GB1568399A - Pyrazolo pyridine derivatives - Google Patents

Pyrazolo pyridine derivatives Download PDF

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GB1568399A
GB1568399A GB42185/76A GB4218576A GB1568399A GB 1568399 A GB1568399 A GB 1568399A GB 42185/76 A GB42185/76 A GB 42185/76A GB 4218576 A GB4218576 A GB 4218576A GB 1568399 A GB1568399 A GB 1568399A
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lower alkyl
alkylene
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D231/38—Nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

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  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
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  • General Chemical & Material Sciences (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

(54) PYRAZOLO PYRIDINE DERIVATIVES (71) We, E. R. SQUIBB & SONS, INC., a corporation of Delaware, United States of America, residing at Lawrenceville Princeton Road, Princeton, New Jersey, Units d States of America, do hereby declare die invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention provides new derivatives of 2,7. - dihydro - 4H - pyrazolo[3,4 pyridine-5-ketones and their salts. The compounds of the invention have the general formula
wherein Rl is lower alkyl, phenyl or phenyllower alkylene; R2 and R4 each is hydrogen or lower alkyl; Ra is lower alkyl, lower alkoxy, hydroxy, phenyl or substituted phenyl wherein the pbenyl substituent is lower alkyl, carboxy, halogen or amino; RS is lower alkyl, cyclolower alkyl, phenyl-lower alkylene, amino lower alkylene, di-lower alkylaminolower alkylene or Het-lower alkylene wherein Het is pyrrolidino, piperidino, (lower alkyl) piperidino, piperazino, (lower alkyl)piperazino or (hydroxy-lower alkyl)piperazino; the inven tron also includes such compounds in physiologically acceptable salt form and pharma Qutical compositions comprising the compounds (or salts) and a pharmaceutical carrier.
The symbols have the same meanings throughout this specification as in formula I above.
The lower alkyl groups are straight or branched chain hydrocarbon groups having up to seven carbon atoms e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, and pentyl. The C1-C4 lower alkyl groups and especially C1-C2 groups are preferred. The term phenyl-lower alkylene means a phenyl group attached to a lower alkyl group as just defined. Phenylmethyl and phenylethyl are representative and preferred.
The lower alkoxy groups are such lower alkyl groups attached to an oxygen. They include, for example, methoxy, ethoxy, propoxy, and isopropoxy. The C1-C4 lower alkoxy groups and especially C1-C2 groups are preferred. The substituted phenyl groups are those wherein the phenyl is simply substitutted, bearing a lower alkyl, carboxy, halogen or amino group. The halogens are the four common halogens, but chlorine and bromine are preferred.
Each of the lower alkylene groups contains 1 to 7 carbon atoms. The C1-C4 and especially Ci-C2 members also are preferred.
The cyclo-lower groups are the C4-C7 cycloaliphatics cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, the C5-C6 members being preferred. The amino-lower alkylene groups include, for example, aminomethyl, amino ethyl, 3-aminopropyl and 2-aminopropyl.
Exemplary of the di-lower alkylamino-lower alkylene groups are dimethylaminomethyl, dimethylaminoethyl, dimethylaminopropyl, diethylaminoethyl and diethylaminopropyl.
Groups containing up to four, but especially up to two, carbons in each of the alkyl groups are preferred.
The heterocyclo-lower alkylene group repre sented by R5 consists of a 5- or 6-membered heterocyclic containing one or two nitrogens and the rest carbon atoms (exclusive of hydrogen) attached to a lower alkylene as defined above. These heterocyclics are unsubstituted or substituted with lower alkyl or hydroxy-lower alkyl, and are pyrrolidine, piperidine, (lower alkyl)piperidine, e.g. 4ethyl-piperidine, piperazine, (lower alkyl) piperazine e.g. 4 - methyl - piperazine and (hydroxy-lower alkyl)piperazine e.g. 4 - (2hydroxyethyl)-piperazine. The lower alkylene groups to which the heterocyclic is attached is preferably a C14 hydrocarbon group, particularly C1C2, and especially methylene.
The heterocyclics are preferably unsubstituted.
Preferred are those compounds wherein Rl is lower alkyl, especially methyl; R2 and R4 each is hydrogen or lower alkyl, especially hydrogen. R3 is lower alkoxy, hydroxy or phenyl, especially ethoxy or phenyl; R3 is lower alkyl, especially methyl or ethyl, dilower alkyl-amino-lower alkylene especially dimethylaminoethyl or dimethylaminopropyl, and also piperidinomethyl or piperazinomethyl.
