AU632399B2 - New derivatives of pyridylsulfonylurea and of pyridylsulfonylthiourea, process for preparing these and pharmaceutical compositions containing them - Google Patents
New derivatives of pyridylsulfonylurea and of pyridylsulfonylthiourea, process for preparing these and pharmaceutical compositions containing them Download PDFInfo
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- AU632399B2 AU632399B2 AU71981/91A AU7198191A AU632399B2 AU 632399 B2 AU632399 B2 AU 632399B2 AU 71981/91 A AU71981/91 A AU 71981/91A AU 7198191 A AU7198191 A AU 7198191A AU 632399 B2 AU632399 B2 AU 632399B2
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- salts
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- pyrid
- sulfonyl
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
Derivatives of formula (I) <IMAGE> in which: - R denotes a cycloalkyl, bicycloalkyl or polycycloalkyl radical, - X denotes an oxygen or sulphur atom, - R1 denotes an alkyl, cycloalkyl, bicycloalkyl or polycycloalkyl radical. Medications.
Description
I
COMMONWEALTH OF AUSTRALIA29 9 Frm1 PATENTS ACT 1952-69 COMPLETE SPECIFICATION
(ORIGINAL)
Class Int. Class Application Number: Lodged: jom plete Specification Lodged: Accepted: 000 Published: 0 33 riority 0 -R.elated Art 0 o-~'Name of Applicant Address of Applicant Actual Inventor: Address for Service ADIR ET COMPAGNIE 1 Rue Carle Hebert, F-92415 Courbevoie Cedex, France.
BERNARD MASEREEL, BERNARD PIROTTE, MARC SCHYNTS and JACQUES DELARGE WATERMARK PATENT TPADEMARK ATTORN]EY0' LOCKED BAG NO, 5, HAWTHORN, VICTOR1IA 3122, AUSTRALIA Complete Specification for the invention entitled: NEW DERIVATIVES OF PYRIDYSULFONYLUREA AND OF PYRIDYLSULFONYLTHIOUREA PROCE$SS FOR PREPARING THESE AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.
The following statement is a full description of this invention, including the best method of performing it known to -la- The present invention concerns new derivatives of pyridylsulfonylurea and of pyridylsulfonylthiourea, their preparation and pharmaceutical preparations containing them.
Numerous sulfonylureas and sulfonylthioureas are known in the literature, endowed in particular with diuretic or hypoglycemic properties. Pyridylsulfonylureas like Torasemide, which is a potent diuretic, are also known.
Other pyridylsulfonylureas have also been described on account of their diuretic and anti-inflammatory properties (French Patents No. 2 267 775 and No. 2 416 225).
Their diuretic effect is due to an inhibitory effect I of Na+/K /2C cotransport in the kidneys.
.I 15 The applicant company has now discovered new pyridylsulfonylureas and pyridylsulphonylthioureas endowed not only with the ability to inhibit la+/K+/2Cl cotransport and the passage of chlorides through the kidneys, but also with properties which block the cellular passage of potassium in the kidneys and the lungs.
These new derivatives differ from the derivatives of the prior art in also having the particularly valuable property of presenting an optimal partition coefficient and optimum pKa for passing through the blood-brain barrier.
The compounds of the invention are thus particularly valuable for the treatment of disorders such as arterial hypertension and edematous conditions of all crigins, including cerebral edema.
I t' More specifically the invention concerns derivatives of formula (I)
R
Sx S S02-NH-CNH--R 0()
N
I i I c 2 in which: R represents a cycloalkyl, bicycloalkyl or polycycloalkyl radical having 3 to 15 carbon atoms, optionally interrupted by one or more heteroatoms chosen from among nitrogen, oxygen and sulfur, X represents an oxygen or sulfur atom, R. represents a straight- or branched-chain alkyl radical comprising 1 to 6 carbon atoms or a cycloalkyl, bicycloalkyl or polycycloalkyl radical containing 3 to 15 carbon atoms, optionally interrupted by one or more heteroatoms chosen from among nitrogen, oxygen and sulfur, with the proviso that, when X is an oxygen atom and at the same time R is a monocyclic or bicyclic alkyl radical, R i cannot represent a linear or branched alkyl radical or a saturated heteromonocyclic group containing nitrogen and able to contain a second heteroatom, 4 4 14 11 #140*1 .6 4 o 0s 44 44 4 44 40 4 4 as well as their addition salts with a pharmaceutically 20 acceptable inorganic or organic acid, and, when R or R, represents a radical having one or more center(s) of asymmetry, their isomers, enantiomers and diastereoisomers.
