CH507961A - Antidiabetic sulphonamides - Google Patents

Antidiabetic sulphonamides

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Publication number
CH507961A
CH507961A CH1361970A CH1361970A CH507961A CH 507961 A CH507961 A CH 507961A CH 1361970 A CH1361970 A CH 1361970A CH 1361970 A CH1361970 A CH 1361970A CH 507961 A CH507961 A CH 507961A
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Switzerland
Prior art keywords
alkyl
benzenesulfonamide
cycloalkyl
pyrimidinyl
ethyl
Prior art date
Application number
CH1361970A
Other languages
German (de)
Inventor
Nat Heerdt Ruth Dr Rer
Nat Huebner Manfred Dr Rer
Nat Schmidt Felix Helmut D Rer
Stach Kurt Ing Dr
Walter Dr Aumueller
Original Assignee
Boehringer Mannheim Gmbh
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Publication date
Application filed by Boehringer Mannheim Gmbh filed Critical Boehringer Mannheim Gmbh
Publication of CH507961A publication Critical patent/CH507961A/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/69—Benzenesulfonamido-pyrimidines

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Sulphonamides of formula:- - (I) where A=opt. subst, alkyl, alkenyl, aryl, aralkyl, aryloxyalkyl, arylmercaptoalkyl, cycloalkyl, cycloalkenyl, alkoxy, alkenyloxy, aralkyloxy, cycloalkoxy, cycloalkylalkoxy, cycloalkenyloxy, cycloalkenylalkoxy or - V and W= same or different H or opt. substd. - alkyl, cycloalkyl, aryl or aralkyl; or = opt. subst, satd. heterocyclic ring; R1=H, lower alkyl or aralkyl; R2=alkyl, cycloalkyl, alkoxyalkyl or alkyl-mercaptoalkyl - X=straight or branched 1-4C hydrocarbyl. - Hypoglycaemic.

Description

  

  Verfahren zur Herstellung von neuen antidiabetisch wirksamen Sulfonamiden    Aus der deutschen Patentschrift Nr, 1147 918, den  britischen Patentschriften Nrn, 913 716 und 939 608  und den belgischen Patentschriften Nrn. 609 270,  622 085, 622 086 und 637 083 sind substituierte  2-Benzolsulfonamido-pyrimidine mit blutzuckersenken  der Wirkung bekannt geworden. Es wurde nun gefun  den, dass Benzolsulfonylamino-pyrimidine, die am  Benzolkern einen Carbamidoalkyl-Substituenten und  am Pyrimidinkern einen substituierten Mercaptorest  tragen, sich durch eine besonders starke und langan  haltende antidiabetische Wirkung auszeichnen.  



  Die vorliegende Erfindung betrifft ein Verfahren  zur Herstellung von neuen blutzuckersenkenden Sulfo  namiden der Formel I  
EMI0001.0000     
    worin  A einen gegebenenfalls substituierten Alkyl-,     Alke-          nyl-,    Aryl-, Cycloalkyl-, Cycloalkenyl-Rest oder eine  gegebenenfalls substituierte Alkoxy-, Alkenyloxy-,  Cycloalkoxy-, Cycloalkenylkoxy-Gruppe oder den Rest  
EMI0001.0003     
         n     wobei V und W Wasserstoff oder gegebenenfalls sub  stituierte Alkyl-, Cycloalkyl- oder Aryl-Reste vorstel  len, die gleich oder verschieden sind und auch zusam  men mit dem Stickstoffatom einen gegebenenfalls sub  stituierten gesättigten heterocyclischen Ring, der einen  anellierten Ring aufweisen kann, bilden können  R1 Wasserstoff oder einen Niederalkyl- bzw.

       Aral-          kyl-Rest,     X einen geradkettigen oder verzweigten Kohlen-    Wasserstoffrest mit 1 bis ss. Kohlenstoffatomen,  R2 eine Alkyl-, Cycloalkyl-, Alkoxyalkyl-,     Alkyl-          mercaptoalkyl-Gruppe,    bedeuten,  sowie von deren physiologisch verträglichen Salzen.  