The compounds of formula I are formed by the following series of reactions. The symbols in the structural formulas have the same meaning as previously described.
A 5-aminopyrazole of the formula
[produced analogously to the procedure described in Angew, Chem. 86, 237 (1974); is made to react with an alkoxymethylene ester of the formula
0 C-R3 Al kyl-O-C=C (III) I R4 by heating at a temperature of 12e130"C.
The resulting compound of the formula
?91 \NH-C C11-R3 is cyclized in an inert organic solvent, such as diphenylether at 230 to 2600, while distilling off the alcohol formed, producing a compound of the formula
Compounds of formula I are now produced by reaction of compounds of formula V with the appropriate alkyl halide (VI) R5-X wherein Rs has the meaning defined above and X is halogen, especially chlorine or bromine. The reaction is effected at 80 to 1000 C. in an organic solvent such as dimethylformamide or formamide, in the presence of an alkali metal carbonate or hydroxide, e.g., potassium carbonate or sodium hydroxide.
Basic compounds of formula I form acid addition salts which are also part of this invention, particularly the non-toxic, physiologically acceptable members. The basic compounds of formula I form salts by reaction with a variety of inorganic and organic acids providing acid addition salts including, for example, hydrohalides (especially hydrochloride and hydrobromide), sulfate, nitrate, borate, phosphate, oxalate, tartrate, maleate, citrate, accetate, ascorbate, succinate, benzenesulfonate, methanesulfonate, cyclohexanesulfamate and toluenesulfonate. The acid addition salts frequently provide a convenient means for isolating the product, e.g., by forming and precipitating the salt in a medium in which the salt is insoluble, then after separation of the salt, neutralizing with a base such as barium hydroxide or sodium hydroxide, to obtain the free base of formula I. Other salts can then be formed from the free base by reaction with one or two equivalents of the acid having the desired acid ion.
Compounds of formula I wherein Rs is hydroxy form salts with bases such as alkali metal hydroxides or alkaline earth hydroxides, e.g., sodium hydroxide, potassium hydroxide, calcium hydroxide. Water soluble salts such as the sodium or potassium salts are particularly useful.
The compounds of this invention have antiinflammatory properties and may be used as anti-inflammatory agents, for example, to reduce local inflammatory conditions such as those of an edematous nature or resulting from proliferation of connective tissue in various mammalian species such as rats, dogs and the like when given orally in dosages of 5 to 50 ing/kg/day, preferably 5 to 25 mg/kg/day, in single or 2 to 4 divided doses, as indicated by the carageenan edema assay in rats. The active substance may be utilized in compositions such as tablets, capsules, solutions or suspensions containing up to 300 mg. per unit of dosage of a compound or mixture of compounds of formula I or physiologically accept- able salt thereof. They may be compounded in conventional manner with a physiologically acceptable vehicle or carrier, optionally with an excipient, binder, preservative stabilizer or flavor as called for by accepted pharmaceutical practice. Topical preparations containing 0.1 to 3 percent by weight of active substance in a lotion, ointment or cream also can be used.
The compounds of this invention are also central nervous system depressants and may be used as tranquilizers or ataractic agents for the relief of anxiety and tension states, for example, in mice, cats, rats, dogs and other mammalian species. For this purpose a compound or mixture of compounds of formula I, or non-toxic, physiologically acceptable acid addition salt thereof, is adminis tered orally or parenterally in a conventional dosage form such as tablet, capsule or sterile injectable preparation. A single dose, or preferably 2 to 4 divided daily doses, provided on a basis of 1 to 50 mg. per kilogram per day, preferably 2 to 15 mg. per kilogram per day, is appropriate. These may be conventionally formulated in an oral or parenteral dosage form by compounding 10 to 250 mg.
per unit of dosage with a conventional vehicle optionally with an excipient, binder, preservative, stabilizer or flavor as called for by accepted pharmaceutical practice.
The following examples are illustrative of the invention and constitute preferred embodiments. They also serve as models for the preparation of other members of the group which can be made by suitable variation of the substituent groups in the starting materials.
All temperatures are in degrees celsius.
Example 1.
