GB2153824A - Furo-(3,4-c)-pyridine derivatives - Google Patents
Furo-(3,4-c)-pyridine derivatives Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
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Abstract
<IMAGE> The compounds I (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-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, di(C1-C5 alkyl)-amino, di(C1-C5 alkyl)-amino-(C1-C5 alkoxy), alpha - or beta -(C1-C5 alkoxy)-N-pyrrolidinyl) are antidepressive agents. They are prepared by reacting corresponding 6-formyl-7-benzyloxy derivatives with 1-dimethylaminomethyl-vinylmagnesium bromide at the boil and hydrolysing the 7-benzyloxy group in the resultant intermediate.
Description
SPECIFICATION
Furo-(3,4-c)-pyridine derivatives
This invention relates to new 6-(1-hydroxy-2-dimethylamino-methyl-allyl)-furo-(3,4-c)-pyridine derivatives, to a process for their preparation and to therapeutic compositions containing them.
The invention provides 1,3-dihydro-6-(1-hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-furo-(3,4-c)- pyridine derivatives of the general formula:
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 carbomonocyclic group, having up to 6 ring atoms, a carbomonocyclic group, a phenylalkyl group our a phenylalkenyl group, each of the groups represented byA1 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 groups has from 1 to 5 carbon atoms or oc 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 for their therapeutical activity, principally as antidepressive agents.
The invention also provides a process for the preparation of the said compounds, the process comprising reacting a 6- formyl - 7- benzyloxy -fu ro-(3,4-c)-pyridine derivative of the general formula II
wherein A1 and A2 have the above meanings with 1 -dimethylaminomethyl-vinylmagnesium bromide at the boil, in a non polar solvent such as tetrahydrofuran and hydrolysing the 7-benzyloxy group of the resultant intermediate by treatment with an acid.
To obtain the 6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine derivative 11 the starting material is the compound
obtained by the method described in our patent No. 2092586 submitted to the following sequence of reactions:
The invention further provides a therapeutical composition comprising a 1,3-dihydro-6-(1-hydroxy-2- dimethylamino-methyl-allyl)-furo-(3,4-c)-pyridine derivative of the general formula I as above defined or a pharmaceutically acceptable salt thereof in admixture with a therapeutically acceptable diluent or carrier.
The following examples illustrate the invention.
EXAMPLE 1 1, 3-dihydro-3-m eth yI-6- (l-hydroxy-2- dimethylamin omethyl-allyl)- 7-hydroxy-furn- (3, 4-c)-p yridine a) Preparation of the organomagnesium reagent
In a two litre reactor fitted with warming, cooling and stirring means were poured, under nitrogen circulation, 19.4 g (0.8 mol) of magnesium, and 100 ml oftetrahydrofuran, preferably distilled on lithium aluminium hydride. The mixture was refluxed.
There was then slowly added 132 g (0.8 mol) of 3-dimethylamino-2-bromo-l -propylene. No external heating was applied, the reflux being maintained and controlled by the addition of this compound. At the end of the addition, one litre of distilled tetrahydrofuran was added. The mixture was refluxed for two hours and then cooled to 10"C.
b) Reaction
To the reaction mixture from the previous step was slowly added, under stirring, 107.6 g (0.4 mol) of 1,3 -dihydro- 3-methyl- 6-formyl- 7-benzyloxy- furo- (3,4-c) - pyridine. The temperature reached about 25"C at the end of the addition. Stirring was maintained overnight at room temperature. The mixture was then cooled to 0 C and 250 ml of water saturated with ammonium chloride and 250 ml of diethyl ether were added to it. After stirring for 15 minutes at room temperature there was obtained a two-phase mixture with an oil supernatant.
The mixture was separated and the aqueous phase was extracted twice with 250 ml aliquots of diethyl ether. The extracts were added to the oily phase, which had been washed with water three times. The oily phase was then dried on magnesium sulphate, treated with carbon black, concentrated to dryness and extracted twice with 250 ml of diisopropylether. The extracts were filtered, concentrated reduction to 114 of initial volume) and cooled overnight, leading to a precipitate, which was separated and washed with diisopropylether. Yield 104 9 (73 %).
c) Debenzylation
Into the above reactor were poured the product of the previous step and 700 ml of hydrochloric acid. The mixture was stirred, warmed to 55 C, maintained at that temperature for three hours, and then cooled to 0 C.