  Als mögliche Substituenten für die als A definier  ten Gruppen kommen inbesondere Halogenatome,  Hydroxyl-, Alkyl-, Alkoxy-, Alkylmercapto-,     Alk-          oxyalkoxy-,    Aryloxy-, Arylmercapto- und     Trifluorme-          thyl-Gruppen    in Frage.  



  Die neuen Verbindungen werden hergestellt, indem  man Sulfonamide der Formel II  physiologisch  
EMI0001.0013     
    mit einem Pyrimidi -Derivat der Formel III  
EMI0001.0014     
    worin T eine reaktive veresterte Carboxylgruppe oder  eine niedermolekulare Trialkylammoniogruppe bedeu  tet, umsetzt und gewünschtenfalls in die  unbedenklichen Salze überführt.  



  Als Ausgangsverbindungen der Formel III kom  men insbesondere 2-Halogen-pyrimidine in Frage; sie  können z. B. durch Umsetzung von     2-Hydroxy-pyrimi-          dinen    mit überschüssigem Phosphoroxychlorid gewon  nen werden. ,  Die erfindungsgemässe Kondensation mit den Ben  zolsulfonamiden der Formel II findet bevorzugt in An  wesenheit einer Base, wie Kaliumcarbonat, statt. An  stelle der 2-Halogen-pyrimidine kann auch das entspre  chende Trialkylammonio-pyrimidin mit dem Sulfona  mid unter Austritt von Trialkylamin zu den     Benzolsul-          fonamidopyrimidinen    umgesetzt werden.

        Als physiologisch unbedenkliche Salze kommen  insbesondere Alkali-, Erdalkali- und Ammoniumsalze  in Frage, die in an sich bekannter Weise hergestellt  werden, beispielsweise durch Umsetzung mit Natron  lauge, Kalilauge, wässrigem Ammoniak bzw. den ent  sprechenden Carbonaten.  



  Das erfindungsgemässe Verfahren wird anhand des  nachstehenden Beispiels näher erläutert.    <I>Beispiel</I>  4-(B-5'-Chlor-2'-methoxy-benzoylamino       äthyl)-N-[5-äthylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid     Aus     4-(ss-5'-Chlor-2'-methoxy-          benzoylamino-äthyl)-benzolsulfonamid     (Fp. 204  C) stellt man zunächst durch Zugabe der  äquivalenten Menge Natriummethylatlösung in Äthanol  das Natriumsalz her und trocknet es gut.

   Ausserdem  setzt man 2-Brom-5-äthylmercaptopyrimidin (das von  der Herstellung etwa 27%     2-Chlor-5-äthylmercapto-          pyrimidin    enthält), Fp. 40 bis 41   C, in Benzol bei  Zimmertemperatur mit Trimethylamin um und erhält       2-Trimethylammonio-5-äthylmercapto-pyrimidin-bro-          mid    (mit einem Gehalt von ca. 32 % des entsprechen  den Chlorids), Fp. 130  C (Zers.).

      3,9 g     4-(ss-5'-Chlor-2'-methoxy-benzoyl-          amino-äthyl)-benzolsulfonamid-natrium    und  2,6 g     2-Trimethylammonio-          5-äthylmercapto-pyrimidin-bromid     werden in 15 ml N,N-Dimethylacetamid bei Zimmer  temperatur 8 Stunden     gerührt    und das Gemisch noch 3  Tage stehen gelassen, danach wird     mit    Wasser auf  100 ml verdünnt. Der Niederschlag wird abgesaugt und  in der Wärme mit verdünnter Sodalösung digeriert;    nicht umgesetztes       4-(ss-5'-Chlor-2'-methoxy-benzoyl-          amino-äthyl)-benzolsulfonamid     bleibt ungelöst und wird durch Absaugen zurückge  wonnen.

