IE48343B1 - Therapeutically useful cyclopentyl-aldehyde derivatives and compositions containing them - Google Patents

Therapeutically useful cyclopentyl-aldehyde derivatives and compositions containing them

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Publication number
IE48343B1
IE48343B1 IE1087/79A IE108779A IE48343B1 IE 48343 B1 IE48343 B1 IE 48343B1 IE 1087/79 A IE1087/79 A IE 1087/79A IE 108779 A IE108779 A IE 108779A IE 48343 B1 IE48343 B1 IE 48343B1
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cyclopentyl
trans
methyl
cis
compound
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IE1087/79A
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IE791087L (en
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Inst Rech Chim Biolog
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Publication of IE48343B1 publication Critical patent/IE48343B1/en

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    • 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

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  • 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)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

Cyclopentyl-aldehyde derivatives of the general formula <IMAGE> 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-, <IMAGE> or <IMAGE> including their geometrical isomers are of value in therapy and may be formulated as therapeutical compositions.

Description

The invention relates to cyclopentyl-aldehyde derivatives, for use in human or animal therapy and to therapeutic compositions containing such derivatives as an active ingredient.
According to the invention a cyclopentyl-aldehyde derivative,for use in the treatment of infectious diseases, pain, allergies or inflammation, is a compound of the general formula JA-X jr-V (I) z r* " y wherein X and Y are independently selected from CHO, CH2OH and COOH Z is εχ-Ο3 alkyl; and A is -CH2~, -(C=CH2>- or -(CH-CH3)-. Compounds of formula (I) may occur in the form of geometric isomers and all therapeutically useful isomers and isomeric mixtures are included within the invention. The invention also includes therapeutic compositions comprising a compound of formula (I) together with a therapeutically acceptable excipient.
Compounds of formula (I) include known compounds 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 1375-1381. There has been no disclosure of pharmaceutical properties of the compounds.
It has been surprisingly found that cyclopentyl-aldehyde derivatives according to formula (I) are (i) active as bacteriostatic, bactericide, antispasmodic, antianaphylactic and antiphologistic agents, and (ii) useful in particular in the treatment of human beings and warm-blooded animals suffering from infectious diseases induced byGram(+)and Gram(-) germs,and allergies such as hay fever.
Oil the other hand cyclopentylaldehydoderivatives of formula I are more interesting, from a pharmaceutical point of view, than the Teucr1um marum 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 following Examples: - F,x, 1: -(2-formyl-3-mcthyl-cyclopentyl)-acetaldehyde (X = Y=CHO; A = CH„; Z = Cit ) , - Ex. 2: 2-(2-hydroxymethyl-3-methyl-cyclopcntyl)ethanol ( X = Y = OLOH; A = CI!„; Z = CH,) , - Ex. 3:o(~(2-cnrboxy~3-metliyl-cyclopentyl)- acetic 15 acid (X = Ϊ = COOH; A = CH,,; Z = CH ) , ~ Εχ· ''t:-(2-formyl-3-methyl-cyclopentyl)-acrylaldehyde (X = Y = CHO; A = ) C = CH„; Z = CH ), - Ex. 5: 2- (2-hydroxymethyl-3-methyl-cyclopentyl)-2propcn-l-ol (X = Y = CI-Ι,,ΟΗ; A =>C ~ CH2; Z = CH ) , _ Ex. 6;o<-(2-carloxy-3-methyl-cyclopcntyl)- acrylic acid (X = Y = COOH; A = ) C = CHg! Z = CH^) , and - Ex, 7; 2-(2-hydroxymethyl-3-methyl-cyclopentyl)propan-l-ol (X = Y = CIl,,OH; A =?CII(CH ); Z = CH ) .
Thev all correspond to the following formula: - X (II) H„C /' (wherein A and X are defined mainly as two isomers: as above). They occur (A) c I C- c: a h3c 8 3 1 3 ίο Thecis-trans isoinor generally is more active than the trans-cisone.
The preferred compounds are those of examples 1 and 4. The most interesting one, from a therapeutical point of view, is the compound of example 4.
The best mode for preparing the acrvl compounds (A = C = CHg) consists in (i) extracting o<-(2-formyl-3- methyl-cyclopentyl)-acrylaldehyde from a Tcucrium species such as Teucrium marum, Teucrium polium, Teucrium roontanum, and (ii) transforming CHO into CIIgOH by reduction or into COOH by oxidation. The compounds wherein A is CH(CH^) (such as example 7) may be obtained by catalytic hydrogenation of C =CHg. The compounds wherein A is CHg may be prepared by synthesis according to a method known -per se.