After addition of water, neutralisation with sodium hydroxide and saturation with sodium chloride, the mixture was extracted three times with 500 ml aliquots of chloroform. The extracts were washed with water, dried on magnesium sulphate, filtered and evaporated to dryness. The residue was recrystallized from methanol. Yield 90.5 g (92 %) of a product melting at 200-205 C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C14H20N203, 2HCI. The overall yield was 67 %.
The preparation of the other compounds of the invention follows the same process except that, in step (b), the starting material is different; the following examples will, accordingly referto example 1 and only mention the new starting material, the overall yield and the characteristics of the compound obtained.
EXAMPLE 2
1,3-dihydro-3-propyl-6-(1-hydroxy-2-dimethylaminomethyl-allyI)-7-hydroxy-furo-(3,4-c)-p yridine
The method of example 1 was repeated, but starting with 119 g (0.4 mol) of 1,3-dihydro-3-propyl-6-formyl 7-benzyloxy-furo-(3,4-c)-pyridine. Yield 89 g (61 %) of a product melting at 187-194 C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C16H24N203r 2HCI.
EXAMPLE 3 l,3-dih ydro-3-cyclohexyl-6-( l-hydroxy.2-dimethylaminomethyl-allyl)-7-hydroxy-furo- (3, 4-c)-p yridine The method of example 1 was repeated, but starting with 135 g (0.4 mol) of 1,3-dihydro-3-cyclohexyl-6 formyl-7-benzyloxfurn-(3,4-c)-pyridine. Yield 92 g (57 %) of a product melting at 180-184 C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C19H28N203r 2HCI.
EXAMPLE 4
l,3-dih ydro-3-phenyl-6-(l-h ydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-furo-(3,4-c)-p yridine
The method of example 1 was repeated, but starting with 135 g (0.4 mol) of 1 ,3-dihydro-3-phenyl-6-formyl- 7-benzyloxy-furo-(3A-c)-pyridine. Yield 77 g (48 %) of a product melting at 210-215"C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C19H22N202, 2HCl.
EXAMPLE 5 1, 3-dih ydro-3-p-chlorop hen yl-6-( i-h ydroxy-2-dimeth ylamin ometh yl-allyl)- 7-h ydroxy-furo- (3, 4-c)-p yridine The method of example 1 was repeated, but starting with 146 g (0.4 mol) of 1 ,3-dihydro-3-p-chlorophenyl- 6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 95 g (55 %) of a product melting at 195-200eC (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C19H21C1N2O3. 2HCI.
EXAMPLE 6
1,3-dihydro-3-62,3-dichlorophenyl)-6-{1-hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-furo-{3,4-c)- pyridine
The method of example 1 was repeated, but starting with 160 g (0.4 mol) of 1 ,3-dihydro-3-(2,3-dichloro- phenyl)-6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 82 g (44 %) of a product melting at 180-184C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C19H20Cl2N203. 2H01.
EXAMPLE 7 i,3-dihydro-3-p-fluorophenyl-6-(i-h ycroxy-2-dimethylammomethyl-allyi)-7-h ydroxy-furo-(3,4-c)-pyridine The method of example 1 was repeated, but starting with 140 g (0.4 mol) of 1 ,3-dihydro-3-p-fluorophenyl- 6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 85 g (51 %) of a product melting at 198"C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C19H21FN2O3.2HCl.
EXAMPLE 8 1, 3dih ydro-3-p -toluyl-6- ( i-h ydroxy-2-dim eth ylaminom ethyl-ally!)- 7-h ydroxy-furo-(3, 4-c)-p yridin e The method of example 1 was repeated, but starting with 138 g (0.4 mol) of 1,3-dihydro-3-p-toluyl-6 formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 81 g (49 %) of a product melting at 203-207 C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C20H24N203.2HCI.
