IE45999B1 - 2-methoxybenzamides - Google Patents
2-methoxybenzamidesInfo
- Publication number
- IE45999B1 IE45999B1 IE2392/77A IE239277A IE45999B1 IE 45999 B1 IE45999 B1 IE 45999B1 IE 2392/77 A IE2392/77 A IE 2392/77A IE 239277 A IE239277 A IE 239277A IE 45999 B1 IE45999 B1 IE 45999B1
- Authority
- IE
- Ireland
- Prior art keywords
- optical isomer
- racemate
- compound
- 2methoxy
- cyclopropylmethyl
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 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
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
THIS INVENTION relates to 2-methoxybenzamides, their addition salts with pharmaceutically acceptable acids, their . preparation and medicaments which contain these compounds.
The main Patent, to which this a Patent of Addition, describes 2-methoxybenzamides which correspond to the following formula:
Ϊ2 Φ- 1 T3 _r_<CH2,n ·=->- =»2—V I OCH3 1 %. in which: n is 1 or 2; represents either a (cycloalkyl)alkyl radical of formula
in which m is an integer from 2 to S inclusive, A is a linear or branched alkylene chain containing 1 to 4 carbon atoms and represents a hydrogen atom or a halbgen atom, in particular fluorine or chlorine, a trifluoromethyl radical, or an alkyl or alkoxy radical containing 1 to 3 carbon atoms; R2 represents a chlorine atom, or an SOjRg group, Rg being an alkyl radical containing 1 to 4 carbon atoms, or an
SOjNRgRy group, Rg and R?, which are identical or different, representing, independently of each other, a hydrogen atom or
- 2 4899 9 an alkyl radical containing 1 to 4 carbon atoms; and represents either a hydrogen atom or an alkyl radical containing 1 to 4 carbon atoms.
The present invention relates to further specific 5 2-methoxybenzamides within that formula, including their racemates and optically active isomers, the compounds being useful as medicaments in human and veterinary medicine acting on the central nervous system.
The compounds (I) of this invention may be prepared 10 by reaction of a halide or an alkyl ester of 2-methoxybenzoic acid (II) with a pyrrolidine (III)
Po
(II) (HI)
X being a halogen, R'^ being the aforesaid (cycloalkyl)alkyl radical, and R2 and R3 being as defined above.
The pyrrolidines (III) are obtained in the manner indicated in the main Patent. The reaction with the halide is carried out preferably at a low temperature (-5° to +30°) in a non-polar solvent, such as a ketone, and in the presence of an alkali metal carbonate. The condensation reaction with the ester is carried out either dry, at a temperature of 50 to 120°C, under nitrogen, or in water, at a temperature of 50 to 100°C, under nitrogen. The optically active isomers are obtained either by resolution or by stereospecific synthesis tf. ο Ο ο α ;
The stereospecific synthesis consists of 1) preparing the optically active pyrrolidine (III) starting from an amino-acid, that is to say glutamic acid or (R)- or (S)-proline, or from a compound derived from these amino-acids (for example pyroglutamic acid or prolinol), via pyrrolidine intermediates containing an asymmetric carbon atom in the α-posifcion to an amino group, by a series of condensations,
- 4 45999 esterifications, saponifications, cyclisations and reductions, and
2) reacting the optically active pyrrolidine (III) with the compound (II).
The following reaction scheme illustrates-the stereospecific synthesis of the pyrrolidines (III).
Reaction scheme
ΓΠζΗ
COOH
SOC12 /C^OH first stage
L-proline (S) nh3 cooc2hs (S)
2nd stage
(S)
- 5 45999
In the scheme» A’ represents a bond or an alkylene radical of 1 to 3 carbon atoms. The reduction is preferably carried out by means of lithium aluminium hydride. The (R)-pyrrolidine may be obtained in the same manner by starting from the (R)-proline.
Example of the preparation of a pyrrolidine (III).
l-Cyclopropylmethyl-2-aminomethyl-(S)(-)-pyrrolidine
Stage 1. 2-Ethoxycarbonyl-(S)-pyrrolidine
34.8 g (0.3 mol) of L-proline (S) and 360 ml of ethanol 10 are introduced into an Erlenmeyer flask. 54.8 g (0.46 mol) of thionyl chloride are added dropwise, whilst cooling In an ice bath.