   Den Sodaauszug säuert man mit verdünnter    Salzsäure an und fällt dadurch das  4-(ss-5'-Chlor-2'-methoxy-benzoylamino-äthyl)       N-[-äthylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid     aus, das aus Methanol umkristallisiert wird. Fp. 166  bis 167  C.

      In analoger Weise lassen sich herstellen:       4-(N-Methyl-ss-5'-chlor-2'-methoxy-benzoylamino-          äthyl)-N-[5-propylmercapto-pyrimidinyl-    so  (2)]-benzolsulfonamid,  Fp. 80 bis 82  C;    4-(ss-5'-Chlor-2'-methoxy-benzoylamino       äthyl)-N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 135  C;  4-(B-5'-Chlor-2'-methoxy-benzoylamino       äthyl)-N-[5-isopropylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 90  C;  4-(ss-5'-Chlor-2'-methoxy-benzoylamino       äthyl)-N-[5-isobutylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 134 bis 136  C ;

      4-(B-5'-Chlor-2'-methoxy-benzoylamino       äthyl)-N-[5-(B-methoxy-äthyl-mercapto)-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 121 bis 122  C;  4-(ss-Cyclohexancarbonylamino-äthyl)       N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 175  C;    4-(B-Äthoxycarbonylamino-äthyl)       N-[5-isopropylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 127 bis 128  C;    4-(ss-Acetylaminoäthyl)       N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 137 bis 140  C;

      4-(ss-Acetylaminoäthyl)       N-[5-äthylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 140  C (aus Äthanol);  4-(ss-Acetylaminoäthyl)       N-[5-isobutyl-mecrapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 166 bis 167  C (aus Essigester);  4-(ss-5'-Brom-2'-methoxy-benzoylamino       äthyl)-N-[5-isobutyl-mercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 151 bis 153  C;    4-(ss-2'-Methoxy-5'-methyl-benzoylamino       äthyl)-N-[5-äthylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 171 bis 173  C (aus Propanol);

    4-(ss-3'-Chlor-benzoylamino-äthyl)       N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 150 bis 152  C (über das Natriumsalz gereinigt);    4-(G-2'-Methoxy-benzoylamino-äthyl)       N-[5-isopropylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 135 bis 137  C;    4-(ss-2'-Äthoxy-benzoylamino-äthyl)       N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 130  C;    4-(ss-4'-Chlor-2'-methoxy-benzoylamino       äthyl)-N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 158 bis 160  C;

      4-(f-Indolin-1-carbonylamino-äthyl)       N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 153  C;  4-(ss-3-Methyl-3-phenylureido-äthyl)  N-[5-propylmercapto-pyrimidinyl-      (2)]-benzolsulfonamid,  Fp. 130  C (aus Isopropanol);  4-(ss-Benzoylamino-äthyl)       N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 186 bis 187  C (gereinigt über das Natriumsalz);    4-(ss-4'-Chlor-benzoylamino-äthyl)       N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 176 bis 177  C (aus Propanol);

      4-(ss-m-Toluoylamino-äthyl)       N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 163  C (aus Isopropanol);    4-(ss-Hydrocinnamoylamino-äthyl)       N-[-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 123 bis 124  C (aus Isopropanol);    4-(ss-Phenylmercapto-acetylamino-äthyl)       N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 129 bis 130  C (aus Isopropanol);    4-(ss-Phenoxy-acetylamino-äthyl)       N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 136 bis 137  C (aus Propanol);

      4-(ss-2',5'-Dimethoxy-benzoylamino-äthyl)       N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 138  C (aus Methanol);    4-(ss-5'-Chlor-2'-methoxy-benzoylamino       propyl)-N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 144 bis 146  C (aus Isopropanol und     anschlies-          send    aus Methanol);  4-(ss-5'-Chlor-2'-methoxy-benzoylamino       methyl)-N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 183 bis 185  C (nach Reinigung über das Natri  umsalz und Umfällung der freien Verbindung aus  Methylenchlorid/Ligroin);

      4-(ss-5'-Chlor-2'-äthoxy-benzoylamino-äthyl)       N-[5-propylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 145 bis 147  C (aus Methanol);    4-(ss-5'-Chlor-2'-methoxy-benzoylamino-äthyl)       N-[5-(ss-methylmercapto-äthylmercapto)-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 156 bis 157  C (aus Methanol);  4-(8-5'-Chlor-2'-methoxy-benzoylamino       äthyl)-N-[5-cyclohexylmercapto-pyrimidinyl-          (2)]-benzolsulfonamid,     Fp. 167 bis 169  C (aus Alkohol und Essigester).