PREPARATION I Obtention of -(2-formyl-3-methyl-cyclopentyl)-acryl20 aldehyde (Example 4) 1210 g of dried and ground Teucrium poll tun (entire plant) were extracted in a column successively with 7.35 1 of hexane and 7.25 .1 of chloroform. The chloroform extract was evaporated t o dryness under vacuum and the residue thus obtained (47 g) was steam distilled. Tho distillate was saturated with sodium chloride then extracted with chloroform. After drying on N'aoS0/( the chloroform was distilled off under reduced pressure (0.3 mm Hg) to give 7·3 g (yield 0.6%) 25° C of a yellow oil (n^ = 1.4842) comprising 89% by weight of n5c ty CHO CfcCHj-CHO ('ds-trans) and 8 3 4 3 11% by weight of PREPARATION II Obtention of<\-(2-formyl-3-methyl-cyclopentyl)-acrylaldehyde (Example 4) kg of dried and ground Teucrium niarum (entire plant) were extracted by lixiviation in a glass column (height: 2m; diameter: 0.225 m) fed in solvent by means of a pump having a delivery of 10 l/h. Two solvents were successively used: hexane (170 1) then chloroform (J 70 1) . The hexane extract was discarded. The chloroform extract was evaporated to dryness under vacuum in order to obtain a brown oily residue (640g) which was steam distilled. The distillate was saturated with NaCl when extracted with chloroform.
IS The chloroform phase was dried over NaSO^, the solvent was evaporated and the remaining oil was distilled (under 1 mm Hg at 6O-78°C) to give 42 g of a yellow 25° C oil = 1.4842) which comprised: ~ 87?ό by weight of the cis-trans isomer , and - 15/ by weight of the trans-cis isomer.
PREPARATION HI 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.4g) in solution in CII_OH (25ml) V» // 3 with NaBHj (1*7 g) , the cis-trans isomer of example 5 (1,19 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-eis'isomer of example 4. 8 3 4 3 PREPARATION IV Obtention of_2-(2-liydr oxymethyl-^mcthyl-cyclopentyl)propan-l-ol (Example 7) Thecis-trans and respectively trans5 cis isomers of example 7 were obtained by hydrogenation on PtOg of the cis-trans and respectively trans-cis isomers of example 5 according to the method disclosed by PAGNONI et al.
The pharmaceutical assays which have been carried out with examples 1 and 4 are summed up liere iua fler. 1°) Assays with example 1 a) Bacteriostatic activity. - ( 2-formy 1,-3-me thyl-cyclopentyl) -acetaldehyde inhibits Gram (+) and Gram (-) bacteriae. Its MIC values are: 0.75 mg/ml on Staphylococcus aureus London , 1.2 mg/ml on Escherichia coli, and 1.5 mg/m1 on Proteus b) Ant i spasmor)ir .ic tivity Tlie ED-50 values of£<-(2-formyl-3-methyl-cyclopentyl)acetaldehyde have been determined (i) in vitro on isolated ileum of guinea-pig against histamine: ED - 50 = 50Tf/ml; (ii) in vivo on the entire animal according tn the method of KONZETT and ROESLLER: ED - 50 = 2.6 mg/kg by i.v. route. c) Antianaphylactc activity Male guinea-pigs are sensitized by two injections at the interval of two days of 0.5 ml of a 2g/l albumen solution. Four weeks after the lethal anaphylactic shock is provoked by i.v. injection of 0.2 ml of a 2g/l ovalbumen solution. The products to be tested are administered 30 minutes before I by i.p. route) or at the time (by i.v.route) 8 3 4 3 of the provoking injection. The results are given in table 3. for example 1 and Promethazine, a reference product.
TABLE I Compound (dose) mortality % protection 0/ /0 control 80% 20% Promethazine (20 mg/kg i.p.) 0% 100% Example 1 (10 mg/kg i.p.) 50% 50% Example I (2mg/kg i.v.) 0% 100% 2°) Assays wi.tli Example 4 (consisting of a mixture of 87% by weight of tho cis-trans isomer and 13% by weight of the trans-cis isomer). a) Bacteriostatic activity Example 4 inhibits Grain ( + ) and Gram (-) bacteriae.
Its MIC values are: 1.5 mg/m on .St aphylococcus aureus, London 1 mg/ml on Esclier ichia coli (strain 548) , 1.75 mg/ml on Proteus vulgaris (strain 1557), 2.5 mg/ml on Klebsiella pneumoniae (strain 433), mg/ml on Salmonella typhi murium (strain IP) , 1.5 mg/ml on Staphylococcus aureus (strain 634), 1.25 mg/ml on Streptococcus (strain 1178), 1.25 mg/ml on Bacillus substiljs, (strains 548, 1557, 435, 634 and 11/8 belonging to the catalogue of the collection of the Centre International de Distribution de Souches et d'Information sur lcs Types Microbicns of Lausanne, and the IP strain being provided from thelnstitut 8 3 · ϊ 3 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 548), mg/ml on Proteus vulgaris (strain 1557), 3 mg/ml on Klebsiella pneumoniae (strain 453), 1.25 mg/ml on Salmonella typhi murium (strain I.P.), 1.75 mg/ml on Staphylococcus aureus (strain 654), mg/ml on Streptococcus (strain 1173), 2.5 mg/ml on Bacillus substilis. c) Antibronchospatic activity Guinea pigs (20 animals (weighing 50θ - 500 g) per dose and per product to be tested) are preliminary subjected to an aerosol of Example 4 (50 g/1 in a water-ethanol solution) or Promethazine (a reference product) for 10 minutes. Then the animals are subjected individually to an histamine aerosol (5s/l of histamine in an aqueous medium containing 200g/l of glycerin). 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 hatch received only the histamine aerosol, Tlie results given in table II show that Example 4 exhibits a bronchodilating effect which opposed the bronchoconstrictor effect of histamine.