5-Benzoyl-2,7-dihydro-2,7-dimethyl-4H- pyrazolo [ 3,4-bl pyridin-4-one.
a) 2-[[1-niethyl1Hpyrazol3yl) amino] methylene] - 3 - oxo - benzene propanoic acid, ethyl ester.
24.8 g. of ethoxymethylene-benzoylacetic acid, ethyl ester (0.1 mol.) and 9.7 g. of 3 amino-1-methylpyrazole (0.1 mol.) are heated together at 120130 C. for 30 minutes. After this time, the alcohol formed is distilled off in vacuo and the oily residue is crystallized with 50 ml. of ether to obtain 2 methyl - 1H - pyrazol - 3 - yl) - amino]methylene] - 3 - oxobenzenepropanoic acid, ethyl ester, yield 25 g. (84%); m.p. 65670.
b) (4 - hydroxy - 2 - methyl - 2H - pyrazolo- [3,4-b] pyridin - 5 - yl) phenylmeth- anone.
310 g. of 2 - [[(1 - methyl - 1H - pyrazol3 - yl)amino]methylene] - 3 - oxobenzenepropanoic acid, ethyl ester (1.04 mol.) are heated with stirring for 15 minutes at 250 in 1 liter of diphenyl ether, while the alcohol formed is continuously distilled off. The solution is cooled and the diphenyl ether removed in vacuo. The residue is crystallized with methanol to obtain (4 - hydroxy - 2 - methyl2H - pyrazolo[3,4-b] - pyridin - 5 - yl)phenylmethanone, yield (156 g. 59.2%); m.p.
282900 (DMF).
c) 5 - benzoyl - 2,7 - dihydro - 2,7 dimethyl - 4H - pyrazoloF3,4-b]pyridin- 4 - one.
25.3 g. of (4 - hydroxy - 2 - methyl - 2H pyrazolof3,4-blpyridin - 5 - yl) - phenylmethanone (0.1 mol.), 15.5 g. of methyl iodide (0.11 mol.) and 21 g. of potassium carbonate (0.15 mol.) are heated in 150 ml. of dimethylformamide with stirring at 800 for 10 hours. After this time, the inorganic precipitate is filtered off and the filtrate evaporated to dryness. The remaining 5 - benzoyl - 2,7dihvdro - 2,7 - dimethyl - 4H - pyrazolo r3,4-blpyridin - 4 - one is recrystallized from butanol, yield 18 g. (67%); m.p. 272-2740.
Example 2.
5 - Benzoyl - 7 - ethyl - 2,7 - dihydro - 2 methyl - 4H - pyrazolo [3,4-bl-pyridin- 4-one.
25.3 g. of (4 - hydroxy - 2 - methyl2H - pyrazolor3,4-bl - pyridin - 5 - yl) t'henvlmethanone (0.1 mol.) 17.1 g. of ethyl iodide (0.11 mol.) and 5 g. of sodium hvdroxide are heated together in 150 ml. of dimethvlformamide for 12 hours with continuous stirring at 1000 C. The mixture is filtered hot, evaporated to dryness and the residue is recrystallized from butanol to obtain 5 - benzoyl - 7 - ethyl - 2,7 - dihydro2 - methyl - 4H - pyrazolo[3,4-b]pyridin - 4one, yield 20.3 g. (72%); m.p. 217218 .
Example 3.
5 - Benzoyl - 2,7 - dihydro - 2 - methyl- 7 - (3 - methylbutyl) - 4H - pyrazolo ] 3,4-b] pyridin - 4 - one.
By substituting for the methyl iodide in the procedure of Example lc 1 - bromo - 3methylbutane, 5 - benzoyl - 2,7 - dihydro2 - methyl - 7 - (3 - methylbutyl) - 4H pyrazolof3,4b]pyridin - 4 - one is obtained, yield 69%; m.p. 231-2330C (butanol).
Example 4.
5 - Benzoyl -- 7 - [3 - (dimethylamino) propyl - 2,7 - dihydro - 2 - methyl- 4H - pyrazolo[3,4-b]pyridin - 4 - one.
