GB2164037A

GB2164037A - 6-aminomethyl-furo-(3,4-c)-pyridine derivatives

Info

Publication number: GB2164037A
Application number: GB08520007A
Authority: GB
Inventors: Andre Esanu
Original assignee: Societe de Conseils de Recherches et dApplications Scientifiques SCRAS SAS
Current assignee: Ipsen Pharma SAS
Priority date: 1984-09-05
Filing date: 1985-08-09
Publication date: 1986-03-12
Also published as: ES8604966A1; BE903121A; FR2569562A1; FR2569699A1; DK159318C; GB8422379D0; IE58583B1; NO160143B; NO160143C; GB8520007D0; SE461394B; NL8502412A; OA08157A; DK159318B; FI82053B; NO853475L; IT1188188B; LU86053A1; PT81087A; HK10489A

Abstract

Compounds of the general formula <IMAGE> (A1,A2 independently = H, C1-C5 hydrocarbon, heterocycle up to 6 ring atoms, carbomonocycle, phenylalkyl, phenylalkenyl; each (except H) unsubstituted or substituted by one or more of F, Cl, CF3, C1-C5alkyl, C1-C5alkoxy, C1-C5alkylthio, di (C1-C5alkyl)amino, di(C1-C5alkyl)amino-(C1-C5alkoxy), alpha - or beta -(C1-C5alkoxy)-N-pyrrolidinyl) and their salts have antiallergic action.

Description

SPECIFICATION 6-Aminoethyl-Furo-(3,4-c)-Pyridine Derivatives The invention relates to 6-aminomethyl-furo-(3,4-c)-pyridine derivatives, to a process for their preparation and to pharmaceutical compositions containing them.

The invention provides the 1 ,3-dihydro-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine derivatives of the general formula I

wherein each of A1 and A2 independently represents a hydrogen atom, a straight chain saturated or unsaturated hydrocarbon group having from 1 to 5 carbon atoms, a heterocyclic group having up to 6 ring atoms, a cycloalkyl group, a phenyl group or a phenylalkyl group, each of the groups represented by A1 and A2 being unsubstituted or being substituted by one or more chlorine or fluorine atoms, trifluoromethyl groups, alkyl groups having from 1 to 5 carbon atoms, alkoxy groups having from 1 to 5 carbon atoms, alkylthio groups having from 1 to 5 carbon atoms, dialkylamino groups in which each alkyl group has from 1 to 5 carbon atoms, dialkylaminoalkoxy groups in which each of the two alkyl groups and the alkoxy group has from to 1 to 5 carbon atoms or (x - or ss -alkoxy-N-pyrrolidinyl groups in which the alkoxy group has from 1 to 5 carbon atoms; and further provides pharmaceutically acceptable salts of such compounds.

The compounds according to the invention are of interest fortheir therapeutical activity, principally in the field of antiallergic action.

The invention also provides a process for the preparation of the above mentioned compounds, the process comprising reacting the 6-formyl-7-hydroxy-furo-(3,4-c)-pyridine derivatives of the general formula II

wherein A1 and A2 have the above meanings with a stoichiometric amount of hydroxylamine and of NaOH, in water, at room temperature, then hydrogenating the oxime thus obtained, at room temperature, under normal pressure, in acetic acid, by hydrogen in the presence of a Pd/C catalyst, according to the following reaction scheme M- CHO

M-CH = N-OH

I The 6- formyl -7 -hydroxy- furo- (3,4,-c) -pyridine derivatives II may be obtained from corresponding 6-methyl-7-hydroxy-furo-(3,4-c)-pyridine derivatives of the general formula Ill

wherein A1 and A2 have the above meanings by the following sequence of reactions:

m-chloro peroxybenzoic acid

(continued)

The compounds Ill are disclosed in our Patent No. 2092586 and Patent Application No. 8407082.

The preparation of one only of the starting compounds,1,3-dihydro-3-p-chlorophenyl-6-formyl-7-hydroxy- furo-(3,4-c)-pyridine, is now described in detail, other starting materials being obtained by the same way.

a) Into a one litre reactor fitted with stirring, warming and cooling means, 22.3 g of 1,3-dihydro-3-p chiorophenyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine were treated at 0 C, in the presence of 300 ml of methylene dichloride, with 18.2 g of m-peroxybenzoic acid, slowly added. After stirring overnight at room temperature, there were added 150 ml of 10% sodium sulphate solution. After stirring and decantation, the methylene dichloride phase was washed with the same amount of sodium sulphate solution, twice with 150 ml of sodium bicarbonate solution and three times with 100 ml of water, and then dried over anhydrous sodium sulphate. On evaporation to dryness, there was obtained a beige precipitate which was washed with petroleum ether, filtered and dried.