EXAMPLE 9 i,3-dihydro-3-p-methoxyphen yl-6-(i-hydroxy-2-dimethylaminometh yl-allyl)-7-h ydrnxy-f'rn-(3,4-c)p yridine The method of example 1 was repeated, but starting with 145 g (0.4 mol) of 1,3-dihydro-3-pmethoxyphenyl-6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 86 g (50 %) of a product melting at 169-170 C (Tottoli), the analysis of which showed a good correspondence with the formula C20H24N204.2HCI.
EXAMPLE 10 i,3-dihydro-3-m-trifluoromethylphen yl-6-(1-hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-furo-(3,4-c)- pyridine
The method of example 1 was repeated, but starting with 161 g (0.4 mol) of 1,3-dihydro-3-mtrifluoromethylphenyl-6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 102 g (54 %) of a product melting at 217-223 C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C20H2tF3N203.2HCI.
EXAMPLE 11 1,3-dihydro-3-p-(diethylaminoethoxy-phenyl)-6-(1-hydroxy-2-dimethylaminomethyl-allylJ-7-hydroxy-furo- (3,4-c)-p yridin e The method of example 1 was repeated, but starting with 178 g (0.4 mol) of 1,3-dihydro-3-p (diethylaminoethoxy-phenyl)-6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 76 g (37 %) of a product melting at 158-160 C (Tottoli), the analysis of which showed a good correspondence with the formula C25H35N304. 2HCl.
EXAMPLE 12
1,3-dihydro-3-p-(pyrrolidinylethoxy-phenyl)-6-(1-hydroxy-2-dimethylaminomethyl-allyl)-7-h ydroxy-furo- (3,4-c)-pyridine The method of example 1 was repeated, but starting with 178 g (0.4 mol) of 1 ,3-dihydro-3-p- (pyrrolidinylethoxy-phenyl)-6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 70 g (34 %) of a product melting at 173 C (Tottoli), the analysis of which showed a good correspondence with the formula C25H32N304. 2HCl.
EXAMPLE 13 i,3-dih ydro-3-meth yl-3-n-pentyl-6-(i-h ydroxy-2-dimeth ylaminom eth yl-allyl)-7-h ydroxy-furo- (3,4-c)-pyridine The method of example 1 was repeated, but starting with 136 g (0.4 mol) of 1 ,3-dihydro-3-methyl-3-n- pentyl-6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 94 g (58 %) of a product melting at 187-191 C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C1H30N2O3. 2HCl.
EXAMPLE 14 i,3-dih ydro-3-m eth yl-3-ph en yl-6-( i-h ydroxy-2-dim eth ylamin om ethyl-ally!)- 7-h ydrox y- furo-(3, 4-c) -p yridine The method of example 1 was repeated, but starting with 138 g (0.4 mol) of 1,3-dihydro-3-methyl-3-phenyl- 6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 104 g (63 %) of a product melting at 178-179 C (Tottoli), the
analysis of which showed a good correspondence with the formula C20H24N203.2HCI.
EXAMPLE 15 1, 3-dih ydro-3-m eth yl-3-a-thien yl-6-( i-h ydroxy-2-dim eth ylaminometh yl-allyl)-7-h ydroxy-furo-(3,4-c)- pyridine
The method of example 1 was repeated, but starting with 140g (0.4mol) of 1,3-dihydro-3-methyl-3- -thienyl-6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 77 g (46 %) of a product melting at 169-1 75'C (Tottoli), with decompostion, the analysis of which showed a good correspondence with the formula C18H22SN203.2HCi.
EXAMPLE 16 1, 3-dih ydro-3-eth yl-3-m-trffluorometh ylph enyl-6-( i-h ydroxy-2-dimeth ylaminom eth yl-allyl)-7-h ydroxy-furo-
(3,4-c)-pyridine The method of example 1 was repeated, but starting with 172 g (0.4 mol) of 1,3-dihydro-3-ethyl-3-m trifluoromethylphenyl-6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 117 g (59 %) of a product melting at 185"C (Tottoli), the analysis of which showed a good correspondence with the formula C22H25F3N203. 2Hcl.
