CA1107761A - Drug containing a cyclopentyl-aldehyde derivative and composition containing some - Google Patents

Drug containing a cyclopentyl-aldehyde derivative and composition containing some

Info

Publication number
CA1107761A
CA1107761A CA328,873A CA328873A CA1107761A CA 1107761 A CA1107761 A CA 1107761A CA 328873 A CA328873 A CA 328873A CA 1107761 A CA1107761 A CA 1107761A
Authority
CA
Canada
Prior art keywords
cyclopentyl
chloroform
cho
trans
cis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA328,873A
Other languages
French (fr)
Inventor
Jacques Debat
Jean Lemoine
Jean-Pierre Riffaud
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institut de Recherches Chimiques et Biologiques Appliquees SARL IRCEBA
Original Assignee
Institut de Recherches Chimiques et Biologiques Appliquees SARL IRCEBA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Institut de Recherches Chimiques et Biologiques Appliquees SARL IRCEBA filed Critical Institut de Recherches Chimiques et Biologiques Appliquees SARL IRCEBA
Application granted granted Critical
Publication of CA1107761A publication Critical patent/CA1107761A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/05—Alcohols containing rings other than six-membered aromatic rings
    • C07C33/12—Alcohols containing rings other than six-membered aromatic rings containing five-membered rings
    • 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]
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/14—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of a —CHO group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/17—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrogenation of carbon-to-carbon double or triple bonds
    • C07C29/172—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrogenation of carbon-to-carbon double or triple bonds with the obtention of a fully saturated alcohol
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C31/00—Saturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C31/27—Polyhydroxylic alcohols containing saturated rings
    • C07C31/272—Monocyclic
    • C07C31/274—Monocyclic with a three to five-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/28—Saturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings
    • C07C47/30—Saturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings with a five-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/38—Unsaturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings
    • C07C47/45—Unsaturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings having unsaturation outside the rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C61/06—Saturated compounds having a carboxyl group bound to a five-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C61/16—Unsaturated compounds
    • C07C61/35—Unsaturated compounds having unsaturation outside the rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

ABSTRACT

This invention is concerned with a new use as drug of a cyclopentyl-aldehyde derivative selected from the group consisting of a) cyclopentyl-aldehyde derivatives of the general formula wherein X and Y, which can be the same or different represent CHO, CH2OH or COOH; Z represents a C1- C3 alkyl group; A represents -CH2-, ?C = CH2 or ?CH(CH3);
and b) their geometrical isomers.
This invention also relates to a therapeutical composition comprising as active ingredient a cyclopentyl-aldehyde derivative of formula 1.

Description

~.~Q7~

A new dru,~ containin,~ a cyclopentvlaldehvde derivative and composition containin,~ same.
This invention is concerned with a new drug which belongs to the family of the cyclo-pentyl-aldehyde derivative, and with a therapeutical composition containing a cyclopentylaldehyde derivative a,s active ingredient.
More precisely the invention relates to a cyclopentyl-aldehyde derivative useful in therapy, which is selected from the group consistinS of a)compounds of the general formula ~ ~ A-X