The mixture is stirred for one hour at ambient temperature and heated under reflux for three hours. The mixture is then evaporated to dryness, and the residual oil is dissolved in chloroform and saturated with ammonia. The ammonium chloride is filtered off and the organic phase is evaporated.
An oil is recovered, which is distilled.
Boiling point (20 mm Hg) = 82°C.
Stage 2. 2-Carbamoyl-(S)(-)-pyrrolidine
200 ml of methanol are introduced into an Erlenmeyer flask and saturated with ammonia while cooling. 17.2 g (0.12 mol) of the ester obtained in Stage 1 are introduced into the methanol. The mixture is stirred for two hours and allowed to stand overnight.
The mixture is evaporated to dryness and a solid is
- 6 45999 recovered» which is recrystallised from benzene.
Melting point = 1O1.5°-1O2°C [a]§5= -78° (c = 1, water)
Stage 3· l-Cyclopropvlcarbonyl-2-carbamoyl-(S)-pyrrolidine
11.4 g (0.1 mol) of (S)-prolinamide, 12-8 g (0.1 mol) of potassium carbonate and some anhydrous acetone are introduced into an Erlenmeyer flask.
The mixture is cooled with an ice bath and 10.45 g (0.1 mol) of cyclopropanecarboxylic acid chloride in acetone are added dropwise.
The mixture is stirred for one hour at the same temperature and is allowed to stand overnight at ambient temperature. It is then evaporated to dryness (T < 30°C), and extracted with chloroform, and the extract is washed with the minimum amount of water. The organic phase is dried over magnesium sulphate and evaporated. A solid which melts at 129°-130°C is recovered.
Stage 4, l-Cyclopropylmethyl-2-amlnoethyl- (S) (-) -pyrrolidine
13·3 g (0.35 mol) of lithium aluminium hydride and
200 ml of anhydrous ether are introduced into an Erlenmeyer flask. 16 g (0.088 mol) of the preceding diamide are added in small amounts and the mixture is heated under reflux for 16 hours. It is then hydrolysed with a 10% strength solution of sodium potassium tartrate and the solid is filtered off, and washed several times with ether. The ether phases are mixed and evaporated.
- 7 45999
An oil is recovered, which is distilled.
Boiling point (20 mm Hg) = 88°C.
[a]g5 =-201.5° (C = 1, D.M.F.) [a]20 =-68.5° (C = 1, D.M.F.)
The other optically active pyrrolidines (III) are prepared In the same manner.
The following examples illustrate the invention.
The analyses, the IR spectra and the NMR spectra confirmed the structure of the compounds.
example 1
Racemic N-(l-cyclopropylmethyl-2-pyrrolidiiiylmethyl)2-methoxy-5-sulphamoylbenzamide, its (S)(-) optical isomer and its (S)(+)-methanesulphonate.
r«i CH2- , R2 = S02NH2 and R? = H]
Racemic compound
7»78 g (0.05 mo3) of the ethyl ester of 2-methoxy-5sulphamovlbenzoic acid, 4.86 g (0.0515 mol) of 2-aminomethyl1-cyclopropylmethylpyrrolidine and 12 ml of water are placed in a 250 ml round-bottomed flask and the mixture is then heated at
100° for 9 hours. A solid appears during heating.
The mixture is allowed to cool and diluted with water; the suspension is stirred and filtered, and then the solid is washed with water and ether before being dried.
Weight = 7.62 g; Yield = 69.14%;‘Melting point =
159.5°-16O.5°C.
(S)(—) isomer
8.8 g (Ο.Ο57 mol) of l-cyclopropylmethyl-2-aminomethyl-8..
(S)(-)-pyrrolidine, 14.07 g (0.054 mol) of the ethyl ester of 2-methoxy-5-sulphamoylbenzoic acid and 18 ml of water are introduced into an Erlenmeyer flask.
