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GB2051799A - 2-(1-Naphthyl)piperidine derivative, its production and use as an anti-mycotic agent - Google Patents

2-(1-Naphthyl)piperidine derivative, its production and use as an anti-mycotic agent Download PDF

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Publication number
GB2051799A
GB2051799A GB8018329A GB8018329A GB2051799A GB 2051799 A GB2051799 A GB 2051799A GB 8018329 A GB8018329 A GB 8018329A GB 8018329 A GB8018329 A GB 8018329A GB 2051799 A GB2051799 A GB 2051799A
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compound
formula
acid addition
addition salt
naphthyl
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Sandoz AG
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    • 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
    • C07D211/70—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • 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
    • C07D211/10—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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14—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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

The invention relates to (R)-N- [trans-3-phenyl-2-propenyl]-2-(1- naphthyl)piperidine; its production and its use as an anti-mycotic agent.

Description

SPECIFICATION 2-(1-Naphthyl)piperidine derivative, its production and use as an anti-mycotic agent This invention relates to the com pound (R)-N-[trans-3-phenyl-2-propenyl]-2-( 1 -naphthyl)piperidine of formula I,
The racemic form of the compound of formula I is disclosed and claimed in European Patent Application Publication No. 0.000.896. The present invention relates to the (R)-antipode, which has been found to have suprisingly superior chemotherapeutic properties not only in comparison with the corresponding (S)-antipode but also the racemate and also to have favourable mammalian toxicity.
The invention also provides processes for the production of the compound of formula I, comprising a) resolving the racemicform of N-[trans-3-phenyl-2-propenyl]-2-(1-naphthyl)piperidine into its optically active antipodes, and isolating the (R)-antipode of formula I, or b) reacting (R)-2-(1 -naphthyl)piperidine of formula II,
with a compound of formula Ill,
in which R is a leaving group.
Process a) may be carried out in conventional mannerforthe resolution of a racemic compound into its optically active antipodes, for example by fractional crystallisation of diastereoisomeric salt pairs with an optically active acid, such as (-)-di-O,O-toluoyl-(L)-tartaric acid.
Process b) may for example be carried out in an inert solvent, such as a lower alkanol, e.g. ethanol, optionally an aqueous alkanoi, an aromatic hydrocarbon, such as benzene or toluene, a cyclic ether such as dioxane, or a carboxylic acid dialkylamide, e.g. dimethylformamide. The reaction temperature is suitably from room temperature to the reflux temperature of the reaction mixture, preferably at room temperature.
The process is suitably carried out in the presence of an acid binding agent, e.g. an alkali metal carbonate, e.g. sodium carbonate Suitable leaving groups Rare well known and include halogen atoms, such as bromine.
The resulting compound of formula I may be isolated and purified in conventional manner. Where required, the free base form thereof may be converted into acid addition salt forms in conventional manner, and vice versa.
The compound of the formula II can be prepared by resolving the racemic form of 2-(1-naphthyl)piperidine into its optically active antipodes, and isolating the (R)-antipode. This process may be carried out under conditions analogous to those described under a) above using for example (+)-camphor-10-sulfonic acid.
The compound of the formula II is new and also forms part of the invention.