Yield 22.9 g (96 %) of 1 ,3-dihydro-3-p-chlorophenyl-6-methyl-7-hydroxy-furo-(3,4-c)-pyridine-N-oxide.

b) In the same reactor as above, the 22.9 g of the compound obtained in the previous step were treated at 0-5"C, in the presence of 175 ml of methylene dichloride, with 4.3 ml of trifluoroacetic anhydride added dropwise under stirring. The mixture was stirred overnight at room temperature, and then cooled and treated dropwise with 95 ml of methanol. After evaporation to dryness, the residue was taken up in 300 ml of chloroform, washed twice with 75 ml of 10 % sodium bicarbonate solution and three times with 100 mt of water and dried on anhydrous sodium sulphate. The chloroform was evaporated off and the residue was washed with diethyl ether and dried under reduced pressure. Yield 21.3 g (93 %) of 1,3-dihydro-3-p chlorophenyl-6-hydroxymethyl-7-hydroxy-fu u ro-(3,4-c)-pyridine.

c) In a 2 litre reactor, the 21.3 g of the compound obtained in the previous step were treated with 27 g of manganese dioxide in the presence of 0.9 litre of chloroform at 28-300C, under stirring for 3 hours. After separation, fitration, washing with cbhloroform and then with ethyl acetate, the solution was evaporated to dryness and the paste treated with isopropyl oxide then with pentane. There was thus obtained 20.1 g (95 %) of 1,3-dihydro-3-p-chlorophenyl-6-formyl-7-hydroxy-fu ro-(3,4-c)-pyridine.

The invention further provides a pharmaceutical composition comprising a 1,3-dihydro-6-aminomethyl-7hydroxy-furo-(3,4-c)-pyridine derivative ofthe general formula I as above defined or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable diluent or carrier.

The invention is illustrated by the following examples.

EXAMPLE 1 7,3-dihydro-3-m eth yl-Saminometh yl-7-h ydroxy-furo-1,4-c)-p yridin e Into a 2 litre reactor, at room temperature, were poured 71.2 g (0.4 mol) of 1,3-dihydro-3-methyl-6-formyl- 7-hydroxy-furo-(3,4-c)-pyridine, 270 ml of 1 N sodium hydroxide and then, dropwise under stirring, 27.8 g (0,4 mol) of hydroxylamine hydrochloride dissolved in 200 ml of water. Stirring was maintained for 10 hours and the reacting mixture was filtered, to give, after washing with water and drying, 74 g (96 %) of the corresponding 6-oxime derivative.

The 74 g of the 6-oxime derivative were then poured with 0.9 litre of acetic acid into a closed reactor fitted with gaseous circulation means ; after circulating nitrogen 15 g of Palladium on Carbon catalyst were placed in the reactor and the mixture was stirred at room temperature with a measured hydrogen addition under normal pressure, for 4 hours.

After filtration of the reacting mixture, it was evaporated to dryness. The residue was treated with toluene and then with methanol from which were recrystallized 70 g (76 %) of the acetate of 1 ,3-dihydro-3-methyl-6- aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine, a beige product melting at 167 C (Tottoli), the analysis of which showed a good correspondence with the formula CgH12N202, C2H402 This compound was insoluble in water.

As the same route was used for all the synthetized compounds, operative details will not be repeated in the following examples. The corresponding bases (without the acetic moiety) and other salts of said bases are obtained as usual.

EXAMPLE 2 1,3-dihydro-3-propyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1,3-dihydro-3-propyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 77 %) a pale beige product, melting at 187 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula CH16N202. C2H402.

EXAMPLE 3 1,3-dihydro-3-(3',4',5'-trimethoxyphenyl)-ethyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1 ,3-dihydro-3-(3',4',5'-trimethoxyphenyl )-ethyl-6-formyl-7-hydroxy-fu ro-(3,4-c)-pyridi ne, there was obtained (yield 61 %), a white product, melting at 140-144"C (Tottoli), insoluble in water, the analysis of which-showed a good correspondence with the formula C19H24N205. C2H402.

EXAMPLE 4 1,3-dihydro-3-cyclohexyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1,3-dihydro-3-cyclohexyl-6-formyl-7-hydroxy-(3,4-c)-pyridine, there was obtained (yield 67 %) a white product, melting at 173-177"C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with-the formula C14H20N202. C2H402.