EXAMPLE 17 1, 3-dih ydro-3-eth yA3-"-lvryi-6-(i-h ydroxy-2-dimethylaminometh yl-allyl)- 7-h ydroxy-furo-(3, 4-c)-p yridine The method of example 1 was repeated, but starting with 140 g (0.4 mol) of 1 ,3-dihydro-3-ethyl-3- a -furyl-6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 68 g (41 %) of a product melting at 164-169 C (Tottoli),
with decomposition, the analysis of which showed a good correspondence with the formula C1gH24N204.
2HCI.
EXAMPLE 18 i,3-dih ydro-3-phen yl-3-p-eth oxyphenyl-6-(i-h ydroxy-2-dimeth ylamin omethyl-allyl)-7-h ydroxy-furo-(3,4-c)- pyridine
The method of example 1 was repeated, but starting with 180 g (0.4 mol) of 1 ,3-dihydro-3-phenyl-3-p- ethoxyphenyl-6-formyl-7-benzyloxy4uro-(3,4-c)-pyridine. Yield 99 g (48 %) of a product melting at 148-149 C
(Tottoli), the analysis of which showed a good correspondence with the formula C27H30N204.2HCI.
EXAMPLE 19 1,3-dihydro-3,3-di-p-fluorophenyl-6-r1-hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-furo-r3,4c)- pyridine
The method of example 1 was repeated, but starting with 178 g (0,4 mol) of 1 ,3-dihydro-3,3-di-p fluorophenyl-6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 115 g (56 %) of a product melting at 1750C (Tottoli), the analysis of which showed a good correspondence with the formula C25H24F2N203.2HCI.
EXAMPLE 20 i,3-dih ydro-3- oL -furyl-3-p-thiomethylphenyl-6-) 1-hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-furo- (3,4-c)oyricllne The method of example 1 was repeated, but starting with 177 g (0.4 mol) of 1,3-dihydro-3- a -furyl-3-p-thiomethylphenyl-6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine. Yield 82 g (40 %) of a product melting at 143-151 C (Tottoli), with decomposition, the analysis of which showed a good correspondence with the formula C24H26SN204. 2HCl.
Toxicity
None of the prepared compounds revealed an important per os toxicity : LD50 was comprised between 0.8 and 1.2 g/kg on rats and between 0.7 and 1 g/kg for mice.
Pharmacology
The activity of the compounds of the invention has been evidence by various tests, three of which are reported in details as follows.
I - Lethality provoked by Yohimbine HCI in mice
This test was conducted on batches of 10 male CD-l (Charles River) mice. Each treated mouse received 0.25 ml/20 g of a suspension containing the tested dose of compound. One hour after the administration, the mice were injected subcutaneously 30 mg/kg of Yohimbine HCI. Percentage of death (L) was determined 18 hours after this injection. A Yohimbine HCI control batch was provided for each compound. The results are reported in the table No. I.
II - Antagonism against catalepsy induced by haloperidol
This experiment was conducted in comparison with two reference compounds, Imipramine and 5-hydroxytrytophane on male Wistar rats of 140/170 g in batches of each 6 rats.
IP administration of haloperidol at 5 mg/kg induces catalepsy. Further oral administration of the tested compounds one hour after haloperidol injection has an adverse action against catalepsy.
Eight of the compounds of the invention were tested at various doses (one batch for each dose of each compound). Action on catalepsy was appreciated 1,2,3,4 and 5 hours after the administration of the tested compounds by placing anterior paws of the rats on a metal bar located at 10 cm above table level (test performed in a noiseless room at 22 C); if the rat was able to stay for 20 seconds, the score was 1 point ; for 40 seconds the score was 2 points and so on up to 100 seconds for 5 points. Average vlaues were calculated for each batch together with the corresponding percentage of antagonism.
The results are reported in the table No. II.
Ill- Despair test on mice
This experiment was conducted on male mice CD-1 (Charles River) in batches of each 10 mice in comparison with Maprotiline as a reference compound. One hour before the test, the mice received in a dose of 0.4 ml/20g of suspension, the appropriate dose in mg/kg of the tested compounds.