The invention also encompasses a process for preparing derivatives of formula which comprises: either condensing a derivative of formula (II)
(II)
in which R has the same meaning as in formula with j 3 an isocyanate or isothiocyanate of formula (III) X C N R (III) in which X and R, have the same meaning as in formula in the presence of an alkaline agent such as a metal hydroxide or a tertiary amine in a polar solvent, to lead, after neutralization of the reaction medium preceded, if desired, by evaporating the solvent and taking up in water, to derivatives of formula which are optionally converted into salts by adding a 10 pharmaceutically acceptable inorganic or organic acid, or which are, if desired, separated into their isomers and then optionally converted into salts by adding a °pharmaceutically acceptable inorganic or organic acid, S or condensing a derivative of formula (IV)
R
NH
S02-NH- COOC2H5 (IV) I N H in which R has the same meaning as in formula with San amine of formula (V) RI NH 2
(V)
t 1 in which R i has the same meaning as in formula by heating in an anhydrous solvent to obtain, if necessary after purification and neutralization, compounds of formula in 'hich X represents an oxygen atom, which are then be optionally converted into salts by means of a pharmaceutically acceptable inorganic or organic acid, or which are, if desired, separated into their isomers and then optionally converted into salt:i by L* 4 4 adding a pharmaceutically acceptable inorganic or organic acid.
Among pharmaceutically acceptable inorganic or organic acids there may be mentioned, without this list being restrictive, hydrochloric, sulfuric, nitric, acetic, tartaric, malic, maleic, camphoric, methanesulfonic, ethanesulfonic and camphosulfonic acids, and the like.
The compounds of the invention possess very valuable pharmacological properties.
They exhibit diuretic properties due to the inhibition of Na+/K /2C1 cotransport and of the passage of chlorides, combined with potassium sparing properties because of inhibition of the membrane passage of 15 potassium.
SThe compounds of the invention therefore find an application in the treatment of hypertension, being all the more valuable because the normalization of blood pressure is not accompanied by the leakage of potassium, which is known to have harmful effects, particularly for heart muscle.
The compounds of the invention also possess a lipophilic character, particularly well adapted to passing the blood-brain barrier, and consequently thnir l. 25 inhibitory effect on Na /K/2Cl- cotransport can exert itself directly on the astrocytes, thus preventing the swelling of the astrocytes which represents a very important part of cerebral edema.
The compounds of the invention therefore find an application in the treatment of edematous conditions and particularly cerebral edema.
Pharmaceutical compositions containing as active principle at least one compound of formula or one of its addition salts with a pharmaceutically acceptable acid, alone or in combination with one or more inert nontoxic excipients or vehicles, are also the subject of the present invention.
Among pharmaceutical compositions according to the invention there may be mentioned more particularly I -'-~w~uR-i;lxrranauaup 5
I
6 those.which are suitable for oral, parenteral, nasal, rectal or cutaneous administration, particularly simple or sugared tablets, capsules, pills and sachets, sublingual tablets, suppositories, skin creams and gels, aerosols, injectable solutions, nasal drops, and the like.
The effective dosage varies according to the age and weight of the patient, the severity of the affection, and also the route of administration. In general, unit dosages range between 0.1 and 500 mg in 1-3 doses daily.
The following examples illustrate the invention, without limiting it in any way.
Starting compounds of general formulae (II) and (IV) are described in the literature (Eur. J. Med. Chem. 299-304 (1980) and 16 65-68 (1981)) or can be prepared in a similar way.
Compounds of formula (II) can be obtained, in particular, by the action of an excess of an amine of formula RNHz, where R has the same meaning as in general formula on a pyridine derivative of formula 4 4 4 4 4 4 t I 4l 1 4 4I 4 S02- NH2 L9 in which Y represents a starting group such as a halogen or SO 3 H, by heating between 80 and 140"C. If necessary after dilution and making the mixture alkaline and then, if desired, clarifying with charcoal, the compounds of formula (II) are precipitated at pH 7-8, spun down, dried and utilized as such in the following reactions.
In the examples that follow, the percentage analysis, and infra-red and 'H NMR spectra agree with those of the expected structures.
i~.
6 'EXAMPLE 1 (4 (-cyclohexylamino)pyrid-3-yl)sulfonyl)-N' cyclohexylurea 0.01 mol of NaOH dissolved in a minimum of water is added to a solution of 0.01 mol of (4-(cyclohexylamino)pyrid-3-yl)sulfonamide in 80 ml of a water/acetone mixture The mixture is stirred with a magnetic rod, and 0.015 mol of cyclohexylisocyanate is added.