EXAMPLE 5 1,3-dihydro-3- a -thienyl-6-aminomethyl-7-hydroxy-furo-63,4-c)-pyridine Starting with 1,3-dihydro-3- a -thienyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 58 %) a yellowish product, melting at 148 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C12H12N202S1. C2H402.

EXAMPLE 6 1,3-dihydro-3-phenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1,3-dihydro-3-phenyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 82 %) a pale beige product, melting at 188 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C14H14N202. C2H402.

EXAMPLE 7 1,3-dihydro-3-p-chlorophenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1,3-dihydro-3-p-chlorophenyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 86 %) a pale beige product, melting at 204-206 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C14H13CIN202. C2H402.

EXAMPLE 8 1,3-dihydro-3-(2',3'-dichlorophenyl)-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1,3-dihydro-3-(2',3'-dichlorophenyl)-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 72%) a pale yellow product, melting at 193-196 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C14H12C12N202. C2H402.

EXAMPLE 9 1,3-dihydro-3-p-fluorophenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1,3-dihydro-3-p-fluorophenyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 69%) a pale beige product, melting at 183-187 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C14H13FN202. C2H402.

EXAMPLE 10 1,3-dihydro-3-p-toluyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1,3-dihydro-3-p-toluyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 78 %) a pale beige product, melting at 158-160 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C15Ha6N202. C2H402.

EXAMPLE 11 1,3-dihydro-3-p-methoxyphenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1,3-dihydro-3-p-methoxyphenyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 62 %) a pale beige product, melting at 144-149 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C15Ha6N203. C2H402.

EXAMPLE 12 1,3-dihydro-3-(3',4',5'-trimethoxy)-phenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1 ,3-dihydro-3-(3',4',5'4rimethoxy)-phenyl-6-formylJ-hydroxy-furn-(3,4-c)-pyridifle, there was obtained (yield 49 %) a whitish product, melting at 137-141 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C17H20N2O5.C2H4O2.

EXAMPLE 13 1,3-dihydro-3-m-trifluoromethylphenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1,3-dihydro-3-m-trifluoromethylphenyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 84 %) of a white product, melting at 197-203 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C15H13F3N2O2.C2H402.

EXAMPLE 14 1,3-dihydro-3-p- dimethylaminoethoxyphen y/- 6aminom eth yl- 7-h ydroxy-furo- /3,4-cJ-p yridine Starting with 1,3-dihydro-3-p-dimethylaminoethoxyphenyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 46 %) a pale yellow product, melting at 160-164 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C9H23N302. C2H402.

EXAMPLE 15 1,3-dihydro-3-meth yl-3-cL -thienyl-6-aminomethyl-7-hydroxy-furo-(3,4c)-pyridine Starting with 1,3-dihydro-3-methyl-3- a -thienyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 66 %) a white product, melting at 206-208 C (Tottoli), poorly soluble in water, the analysis of which showed a good correspondence with the formula C13H14N2O2S.C2H4O2.

EXAMPLE 16 1,3-dihydro-3-ethyl-3-phenyl-7-aminoethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1,3-dihydro-3-ethyl-3-phenyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 80 %) a white product, melting at 207 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C16H18N2O2. C2H402.

EXAMPLE 17 1,3-dihydro-3-phenyl-3-p-trifluoromethylphenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1,3-dihydro-3-phenyl-3-p-trifluoromethylphenyl-6-formyl-7-hydroxy-fu ro-(3,4-c)-pyridine, there was obtained (yield 65 %) a white product, melting at 221 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C21H17F3N2O2. C2H402.

EXAMPLE 18 1,3-dihydro-3-phenyl-3-α-methoxypyrrolidinyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)pyridine Starting with 1,3-dihydro-3-phenyl-3- α-methoxypyrrolidinyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 41 %) a yellowish product, melting at 129-132 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C1gH22N303. C2H402.

EXAMPLE 19 1,3-dihydro-3,3-di-p-fluorophenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1,3-dihydro-3,3-di-p-fluorophenyl-6-formyl-7-hydroxy-fu ro-(3,4-c)-pyridine, there was obtained yield (81 %) a pale yellow product, melting at 21 40C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C20H16F2N2O2. C2H402.

EXAMPLE 20 1,3-dihydro-3- α-furyl-3-p-thiomethylphenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine Starting with 1 ,3-dihydro-3- a -furyl-3-p-thiomethylphenyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 63 %) a whitish product, melting at 153-157 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C19H18N203S. C2H402.