TABLE II Product Apparition of Variation with (dose) apnea (in seconds) respect to control Control 108 + 18 Promethazine (0.1 mg/kg > Got) - 8 3 4 3 TABLE II cont.
Product (dose) Apparition of apnea (in seconds) Variation with respect to control Ex 4 (1 mg/kg) 130 + 23 * + 20% Ex 4 (10 mg/kg) 169 + 32 * + 56% Note: * statistically s ignificant (p^0.05) d) Antianaphylactic activity in vitro Male guinea pigs are sensitized by an i.p. injection of 100 mg/kg of ovalbutnen in an equal volume of Freund's adjuvant. Four weeks after the animals are slaughtered, each ileum is recovered and placed at 33°C in a Thyrode medium. Constriction is obtained by addition of 200 jug of albumen to the liquid of surviving. The amplitude 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 guinea pig ileum, said reduction being statistically significant. in vivo Guinea pigs (male or female) are sensitized as indicated above with ovalbumen four weeks before the beginning of the experiment. Each animal is subjected to an ovalbumen aerosol (obtained from an aqueous medium containing 50g/l of ovalbumen).
The anaphylactic shock comes out by apparition 8 3 13 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 (dose) number of animals constriction amplitude amplitude variation with respect to control animals control 20 147 + 32 - 15 Ex 4 (5 JJg/ml 30 91 + 37* - 38% Ex 4 (10 pg/ml) 20 52 + 16* - 65% 20 Note * statistLcnlly (p< 0.05) sign! I'icant • 8 3 13 TABLE IV Product (dose) Ntimbci’ of animals Dyspnea time of apparition (seconds) time variation with respect to control animals control 20 94 + 59 - Ex 4 (1 mg/kg 20 120 + 52 + 28% 10 Ex 4 (10 mg/kg) 20 130 + 3ά· + e) Antiphlogistic activity The antiphlogistic activity of example 4 was studied on female rats (weighing 100 g) according to the carrageen oedema test. The results are given in table V in which Indometacin is used as a reference product.
TABLE V Product Number of animal dose (per rat) inhibition respect to animal with control Ex 4 10 10 ;ig 26% Ex 4 ,1 0 50 jug 25%. Ex 4 JO 200 jug 4i?; 25 Indometacin 10 200 jig 57% f) Antispasmodic activity The antispasmodic activity of example 4 was studied on isolated rat duodenum against acetylcholine and baryum chloride. The ED-50 values of example 4 are: JO (i) 15 jug/ml against acetylcholine (0.2 jig/ml) , and (ii) 10 jig/ml against BaClg (0.3 pg/ml) - 48343 g) Toxicity.
The LD - 50 values on mice of Example 4 are LD—50 i.p = 18 + 3 mg/kg LD-50 i.v. = 20 ± 3 mg/kg LD-50 p.o. = 282 ± 3 mg/kg LD-50 s.c, > 1000 mg/kg LG-50 aerosol =22+3 mg/kg As mentioned above, the invention includes also therapeutic compositons. These will comprise a pharmaceutically effective amount of the active ingredient together with a physiologically acceptable excipient. The nature of the composition will be chosen having regard to the method of administration. Administration can be orally, e.g. in the form of tablets, dragees, syrups or potable ampoules or by injection or by spray or other methods. When the composition is to be administered in the form of a spray or aerosol the active ingredient is preferably in solution in Carbitol Regi stered (Trade Mark) or in suspension in Freon (Trade Mark) or in a Freon-alcohol mixture. A spray or aerosol will generally contain 0.1 to 10% of the active ingredient. Capsules may be in the form of soft capsules, comprising the compound in oil solution or gelules, comprising the compound with viscous or solid excipient, the preferred excipient being polyoxyethylenated oleic glycerides obtained by alcoholysis of a natural vegetable oil and which are sold under the name of Labrafil ( Trade Mark).
The best mode for carrying out the invention comprises administering to human beings and warm-blooded animals a compound of Example 4, preferably in the form of its Cistrans isomer. Administration is preferably by spray or aerosol or peros in the form of soft capsules or gelules as described above.
The compounds of formula (I) inlcuding in particular the compound of Example 4 and especially 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 algiae.