Stirring is continued, while the reaction is followed by TLC (silica gel 60F254, mobile phase: ethyl acetate 9, methanol 1, triethylamine Gentle heating can accelerate the reaction. The mixture is evaporated under reduced pressure, and the residue is taken up in 100 ml "o of 0.2 N NaOH. Any insoluble material is filtered out and o 15 the solution is corrected to pH 6.5-7 and left to ocrystallize for 1 hour in the refrigerator. The pre- S* cipitate collected is suspended in 100 ml of a water/ acetone mixture saturated with NaHCO 3 The mixture is stirred for 1 hour and then filtered, and the filtrate is brought back to pH 6.5-7 and left to crystallize in the refrigerator. The crystals are collected, washed in 4 cold water and dried under vacuum at normal temperature.
Yield is around 50-60%. Melting point: 165-167 0
C.
EXAMPLE 2: N-((4-(cycloheptylamino)pyrid-3-yl)sulfonyl)-N'cyclohexylurea ml of anhydrous toluene are added to 0.01 mol of ethyl N-( 4 -cycloheptylamino)pyrid-3-yl)sulfonyl carbamate, 0.05 mol of cyclohexylamine and 3 g of 4A molecular sieve, and subjected to reflux for several hours, with the reaction being followed by TLC (silica gel 60F254; mobile phase: ethyl acetate 9, methanol 1, acetic acid The molecular sieve is separated out and the mixture is evaporated under reduced pressure. The residue is taken up in 100-150 ml of 0.2 N NaOH, and extracted twice with 50 ml of ether. The aqueous phase is corrected to pH 6.5-7 and left to crystallize for 1 hour in the refrigerator. The procedure is then continued as 7 in Example 1. Yield is around 50-60%. Melting point 165-169 0
C.
EXAMPLE 3 N-((4-(cyclooctylamino)pyrid-3-yl)sulfonyl-N'cyclooctylurea nitrate The same operating conditions are used as in Example 2, but with ethyl N-(4-(cyclooctylamino)pyrid- 3-yl)sulfonyl carbamate and cyclooctylamine being used as the starting materials. After separating out the molecular sieve and evaporating under reduced pressure, the mixture is taken up in 75-100 ml of 0.2 N NaOH and extracted twice with 50 ml of ether, and 5-1.0 ml of nitric acid is added to the aqueous phase. It is then left overnight in the refrigerator.
The crystals are collected on filter paper, washed with a minimum of iced water and dried under vacuum at normal temperature. Yield is around 60-70%. Melting point: 144-146 0
C.
EXAMPLE 4: N-((4-(cycloheptylamino)pyrid-3-yl)sulfonyl)-N'cyclohexylthiourea 0.01 mol of NaOH dissolved in a minimum of water is t* added to a solution of 0.01 mol of (4-(cycloheptylamino)pyrid-3-yl)sulfonamide in 80 ml of a water/acetone mixture The mixture is stirred with a magnetic rod, and 0.015 mol of cyclohexylisothiocyanate is added.
Stirring is continued, while the reaction is followed by TLC (silica gel 60F254; moblile phase: ethyl acetate 9, methanol 1, triethylamine Gentle heating can accelerate the reaction. The mixture is evaporated under reduced pressure and the residue is taken up in 100 ml of 0.2 N NaOH. Any insoluble material is filtered out and the solution is corrected to pH 6.5-7 and left to crystallize for 1 hour in the refrigerator. The precipitate collected is suspended in 100 ml of a water/acetone mixture saturated with NaHCO 3 The mixture is stirred for 1 hour and then filtered, and the v
LL
i 8 filtrate, brought back to pH 6.5-7, is left to crystallize in the refrigerator. The crystals are collected, washed in cold water and dried under vacuum at normal temperature. Yield is around 50-60%. Melting point: 195-197 0
C.
EXAMPLE N-(4-(bicyclo[2.2.1]heptanylamino)pyrid-3-yl)sulfonyl-N isopropylthiourea 2 g of 4 -(bicyclo[2.2.5]heptanylamino)pyrid- 3-yl)sulfonamide are dissolved in 20 ml of acetone and ml of isopropylisothiocyanate and 5 ml triethylamine are added. The mixture is heated under reflux while the °o o- reaction is followed by TLC (silica gel 60F254; mobile oO°, phase: ethyl acetate 9, methanol 1, triethylamine 0.2).