EXAMPLE 21 1,3-dihydro-3,3-di-α -furyl-6-amin ometh yl-7-hydroxy-furo-(3,4-c)-p yridine Starting with 1,3-dihydro-3,3-di- a -furyl-6-formyl-7-hydroxy-furo-(3,4-c)-pyridine, there was obtained (yield 72 %) a white product, melting at 178 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C16Hl4N204. C2H402.

EXAMPLE 22 1,3-dEhydro-3-cycloheXyl-3-r2',3',-dichloro)-phenyl-6-amino-methyl-7-hydroxy-furo- '3,4-c)-p yridine Starting with 1,3-di hydro-3-cyclohexyl-3-(2',3'-dich 1 orophenyl )-6- formyl -7-hydroxy - furo -(3,4-c)- pyridine, there was obtained (yield 59 %) a yellow product, melting at 213 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C20H22C12N202. C2H402.

EXAMPLE 23 1,3-dihydro-3-vinyl-3-p-thiomethylphenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-p y idine Starting with 1,3-dihydro-3-vinyl-3-p-thiomethylphenyl-6-formyl-7-hydroxy-fu ro-(3,4-c)-pyridine, there was obtained (yield 66 %) a beige product, melting at 1550C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C17Hn8N202S. C2H402.

EXAMPLE 24 1,3-dihydro-3-dimethylaminopropyl-3-p-chlorophenyl-6-amino-methyl-7-h ydroxy-furo-(3, 4-c)-p yridine Starting with 1 ,3-dihyd ro3-dimethyla minopropyl-3-p-ch lorophenyl-6-f ormyl-7-hydroxy-f u ro-(3,4-c)- pyridine, there was obtained (yield 47 %) a white product, melting at 169 C (Tottoli), insoluble in water, the analysis of which showed a good correspondence with the formula C19H24Cl N302. C2H402.

Toxicity DL50 was determined per os and IP on mice. According to the compounds, it was comprised between 0.7 to over 2.4 g/Kg (per os) and 0.6 to 1.65 g/Kg IP.

Pharmacology A complete pharmacological experimentation was conducted and the following tests are reported below.

A - Passive cutaneous anaphylaxy This experiment was conducted as described in Fiche Technique n 48 of J.Pharm. Paris 1979 10 (1) pages 69-72.

Male Sprague-Dawley rats (180-200 g) received two intra-dermal injections of immunserum in the back; 72 hours later, they received a IV (penis vein) injection of 1 ml of a mixture of ovalbumine (5 mg/ml) and Evans blue (2.5 mg/ml) : this induced the formation of weals around the places of injection of immunserum.

Wheals were taken 30 minutes after this formation, measured then incubated for 24 hours at 65 C in 4 ml of formamide (for extracting the Evans blue). Optical density of the supernatant was determined at 620 nm by a spectrophotometer.

A first batch of 8 rats was used for control ; a second batch (8) was used for treatment by a reference compound (theophylline, 25 mg/Kg) and ten other batches (all of 8 rats) were used for the treatment by 10 of the compounds of the present invention (all at 25 mg/Kg) identified by their example number; for these eleven batches, the appropriate compound was administered per os, one hour before the injection of ovalbumine/Evans blue mixture. The percentage of weals reduction, in surface and in colour was determined by comparison with the control. The results are reported on the left part of the following table.

B - Anti-histaminic action This experiment was conducted as described by Doepfner W. and Cerletti A., Int. Arch. Allergy 12,89 1958 and J. Pharmac. and exp. Ther. (1974) 191 (2) pages 300-310.

Male Sprague-Dawley rats (140-160 g) were submitted to hydric fast for 18 hours before receiving 1 ml/Kg of water (for control), 0.2 of an aqueous solution or suspension of experimental compounds. The volume of the left posterior paw was measured by plethysmography, then 0.1 of 5 % histamine hydrochloride was injected. The inflammatory response was evaluated by a subsequent volume determination one hour later.

Batches of each 8 animals were used : one for control, ten for tested compounds (the same as in A above) and two for reference compounds mequitazine and promethazine, all at the dose of 25 mg/Kg. The percentage of reduction of inflammatory response was obtained by comparison with control. The results are reported in the right part of the following table.

From these two experiments, it clearly appears that the compounds of the invention present a strong anti-histaminic action.

Presentation - posology For human use by oral route, tablets or gelatine capsules containing 0.20 g of a compound according to the invention are preferred. By IV route, phials containing the same amount, to be injected with a perfusion are retained. Daily doses in human therapy are from 0.20 to 2 g per os and 0.2 to 1 g, IV.