Claims (8)

1. CLAIMS! 1.I. A compound for use in the treatment of infectious diseases, p; formula (I) wherein X and Y are independently selected from CHO, CH 2 OH and COOH; Z is c ^_ 3 alkyl; and A is -CH 2 ~, -(C=CH 2 )~ or -(CH-CH-j)-.
2. A compound according to claim 1, in which X and Y are each CHO; Z is methyl; and A is -CH 2 ~.
3. A compound according to claim 1, in which X and Y are each CHjOH; Z is methyl; and A is -CH^-.
4. A compound according to claim 1, in which X and Y are each CHO; Z is methyl; and A is -(C=CH 2 )-.
5. A compound as claimed in claim 1, in which X and Y are each CH 2 OH; Z is methyl; and A is -(C=CH 2 >-.
6. A compound according to any preceding claim, in the form of at least one geometrical isomer selected from cis-trans and trans-cis isomer of the formulae •AA-X r ^*^^ - A-X and h 3 c wherein A and X are as defined above.
7. A compound according to claim 6, which is mainly in the form of the cis-trans isomer.
8. A therapeutic composition comprising a compound of formula (I) and as defined in any preceding claim, in association with a physiologically acceptable excipient.
IE1087/79A 1978-06-03 1979-08-08 Therapeutically useful cyclopentyl-aldehyde derivatives and compositions containing them IE48343B1 (en)

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JP (1) JPS5513269A (en)
AT (1) ATE715T1 (en)
AU (1) AU4760079A (en)
BE (1) BE876713A (en)
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DE (1) DE2962180D1 (en)
FR (1) FR2427094B1 (en)
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IE (1) IE48343B1 (en)
IL (1) IL57433A (en)
IT (1) IT1120984B (en)
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ZA (1) ZA792678B (en)

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EP0505572A4 (en) * 1990-10-09 1993-03-10 Tsumura & Co. Iridoide derivative and its use as medicine
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.
US20230159426A1 (en) * 2020-04-14 2023-05-25 Firmenich Sa Lily of the valley odorant

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DE2962180D1 (en) 1982-03-25
IT1120984B (en) 1986-03-26
FR2427094A1 (en) 1979-12-28
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EP0006061A1 (en) 1979-12-12
AU4760079A (en) 1979-12-13
EP0006061B1 (en) 1982-02-24
IT7968189A0 (en) 1979-06-01
NZ190628A (en) 1984-11-09
GB2022413A (en) 1979-12-19
BE876713A (en) 1979-12-03
ATE715T1 (en) 1982-03-15
IL57433A (en) 1982-08-31
CH639929A5 (en) 1983-12-15
CA1107761A (en) 1981-08-25
FR2427094B1 (en) 1986-07-25
GB2022413B (en) 1983-02-16
IL57433A0 (en) 1979-09-30
IE791087L (en) 1979-12-03
LU81352A1 (en) 1980-01-22
ZA792678B (en) 1980-08-27

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