Racemic 2-(1-naphthyl)pipeddine can be prepared for example by reducing the corresponding 6-(1 naphthyl)-2,3,4,5-tetra hydropyridine of the formula Iv
in a conventional manner for example employing sodium borohydride.
The compounds of the formula III and IV are either known or can be prepared in conventional manner e.g.
as hereinafter described with reference to the examples.
The compound of formula I and its acid addition salts possess advantageous chemotherapeutic properties. In particularthey are useful as antimycotic agents, as indicated in vitro in various families and tvpes of mycetes and in vivo in the experimental skin mycosis model in guinea pigs. In this model, guinea pigs are infected by subcutaneous application of Trichophyton quinkeanum. The test substance is administered once daily for 7 days beginning 24 hours after the infection either by local application by rubbing the test substance (taken up in polyethylene glycol) on the skin surface, or perorally (systemic) the test substance being administered as a solution.
These tests show that the compound of the formula I has a markedly superior antimycotic acitivity to that of both its (S)-antipode and its racemate.
The compound can thus be used e.g. in the topical treatment of Candida sp. and the topical and oral treatment of Dermatophytes.
A further aspect of the invention therefore concerns a method of treating mycotic diseases in a subject and also the use of the compound of the formula I as a chemotherapeutic, e.g. anti-mycotic. agent and its use in the treatment of the human or animal body by therapy.
In the following Tables I to IV, A stands for the compound of the formula I. B for the corresponding (Si-antipode and C for the racemate.
TABLE i Antimycotic ctivitv spectrum 1s vlrro (series dilution testis Min:mum inhibitory concentration Test Strains MIC in ug m@ T. ubrum -152 0 05 0.78 5.1 T. rubrum 106 0.05 1.56 0.1 T. mentagrophvtes -517 0.05 0.78 0.2 T.mentagrophvtes -107 0.05 0.78 0.1 T. mentagrophytes -191 0.1 1.56 0.2 T. mentagrophytes var.
quinckeanum -222 0.05 0.78 0.1 T.granulosum -142 0.1 156 0.1 T.terrestre 518 1.56 1 5 3.13 T.tonsurans 105 0.1 1.56 0.1 T. schoenieini, -227 0 1 0.2 0.2 T. verrucosum 103 0.05 Q 78 3.05 E.floccosum -104 0.1 0.78 0.2 E. floccosum -188 0.05 0.2 0.05 M. canis 241 0.05 1 56 0.1 M. gypseum -514 0.2 1.56 0.2 M. persicolor -100 0.05 C.39 0.05 M. racemosum 101 0.2 0.78 0.2 C. aloicans 1 12.5 > 100 25 C. albicans -. 3 6.25 25 12.5 C. albcans 420 25 > 100 50 C. albicans 248 50 > 100 50 Candida spec. ~ 44 0.78 12.5 3.13 C. kruser 19 12.5 12.5 12.5 C. kruse; 132 6.25 6.25 6.25 C. parapsilosis 264 100 100 > 100 C. tropicais ~ 42 100 100 > 100 C. tropicaiis - 43 25 > 100 > 100 C. tropicalis -387 12.5 > 100 > 100 T.glabrata -113 12.5 > 100 25 Trichosp. cutaneum -695 50 > 100 > 100 Asperg. fumigatus -704 0.78 6.25 0.78 Asoerg. niger -921 1.56 25 6.25 S. schenkll -177 1.56 25 1.56 TABLE II Topical Acitivity in vivo - Experimental Skin Mycosis Model in Guinea Pigs active activity in % x/y Compound substance animals conc. in clinical mycological mycologically healed 0.125 31 15 0/7 A 0.5 38 72 2/8 2.0 66 94 6/8 0.125 0 0 0/8 B 0.5 0 0 0/8 2.0 13 19 0/8 TABLES Ill AND IV Oral activity in vivo - Systemic Guinea Pig Trichophytis Model active activity in % x/y Compound substance animals conc. in clinical mycological mycologically healed 37.5 5 0 0/10 A 75 74 58 1/10 A 150 100 100 10/10 300 100 100 10/10 37.5 0 0 0/10 75 23 8 0/10 C 150 52 35 2/10 300 95 100 10/10 TABLE IV active activity in % x/y Compound substance animals in mg/kg clinical mycological mycologically healed A 150 95 94 11/15 B 150 0 0 0/15 These four tables clearly demonstrate the significantly improved activities of the compound of the formula I as compared with both its (S)-antipode and its racemate.
