuccinimide or N-chlorosuccinimide in a solvent such as carbon tetrachloride with sulphuryl chloride in a solvent such as chloroform or with chlorine or bromine). However, for superior yields, we prefer to brominate using aqueous potassium bromate in aqueous hydrobromic acid orto chlorinate with an aqueous solution of Chloramine T (N-chloro-4-methylbenzenesulphonamide sodium salt).
The halogenation step (XIII) to (IX) may also be carried out by methods known in the art. Preferably in this step Xis bromine and the bromination may be carried out, e.g. with bromine in, for example, sodium acetate/acetic acid or with N-bromosuccinimide in, for example, carbon tetrachloride. However, preferably the bromination is effected with N-bromosuccinimide in a more polar solvent such as dichloroethane or acetonitrile.
the steps (Xl) to (XIII) and (XII) to (IX) may be carried out by methods known in the art, for example (XI) or (XII) may be reacted with an alcohol in a solvent such as toluene in the presence of an acid with azeotropic removal of water. An alternative method of alkylation is described and claimed in ourcopending U.K.
application filed concurrently herewith which claims priority from U.K. patent applications 8136364 and 8211201 and which has the title "3-Alkoxycycloalk-2-en-1-ones" (our ref H-312/317). Reaction of compounds (XII) or (XIII) with silylating agents (such as trimethylsilyl chloride in the presence of an organic base) gives compounds in which Q is trialkyl-, triaryl- ortriaralkyl-silyloxy.
The following Examples illustrate the invention:
EXAMPLE 1 3-(2-Chloro-3-oxocyclohex- 1-enyl)-hexahydryo- 1-methylazepin-2-one
Lithium disiopropylamide was prepared from n-butyllithium (1.55M in hexane, 6.45 ml) and diisopropylamine (1.4 ml) in tetrahydrofuran (10 ml). It was treated at 0 C with 1-methylcaprolactam (1.27g) and then with 2-chloro-3-methoxycyclohexenone (1.61 g) in THF (5 ml). The reaction mixture was stirred for 5 minutes and then poured on to cold 2N hydrochloric acid. After 2 hourtoluene was added and the layers separated.The organic phase was washed with aqueous NaOH and water, dried and evaporated to give the crystalline product (1.9 g) m.p. 118-120"C. (Found: C, 61.4; H, 7.3; N, 5.3%. C13H18CIN02 requires C, 61.1; H, 7.1; N, 5.5%).
EXAMPLE 2 3-(2-Brorno-3-oxocyclohex- 1-en yl)-hexah ydro- 1-meth ylazepin-2-one Lithium diisopropylamidewas made from n-butyl lithium (1.55M in hexane, 12.9 ml) and diisopropylamine (2.8 ml) in THF (13 ml). The mixture was treated with 1-methyl-caprolactam (2.54 g) and then with 2-bromo-3-methoxycyclohexenone (4.1 g) in THF (15 ml). After 1 min. the reaction mixture was poured onto 5NHCI (8 ml) and cold water (100 ml). After 0.5 h ether was added and the organic phase separated, dried and evaporated. Recrystallisation of the residue from ethyl acetate gave the title compound (4.9 g), m.p.
112-115"C (d). (Found: C, 51.7; H, 6.2; N, 4.7%. C13H18BrN02 requires: C, 52.0; H, 6.0; 4.7%).
EXAMPLE 3
Following the procedures of Examples 1 and 2 but using the appropriate halomagnesium anion of 3-ethyl-1-methylhexahydroazepin-2-one, the following compounds were prepared:
(a) 3-(2-bromo-3-oxocyclohex-1-enyl)-3-ethyl-hexahydro-1 -methylazepin-2-one, m.p.106-7 C (Found: C, 54.7; H, 6.8; N, 4.2%. C,5H22BrNO2 requires: C, 54.9; H, 6.8; N, 4.3%) (b) 3-(2-chloro-3-oxocyclohex-1-enyl)-3-ethylhexahydro-1 -methylazepin-2-one, m.p. 115-11 6"C (Found:
C, 63.7; H, 7.9; N, 4.85%. C,5H22CINO2 requires C, 63.5; H, 7.8; N, 4.9%).
EXAMPLE 4 llexahydro-3-(3-hydroxyphenyl)- 1-methyl-2H-azepine-2-one (a) 3-(2-Bromo-3-oxocyclohex-1-enyl)-hexahydro-1-methylazepin-2-one (1.48 g) in methylene chloride (10 ml) was treated with 48% HBr in acetic acid. After 3 hours water was added and the organic solvent removed under reduced pressure. The product (844 mg) crystallised from the aqueous solution, m.p.