The mixture is heated at 100°C for 10 hours. A solid 5 appears on cooling. Ether and water are added and the mixture is stirred. The solid is filtered off and dissolved in chloroform and the solution is dried over magnesium sulphate, and then evaporated. A solid is recovered, which is recrystallised from ethyl acetate.
Melting point = 134°-134.5°C [a]*0 = -77° (c «= 1, D.M.F.) (S)(+)-Methanesulphonate
The methanesulphonate is prepared by reaction of the benzamide with methanesulphonic acid in acetone.
Melting point = 120.5°-121.5°C.
[aj*0 = +5.2° (c = 1, D.M.F.)
EXAMPLE 2
N-(l-Cyclopentylmethyl-2-pyrrolidinylmethyl)-2-methoxy5-sulphamoylbenzamide, in the fora of the (S)(-) optical isomer, and its (S)(+)-methanesulphonate.
[R£ = O~CH2 ’ R2 b s°2NH2 and R3 “
13·2. g (0.0724 mol) of l-cyclopentylmethyl-2-aminooethyl-(S)(-)-pyrrolidine, 10 g of potassium carbonate and some acetone are introduced into an Erlenmeyer flask. At a temperature of i. 10°C, 18 g (0.0724 mol) of 2-methoxyT525 sulphamoylbenzoic acid chloride are added dropwise. The mixture is stirred for two hours.
The mixture is evaporated to dryness and triturated
- 9 45899 with a mixture of water and ether. A solid is filtered off, and is dissolved in chloroform. The solution is dried over magnesium sulphate and evaporated.
A solid is recovered, which is recrystallised from ethyl acetate.
Melting point = 123°-125.5°C [kIq0 = -99-5° (e = 0.5, D.M.F.)
The methanesulphonate of this benzamide is obtained by reaction of the benzamide with methanesulphonic acid in acetone. It is a white solid which is filtered off and recrystallised .from isopropanol.
Melting point = 123°-124°C [
EXAMPLE 5
Racemic N-(l-cyclohexylmethyl-2-pyrrolidinylmethyl)-2methoxy-5-sulphamoylbenzamide and its methanesulphonate.
[R’ = CH2 , R2 = S02NH2 and R? =» H] g (0.061 mol) of l-cyclohexylmethyl-2-aminomethylpyrrolidine, 8.44 g (0.061 mol) of potassium carbonate and some acetone are introduced into an Erlenmeyer flask.
At a temperature of <10°C and under a stream of nitrogen, 15-2 g (0.061 mol) of 2-methoxy-5-sulphamoylbenzoic acid chloride in acetone are added dropwise. The mixture is stirred for two hours.
The mixture is evaporated to dryness and the residue is triturated with a mixture of water and ether. The solid is filtered off and dissolved in chloroform; the solution is
- 1045999 dried over magnesium sulphate and evaporated. A solid is recovered which is recrystallised from ethyl acetate.
Melting point = 155-5° - 156°C
The methanesulphonate is obtained by reaction of the benzamide with methanesulphonic acid in methanol.
The solid is recrystallised from isopropanol.
Melting point = l62°-l63°C.
EXAMPLE 4
N-(l-Cyclobutylmethyl-2-pyrrolidinylmethyl)-2-methoxy10 5-sulphamoylbenzamide in the form of the (S)(-) optical isomer and its (S)(+)-rmethanesulphonate and in the form of the racemate.
[R{ = ~CH2 , R2 = S02NH2 and R3 =. H]
8.4 g (0.0499 mol) of l-cyclobutylmethyl-2-aminomethyl15 (S)(-)-pyrrolidine, 6.9 g (0.0499 mol) of potassium carbonate and 100 ml of acetone are Introduced into an Erlenmeyer flask. At a temperature of £lO°C, 12.46 g (0.0499 mol) of 2-methoxy5-sulphamoylbenzoic acid chloride in acetone are added dropwise.
The mixture is stirred at the same temperature for two hours; it is then evaporated to dryness and the solid is taken up again in water and ether. The solid is filtered off and dissolved in chloroform; the organic phase is dried over magnesium sulphate and evaporated to dryness. The solid is recrystallised from a mixture of ether and ethyl acetate and insoluble material is filtered off from the hot solution.