5.1 g. of (4 - hydroxy - 2 - methyl - 2Hpyrazolo[3,4-b]pyridin - 5 - yl)phenylmethanone (0.02 mol.), 4.8 g. of dimethylaminopropyl chloride (0.04 mol.) and 5.6 g.
of potassium carbonate (0.04 mol.) are heated in 50 ml. of dimethylformamide at 800 for 12 hours with stirring. The mixture is filtered hot, evaporated to dryness and the residue is recrystallized from ethyl acetate to obtain 5benzoyl - 7 - [3 - (dimethylamino) - propyl]2,7 - dihydro - 2 - methyl - 4H - pyrazolo [3,4-b]pyridin - 4 - one, yield 4.6 g. (68%); m.p. 186--1880C.
The hydrochloride is tormed by treatment with ethanolic HCI.
Example 5.
7 - Ethyl - 4,7 - dihydro - 2 - methyl - 4 oxo - 2H - pyrazolo] 3,4 - b]primidine 5 - carboxylic acid, ethyl ester.
a) [[(1 - methyl - 1H - pyrazol - 3 - yl) amino] methylene] propanedioic acid, ethyl ester.
194 g. of 3 - amino - 1 - methylpyrazole (2 mol.) and 432 g. of ethoxymethylenemalonic acid, diethyl ester are stirred together for 1 hour at 1000. The alcohol formed is removed in vacuo and the residue is crystallized with ether to obtain [[(1 - methyl 1H - pyrazol - 3 - yl)amino]methylene)propanedioic acid, ethyl ester, yield 425 g.
(80%); m.p. 6era30.
b) 4 - hydroxy - 2 methyl - 2H - pyrazolo [3,4-b]pyridine - 5 - carboxylic acid, ethyl ester.
534 g. of [[(1 - methyl - 1H - pyrazol- 3 - yl)amino]methylene] - propanedioic acid, ethyl ester (2 mol.) are added to about 3 liters of hot (240 ) diphenyl ether (oil bath temperature 28(r--2900) with stirring. The temperature of the solvent decreases to about 2000. After the temperature has again reached 2200, this temperature is maintained for 30 minutes. The alcohol formed is continuously removed by distillation. The solution is cooled to about 100" and the diphenyl ether is distilled off; (b.p. 90-950/oo4). The oily residue is treated with 500 ml. of acetonitrile and after standing overnight, the product, 4 - hydroxy2 - methyl - 2H - pyrazolo[3,4-b] - pyridine5 - carboxylic acid, ethyl ester, crystallizes alld is purified by recrystallation from n propyl alcohol, yield 235 g. (67%); m.p. 215 2180.
c) 7 - ethyl - 4,7 - dihydro - 2 - methyl 4 - oxo - 2H - pyrazolo [3,4-b]pyridine- 5 - carboxylic acid, ethyl ester.
22.1 g. of 4 - hydroxy - 2 - methyl - 2H pyrazolo[3,4-b]pyridine - 5 - carboxylic acid, ethyl ester (0.1 mol.), 17.1 g. of ethyl iodide and 21 g. of potassium carbonate (0.15 mol.) are stirred together in 200 ml. of dimethylformamide at 800C for 12 hours. The inorganic precipitate is filtered off and the filtrate evaporated to dryness. Recrystallization of the residue with ethyl acetate yields 18.2 g. of 7 - ethyl - 4,7 - dihydro - 2 - methyl - 4oxo - 2H - pyrazolo[3,4b]pyridine - 5carboxylic acid, ethyl ester, yield (73%); m.p. 17iW172 .
Example 6.
4,7 - Dihydro - 2,7 - dimethyl - 4 - oxo 2H - pyrazolo[3,4-b]pyridine - 5 - carb oxylic acid, ethyl ester.
By substituting methyl iodide for the ethyl iodide in the procedure of Example 5c, 4.7dihydro - 2,7 - dimethyl - 4 - oxo - 2Hpyrazolo[3,4-b]pyridine - 5 - carboxylic acid, ethyl ester is obtained, yield 58%; m.p. 2352400 (butanol).
Example 7.
4,7 - Dihydro - 2 - methyl - 7 - (3 - methyl butyl) - 4 - oxo - 2H - pyrazolo[3,4-b] pyridine - 5 - carboxylic acid, ethyl ester.