190-192"C, identical with authentic material.
(b) A solution of 3-(2-bromo-3-oxocyclohex-1 -enyl)-hexahydro-1 -methylazepin-2-one (6 g) in chloroform (60 ml) was treated with 48% HBr in acetic acid (1 ml). After 4 hous, NMR indicated completion. Aqueous ammonia was added and the organic solvent removed under reduced pressure to yeild the title compound as a crystalline solid, m.p.192-3 C (EtOAc).
EXAMPLE 5 Hexahydro-3- (3-h ydroxyphenyl)- 1-methyl-2H-azepin-2-one (a) Using chloroform as solvent. A solution of 3-(2-chloro-3-oxocyclohex-1 -enyl)-hexahydro-1- methylazepin-2-one (5.12 g) in chloroform (50 ml)was treated with 48% HBr in acetic acid (2 ml). After 12 hours the organic solvent was removed under reduced pressure and the residue triturated with aqueous ammonia to yield the title compound m.p. 1 92-3'C (EtOAc).
(b) Using acetic acid as solvent A solution of 3-(2-ch loro-3-oxocyclohex-1 -enyl )-hexahydro-1 methylazepin-2-one (5.12 g) in glacial acetic acid (50 ml) was treated with 48% HBr in acetic acid (2 ml). After 12 hours the reaction mixture was poured on to water and the resulting precipitate removed by filtration to yield the title compound m.p. 1 92-30C (EtOAc).
EXAMPLE 6 Hexah ydro-3-eth yl-3- (3-h ydroxyphen yl)- 1-methyl-2H-azepin-2-one A solution of 3-(2-bromo-3-oxocyclohex-1 -enyl)-3-ethylhexahydro-1 -methylazepin-2-one (6.57 g) in dichloromethane (70 ml) was treated with 48% HBr in acetic acid (1 ml). After 3 hours NMR indicated completion.
The solvent was removed under reduced pressure and the residue triturated with aqueous ammonia to yield the title compound as a white crystalline solid, m.p. 178-80"C (EtOAc).
EXAMPLE 7 Hexah ydro-3-eth yl-3-(3-h ydroxyphenylj- 1-methyl-2H-azepin-2-one
A solution of 3-(2-chloro-3-oxocyclohex-1 -enyl)-3-ethyl-hexahydro-1 -methylazepin-2-one (5.68 g) in dichloromethane (60 ml) was treated with 48% HBr in acetic acid (2 ml). After 12 hours the mixture was treated with excess aqueous ammonia, the organic solvent removed under reduced pressure and the resulting solid removed by filtration to give the title compound, m.p. 178-80 C (EtOAc).
EXAMPLE 8 3-(2-Brnrno-3-oxocyclohex- 1-en yl)- 1-propyl-2-piperidone
A solution of 1 -propy-2-piperidone (50 mM) in benzene (40 ml) was added dropwise to a solution of lithium di-isopropylamide [ex n-butyl lithium in hexane (32.3 ml, 50 mM), di-isopropylamine (7 ml, 50 mM) and THF (33 ml)]. A solution of 2-bromo-3-methoxycyclohex-2-en-1 -one (10.259,50 mM) in THF (40 ml) was added, and after 5 minutes the mixture was quenched by pouring on to excess aqueous hydrochloric acid. Ether extraction followed by passage through a short silica pad using ethyl acetate as eluant gave the title compound as a colourless oil (10.75 g).
EXAM PLE9 3-f3-Hydroxyphenyl)- 1-prop yl-2-piperidone The product of Example 8 (10.5 g, 33.4 mM) in dichloromethane (70 ml) was treated with 48% hydrogen bromide in acetic acid (ca 0.5 ml). After 16 h the solvent was evaporated under reduced pressure and the residue was partitioned between chloroform and water. The organic phase was dried and evaporated and the residue was chromatographed on alumina (neutral, grade 3) using 4% methanol in chloroform as eluant
The appropriate fractions were avaporated and recrystallised from ether to yield the title compound (6.8 g) m.p. 61-3 C (Found: C, 71.9; H, 7.8; 5.6% C,4H19NO2 requires C, 72.1; H, 8.2; 6.0%).
EXAMPLE 10 3-(1-Prop yl-3-piperidin yl)phenol The product of Example 9 (4.87 g, 21 mM) in THF (50 ml) was treated with borane - THF (63 ml, 63 mM).