- IX
Melting point = 153°-153.5°C = -92° (c = 0.5, D.M.P.)
The methanesulphonate is prepared by reaction of the benzamide with methanesulphonic acid.
Melting point = 120°-121°C [a]20 = +2>4o (c = 0>5} D.M.p.)
The racemic compound is prepared by reaction of 2methoxy-5-sulphamoylbenzoic acid chloride with 1-cyclobutylmethyl-2-aminomethylpyrrolidine.
Melting point = 197.5°-198°C
The methanesulphonate melts at 154.5°-155°c·
EXAMPLE 5
Racemic N-(l-eyclopropylmethyl-2-pyrrolidinylmethyl)2-methoxy-5-methylsulphonylbenzamide and its methanesulphonate [Rj = [>— CH2 , R2 = S02CH3 and = H]
7-71 g (0.05 mol) of 2-aminomethyl-l-cyclopropylmethyl pyrrolidine in 200 ml of acetone and 6.91 g (0.05 mol) of potassium carbonate are placed in a 500 ml Erlenmeyer flask and the mixture is cooled in ice.
Whilst stirring magnetically and maintaining the temperature below 10°C, a solution of 12.43 g (0.05 mol) of 2methoxy-5-methylsulphonylbenzoic acid chloride in 220 ml of acetone is introduced dropwise into the mixture. The reactants are left in contact in the melting ice for 2 hours.
When the reaction is complete, the acetone is evaporated to dryness, the solid residue is taken up again between water and chloroform; the organic phase is decanted off, washed with water and dried over magnesium sulphate in the presence of . charcoal. After filtration of the solid, the chloroform is driven off from the filtrate and a viscous yellow oil is obtained, which crystallises very rapidly when it is stirred in the presence of ether.
After purification, the solid is yellowish white.
The methanesulphonate melts at 124.5°-126OC.
EXAMPLE 6
Racemic N-(l-cyclopropylmethyl-2~pyrrolldinylmethyl)2-methoxy-5-ethylsulphonylbenzamide and its hydrochloride.
[R{ = J>— CH2 , R2 = S02C2H5 and = H]
The reaction is carried out as in Example 5, employing
2-methoxy-5-ethylsulphonylbenzoic, acid chloride.
The hydrochloride is prepared by reaction of the oily base with a solution of hydrogen chloride in ether.
Melting point = 187.5°-188.5°C
EXAMPLE 7
Racemic N-(l-cyclopropylmethyl-2-pyrrolidinylmethyl)2-methoxy-5-dimethylsulphamoylbenzamide and its hydrochloride.
The procedure followed is as in Example 5 using 2methoxy-5-dimethylsulphamoylbenzoic acid chloride.
The hydrochloride is prepared from the base.
Melting point «= 159.5°-160.5°C
EXAMPLE 8
Rac emic N~(l-cyclopropylmethyl-2-pyrrolidinylmethyl)2-methoxy-5-chlorobenzamide and its hydrochloride.
- 13 45999 [R£ = f>— CH2 , R2 = Cl and Rj = H]
.43 g (0.0676 mol) of 2-aminomethyl-l-cyclopropylmethylpyrrolidin'e, 13·04 g (0.065 mol) of methyl ester of 2-methoxy-5-chlorobenzoic acid and 20 ol of water are intro5 duced into an Erlenmeyer flask under an atmosphere of nitrogen.
The mixture is heated at 100°C for 14 hours. The mixture is cooled and extracted with ether, and the organic phase is separated off, dried over magnesium sulphate and evaporated. Αή oil is recovered.
The hydrochloride is prepared in a mixture of ether and
HCl. A white solid crystallises. This is filtered off and recrystallised from isopropyl alcohol.
Melting point = 181°-182°C
The compounds of the invention are shown in Table I below. (Rj «= H).