V 15 It is evaporated to dryness, taken up in 120 ml of 0.2 N NaOH and filtered. The solution is extracted 3 times with a 150 ml of ether, clarified with charcoal and corrected to pH 7.5. The product crystallizes out. Yield is around Melting point 194-196"C.
20 EXAMPLE 6 oe o N-((4-(cyclooctylamino)pyrid-3-yl)sulfonyl)-N'ethylthiourea e *o° The procedure is identical to that of Example using (4-(cyclooctylamino)pyrid-3-yl)sulfonamide and ethylisothiocyanate as the starting materials. Yield is similar. Melting point 196-198'C.
By using the procedures described in the preceding examples, the derivatives of Examples 7 to 17 are obtained in the same way.
EXAMPLE 7 N-((4-(cyclohexylamino)pyrid-3-yl)sulfonyl)-N'cyclooctylurea Melting point 133-137"C
I
E. e 1 0 EXAMPLE 8 N c y c oactylIa mi n py r id-3- y s uIton y -N y c I h ept yIu re a Melting point 156-1600C EXAMPLE 9 N.-((4(cyclahexylamino)pyrid-3-yI)sulfonyI)-N'-cyclaheptylurea Melting point :145-1500C EXAMPLE N-((4-(cyclooctylarnina)pyrid-3-yI)sulfonyl)-N'-cyclohexylurea Melting point 144-148C EXAMPLE 11 N-((4-(cyclaheptylamina)pyrid-3-yI)sulfonyl)-N'-cyclooctylurea Melting point 140-1450C EXAMPLE 12 H (c ycia lie pt yla m ina) pyr id-3- yl )suIfa nyl)- N'-isa p rop y It hi ou r ea Melting point :196-198C I EXAMPLE 13 N y c Ioa cItyIa m in o) py r id 3-y 1) suIf o ny1) is op ro py It h io ure a j .:Melting point 194-1950C EXAMPLE 14 N-((4-(cycloh exylamina) pyrid-3-yI)suIf ony 1)-N '-ethylth iou rea Melting point :186-1870C -1 EXAMPLE N-((4-(2-(aza-2-bicyclo[3.3.O]octyl)amino)pyrid-3-yI)sulfonyl)-N'isopropylurea Melting point 185-1 8600
T(
I I I EXAMPLE 16 Determination of partition coefficients and pKa The coefficients of partition between n-octanol and water were determined at pH 7.4 by conventional techniques and are expressed as logarithms to base 10 (Log
P).
The pKa values represent the proton acidity constants of S0 2
-NH-CO-
EXAMPLES
e ollall a 0 O a eea 0 ft 0 a *o
OO
0000 a 6 8 o a i a cooe ae a 0 u 6^ a +e 00oooao 6 a a o o a oi 0 9 D 6 0 i Torasemide Ex 1 Ex 2 Ex 3 Ex 7 Ex 8 Ex 10 These would favor passage Log P 0.449 1.331 1.665 2.704 2.074 2.449 2.063 6.82 9.02 9.39 7.74 9.13 9.15 8.95 results indicate a lipophilic character at physiological pH which through the blood-brain barrier.
EXAMPLE 17 Inhibition of Na+/K+/2CI- cotransport and CI- passage The 50% inhibitory concentration for Na+/K+/2CI- cotransport in vivo is decreased, in the case of the compound of Example 3, by about 60% relative to Torasemide (luminal membrane of the ascending branch of the loop of Henl1 in the nephron of perfused rabbits ~cuncar~~~ 11 (Arzneim. Forsch. (1988) 38 151-152)), and by relative to Torasemide in the case of the compound oP Example 10 (erythrocyte membrane in normotensive rats).
The 50% inhibitory concentration for Cl1 passage in the kidneys in vivo is decreased, in the case of the compound of Example 8, by about 50% relative to Torasemide.