22.1 g. of 4 - hydroxy - 2 - methyl - 2H pyrazolo[3,4-b] pyridine - 5 - carboxylic acid, ethyl ester (0.1 mol.), 17 g. of 1 - bromo3 - methylbutane and 21 g. of potassium carbonate are heated together with stirring in 100 ml. of dimethylformamide at 1000 for 12 hours. The mixture is filtered hot, evaporated to dryness and the residue recrystallized from ethyl acetate to obtain 4,7 - dihydro - 2methyl - 7 - (3 - methylbutyl) - 4 - oxo - 2Hpyrazolo[3,4-b]pyridine - 5 - carboxylic acid, ethyl ester, yield (63%); m.p. 105106 .
Example 8.
7 - [3 - (Dimethylamino) propyl] - 4,7 dihydro - 2 - methyl - 4 - oxo - 2H pyrazolo[3,4-b]pyridine - 5 - carboxylic acid, ethyl ester.
By substituting 3 - (dimethylamino)propyl chloride for the ethyl iodide in the procedure of Example 5c, 7 - [3 - dimethylamino)propyl] - 4,7 - dihydro - 2 -methyl4 - oxo - 2H - pyrazolo[3,4-b]pyridine - 5carboxylic acid, ethyl ester is obtained, yield (48%); m.p. 120--1210 (ethyl acetate).
Example 9.
7 - Ethyl - 4,7 - dihydro - 2 - methyl - 4 oxo - 2H - pyrazolof3,4-b]pyridine - 5 carboxylic acid.
24.9 g. of 7 - ethyl - 4,7 - dihydro - 2methyl - 4 - oxo - 2H - pyrazolo[3,4-b]- pyridine - 5 - carboxylic acid, ethyl ester (0.1 mol.) are treated with 10 g. of potassium hydroxide in 100 ml. of ethyl alcohol at reflux temperature for 12 hours with stirring. The solvent is removed in vacuo and the crystalline, residual potassium salt is dissolved in 100 ml. of water. After acidifying the solution with acetic acid, 7 - ethyl - 4,7 - dihydro2 - methyl - 4 - oxo - 2H - pyrazolo[3,4-b]- pyridine - 5 - carboxylic acid crystallizes, yield 19 g. (68%); m.p. 273275 (DMF).
The following additional products are produced by the methods of the previous examples by appropriate substitution of the reactants:
Example Rl R2 R3 R4 R5
Example Rl R2 R3 R4 R5
WHAT WE CLAIM IS:1. A compound of the formula
wherein R1 is lower alkyl, phenyl or phenyllower alkylene; R2 and R4 each is hydrogen or lower alkyl; R3 is lower alkyl, lower alkoxy, hydroxy, phenyl or substituted phenyl wherein the phenyl substituent is lower alkyl, carboxy, halogen or amino; Rs is lower alkyl, cyclolower alkyl, phenyl-lower alkylene, aminolower alkylene, di-lower alkylamino-lower alkylene or Het-lower alkylene wherein Het is pyrrolidino, piperidino, (lower alkyl)piperidino, piperazino, (lower alkyl)-piperazino or (hydroxy-lower alkyl)piperazino; or such a compound in phyhiologically acceptable salt form.
2. A compound as in Claim 1 wherein R1 is lower alkyl.
3. A compound as in Claim 1 wherein R' is methyl.
4. A compound as in Claim 1, 2 or 3 wherein R and R4 each is hydrogen.
5. A compound as in Claim 1, 2, 3 or 4 wherein Rs is phenyl.
6. A compound as in Claim 1, 2, 3 or 4 wherein R3 is hydroxy.
7. A compound as in Claim 1, 2, 3 or 4 wherein Rs is lower alkoxy.
8. A compound as in Claim 1, 2, 3 or 4 wherein RS is ethoxy.
9. A compound as in any one of Claims 1 to 8 wherein R5 is lower alkyl.
10. A compound as in any one of Claims 1 to 8 wherein R5 is methyl.
11. A compound as in any one of Claims 1 to 8 wherein R5 is ethyl.
12. A compound as in any one of Claims 1 to 8 wherein R5 is di-lower alkylaminolower alkylene.
13. A compound as in any one of Claims 1 to 8 wherein R5 is dimethylaminopropyl.
14. A compound as in any one of Claims 1 to 8 wherein R5 is piperidinomethyl.
15. A compound as in any one of Claims 1 to 8 wherein R5 is piperazinomethyl.
16. A compound as in any one of Claims 1 to 8 wherein R5 is cyclo-lower alkyl.
17. A compound as in any one of Claims 1 to 8 wherein R5 is phenyl-lower alkylene.
18. A compound as in any one of Claims 1 to 8 wherein R5 is amino-lower alkylene.
19. A process for the preparation of a compound of the formula (I) as defined in Claim 1 and physiologically acceptable salts thereof which comprises reacting a compound of the formula
**WARNING** end of DESC field may overlap start of CLMS **.

Claims (24)

  1. **WARNING** start of CLMS field may overlap end of DESC **.