Z~Y
wherein X and Y, which can be the same or different represent CHO, CH20H or COO}~; Z represents a Cl-C3 alkyl group; A represents -CH2-, `C=CH2 or ~CH(CH3);
and b) their geometrical isomers.
Compounds of formula I are known compound~ which can be prepared either by synthesis or by extraction from a plant belonging to the Labiatae family such as the Teucrium marum , Teucrium polium and Teucrium montanum species. For instance they can be extracted from Teucrium marum according to the method __ disclosed by PAGNONI et al., in Aust~ J~ Chem~ (1976), 29~ pages 1375-13817 article wherein their pharmaceutical properties are not described .
Now it has been surprisingly found that cyclopentyl-aldehyde derivatives according to formula I are (i) active as bacteriostatic, bacteri-cide, antispasmodic, antianaphylactic and antiphlogistic agents, and (ii) useful in particular in the treatment of human beings and warm-blooded animals suffering ~k ~7~1 from infections diseases induced by"Gram(~) and Gram(-)"
germs ,.~nd all~r~ies such as hay fever.
On the other hand cyclopentyl-aldehy(lederivatives of formula I are more interesting~
from a pharmaceutical point of view, than the Teucrium mRrum extracts according to US patent No. 4 151 278.
Amongst the compounds included within the definition of the general formula I, can be cited the fo]lowing ones:
- x. 1:D~ -(2-formyl-3-methyl-cyclopentyl)-acetaldehyde (X = Y-CHO; A = CH2; Z = CH3), - Ex. 2- 2-(2-hydroxymethyl-3-methyl-cyclopentyl)-ethanol ( X = Y = CH20H;A = CH2; Z = CH3), - ~x. 3:o<-(2-carboxy-3-methyl-cyclopentyl)- acetic acid (X = Y = COOH; A = CH2; Z = CH3), - Ex. 4:0~ -(2-formyl-3-methyl-cyclopentyl)-acrylaldehyde (X ~ Y = CHO; A = ~C = CH2; Z = CH3), - Ex~ 5: 2- (2-hydroxymethyl-3-methyl-cyclopentyl)-2-propen-l-ol (X = Y = C1l20H; A = ~ C = CH2; Z = CH3), - Ex. 6: ~ -(2-carboxy-3-methyl-cyclopentyl)- acrylic acid (X = Y . COO~; A =~ C = CH2; Z = CH3), and - Ex. 7: 2-(2-hydroxymethyl-3-methyl-cyc]opentyl)-propan-l-ol rx = Y = CH20H; A = ` CH(CH3); Z = CH37, which all correspond to the following formu~a:
/ A - X
(II) 1-~3C X
(wherein A and X are defined as above), and present 3 mainly t~o isomers:

~ -X ~ ~ ~A-X

35H3C~ ~ X H3C ~ X
(A) (B) ~'cis-trans~ tral~s-c:is'~
A

1~77~1 the"cis-trans" isomer being, in a general manner, more active tl~a1l the "trans-cis"one.
The preferred compounds are those of examp~es l and 4. The most interesting one, from a therapeu~cal point of view, is the compound of example 4.
The best mode for preparing the "acryl" compounds (A=, C = CH2) consists in (i) extracting ~-(2-formyl-3- methyl-cyclopentyl)-acrylal-dehyde from a Teucrium species such as Teucrium marum, Teucrium polium, Teucrium montanum, and (ii) transforming Cl-10 into CH20H by reduction or into COOH
by oxidation. The compounds wherein A is CH(CH3) such as example 7 are obtained by catalytic hydrogenation f C =C~2 The compounds wherein A is CH2 are in particular prepared by synthesis according to a method kno~n ~per se.
PREPARATION I
obtention of ~ -(2-form~1-3-methyl-~yclopentyl)_acryl_ _______________________ ___________________________ __ aldehyde (Example 4) 1210 g of dried and ground Teucrium polium (entire plant) were extracted in a column ~uccessively with 7.35 l of hexane and 7.25 l of chloro-form. The chloroform extract was evaporated to dryness under ~acuum and the residue thus obtained (47 g) waY steam distilled. The distillate was satura~ed with sodi-~m chloride then extracted with chloroform. After drying on Na2S04 the chloroform wa,s distilled off under reduced pressure (0.3 mm ~Ig) to give 7.3 g (yield o.6%) ~ ~ C~CH )-CHO
8~o/o by weight of f "~" 2 H3C ~ ~// CHO
~'~is-trans") and ~1~377~

11% by weight of / ~ C(=CH2)-CHO
~ .

(~trans-cis~l) 5 PREPA~ATION II
.. ...
Obtention ofQc-(2-formyl-3-methyl-cyclopentyl)-acr aldehyde (example 4) _____ ______________ .
25 1cg of dried and ground Teucrium_ marum (entire plant) were extracted b~r lixiviation in a glass column (height: 2m; diameter: 0.225 m) fed in solvent by means of a pomp having a delivery o~ lO l/h.
Two sol~ents were successively used: hexane (170 l) then chloroform (170 l~.The hexane extract was discarded.
The chloroform extract was evaporated to dryness under vacuum in order to obtain a brown oily residue (640g) which wa~ steamdistilled. The di~tillate was saturated with NaCl when extracted with chloroform.
The chloroform phase wa~ dried o~er NaSO~, the solvent wa3 evaporated and the remaining oil was distilled (under 1 mm Hg at 60-780C) to give 42 g of a yellow il (n25C = l.4842) which comprised:
- 87% by weight of the "cis-trans" isom~r , and - 13% by wei~ht of the "trans-cis" isomer.
P~EPARATION I_ Obtention of 2-(2-hydroxymethYl-3-methyl-cyclopentyl)-______________________________________________________
2-propen-l-ol ~example 5) _______________________ _ By reduction of the cis-trans' isomer of example 4 (l.4~) in 5 0 lution in CH30H (25ml) with NaBH4 (1.7 g), the cis-transisomer of example 5 (1019 g) is obtained in the form of an oil~ According to the same method the trans-cis isomer of example 5 is prepared from the -trans-cis isomer of example 4.