  Process for the preparation of new anti-diabetic sulfonamides From the German patent specification No. 1147 918, the British patent specification No. 913 716 and 939 608 and the Belgian patent specification No. 609 270, 622 085, 622 086 and 637 083 are substituted 2-benzenesulfonamido- pyrimidine's effects have become known to lower blood sugar. It has now been found that benzenesulfonylamino-pyrimidines, which have a carbamidoalkyl substituent on the benzene nucleus and a substituted mercapto radical on the pyrimidine nucleus, are distinguished by a particularly strong and long-lasting antidiabetic effect.



  The present invention relates to a process for the preparation of new blood sugar-lowering sulfo namides of the formula I.
EMI0001.0000
    wherein A is an optionally substituted alkyl, alkenyl, aryl, cycloalkyl, cycloalkenyl radical or an optionally substituted alkoxy, alkenyloxy, cycloalkoxy, cycloalkenylkoxy group or the radical
EMI0001.0003
         n where V and W are hydrogen or optionally substituted alkyl, cycloalkyl or aryl radicals which are identical or different and also together with the nitrogen atom form an optionally substituted saturated heterocyclic ring which may have a fused ring R1 can be hydrogen or a lower alkyl or

       Aralkyl radical, X a straight-chain or branched hydrocarbon radical with 1 to ss. Carbon atoms, R2 denote an alkyl, cycloalkyl, alkoxyalkyl, alkyl mercaptoalkyl group, and their physiologically acceptable salts.



  Possible substituents for the groups defined as A are, in particular, halogen atoms, hydroxyl, alkyl, alkoxy, alkyl mercapto, alkoxyalkoxy, aryloxy, aryl mercapto and trifluoromethyl groups.



  The new compounds are prepared by taking sulfonamides of the formula II physiologically
EMI0001.0013
    with a pyrimidine derivative of the formula III
EMI0001.0014
    where T means a reactive esterified carboxyl group or a low molecular weight trialkylammonio group, converted and, if desired, converted into the harmless salts.



  Possible starting compounds of the formula III are, in particular, 2-halopyrimidines; you can z. B. won by reacting 2-hydroxy-pyrimidines with excess phosphorus oxychloride. The inventive condensation with the benzene sulfonamides of the formula II preferably takes place in the presence of a base, such as potassium carbonate. Instead of the 2-halopyrimidines, the corresponding trialkylammonio-pyrimidine can also be reacted with the sulfonamide with the escape of trialkylamine to give the benzenesulfonamidopyrimidines.

        Physiologically harmless salts are in particular alkali, alkaline earth and ammonium salts which are prepared in a manner known per se, for example by reaction with sodium hydroxide, potassium hydroxide, aqueous ammonia or the corresponding carbonates.



  The method according to the invention is explained in more detail using the following example. <I> Example </I> 4- (B-5'-chloro-2'-methoxy-benzoylamino ethyl) -N- [5-ethylmercapto-pyrimidinyl- (2)] - benzenesulfonamide From 4- (ss-5 ' -Chlor-2'-methoxy-benzoylamino-ethyl) -benzenesulfonamide (melting point 204 ° C.) is first prepared by adding the equivalent amount of sodium methylate solution in ethanol and drying it thoroughly.