For the above-mentioned use, the dose administered will of course vary depending on the compound employed (e.g. free base or salt), mode of administration and treatment desired. However, in general, satisfactory results are obtained when administered at a daily dosage of from 3 to 200 mg/kg of animal body weight, conveniently given in divided doses two to four times daily, or in sustained release form. For the larger mammals, the corresponding daily dosgages are in the range of from 200 to 1,500 mg, and dosage forms suitable for oral administration comprise from 50 to 750 mg.
The compounds may be used in free base form or in the form of chemotherapeutically acceptable acid addition salts; suitable acids for salt formation include inorganic acids, such as hydrochloric acid, and organic acids, such as naphthaline-1 ,5-disulphonic acid, camphorsulfonic acid and fumaric acid (to produce the hydrogen furmarate).
The compounds may advantageously be administered orally in admixture with chemotherapeutically acceptable diluents and carriers, and, optionaliy, other excipients to form tablets or capsules. The compounds may alternatively be administered topically in such conventional forms as ointments or creams.
The concentration of the active substance in such topical application forms will of course vary depending on the form of the compound employed, the treatment desired and the nature of the form etc. In general, however, satisfactory results are obtained at concentration of from 0.05 to 5, in particular 0.1 to 1 wt. %. The compound may also be administered parenterally. Such compositions also form part of the invention.
The following Examples illustrate the invention. All temperatures are in C.
Example 1: (R)-N-[trans-3-phenyl-2-propenyl]-2-(1 -naphthyl)piperidine (process b) 7.9 g of Cinnamylbromide, dissolved in 20 ml of dimethylformamide, were added dropwise, with stirring and with the exclusion of moisture to a mixture of 8.5 g (R)-2-(1 -naphthyl)piperidine, 4.2 g sodium carbonate and 80 ml dimethylformamide. After stirring for 18 hours at room temperature the reaction mixture was filtered, concentrated in vacuo and partitioned between water and ethyl acetate. The organic phase was washed three times with diluted, aqueous tartaric acid, then with saturated aqueous NaHCO3 and saturated aqueous NaCI, dried and concentrated in vacuo. The free base was obtained as a yellow oil.
Free base: NMR (CDCI3,TMS, room temperature): 6 = 8.4 - 8.8 (br, 1H), 7.1 - 7.9 (m, 11 H), 3.8 - 4.0 (br, C2pipH), 3.25 - 3.45 (C6pip-HH), 2.0 - 2.3 (Cpjp-HH), 1.2 - 2.0 (6H), in addition an ABXY-system for
VA = 6.29,v5 = 6.19,Vx = 3.36, Vy = 2.68 with JAB = 16.0Hz, Jx = -1.4Hz, JAy = -0.5Hz, Jex = 4.5 Hz,J5y = 7.5 Hz, JXY = -14Hz.
[a]020 = +17.1 (c = 11 mg/ml in chloroform) [a]020 = + 7.9 (c = 13 mg/ml in methanol) DC: RF = 0.45 (toluene/ethylacetate = 4/l) Rf = 0.34 (chloroform/methanol/water/formic acid = 90/10/1,5/1) Example 2: (R)-N-[trans-3-phenyl-2-propenyl]-2-(1 -naphthyl)-piperidine hydrochloride 59.7 g (R)-N-[trans-3-phenyl-2-propenyl]-2-(1 -naphthyl)-piperidine were dissolved in absolute ethanol, reacted with 1.2 equivalents of ethanolic HCI and concentrated in vacuo. The residue was dissolved with heating in 250 ml. of isopropanol, treated with 750 ml of ether and seeded.The crystalline hydrochloride was obtained: M.p.: From 140 crystal conversion with partial melting particularly marked atfrom 175 - 190 , decomposition between 195 and 205 [a1o20= +13.3"(13 mg/ml in chloroform) [a]D = -57.5 (16 mg/ml in methanol) Example 3: (R)-N [trans-3-phenyl-2-propenyl]-2-(1 -naphthyl)-piperidine camphorsulfonate 115 g of (R)-N-[trans-3-phenyl-2-propenyl]-2-(1 -naphthyl)-piperidine were dissolved with heating in 500 ml of isopropanol and quickly added to a solution of 88 g of (+)-camphor-10-suifonic acid monohydrate in 500 ml of isopropanol.After seeding, the reaction mixture is allowed to cool whereupon the crystalline camphorsulfonate was obtained m.p. 242 - 248 .