After 3h the mixture was poured on to water and the THF evaporated under reduced pressure. The residue was acidified with 2N hydrochloric acid and the resulting solid removed by filtration. The filtrate was basified (pH10) and extracted with chloroform and the organic phase was dried and evaporated. The resulting oil was converted to the hydrobromide salt (3.0 g) m.p. 144-5 C (Found: C, 55.1; H, 7.3; N, 4.6% C14H21N0.+H20 requires: C, 55.2; H, 7.3; N, 4.6%).
Claims (15)
1. A process for preparing a m-hydroxyphenyl substituted compound of the general formula
where R is an organic radical and R1 is hydrogen or a organic radical, which process comprises dehydrohalogenating a compound of the general formula
(where R is an organic radical, R1 is hydrogen or an organic radical and X is chlorine or bromine) in the presence of a strong nucleophilic acid catalyst.
2. A process as claimed in Claim 1 wherein R' is hydrogen.
3. A process as claimed in Claim 1 or 2 wherein R is an optionaily substituted pyrrolidine, piperidine or hexahydroazepine radical.
4. A process as claimed in Claim 1 or 2 wherein R is
where n is 2,3 or 4, R2 is hydrogen or lower alkyl and R3 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl(lower)alkyl or aryl(lower)alkyl.
5. A process as claimed in Claim 4 wherein n is 4.
6. A process as claimed in Clam 2 in which R is
7. A process as claimed in any one of the preceding claims in which the nucleophilic acid catalyst is hydrogen bromide or hydrogen chloride.
8. A compound of general formula
wherein R1 and X are as defined in Claim 1, n is 2,3 or 4, R2 is hydrogen or lower alkyl and R3 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl(lower)alkyl or aryl(lower)alkyl.
9. 3-(2-Chloro-3-oxocyclohex-1 -enyl)-hexahydro-1 -methylazepin-2-one or 3-(2-bromo-3-oxocyclohex-1 enyl)-hexahydro-1 -methylazepi n-2-one or 3-(2-bromo-3-oxocyclohex-1 -enyl)-3-ethyl-hexahydro-1 methylazepin-2-one or 3-(2-chloro-3-oxocyclohex-3-enyl )-3-ethyl-hexahydro-1 -methylazepin-2-one.
10. 3-(2-Bromo-3-oxocyclohex-1-enyl)-1-propyl-2-piperidone.
11. A process for preparing a compound claimed in Claim 8 which comprises reacting a 2halocyclohexenone derivative of general formula
where X and R1 are as defined in Claim 1 and Q is a hydrolysable protecting group with an anion or dianion of a lactam of general formula (X)
where n is 2,3 or 4, R2 is hydrogen or lower alkyl and R5 is hydrogen, lower alkyl, aryl(lower)alkyl or trialkyl-, triaryl- or trialkyl-silyl, and subjecting the product to hydrolysis.
12. A process for preparing a m-hydroxyphenyl substituted compound substantially as hereinbefore described with reference to any one of Examples 4a, 4b, 5a, 5(b), 6, 7 and 9.
13. A m-hydroxyphenyl substituted compound whenever prepared by the process claimed in any one of
Claims 1 to 7 and 12.
14. A process for preparing a compound as claimed in Claim 8 substantially as hereinbefore described with reference to any one of Examples 1,2, 3a, 3b and 8.
15. A compound whenever prepared by the process claims in Claim 11 or 14.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08232536A GB2113676B (en) | 1981-12-02 | 1982-11-15 | M-hydroxypheny1 substituted compounds |
| GB08424826A GB2145089B (en) | 1981-12-02 | 1984-10-02 | Pyrrolidines, piperidones and hexahydroazepinones |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8136364 | 1981-12-02 | ||
| GB8220721 | 1982-07-16 | ||
| GB08232536A GB2113676B (en) | 1981-12-02 | 1982-11-15 | M-hydroxypheny1 substituted compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2113676A true GB2113676A (en) | 1983-08-10 |
| GB2113676B GB2113676B (en) | 1985-05-01 |
Family
ID=27261391
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08232536A Expired GB2113676B (en) | 1981-12-02 | 1982-11-15 | M-hydroxypheny1 substituted compounds |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2113676B (en) |
-
1982
- 1982-11-15 GB GB08232536A patent/GB2113676B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB2113676B (en) | 1985-05-01 |
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| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 20001115 |