TABLE I
CompoundRi r2 Characteristic melting points (°C) 1 racemic so2NH2 231-232 (HCl) 159.5-160 (base) (S)(+) so2nh2 1 134-134.5 (base) (S)(-) 120.5-121.5 (methane- sulphonate) (S)<+) (S)(+) D~“2 S02NH2 ' ' 1 j 123-124 (methanesulphonate) 3 racemic S02NH2 162-163 (methanesulphonate) (S)(+) racemic 0=¾ SOgNHg 120-121 (methanesulphonate) 154.5-155 (methaneaulphonate) 5 racemic 0—CH2 S02CH3 60-64 (base) 124.5-126 (methanesul- phonate) 6 racemic t>-C»2 so2c2h5 187.5-188.5 (with decomposition) (HCl] 7 racemic C^~Ch2 S02N(CH3)2 I59.5-169.5 kHCl) 8 racemic [>-ch2 Cl 181-182 (HCl)
,35999
The compounds of the invention were subjected to pharmacological tests.
The toxicity was evaluated intraperitoneally on male, Swiss CD 1 mice, of a mean weight of 20 g.
The neuroleptic activity was determined by the antagonism towards the climbing induced' in the mice by apomorphine (C. Gouret, J. Pharmacol. (Paris), (1973), 4, 341).
The results of these tests are indicated in Table II below.
TABLE II
COMPOUND , LD 50 administered intraperitoneally to mice (mg/kg) Antiapomorphine act- | ivity in mice AD 50 (mg/kg) administered intraperitoneally 1 racemic hydrochloride 400 15 1 (S)(+)-methanesulphonate 350 1 3 360 8 5 235 1-5 ί 7 240 3 8 135 0.1 6 310 3
Furthermore, certain compounds possess an antiemetic 20 activity. This was determined by the antagonism towards the emetic effect induced in dogs by apomorphine (Shallek et al, Arch. Int. Pharmacodyn., (1968), 174, No.2, 350-372; Boissier
- 16 _ et al, Med. Exp·, (1962), 6, 320-326). The results are given below.
COMPOUND Antiemetic activity in dogs AD 50 lig/kg administered orally 1 Racemic hydrochloride 37 1 (S)(+)-Methanesulphonate of (s)(-) isomer 14 7 Racemic hydrochloride 40
An examination'of the various results shows that the compounds of the invention are applicable in the treatment of various psychosomatic complaints, such as gastro-duodenal ulcers, migraine, dizziness, depressive and psychic disturbances, in particular senescence and, in stronger doses,in psychoses, by virtue of their neuroleptic properties.
Furthermore, certain compounds may be used in the treatment as well as in the prevention of vomiting and nausea of all origins.
The invention includes all pharmaceutical compositions containing the compounds (I) and their salts as active principles, in association with all excipients which are appropriate to their oral, endorectal or parenteral administration.
All the pharmaceutical forms which are appropriate to the oral, endorectal or parenteral methods are suitable , the usual daily dosage ranging from 5 to 300 mg.
Claims (14)
1. CLAIMS:1. The (S)(-) isomer of N-(l-cyclopropylmethyl-2pyrrolidinylmethyl)-2-methoxy-5-sulphamoylbenzamide.
2. N- (l-Cyclopentylmethyl-2-pyrrolidinyImethy1)-25 ; methoxy-5-sulphamoylbenzamide in the form of the racemate or an optical isomer.
3. N-(l-Cyclohexylmethyl-2-pyrrolidinyImethy1)-2methoxy-5-sulphamoylbenzamide in the form of the racemate or of an optical isomer. 10
4. N-(l-Cyclobutylmethyl-2-pyrrolidinylmethyl)-2methoxy-5-sulphamoylbenzamide in the form of the racemate or of an optical isomer. !
5. ¾ · N-( J-CycIopropylmethyi-'2-p'yrrolidinylmethyl)-2methoxy-5-methyl-sulfonylbenzamide in the form of the race15 mate or of an optical isomer.
6. N-(l-Cyclopropylmethyl-2-pyrrolidinylmethyl)-2methoxy-5-ethylsulphonylbenzamide in the form of the racemate or of an optical isomer.
7. N- (l-Cyclopropylmethyl-2-pyrrolidinylmethyl)-22o methoxy-5-dimethylsulphamoylbenzamide in the form of the racemate or of an optical isomer.