   In addition, 2-bromo-5-ethylmercaptopyrimidine (which contains about 27% 2-chloro-5-ethylmercaptopyrimidine from the preparation), melting point 40 to 41 ° C., is reacted with trimethylamine in benzene at room temperature and 2-trimethylammonio- 5-ethylmercapto-pyrimidine-bromide (with a content of about 32% of the corresponding chloride), melting point 130 ° C. (decomp.).

      3.9 g of 4- (ss-5'-chloro-2'-methoxy-benzoyl-amino-ethyl) -benzenesulfonamide sodium and 2.6 g of 2-trimethylammonio-5-ethylmercapto-pyrimidine bromide are dissolved in 15 ml of N. , N-dimethylacetamide is stirred at room temperature for 8 hours and the mixture is left to stand for a further 3 days, after which it is diluted to 100 ml with water. The precipitate is filtered off and digested in the warm with dilute soda solution; Unreacted 4- (ss-5'-chloro-2'-methoxy-benzoyl-amino-ethyl) -benzenesulfonamide remains undissolved and is recovered by suction.

   The soda extract is acidified with dilute hydrochloric acid and the 4- (ss-5'-chloro-2'-methoxy-benzoylamino-ethyl) N - [- ethylmercapto-pyrimidinyl- (2)] - benzenesulfonamide is precipitated from methanol is recrystallized. Mp. 166 to 167 C.

      The following can be prepared in an analogous manner: 4- (N-methyl-ss-5'-chloro-2'-methoxy-benzoylamino-ethyl) -N- [5-propylmercapto-pyrimidinyl- so (2)] -benzenesulfonamide, melting point. 80 to 82 C; 4- (ss-5'-chloro-2'-methoxy-benzoylamino ethyl) -N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 135 C; 4- (B-5'-chloro-2'-methoxy-benzoylamino-ethyl) -N- [5-isopropylmercapto-pyrimidinyl- (2)] -benzenesulphonamide, melting point 90 ° C .; 4- (ss-5'-chloro-2'-methoxy-benzoylamino ethyl) -N- [5-isobutylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 134 to 136 ° C;

      4- (B-5'-chloro-2'-methoxy-benzoylamino-ethyl) -N- [5- (B-methoxy-ethyl-mercapto) -pyrimidinyl- (2)] -benzenesulfonamide, melting point 121 to 122 ° C; 4- (β-cyclohexanecarbonylamino-ethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 175 C; 4- (B-ethoxycarbonylamino-ethyl) N- [5-isopropylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, m.p. 127 to 128 C; 4- (β-acetylaminoethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 137 to 140 ° C;

      4- (β-acetylaminoethyl) N- [5-ethylmercapto-pyrimidinyl- (2)] benzenesulfonamide, melting point 140 ° C. (from ethanol); 4- (β-acetylaminoethyl) N- [5-isobutyl-mecrapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 166 to 167 ° C. (from ethyl acetate); 4- (ss-5'-bromo-2'-methoxy-benzoylamino ethyl) -N- [5-isobutyl-mercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 151 to 153 ° C; 4- (ss-2'-methoxy-5'-methyl-benzoylamino ethyl) -N- [5-ethylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 171 to 173 ° C. (from propanol);

    4- (ss-3'-chloro-benzoylamino-ethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 150 to 152 ° C. (purified over the sodium salt); 4- (G-2'-methoxy-benzoylamino-ethyl) N- [5-isopropylmercapto-pyrimidinyl- (2)] -benzenesulphonamide, m.p. 135 to 137 C; 4- (ss-2'-ethoxy-benzoylamino-ethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, m.p. 130 C; 4- (ss-4'-chloro-2'-methoxy-benzoylamino ethyl) -N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 158 to 160 ° C;

      4- (f-indoline-1-carbonylamino-ethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, m.p. 153 C; 4- (ss-3-methyl-3-phenylureido-ethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 130 ° C. (from isopropanol); 4- (β-benzoylamino-ethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 186 to 187 ° C. (purified over the sodium salt); 4- (ss-4'-chloro-benzoylamino-ethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 176 to 177 ° C. (from propanol);