% of wheals reduction Histamine induced Oedema % of inflammatory Compounds Surface Colour reduction Theophylline - 60 - 62 Ex 1 - 77 - 86 - 48 Ex 2 - 58 - 60 - 77 Ex 4 - 61 - 66 - 59 Ex 5 - 49 - 60 - 68 Ex 6 - 75 - 84 - 79 Ex 9 - 68 - 72 - 83 Ex10 - 68 - 72 - 66 Ex 14 - 71 - 81 - 51 Ex16 - 53 - 59 - 54 Ex18 - 65 - 69 - 62 Mequitazine - 60 Promethazine - 41

Claims

1. A 1,3-dihydro-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine derivative having the general formula I as herein defined.

2. 1,3-dihydro-3-methyl-6-aminomethyl-7-hydroxy-furo-(3,4c)-pyridine.

3. 1 ,3-dihydro-3-propyl-6-ami nomethyl-7-hydroxy-fu ro-(3,4-c)-pyridine.

4. 1 ,3-dihydro-3-(3',4',5"-trimethoxyphenyl )-ethyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine.

5. 1,3-dihydro-3-cyclohexyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine.

6. 1,3-dihydro-3-α-thienyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine.

7. 1,3-dihydro-3-phenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine.

8. 1 ,3-dihydro-4p-chIorophenyl-6-aminomethyI-7-hydroxyfurn-(3,4c)-pyridine.

9. 1,3-dihydro-3-(2',3'-dichlorophenyl)-6-aminomethyl-7-hydroxy-furo-(3,4-c}-pyridine.

10. 1,3-dihydro-3-p-fluorophenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)pyridine.

11. 1 ,3-dihydro-p-toluyl-6-aminomethyl-7-hydroxy ro-(3,4-c)-pyridine.

12. 1,3-dihydro-4-p-methoxyphenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridi ne.

13. 1 ,3-dihydro-3-(3',4',5'-trimethoxy)-phenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine.

14. 1,3-dihydro-3-m-trifluoromethylphenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine.

15. 1 ,3-dihydro-3o-dimethylaminoethoxyphenyl-6-aminomethyl-7-hydroxy4ur-(3,4-c)-pyridine.

16. 1,3-dihydro-3-methyl-3-α-thienyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine.

17. 1,3-dihydro-3-ethyl-3-phenyl-6-ami nomethyl-7-hydroxy-fu ro-(3,4-c)-pyridine.

18. 1 ,3-dihydro-3-phenyl-3-p-trifluoromethylphenyl-6-aminomethyl-7-hydroxy4uro-(3,4-c)-pyridine.

19. 1,3-dihydro-3-phenyl-3-α-methoxypyrrolidinyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine.

20. 1 ,3-dihydro-3,3-di-p-fluorophenyl-6-aminomethyl-7-hydroxy4uro-(3,4-c)-pyridine.

21. 1 ,3-dihydro-3-a-furyI-3o-thiomethylphenyI-6-aminomethylJ-hydroxy4uro(3,4-c)-pyridine.

22. 1,3-dihydro-3,3-di-α-furyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine.

23. 1,3-dihydro-3-cyclohexyl-3-(2',3',-dichloro)-phenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine.

24. 1 ,3-dihydro-3-vinyl-3-p-thiomethyl phenyl-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine.

25. 1,3-dihydro-3-dimethylaminopropyl-3-p-chlorophenyl-6-aminomethyl-7-hydroxy4urn-(3,4-c)- pyridine.

26. A process for the preparation of a 1,3-dihydro-6-ami nomethyl-7-hyd 1,3-dihydro-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine derivative having the general formula I as herein defined, the process comprising reacting a 6-formyl-7 hydroxy4uro-(3,4-c)-pyridine derivative having the general formula II as herein defined with a stoichiometric amount of hydroxylamine in water under basic conditions, and catalytically hydrogenating the resultant oxime.

27. A process according to claim 26 in which the reaction of the derivative Il with hydroxylamine is carried out in aqueous sodium hydroxide solution at ambient temperature.

28. A process according to claim 26 or claim 27 in which the oxime is dissolved in acetic acid and hydrogenated under normal pressure at ambient temperature in the presence of a palladium-on-carbon catalyst.

29. A process for the preparation of a 1 ,3-dihydro-6-aminomethyl-7-hydroxy-furo-(3,4-c)-pyridine derivative having the general formula I as herein defined, the process being substantially as described herein with reference to any of the Examples.

30. A pharmaceutical composition comprising a 1,3-dihydro-6-aminomethyl-7-hydroxy-furo-(3,4-c)- pyridine derivative according to any of claims 1 to 25 in admixture with a pharmaceutically acceptable diluent or carrier.