The mice were placed in plexiglass cylinder (height 25 cm, diameter 10 cm) containing water at 22"C. The measure of immobility period was effected between the 2nd and 6th minute. There was one control batch for each compound and one batch per tested dose.
The results are reported in the table No. Ill wherein A stands for the average immobility period and B stands for the % of variation with regard to control;
Presentation -posology
More commonly used forms in human therapy comprise tablets or gelatine capsules containing 0.1 g of active ingredient per dosage unit or phials containing the same amount in a dissolved or suspended form for
IV injection.
Usual posology is up to 0.5 g/day for at least two weeks, for oral forms or up to 0.2 g/day for at least one week for the injectable form, this treatment being followed by at least one week of oral administration.
TABLE No. I
Products Doses L YohimbineHCl 30 mg/kg SC 20 % Ex.1 30 mg/kg PO 40 % 100 mg/kg PO 60 % Yohimbine HCI 30 mg/kg SC 20 % Ex. 4 30 mg/kg PO 50 %
60 mg/kg PO 60 %
Yohimbine HCI 30 mg/kg SC 20 % Ex.5 10 mg/kg PO 60 % 30 mg/kg PO 60 %
Yohimbine HCI 30 mg/kg SC 20 % Ex. 7 3 mg/kg PO 50 %
10 mg/kg PO 50 % Yohimbine HCI 30 mg/kg SC 20 % Ex. 11 30 mg/kg PO 30 % 100 mg/kg PO 90 % Yohimbine HCI 30 mg/kg SC 20 % Ex.12 30 mg/kg PO 40 % 60 mg/kg PO 50 % Yohimbine HCI 30 mg/kg SC 20 % Ex.17 30 mg/kg PO 80 % 100 mg/kg PO 90 % Yohimbine HCI 30 mg/kg SC 20 % Ex. 20 30 mg/kg PO 50 % 100 mg/kg PO 60 % TABLE No.II
Dose Antagonism in % after : (hours)
Examples mglkg
peros ih 2h 3h 4h 5h
Imipramine 15 100 52.3 42.3 48.2 50
60 68.7 76.1 42.3 31 33.3 5 HTP 30 53.3 42.8 20.6 13.8 16.6
100 33.3 46.4 31 13.8 16.6 Vex. 1 30 60 63.6 44 35.7 25
100 100 50 54.5 46.4 40
Ex.4 1 58.3 70 50 33.7 16.6
3 100 75 80 56.6 50
Ex.5 10 100 100 78 78 64
30 37 75 46 50 47
Ex.7 3 0 58.3 60.7 41.4 48.2
10 28.5 79.1 78.6 79.3 72.4
Ex.11 10 50 100 60 53.3 53.3
30 100 80.7 62.9 55.1 41.4
Ex. 12 10 0 30.4 37 43.3 46.6
30 0 30.4 40.7 46.6 40
Ex.17 3 100 54.5 48.3 24.1 26.6
10 100 59 51.7 24.1 40 Ex.20 10 93.3 76 70 60.7 55.1
30 100 68 50 54.5 51.7
TABLE No. III Examples Doses A B
Control - 204
Maprotiline 10mg/kgPO 156.3 -23.4
30 mg/kg PO 143.3 - 29.7
100 mg/kg PO 86.5 - 57.6
Control - 203.8
Ex.1 lmglkgPO 157.4 - 25
3 mg/kg PO 133.1 - 34.7
10 mg/kg PO 82.1 - 59.6
Control - 198.3
Ex.4 10mg/kgPO 136.4 -31.2
30 mg/kg PO 135.6 -31.6
100 mg/kg PO 138.3 -30.3
Control - 207.1
Ex. 5 10 mglkg PO 145.4 - 29.8
30 mg/kg PO 124.4 - 39.9
100 mg/kg PO 86.7 - 58.1
Control - 189.9
Ex.7 3 mg/kg PO 137 - 27.9
10 mg/kg PO 135.2 - 28.8
30 mg/kg PO 101.1 -46.6
Control - 200.3
Ex.11 10mglkgPO 144.6 -27.8
30 mg/kg PO 136.6 -31.8
100mglkgPO 118.1 -41.4
Control - 148.5
Ex.12 30 mg/kg PO 106.1 -28.6
100 mg/kg PO 99.0 - 33.3
300 mg/kg PO 77.4 - 47.9
Control - 200
Ex. 17 10 mg/kg PO 175.2 - 12.4
30 mg/kg PO 142.7 - 28.6
100 mg/kg PO 155.4 - 22.3
Control - 213.5
Ex. 20 10 mglkg PO 183.4 - 14.1
30 mg/kg PO 86.3 - 59.6
60 mg/kg PO 97.2 - 54.5
Claims (25)
1. A 1 ,3-di hydro-6-(1 -hydroxy-2-dimethylaminomethyl-al lyl)-7-hydroxy4uro-(3,4-c)-pyridine derivative having the general formula I as defined herein or a pharmaceutically acceptable salt thereof.