    Example Rl R2 R3 R4 R5
    WHAT WE CLAIM IS:1. A compound of the formula
    wherein R1 is lower alkyl, phenyl or phenyllower alkylene; R2 and R4 each is hydrogen or lower alkyl; R3 is lower alkyl, lower alkoxy, hydroxy, phenyl or substituted phenyl wherein the phenyl substituent is lower alkyl, carboxy, halogen or amino; Rs is lower alkyl, cyclolower alkyl, phenyl-lower alkylene, aminolower alkylene, di-lower alkylamino-lower alkylene or Het-lower alkylene wherein Het is pyrrolidino, piperidino, (lower alkyl)piperidino, piperazino, (lower alkyl)-piperazino or (hydroxy-lower alkyl)piperazino; or such a compound in phyhiologically acceptable salt form.
  2. 2. A compound as in Claim 1 wherein R1 is lower alkyl.
  3. 3. A compound as in Claim 1 wherein R' is methyl.
  4. 4. A compound as in Claim 1, 2 or 3 wherein R and R4 each is hydrogen.
  5. 5. A compound as in Claim 1, 2, 3 or 4 wherein Rs is phenyl.
  6. 6. A compound as in Claim 1, 2, 3 or 4 wherein R3 is hydroxy.
  7. 7. A compound as in Claim 1, 2, 3 or 4 wherein Rs is lower alkoxy.
  8. 8. A compound as in Claim 1, 2, 3 or 4 wherein RS is ethoxy.
  9. 9. A compound as in any one of Claims 1 to 8 wherein R5 is lower alkyl.
  10. 10. A compound as in any one of Claims 1 to 8 wherein R5 is methyl.
  11. 11. A compound as in any one of Claims 1 to 8 wherein R5 is ethyl.
  12. 12. A compound as in any one of Claims 1 to 8 wherein R5 is di-lower alkylaminolower alkylene.
  13. 13. A compound as in any one of Claims 1 to 8 wherein R5 is dimethylaminopropyl.
  14. 14. A compound as in any one of Claims 1 to 8 wherein R5 is piperidinomethyl.
  15. 15. A compound as in any one of Claims 1 to 8 wherein R5 is piperazinomethyl.
  16. 16. A compound as in any one of Claims 1 to 8 wherein R5 is cyclo-lower alkyl.
  17. 17. A compound as in any one of Claims 1 to 8 wherein R5 is phenyl-lower alkylene.
  18. 18. A compound as in any one of Claims 1 to 8 wherein R5 is amino-lower alkylene.
  19. 19. A process for the preparation of a compound of the formula (I) as defined in Claim 1 and physiologically acceptable salts thereof which comprises reacting a compound of the formula
    with an alkyl halide of the formula RssX wherein X is halogen.
  20. 20. A compound according to Claim 1 when prepared by a process according to Claim 19.
  21. 21. A compound according to Claim 1 as named or shown in any of the Examples.
  22. 22. A pharmaceutical composition comprising a compound according to any one of Claims 1 to 18, 20 and 21 and a pharmaceutical carrier.
  23. 23. A compostion according to Claim 22, in the form of a tablet, capsule, sterile injectable preparation, lotion, ointment or cream.
  24. 24. A composition according to Claim 22 or 23, including an excipient, binder, preservative, stabilizer or flavor.
GB42185/76A 1975-10-16 1976-10-11 Pyrazolo pyridine derivatives Expired GB1568399A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0114273A1 (en) * 1982-12-20 1984-08-01 GRUPPO LEPETIT S.p.A. New pharmacologically active pyrazolopyridines

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0114273A1 (en) * 1982-12-20 1984-08-01 GRUPPO LEPETIT S.p.A. New pharmacologically active pyrazolopyridines

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FR2327780A1 (en) 1977-05-13
DE2646670A1 (en) 1977-04-21
JPS5251393A (en) 1977-04-25

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