5 ~ 77~1 PREPARATIO~ IV
Obtention of 2-(2-hydroxymethyl-3-methyl-cyclopentyl)-_______________~______________________________________ propan-l-ol (example 7) ____________ The"cis-trans" and respectively "trans-cis" isomers of e~ample 7 were obtained by hydrogenation on PtO2 of the "cis-trans" and respectively "trans-cis"
isomers of example 5 according to the method disclosed by PAGNO~I et al.
The pharmaceutical assays which have been carried out with examples 1 and 4 are summed up hereinafter.
1) Assays with example 1 a) Bacteriostatic activ~ty.
~ -(2-formyl-3-methyl-cyclopentyl)-acetaldehyde inhibits Gram (~) and Gram (-) bacteriae. Its MIC
values are: 0.75 mg/ml on Staphylococcus aureus London, 1.2 mg/ml on Eschericllia coli, and .
1.5 mg/ml on roteus b) Antis~asmodic activity The ED-50 values of~<-(2-formyl-3-methyl-cyclopentyl)_ acetaldehyde have been determined (i) ln vitro on isolated ileum of guinea-pig against histamine:
ED - 50 = 50 ~/ml;
(ii) in vivo on the entire animal according to the metllod of KONZETT and ROESLLER:
ED - 50 = 2.6 mg/kg by i.v. rou-te.
c) Antianaphylactic activity Male guinea-pigs are sensitized by two in~ectio~s at the interval of two days oI V.5 ml of a 2g/1 albumen solution. Four weeks after the lethal anaphylactic shock is provoked by i.v.
injection of 0~2 ml of a 2g~1 ovalbumen solution. The prodncts to be tested are administered 30 minutes before (by i.p. route) or at the time (by i.v.route) 77~1 of the provoking injection. The results are given in table 1 for example 1 and Promethazine~ a reference product.
TABLE I
- . . , 5Compound mortality protection (dose) % %
====================== ===_=======_= ============-=====
control 80% 20%
. _ .
Promethazine (20 mg/kg i.p.) % 100%
_ . . . .. _ . _ , Example I .
(10 mg/kg i.p.) 50~o 50%
. ~ ._ Example I
(2mg/kg i.~.) % 10~/o _ _ ...... _ ._. .... ._ __ _ 2~ Assays with Example 4 (consisting of a mixture f 87% by weight of the ~'cis-trans~' isomer and 13%
by weight of the "trans-cis~' isomer).
a) Bacter~static activity Example 4 inhibits Gram (+) and Gram (-) bacteriae.
Its MIC values are:
1.5 mg/m on Staphylococcus aureus, London 1 mg/ml on Escherichia coli (strain 548), 1~75 mg/ml on Proteus vul~aris (strain 1557~, 2.5 mg/ml on Klebsiella pneumoniae (strain 433), 1 mg/ml on Salmonella ty ~ murium ~strain IP), 1~5 mg/ml on Sta~hylococcus aureus (strain 634), 1~25 mg/ml on Streptococcus (strain 1178), 1.25 mg/ml on Bacillus substilis, (strains 548, 1557, 433, 634 and 1178 belonging to the catalogue of the collection of the "Centre International de Distribution de Souches et d~Information sur les Types Microbiens~ of Lausanne, and the "IP"
strain being provided ~rom the Institut 11~7'7~1 Pasteur" of Paris) b) Bactericide activity Example 4 kills Gram (+) and Gram (-) bacteriae.
Its MBC (minimal bactericide concentration) values determined on solid medium (when less than 0.01 %
of the germs survives) are:
1.75 mg/ml on Staphylococcus aureus London, 1.5 mg/ml on Escherichia coli (strain 5~8), 2 mg/ml on Proteus vulgaris (strain 1557),
3 mg/ml on Klebsiella pneumoniae (strain 433), 1.25 mg~ml on Salmonella typhi murium (strain I.P.), 1.75 mg/ml on Staphylococcus aureus (strain 634), 2 mg/ml on Streptococcus (strain 1178), 2.5 mg/ml on Bacillus substilis.
c) Antibronchos~atic activity Guinea pigs (20 animals (weighing 300 - 500 g) per dose and per product to be tested) are preliminary subj(-cted to an aerosol of Example 4 (50 g/l in A
water-ethanol solution) or Promethazine (a reference product) for 10 minutes. Then the animals are subjected individually to an histamine aerosol (3g/1 of histamine in an aqueous medium containing 200g/1 of glycerin)0 The time comprised between the beginning of the exposure to the histamine aerosol and the apnea with fall of the animal is measured.The control batch received only the histamine aerosol. The results given in table II show that Example 4 exhibits a bronchodilating effect which opposed the broncho-constrictor effect of histamine.
TABLE II
. _ _. _ _ Product Apparition of Variation ~th ~dose) apnea respect to control (in seconds~
- _ _, Control lOo ~ 18 Promethazine _ (0~1 mg/kg ~600 ~.. --.. _ . __ . .. ._ .. _ ._ __ 1~7761 TABLE II cont.