      4- (ss-m-toluoylamino-ethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 163 ° C. (from isopropanol); 4- (β-Hydrocinnamoylaminoethyl) N - [- propylmercapto-pyrimidinyl- (2)] - benzenesulfonamide, melting point 123 to 124 ° C. (from isopropanol); 4- (ß-phenylmercapto-acetylamino-ethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 129 to 130 ° C. (from isopropanol); 4- (β-phenoxy-acetylamino-ethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 136 to 137 ° C. (from propanol);

      4- (ss-2 ', 5'-dimethoxy-benzoylamino-ethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 138 ° C. (from methanol); 4- (ss-5'-chloro-2'-methoxy-benzoylamino propyl) -N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 144 to 146 ° C. (from isopropanol and then from methanol ); 4- (ss-5'-chloro-2'-methoxy-benzoylamino methyl) -N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 183 to 185 ° C. (after purification via the sodium salt and reprecipitation the free compound from methylene chloride / ligroin);

      4- (ss-5'-chloro-2'-ethoxy-benzoylamino-ethyl) N- [5-propylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 145 to 147 ° C. (from methanol); 4- (ss-5'-chloro-2'-methoxy-benzoylamino-ethyl) N- [5- (s-methylmercapto-ethylmercapto) -pyrimidinyl- (2)] -benzenesulfonamide, melting point 156 to 157 ° C. (from methanol ); 4- (8-5'-chloro-2'-methoxy-benzoylamino-ethyl) -N- [5-cyclohexylmercapto-pyrimidinyl- (2)] -benzenesulfonamide, melting point 167 to 169 ° C. (from alcohol and ethyl acetate).

Claims (1)

PATENTANSPRUCH Verfahren zur Herstellung von neuen blutzucker senkenden Sulfonamiden der Formel I EMI0003.0026 und deren physiologisch verträglichen Salzen, worin A einen gegebenenfalls substituierten Alkyl-, Alke- nyl-, Aryl-, Cycloalkyl-, Cycloalkenyl-Rest oder eine gegebenenfalls substituierte Alkoxy-, Alkenyloxy-, Cycloalkoxy-, Cycloalkenyloxy-Gruppe oder den Rest he EMI0003.0029 wobei V und W Wasserstoff oder gegebenenfalls sub stituierte Alkyl-, Cycloalkyl- oder Aryl-Reste vorstel len, die gleich oder verschieden sind und auch zusam men mit dem Stickstoffatom einen gegebenenfalls sub terocyclischen Ring, der einen stituierten gesättigten anellierten Ring aufweisen kann, bilden können, R1 Wasserstoff oder einen Niederalkyl- bzw. PATENT CLAIM Process for the production of new blood sugar lowering sulfonamides of the formula I. EMI0003.0026 and their physiologically tolerable salts, where A is an optionally substituted alkyl, alkenyl, aryl, cycloalkyl, cycloalkenyl radical or an optionally substituted alkoxy, alkenyloxy, cycloalkoxy, cycloalkenyloxy group or the radical he EMI0003.0029 where V and W represent hydrogen or optionally substituted alkyl, cycloalkyl or aryl radicals which are identical or different and can also form, together with the nitrogen atom, an optionally sub terocyclic ring which may have a substituted, saturated fused ring , R1 is hydrogen or a lower alkyl or Aral- kyl-Rest, X einen geradkettigen oder verzweigten Kohlen wasserstoffrest mit 1 bis 4 Kohlenstoffatomen, R2 eine Alkyl-, Cycloalkyl-, Alkoxyalkyl-, Alkyl- mercaptoalkyl-Gruppe, bedeuten, dadurch gekennzeichnet, dass man Sulfonamide der Formel II EMI0003.0035 mit einem Pyrimidin-Derivat der Formel III EMI0003.0036 worin T eine reaktive veresterte Carboxylgruppe oder eine niedermolekulare Trialkylammoniogruppe bedeu tet, umsetzt. Aralkyl radical, X a straight-chain or branched hydrocarbon radical with 1 to 4 carbon atoms, R2 an alkyl, cycloalkyl, alkoxyalkyl, alkyl mercaptoalkyl group, characterized in that sulfonamides of the formula II EMI0003.0035 with a pyrimidine derivative of the formula III EMI0003.0036 wherein T is a reactive esterified carboxyl group or a low molecular weight trialkylammonio group meaning, converts. UNTERANSPRUCH Verfahren nach Patentanspruch, dadurch gekenn zeichnet, dass man die erhaltenen Verbindungen der Formel I in ihre physiologisch unbedenklichen Salze überführt. <B><I>Anmerkung des</I></B> Eidg. <B><I>Amtes für geistiges Eigentum: SUBSTANTIAL CLAIM Process according to patent claim, characterized in that the compounds of the formula I obtained are converted into their physiologically harmless salts. <B> <I> Note from </I> </B> Federal <B> <I> Office for Intellectual Property: </I></B> Sollten Teile der Beschreibung mit der im Patentanspruch gegebenen Definition der Erfindung nicht in Einklang stehen, so sei daran erinnert, dass gemäss Art. 51 des Patentgesetzes der Patentanspruch für den sachlichen Geltungsbereich des Patentes massgebend ist. </I> </B> If parts of the description are not in accordance with the definition of the invention given in the patent claim, it should be remembered that according to Art. 51 of the Patent Act, the patent claim is decisive for the material scope of the patent.
CH1361970A 1967-02-01 1968-01-30 Antidiabetic sulphonamides CH507961A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE1967B0090983 DE1670188A1 (en) 1967-02-01 1967-02-01 Process for the production of new antidiabetic sulfonamides
CH136368A CH507960A (en) 1967-02-01 1968-01-30 Antidiabetic sulphonamides