18 EXAMPLEA 2 Tablets containing 5 mg of N-((4-(cyclohexylamino)pyrid- 3-yl) sulfonyl) -cyclohexylurea o 15 0 0 o a 0 Formulation for 10,000 tablets N- ((4-(cyclohexylamino) pyrid-3-yl) sulfonyl) N'-cyclohexylurea Lactose Corn starch Colloidal silica Magnesium stearate 50 grams 150 grams 750 grams 2 grams 1 gram 0 0c o 00o 0 0 9
Claims (7)
1. A derivative of formula (I) R S02-t'H- C NH-R1 (I) N in which: o 5 R represents a cycloalkyl, bicycloalkyl or 0. polycycloalkyl radical having 3 to 15 carbon atoms, 9 optionally interrupted by one or more heteroatoms chosen from among nitrogen, oxygen and sulfur, X represents an oxygen or sulfur atom. R, represents a straight- or branched-chain alkyl radical comprising 1 to 6 carbon atoms or a cycloalkyl, Sbicycloalkyl or polycycloalkyl radical containing 3 to carbon atoms, optionally interrupted by one or more S* heteroatoms chosen from among nitrogen, oxygen and sulfur, with the proviso that, when X is an oxygen atom and at the same time R is a monocycl c or bicyclic alkyl radical, R, cannot represent a linear or branched alkyl Sradical or a saturated heteromonocyclic group containing nitrogen and able to contain a second heteroatom, as well as its addition salts with a pharmaceutically acceptable inorganic or organic acid, and, when R or R i represents a radical comprising one or more centers of asymmetry, its isomers, enantiomers ind diastereoisomers.
2. A compound as claimed in claim 1, such that R and Ad 13 R 1 represent' a cycloalkyl, bicycloalkyl or polycycloalkyl radical having 3 to 15 carbon ato.ns, optionally interrupted by one or more nitrogen atoms, as well as its salts, enantiomars and diastereoisomers,
3. N-((4-(cyclohexylamino)pyrid-3-yl)sulfonyl)-N'-cyclohexylurea and its salts.
4. N-((4-(cycloheptylamino)pyrid-3-yI)sulfonyl)-N'-cyclohexylurea and its salts. N-((4-(cyclooctylamino)p-r~d-3-yl)sulfonyl)-N'-cyclooctylurea and its salts. N-((4-(cycloheptylamino)pyrid-3-yl)sulfonyl)-N'- cyclohexylthiourea and its salts.
7. N-((4-bicyclo[2.2.1 ]heptylamino)pyrid-3-yl)sulfonyl)-N'- isopropylthiourea and its salts.
8. N-((4-(cyclooctylamiro)pyrid-3-y'l)sulfonyl)-N' iYlthiourea and a aits salts. a (2-(aza-2-bicyclo[3.3.O]octyl) amino) pyrid-3-yl)suIf onyl)- a~aN'-isopropylurea, its salts and its diastereoisomers. 1 0. A process for preparing derivatives of formula which comprises: either condensing a derivative of formula (II) NH S02- NH2 0 (I LN I I in which R has the same meaning as in formula with an isocyanate or isothiocyanate of formula (iii) X =C N R (I II) in which X and have the same meaning asin formula a attto fi If'' a a a a If a at a I a 'I 'at' a, a C 44
61--N 14 in the presence of an alkaline agent such as a metal hydroxide or a tertiary amine in a polar solvent, to lead, after neutralization of the reaction medium preceded, if desired, by evaporating the solvent and taking up in water, to derivatives of formula which are optionally converted into salts by adding a pharmaceutically acceptable inorganic or organic acid, or which are, if desired, separated into their isomers and then optionally converted into salts by adding a pharmaceutically acceptable inorganic or organic acid, or condensing a derivative of formula (IV) 0 NH SS02-NH- (IV) N in which R 'as the same meaning as in formnula with an amine of formula (V) 0 15 R, NH (V) SQ in which RI has the same meaning as in formula by heating in an anhydrous solvent to obtain, if necessary after purification and neutralization, compounds of formula in which X represents an oxygen atom, which are then optionally converted into salts by means of a pharmaceutically acceptable inorganic or organic acid, or which are, if desired, separated into their isomers and then optionally converted into salts by adding a pharmaceutically acceptable inorganic or organic acid. I S3. A pharmaceutical composition containing as active 1-^ ~'~-~;iiiiiii~~ *09404 S* 0 00 principle at least one compound as claimed in any one of claims 1 to 10, alone or in combination with one or more inel .on-toxic excipents. 12. A pharmaceutical composition as claimed in claim 11 when used in the treatment of arterial hypertension and edematous conditions. DATED this 2nd day of October, 1992. ADIR ET COMPAGNIE WATERMARK PATENT TRADEMARK ATTORNEYS THE ATRIUM 290 BURWOOD ROAD HAWTHORN VICTORIA 3122 AUSTRALIA 0 a 00, 00 Lil a* i4 e Q ~It