Product Apparition of Variation ~7ith (dose) apnea respect to (in seconds) control .~_ . ................. _ .
Ex 4 (1 mg/kg) 130 + 23 * + 20/~ ' Ex 4 (10 mg/kg3 ~ 169 ~ 32 , Note:
* statistically significant (p< 0.05) . . . , _ _ d) Antianaphylactic activity in vitro _ _ _ _ _ _ _ _ _ Male guinea pigs are sensitized by an i.p. injection of 100 mg/kg of ovalbumen in an equal volume of Freund~s adjuvant. Four weeks after the animals are slaughtered, each ileum is recovered and p]aced at 33C in a Thyrode medium.
Constriction is obtained by addition of 200 ~g of albumen to the liquid of surviving. The ampli-tude of the constrictions of the control ileum is compared with the amplitude of the constrictions after putting into contact example 4 for 2 minutes.
The results given in Table III show that example
4 reduces the constriction amplitude of isolated gui-nea pig ileum, said reduction being statistically significant.
in vivo _ ~ _ _ _ _ _ _ Guinea pigs (male or female) are ,sensiti~ed as indicated above with ovalbumen four weeks before the beginning of the experimentO Each ani,mal is subjected to an ovalbumen aerosol (obtained from an aqueous medium containin~ 50g/1 of ovalbumen).
, The anaphylactic shock comes out by appari,tion ,'~, .

~)77~1 of intense dyspnea. The apparition times of said dyspnea are compared between control animals and treated animal preliminary treated with an aerosol of example 4 (50 g/l in a water-ethanol solution). The results given in Table IV show that example 4 increases the time of apparition of respiratory troubles induced by ovalbumen aerosol.

TABLE III

~ .
Product number constriction amplitude (dose) of amplitude variation with animals ~ respect to control animals .. . ... __ . .

control 20 147 1 32 Ex 4 (5 ~g/ml Z0 91 + 37~ _ 30o/o (10 ~g/ml) 20 52 ~ 16* - 65%

. .. _. .. . .
Note ~ statistically significant (p ~ 0.05) . _ , _ _ _ .. . . .