2. 1 ,3-dihydro-3-methyl-6-(1 -hydroxy-2-dimethylaminomethyl-al lyl )-7-hydroxy-furo-(3,4-c)-pyridine.
3. 1 ,3-dihydro-3-propyl-6-(1 -hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-fu ro-(3,4-c)-pyridine.
4. 1 ,3-dihydro-3-cyclohexyl-6-( 1 -hydroxy-2-dimethylaminomethyl-al lyl )-7-hydroxy-furo-(3,4-c)-pyridine.
5. 1,3-dihydro-3-phenyl-6-(1 -hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-furo-(3,4-c)-pyridine.
6. 1 ,3-dihydro-3-p-chlorophenyl-6-(1 -hydroxy-2-dimethylami nomethyl-allyl)-7-hydroxy-fu ro-(3,4-c)- pyridine.
7. 1 ,3-dihydro-3-(2,3-dichlorophenyl)-6-(1 -hydroxy-2-dimethylaminomethyl-al Iyl)-7-hydroxy-furo-(3,4-c)- pyridine.
8. 1 ,3-dihydro-3-p4I uorophenyl-6-( 1 -hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-furo-(3,4-c)- pyridine.
9. 1 ,3-dihydro-3-p-toluyl-6-) 1 -hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy-furo-(3,4-c)-pyridine.
10. 1 ,3-dihydro-3-p-methoxyphenyl-6-(1 -hydroxy-2-dimethylaminomethyl-allyl)-7 hydroxy-furo-(3,4-c)pyridine.
11. 1,3-di 1 ,3-dihydro-3-m-trifluoromethylphenyl-6-(1 -hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy4uro (3,4-c)-pyridine.
12. 1 ,3-dihydro-3-(p-diethylaminoethoxy-phenyl)-6-(1 -hydroxy-2-dimethylaminomethyl-allyl)-7hydroxy-furo-(3,4-c)-pyridine.
13. 1,3-dihydro-3-(p-pyrrolidinylethoxy-phenyl)-6-(1-hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy- furo(3,4-c)-pyridine.
14. 1 ,3ihydrn-3-methyI-3-n-penl-6-(1 -hydrnxy-2dimethylaminomethyl-allyl)J-hydroxyJuro-(3A-c)- pyridine.
15. 1 ,3-dihydro-3-methyl-3-phenyl-6-(1 -hydroxy-2-dimethylaminomethyl-aIlyl)-7-hydroxy4uro-(3,4-c)- pyridine.
16. 1 ,3-dihydro-3-methyl-3- a -thienyl-6-(1 -hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy4uro-(3,4c)-pyridine.
17. 1 ,3-dihydro-3-ethyl-3-m-trifluoromethyl phenyl-6-(1 -hydroxy-2-dimethylaminomethyl-allyl)-7- hydroxy-furo-(3,4-c)-pyridine.
18. 1 ,3-dihydro-3-ethyl-3-a -furyl-6-(1 -hydroxy-2-dimethylaminomethyl-al lyl )-7-hydroxy-fu ro-(3,4-c)pyridine.
19. 1 ,3-dihydro-3-phenyl-3-p-ethoxyphenyl-6-(1 -hydroxy-2-dimethylaminomethyl-allyI)-7-hydrnxyJurn (3,4-c)-pyridine.