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CH507961A true CH507961A (en) 1971-05-31

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CH1361970A CH507961A (en) 1967-02-01 1968-01-30 Antidiabetic sulphonamides
CH1361770A CH542215A (en) 1967-02-01 1968-01-30 Process for the production of new antidiabetic sulfonamides
CH136368A CH507960A (en) 1967-02-01 1968-01-30 Antidiabetic sulphonamides
CH1361870A CH542855A (en) 1967-02-01 1968-01-30 Process for the production of new antidiabetic sulfonamides

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CH1361770A CH542215A (en) 1967-02-01 1968-01-30 Process for the production of new antidiabetic sulfonamides
CH136368A CH507960A (en) 1967-02-01 1968-01-30 Antidiabetic sulphonamides
CH1361870A CH542855A (en) 1967-02-01 1968-01-30 Process for the production of new antidiabetic sulfonamides

Country Status (6)

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AT (4) AT280297B (en)
CH (4) CH507961A (en)
DE (1) DE1670188A1 (en)
FR (1) FR1595528A (en)
GB (1) GB1148287A (en)
NL (1) NL6801402A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0007687A1 (en) * 1978-05-30 1980-02-06 E.I. Du Pont De Nemours And Company Sulfonamides, processes for their preparation, compositions containing said sulfonamides and a method for controlling the growth of vegetation

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2021962C3 (en) * 1970-04-28 1981-12-24 Schering Ag Berlin Und Bergkamen, 1000 Berlin Blood sugar lowering sulfamoylpyrimidines with an asymmetric carbon atom

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0007687A1 (en) * 1978-05-30 1980-02-06 E.I. Du Pont De Nemours And Company Sulfonamides, processes for their preparation, compositions containing said sulfonamides and a method for controlling the growth of vegetation

Also Published As

Publication number Publication date
CH542215A (en) 1973-11-15
CH542855A (en) 1973-11-30
AT280292B (en) 1970-04-10
FR1595528A (en) 1970-06-15
AT280297B (en) 1970-04-10
GB1148287A (en) 1969-04-10
AT280299B (en) 1970-04-10
AT280298B (en) 1970-04-10
CH507960A (en) 1971-05-31
DE1670188A1 (en) 1971-03-25
NL6801402A (en) 1968-08-02

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