1~7761 ~ABLE IV
-_ . . . .
Product Number of D~pnea (dose) animals time of time varia-apparition tion with (seconds) respect to control animals _ . . ._ I ..
control 20 . 94 + 39 _ (1 mg/kg 20 120 + 52 + 28%
Ex 4 (10 mg/kg) . . 130 + 54 ~ 38~o e) AntiphloSistic activity The antiphlogistic activity of example 4 waa studied on female rats (weighing 100 g) according to the carrageen oedema test. The results are given in table V in which Indometacine is used as a reference product.
TABL~ V
. . _ Product Number dose inhibition with of (per rat) respect to control animal animal , ~
Ex 4 10 10 ~g 25%
Ex 4 10 5 ~g 25%
Ex 4 10200 ~g 41%
Indometacine 10 200 ,ug 57%
, ...... _ . .. _ . . __ .
f) Antispasmodic activity The antispasmodic activity of example 4 was studied on isolated rat duodenum against acetylcholine and baryum chloride~ The ED-50 ~alues of example 4 are:
(i) 13 ~g/ml against acetylcholine (0~2 ~g/ml), and (ii) 10 ~g/ml against BaC12 (0.3 ~g/ml) 1~7761 g) Toxicity.
The LD - 50 values on mice of example 4 are LD-50 i.p = 18 + 3 mg/kg LD-50 i.~ =20 + 3 mg/kg LD-50 p.o.= 282+ 3 mg/kg LD-50 s.c. ~1000 mg/kS
LD-50 aerosol = 22 + 3 mg/kg The invention includes within its scope a therapeutic composition comprising,in association with a physiologically acceptable excipient, a pharmaceutically effective amount of a cyclopentyl-aldehyde derivative of formula I
Such-a composition can be administe-red orally in the form of tablets, dragees, syrups and potable ampoules, by injection, and by spray.
The best mode for carryin~ out the invention consists in administering to human beings and warm-blooded animals the compound of example 4 or its ~cis-trans" isomer, preferably in the form of spray or aerosol (in solution in carbitol or in su~pension in freon or in a freon-alcohol mixture)u When a spray or an aerosol is used it will contain from 0.1 to 10% of example 4 or its ~'cis-trans" isomer.
Example 4 and its "cis-trans"isomer can also be administered per os in the form of soft capsule~ (in oily solution) gelules (with a viscous or solid excipient?, the preferred exipient being polyoxy-ethylenated oleic glycerides obtained by alcoholysis of a natural vegetal oil and which are sold under the name of LABRA~IL.
The co~pounds of Formula 1, in particul æ Example 4 and its "cis-trans" isomer, are useful in the treatment of infectious diseases, allergies such as hay fever and asthma (taking into account their antianaphylactic activity), inflammations and al~iae.

Claims (4)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:
1. A process for the preparation of a) cyclopentyl-aldehyde derivatives of the general formula (I) wherein X and Y, which can be the same or different represent CHO or CH2OH, Z represents a C1-C3 alkyl group, A represents ?C = CH2; and b) their geometrical isomers, comprising extracting a compound of formula (I) where X and Y are CHO from a Teucrium species with hexane and then with chloroform, evaporating the chloroform extract to dryness under vacuum, steam distilling the residue thus obtained, saturating the distillate with sodium chloride, extracting the compound with chloroform, drying the chloroform phase over sodium sulphate, and distilling off the chloroform, and, if necessary, reducing CHO to CH2OH.
2. A process according to claim 1 wherein Z represents CH3.
3. A process according to claim 1 wherein X = Y = CHO and Z = CH3.
4. A process according to claim 1 wherein X = Y = CH2OH
and Z = CH3.
CA328,873A 1978-06-03 1979-05-30 Drug containing a cyclopentyl-aldehyde derivative and composition containing some Expired CA1107761A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB26,316 1978-06-03
GB7826316 1978-06-03

Publications (1)

Publication Number Publication Date
CA1107761A true CA1107761A (en) 1981-08-25

Family

ID=10497850

Family Applications (1)

Application Number Title Priority Date Filing Date
CA328,873A Expired CA1107761A (en) 1978-06-03 1979-05-30 Drug containing a cyclopentyl-aldehyde derivative and composition containing some

Country Status (16)

Country Link
EP (1) EP0006061B1 (en)
JP (1) JPS5513269A (en)
AT (1) ATE715T1 (en)
AU (1) AU4760079A (en)
BE (1) BE876713A (en)
CA (1) CA1107761A (en)
CH (1) CH639929A5 (en)
DE (1) DE2962180D1 (en)
FR (1) FR2427094B1 (en)
GB (1) GB2022413B (en)
IE (1) IE48343B1 (en)
IL (1) IL57433A (en)
IT (1) IT1120984B (en)
LU (1) LU81352A1 (en)
NZ (1) NZ190628A (en)
ZA (1) ZA792678B (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU651849B2 (en) * 1990-10-09 1994-08-04 Tsumura & Co. Iridoid derivatives and their use as medicines
CN102942605B (en) * 2012-11-30 2016-06-15 沈阳药科大学 The preparation method of iridoid and application thereof in Jasminum lanceolarium Roxb.
JP2023523517A (en) * 2020-04-14 2023-06-06 フイルメニツヒ ソシエテ アノニム scent of lily of the valley