20. 1,3-dihyd ro-3,3-di-p-fluorophenyl-6-(1 -hydroxy-2-dimethylaminomethyl-al lyl )-7-hydroxy4uro-(3,4-c)pyridine.
21. 1,3-dihydro-3- a -furyl-3-p-thiomethyl phenyl-6-( 1 -hydroxy-2-dimethylaminomethyl-al Iyl)-7-hydroxyfuro-(3,4-c)-pyridine.
22. A process for the preparation of a 1,3-dihydro-6-(1-hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxy- furo-(3,4-c)-pyridine derivative having the general formula I as defined herein, the process comprising reacting a 6-formyl-7-benzyloxy-furo-(3,4-c)-pyridine derivative having the general formula II as defined herein with 1-dimethylaminomethyl-vinylmagnesium bromide at the boil in a non-polar solvent and hydrolysing the 7-benzyloxy group of the resultant intermediate by treatment with an acid.
23. A process according to claim 22 in which the non-polar solvent is tetrahydrofuran.
24. A process for the preparation of a 1 ,3-dihydro-6-(1 -hydroxy-2-dimethylaminomethyl-allyl)-7-hydroxyfuro-(3,4-c)-pyridine derivative having the general formula I as defined herein, the process being substantially as described herein with reference to any of the Examples.
25. A pharmaceutical composition comprising a 1 ,3-dihydro-6-(1 -hydroxy-2-dimethylaminomethyl-allyl)- 7-hydroxy-furo-(3,4-c)-pyridine derivative having the general formula I as defined herein or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable diluent or carrier.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08502740A GB2153824B (en) | 1984-02-02 | 1985-02-04 | Furo-(3,4-c)-pyridine derivatives |
| MYPI87001064A MY101964A (en) | 1984-02-02 | 1987-07-20 | Furo-(3,4-c)- pyridine derivatives |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB848402740A GB8402740D0 (en) | 1984-02-02 | 1984-02-02 | Furo-(3 4-c)-pyridine derivatives |
| GB08502740A GB2153824B (en) | 1984-02-02 | 1985-02-04 | Furo-(3,4-c)-pyridine derivatives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8502740D0 GB8502740D0 (en) | 1985-03-06 |
| GB2153824A true GB2153824A (en) | 1985-08-29 |
| GB2153824B GB2153824B (en) | 1987-04-01 |
Family
ID=26287265
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08502740A Expired GB2153824B (en) | 1984-02-02 | 1985-02-04 | Furo-(3,4-c)-pyridine derivatives |
Country Status (2)
| Country | Link |
|---|---|
| GB (1) | GB2153824B (en) |
| MY (1) | MY101964A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2569698A1 (en) * | 1984-08-31 | 1986-03-07 | Scras | NOVEL PROCESS FOR THE PREPARATION OF SUBSTITUTED FURO- (3,4-C) -PYRIDINE DERIVATIVES IN POSITION 6 |
| GB2234244A (en) * | 1989-07-27 | 1991-01-30 | Scras | Asymmetric synthesis of 7-hydroxyfuro[3,4-c]pyridine derivatives |
-
1985
- 1985-02-04 GB GB08502740A patent/GB2153824B/en not_active Expired
-
1987
- 1987-07-20 MY MYPI87001064A patent/MY101964A/en unknown
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2569698A1 (en) * | 1984-08-31 | 1986-03-07 | Scras | NOVEL PROCESS FOR THE PREPARATION OF SUBSTITUTED FURO- (3,4-C) -PYRIDINE DERIVATIVES IN POSITION 6 |
| GB2234244A (en) * | 1989-07-27 | 1991-01-30 | Scras | Asymmetric synthesis of 7-hydroxyfuro[3,4-c]pyridine derivatives |
| GB2234244B (en) * | 1989-07-27 | 1993-01-06 | Scras | Asymmetric synthesis of furo[3,4-c]pyridine derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| GB8502740D0 (en) | 1985-03-06 |
| GB2153824B (en) | 1987-04-01 |
| MY101964A (en) | 1992-12-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19990204 |