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9002659 | 1990-03-02 | ||
| FR9002659A FR2659080B1 (en) | 1990-03-02 | 1990-03-02 | NOVEL PYRIDYLSULFONYLUREA AND PYRIDYLSULFONYLTHIOURAE DERIVATIVES, THEIR PREPARATION PROCESS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU7198191A AU7198191A (en) | 1991-09-05 |
| AU632399B2 true AU632399B2 (en) | 1992-12-24 |
Family
ID=9394324
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU71981/91A Ceased AU632399B2 (en) | 1990-03-02 | 1991-03-01 | New derivatives of pyridylsulfonylurea and of pyridylsulfonylthiourea, process for preparing these and pharmaceutical compositions containing them |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0445039B1 (en) |
| JP (1) | JPH07119216B2 (en) |
| AT (1) | ATE106873T1 (en) |
| AU (1) | AU632399B2 (en) |
| CA (1) | CA2037189A1 (en) |
| DE (1) | DE69102310T2 (en) |
| DK (1) | DK0445039T3 (en) |
| ES (1) | ES2057795T3 (en) |
| FR (1) | FR2659080B1 (en) |
| IE (1) | IE66021B1 (en) |
| NZ (1) | NZ237271A (en) |
| OA (1) | OA09485A (en) |
| PT (1) | PT96926B (en) |
| ZA (1) | ZA911524B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2685917A1 (en) * | 1992-01-06 | 1993-07-09 | Adir | NOVEL PYRIDYLSULFONYLUREE DERIVATIVE OF PREPARATION METHODS AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME |
| AU2001255421B2 (en) | 2000-04-14 | 2007-08-23 | Gerardo Gamba | Purified and isolated potassium-chloride cotransporter nucleic acids and polypeptides and therapeutic and screening methods using same |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4244950A (en) * | 1978-01-31 | 1981-01-13 | A. Christiaens Societe Anonyme | Derivatives of 4-amino-3-sulfonamido-pyridine, their preparation and use |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1477664A (en) * | 1974-04-17 | 1977-06-22 | Christiaens Sa A | Pyridine derivatives |
-
1990
- 1990-03-02 FR FR9002659A patent/FR2659080B1/en not_active Expired - Fee Related
-
1991
- 1991-02-27 CA CA002037189A patent/CA2037189A1/en not_active Abandoned
- 1991-03-01 ES ES91400563T patent/ES2057795T3/en not_active Expired - Lifetime
- 1991-03-01 NZ NZ237271A patent/NZ237271A/en unknown
- 1991-03-01 ZA ZA911524A patent/ZA911524B/en unknown
- 1991-03-01 IE IE68491A patent/IE66021B1/en not_active IP Right Cessation
- 1991-03-01 OA OA59965A patent/OA09485A/en unknown
- 1991-03-01 JP JP3036079A patent/JPH07119216B2/en not_active Expired - Lifetime
- 1991-03-01 PT PT96926A patent/PT96926B/en not_active IP Right Cessation
- 1991-03-01 AU AU71981/91A patent/AU632399B2/en not_active Ceased
- 1991-03-01 AT AT91400563T patent/ATE106873T1/en active
- 1991-03-01 DE DE69102310T patent/DE69102310T2/en not_active Expired - Fee Related
- 1991-03-01 DK DK91400563.2T patent/DK0445039T3/en active
- 1991-03-01 EP EP91400563A patent/EP0445039B1/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4244950A (en) * | 1978-01-31 | 1981-01-13 | A. Christiaens Societe Anonyme | Derivatives of 4-amino-3-sulfonamido-pyridine, their preparation and use |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH04211659A (en) | 1992-08-03 |
| DE69102310D1 (en) | 1994-07-14 |
| EP0445039A1 (en) | 1991-09-04 |
| JPH07119216B2 (en) | 1995-12-20 |
| OA09485A (en) | 1992-11-15 |
| AU7198191A (en) | 1991-09-05 |
| NZ237271A (en) | 1993-04-28 |
| DE69102310T2 (en) | 1994-11-03 |
| DK0445039T3 (en) | 1994-10-31 |
| ZA911524B (en) | 1991-12-24 |
| FR2659080A1 (en) | 1991-09-06 |
| CA2037189A1 (en) | 1991-09-03 |
| IE66021B1 (en) | 1995-11-29 |
| PT96926B (en) | 1998-07-31 |
| IE910684A1 (en) | 1991-09-11 |
| ES2057795T3 (en) | 1994-10-16 |
| PT96926A (en) | 1991-10-31 |
| ATE106873T1 (en) | 1994-06-15 |
| EP0445039B1 (en) | 1994-06-08 |
| FR2659080B1 (en) | 1994-07-08 |
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