Also Published As

Publication number Publication date
LU81352A1 (en) 1980-01-22
FR2427094A1 (en) 1979-12-28
GB2022413A (en) 1979-12-19
DE2962180D1 (en) 1982-03-25
IL57433A0 (en) 1979-09-30
IE48343B1 (en) 1984-12-12
IE791087L (en) 1979-12-03
ATE715T1 (en) 1982-03-15
AU4760079A (en) 1979-12-13
IT7968189A0 (en) 1979-06-01
EP0006061A1 (en) 1979-12-12
GB2022413B (en) 1983-02-16
JPS5513269A (en) 1980-01-30
BE876713A (en) 1979-12-03
NZ190628A (en) 1984-11-09
EP0006061B1 (en) 1982-02-24
ZA792678B (en) 1980-08-27
FR2427094B1 (en) 1986-07-25
IT1120984B (en) 1986-03-26
IL57433A (en) 1982-08-31
CH639929A5 (en) 1983-12-15

Similar Documents

Publication Publication Date Title
Boyd et al. Lung-toxic furanoterpenoids produced by sweet potatoes (Ipomoea batatas) following microbial infection
EP1045822B1 (en) Certain diterpenes and extracts or concentrates of curcuma amada containing them for use as medicaments
DE60005152T2 (en) MEDICINAL PRODUCTS, FOOD ADDITIVES AND COSMETIC PREPARATION CONTAINING A FATTY ACID AND GINGER
US6083921A (en) Pharmaceutical compositions and method of using same
Todd et al. Tropane alkaloids and toxicity of Convolvulus arvensis
Evans Environmental hazards of diterpene esters from plants
JP2000505777A (en) Anti-inflammatory drug
US7658957B2 (en) Anti-arthritic herbal composition and method thereof
Laurens et al. Antivectorial Activities of Cashew Nut Shell Extracts from Anacardium occidentaleL.
CA1107761A (en) Drug containing a cyclopentyl-aldehyde derivative and composition containing some
CN108605931B (en) Application of four compounds in preparation of nematocide
CN112674090B (en) Application of compound extracted from plant source as rust disease prevention and control drug
WO2007029263A1 (en) Pharmaceutically active extracts of vitex leucoxylon, a process of extracting the same and a method of treating diabetes and inflammatory diseases therewith
Bae et al. The antibacterial component from Cinnamomi Cortex against a cariogenic bacterium Streptococcus mutans OMZ 176
JP2007001898A (en) Anti-inflammatory
US3463861A (en) Compositions and method of treating mycobacterium tuberculosis with 2,2&#39;-(ethylenediimino)-di-1-butanols
EP1496920B1 (en) Pharmaceutical composition containing an extract from barleria prionitis linn and its process of preparation
KR101288540B1 (en) Composition of acaricidal components containing Lycopus lucidus TURCZ essential oil or Octene&#39;s derivatives and acaricide using the same
Rudani et al. Alstonia scholaris: a potent Asian medicinal plant (a comprehensive phytopharmacological review).
EP0208714B1 (en) Antiviral chamigrene derivative
US4263285A (en) Globularia extract, its method of preparation and its use as pharmaceutical
Barman et al. Clerodendrum inerme (L.) Gaertn.: a critical review on current progress in traditional uses, phytochemistry, pharmacological aspects and toxicity
Shareef et al. A COMPREHENSIVE REVIEW OF CLERODENDRUM PHLOMIDIS
Fathima EVALUATION OF THE DIURETIC AND URINARY ELECTROLYTE EFFECTS OF ETHANOLIC EXTRACT OF WHOLE PLANT OF GARDENIA GUMMIFERA
CN114009434A (en) Application of turmeric extract compound in preventing and treating wheat powdery mildew

Legal Events

Date Code Title Description
MKEX Expiry