8. N-(l-Cyclopropylmethyl-2-pyrrolidinylmethyl)-2methoxy-5-chlorobcnzamidc in the form of the racemate or of an optical isomer. 25
9. A pharmaceutically acceptable acid addition salt of a compound according to any one of the preceding claims.
10. A process for the preparation of a compound (I) according to any one of claims 1 to 8, wherein a halide or an alkyl ester of 2-methoxybenzoic acid (II) is caused to react with a racemic or optically active 2-i.ruino.i.cthylpyrrolidine (III) according to the following formula: I the radicals R 1 ^, R 2 and being chosen appropriately for the compound I to be produced and X being halogen.
11. A process according to claim 10, substantially as described in any one of the foregoing Examples 1 to 8.
12. A compound (I) produced by a process according to claim 10 or 11.
13. A medicament containing as the active principle a compound claimed in any one of claims 1 to 8 and 12, or its pharmaceutically acceptable acid addition salt.
14. A pharmaceutical composition comprising a compound according to any one of claims 1 to 8 and 12, or its pharmaceutically acceptable acid addition salt, together with a pharmaceutically acceptable carrier or diluent therefor
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7717988A FR2394529A2 (en) | 1977-06-13 | 1977-06-13 | 2-METHOXY BENZAMIDES AND THEIR THERAPEUTIC APPLICATION |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE45999L IE45999L (en) | 1978-12-13 |
| IE45999B1 true IE45999B1 (en) | 1983-01-26 |
Family
ID=9192010
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2392/77A IE45999B1 (en) | 1977-06-13 | 1977-11-25 | 2-methoxybenzamides |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS545969A (en) |
| AU (1) | AU509543B2 (en) |
| BE (1) | BE861866R (en) |
| FR (1) | FR2394529A2 (en) |
| GB (1) | GB1560019A (en) |
| IE (1) | IE45999B1 (en) |
| IT (1) | IT1206606B (en) |
| LU (1) | LU78681A1 (en) |
| NL (1) | NL7713631A (en) |
| ZA (1) | ZA776950B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1095415B (en) * | 1978-02-16 | 1985-08-10 | Ravizza Spa | PROCESS FOR THE PRODUCTION OF AN OPTICALLY ACTIVE BENZAMIDE, OPTICALLY ACTIVE BENZAMIDE SO OBTAINED AND COMPOSITIONS |
| AU542211B2 (en) * | 1980-03-07 | 1985-02-14 | Gruppo Lepetit S.P.A. | Mercaptocycloalkyl carbonyl prolines |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR5916M (en) * | 1966-01-21 | 1968-05-06 |
-
1977
- 1977-06-13 FR FR7717988A patent/FR2394529A2/en active Granted
- 1977-11-21 ZA ZA00776950A patent/ZA776950B/en unknown
- 1977-11-21 GB GB48451/77A patent/GB1560019A/en not_active Expired
- 1977-11-25 IE IE2392/77A patent/IE45999B1/en unknown
- 1977-12-09 NL NL7713631A patent/NL7713631A/en not_active Application Discontinuation
- 1977-12-13 AU AU31514/77A patent/AU509543B2/en not_active Expired
- 1977-12-13 LU LU78681A patent/LU78681A1/xx unknown
- 1977-12-14 BE BE183469A patent/BE861866R/en not_active IP Right Cessation
- 1977-12-15 JP JP15158377A patent/JPS545969A/en active Pending
-
1978
- 1978-05-24 IT IT7823749A patent/IT1206606B/en active
Also Published As
| Publication number | Publication date |
|---|---|
| FR2394529A2 (en) | 1979-01-12 |
| AU3151477A (en) | 1979-06-21 |
| BE861866R (en) | 1978-06-14 |
| AU509543B2 (en) | 1980-05-15 |
| IT7823749A0 (en) | 1978-05-24 |
| IT1206606B (en) | 1989-04-27 |
| NL7713631A (en) | 1978-12-15 |
| IE45999L (en) | 1978-12-13 |
| LU78681A1 (en) | 1978-07-11 |
| GB1560019A (en) | 1980-01-30 |
| ZA776950B (en) | 1978-09-27 |
| JPS545969A (en) | 1979-01-17 |
| FR2394529B2 (en) | 1980-01-18 |
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