[a] j2 = +40.3"(15 mg/ml in chloroform) [a1o20= 24.50(15 mg/ml in methanol) Example 4: (R)-N-[trans-3-phenyl-2-propenyl]-2-(1-naphthyl)piperidine (process a) 30 g of racemic N-[trans-3-phenyl-2-propenyl]-2-(1-naphthyl)piperidine were dissolved in 60 ml of ethyl acetate and heated to refluxwith stirring. Asolution of 18.5 g (-)-di-0,0-p-toluoyl-L-tartaric acid in 70 ml of ethyl acetate were then added within 15 minutes and the whole mixture refluxed for a further 15 minutes.On cooling the mixture began to cloud at ca.50 and to crystallise at ca. 350. The suspension was stirred at room temperature for 20 hours, the precipitate filtered under suction, washed twice with 2x 10 ml ethyl acetate and dried in vacuo at 60". 29.75 g of the crystals thus obtained were stirred at room temperature until dissolved (ca. 1/2 hour), in 200 ml oftoluene, 200 ml water and 10 ml of NaOH. Thetoluene phase was removed and washed 3 times with 50 ml of water each time. This organic phase was then evaporated to dryness in vacuo.
The necessary starting materials can be prepared as follows: 6-Methoxy-2, 3,4, 5-tetrah ydrop yridine 600 g of valerolactam were dissolved in 2.1 1 of dried benzene, warmed to 70 - 80" and, with stirring, mixed dropwise with 576 ml of dimethylsulphate (time for addition 7 hours) and then refluxed for a further 3 hours.
After cooling the reaction mixture was made alkaline with conc. Na2CO3 solution (violent foaming) and extracted with benzene. The organic phase was dried over MgSO2 and distilled (not in vacuo) to remove the benzene. B.p. 67 - 70 /80 mbar.
6-(l-naphtnyl)-2,3,4,5-tetrahydropyridine 51.05 g of magnesium were placed in a multi-necked flask and etched by warming with a little iodine. After the addition of 560 ml of absolute ether the mixture was heated to reflux and 434.8 g of bromonaphthaline added dropwise. After commencement of the reaction the heat source was removed and after completion of the addition the mixture boiled for a further 2 hours. The ether was removed by bubbling dry nitrogen through the mixture and replaced by 600 ml of abs. benzene. 80.3 g of 6-methoxy-2,3,4,5-tetrahydropyridine were then slowly added, dropwise, to the boiling reaction mixture which was then refluxed for 8 hours. The mixture was cooled (acetone/dry ice) and mixed with conc. aqueous NH4CI and extracted with ether.The product was removed from the organic phase witth 2N HCI and finally, after neutralisation, extracted with ether. This organic solution was dried and evaporated.
2-(l-naphthyl)piperidine 90 g 6-(1-naphthyl)-2,3,4,5-tetrahydropyridine are dissolved in 11 methanol and reacted portionwise over 1 hour with 65.1 g Na BH4 at 500 with stirring. The mixture was held at 50 for 1 hour, the solvent evaporated off, the residue taken up in chloroform and shaken twice with NaHCO3 solution. The organic phase was dried over MgS04 and evaporated.The oily residue was then dissolved in a little ethanol, treated with ethanolic HCI and the hydrochloride precipitated by the addition of ether m.p. 287 - 289" (after intensive drying under high vacuum m.p. 328 - 329 ) (RJ-2-(l-naphthyllpiperidine 25.2 g of racemic 2-(1-naphthyl)piperidine were dissolved in 800 ml of acetone, heated to boiling and rapidly mixed with 30.4 g (+)-camphor-10-sulfonic acid monohydrate in 200 ml acetone. After seeding with crystals of the 1-base a practically spontaneous crystallisation followed. The crystals were separated after 16 hours at room temperature, the mother liquor evaporated to about 700 ml and after further seeding with crystals of the salt of the d-base and standing for 4 days crystals of the more readily soluble salt pair isolated. The mother liquor was then further concentrated to about 100 ml, mixed with ether and further crystals precipitated. The base was liberated by partitioning between diluted aqueous NaOH and ether.
[a]2 = +70 (c = 12 mg/ml in chloroform).

Claims (11)

1. A process for preparing the compound of the formula I
or an acid addition salt thereof which comprises a) resolving the racemic form of N-[trans-3-phenyl-2-prnpenyl]-2-(1-naphthyl)pipendine into its optically active antipodes, and isolating the (R)-antipode of formula I, or b) reacting (R)-2-(1 -naphthyl)piperidine of formula II,
with a compound of formula III,
in which R is a leaving group and when required converting the compound of the formula I thus obtained into an acid addition salt thereof or converting an acid addition salt of the compound of the formula I thus obtained into the free base or into another acid addition salt thereof.
2. A process as claimed in Claim 1, substantially as hereinbefore described with reference to the examples.
3. The compound of the formula I or an acid addition salt thereof whenever prepared by a process according to Claim 1 or 2.
4. The compound of the formula I as shown in Claim I or an acid addition salt thereof.
5. The compound as claimed in Claim 4, in free base form.
6. The compound as claimed in Claim 4, in the form of its hydrochloride.
7. A chemotherapeutical composition comprising a chemotherapeutically effective amount of a compound of the formula I as claimed in Claim 4, or a chemotherapeutically acceptable acid addition salt thereof, together with a chemotherapeutically acceptable diluent or carrier therefor.
.
8. The use of the compound of the formula I as claimed in Claim 4, or a chemotherapeutically acceptable acid addition salt thereof as chemotherapeutical agent.
9. The use of the compound of the formula I as claimed in Claim 4, or a chemotherapeutically acceptable acid addition salt thereof as an anti-mycotic.
10. The use of the compound of the formula I as claimed in Claim 4 or a chernotherapeutically acceptable acid addition salt thereof in a method of treatment of the human or animal body by therapy.
11. A method of treating mycotic diseases in a subject which comprises administering to a subject in need of such treatment an anti-mycotically effective amount of the compound of the formula I as claimed in Claim 4, or of a chemotherapeutically acceptable acid addition salt thereof.
GB8018329A 1979-06-08 1980-06-04 2-(1-Naphthyl)piperidine derivative, its production and use as an anti-mycotic agent Withdrawn GB2051799A (en)

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JP (1) JPS562964A (en)
AU (1) AU5912180A (en)
BE (1) BE883673A (en)
DE (1) DE3020113A1 (en)
DK (1) DK247180A (en)
ES (1) ES8105287A1 (en)
FR (1) FR2462426A1 (en)
GB (1) GB2051799A (en)
IL (1) IL60248A0 (en)
IT (1) IT8048887A0 (en)
NL (1) NL8003250A (en)
PT (1) PT71362B (en)
SE (1) SE8004234L (en)
ZA (1) ZA803403B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0466585A1 (en) * 1990-07-10 1992-01-15 Adir Et Compagnie Novel piperidin, tetrahydropyridine and pyrrolidine derivatives, process for their preparation and pharmaceutical compositions containing them
US5935998A (en) * 1995-07-06 1999-08-10 Novartis Ag Use of all allylamine derivatives such as terbinafine, in the manufacture of a medicament for the treatment of helicobacter pylori infection or associated diseases

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4859552B2 (en) * 2006-06-21 2012-01-25 株式会社ダイゾー Aerosol products

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2862103D1 (en) * 1977-08-19 1982-11-18 Sandoz Ag Propenyl amines, processes for their production and pharmaceutical compositions containing them

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0466585A1 (en) * 1990-07-10 1992-01-15 Adir Et Compagnie Novel piperidin, tetrahydropyridine and pyrrolidine derivatives, process for their preparation and pharmaceutical compositions containing them
FR2664592A1 (en) * 1990-07-10 1992-01-17 Adir NOVEL DERIVATIVES OF PIPERIDINE, TETRAHYDROPYRIDINE AND PYRROLIDINE, PROCESS FOR PREPARING THEM AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME
AU635851B2 (en) * 1990-07-10 1993-04-01 Adir Et Compagnie New piperidine, tetrahydropyridine and pyrrolidine derivatives, process for preparing these and pharmaceutical compositions containing them
US5935998A (en) * 1995-07-06 1999-08-10 Novartis Ag Use of all allylamine derivatives such as terbinafine, in the manufacture of a medicament for the treatment of helicobacter pylori infection or associated diseases

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DE3020113A1 (en) 1980-12-18
JPS562964A (en) 1981-01-13
ES492149A0 (en) 1981-05-16
ES8105287A1 (en) 1981-05-16
SE8004234L (en) 1980-12-09
IT8048887A0 (en) 1980-06-04
PT71362A (en) 1980-07-01
ZA803403B (en) 1982-01-27
DK247180A (en) 1980-12-09
BE883673A (en) 1980-12-08
NL8003250A (en) 1980-12-10
IL60248A0 (en) 1980-09-16
AU5912180A (en) 1980-12-11
FR2462426A1 (en) 1981-02-13
PT71362B (en) 1981-06-25

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