CS244670B2 - Production method of aryloxypropanolamines - Google Patents

Production method of aryloxypropanolamines Download PDF

Info

Publication number
CS244670B2
CS244670B2 CS821080A CS108082A CS244670B2 CS 244670 B2 CS244670 B2 CS 244670B2 CS 821080 A CS821080 A CS 821080A CS 108082 A CS108082 A CS 108082A CS 244670 B2 CS244670 B2 CS 244670B2
Authority
CS
Czechoslovakia
Prior art keywords
aminomethyl
dose
cor
amino
lower alkyl
Prior art date
Application number
CS821080A
Other languages
English (en)
Other versions
CS108082A2 (en
Inventor
Fritz Wiedemann
Wilfgang Kampe
Karl Dietmann
Gisbert Sponer
Original Assignee
Boehringer Mannheim Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boehringer Mannheim Gmbh filed Critical Boehringer Mannheim Gmbh
Publication of CS108082A2 publication Critical patent/CS108082A2/cs
Publication of CS244670B2 publication Critical patent/CS244670B2/cs

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C07D215/46—Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems 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 carbon atoms of the ring system
    • C07D219/08—Nitrogen atoms
    • C07D219/10—Nitrogen atoms attached in position 9
    • C07D219/12—Amino-alkylamino radicals attached in position 9
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
    • C07D231/28—Two oxygen or sulfur atoms
    • C07D231/30—Two oxygen or sulfur atoms attached in positions 3 and 5
    • C07D231/32—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
    • C07D231/38—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
    • C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
    • C07D231/52—Oxygen atom in position 3 and nitrogen atom in position 5, or vice versa
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three 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
    • C07D237/20—Nitrogen atoms
    • 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
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • 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
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other 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
    • 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
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other 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
    • C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other 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 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
    • 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
    • C07D239/56—One oxygen atom and one sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
    • C07D239/84—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/36—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/32—Nitrogen atom
    • C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pyridine Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyrane Compounds (AREA)
  • Luminescent Compositions (AREA)
  • Mechanical Treatment Of Semiconductor (AREA)
  • Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
  • Steering-Linkage Mechanisms And Four-Wheel Steering (AREA)

Description

Na rozdíl od podobných sloučenin, jaké jsou chráněny v DOS č. 28 19 629 a 28 44 497, je možno při použití sloučenin obecného vzorce I docílit překvapivého zlepšení účinnosti.
Vynález popisuje nové aryloxyprepanolaminy obecného vzorce I ve kterém
(I) každý ze symbolů R^, R2, vodíku, kyanoskupinu,
R-j a R^, které mohou být stejné nebo rozdílné, znamená atom atom halogenu, hydroxylovou skupinu, alkoxyskupinu s 1 až 6 atomy uhlíku, nebo fenylalkoxyskupinu s 1 až .6 atomy uhlíku v alkylové části.
každý ze symbolů Rg a Rg, které mohou být stejné nebo rozdílné, znamená atom vodíku nebo alkylovou skupinu s 1 až 6 atomy uhlíku,
X představuje přímý nebo rozvětvený alkylenový řetězec se 2 až 6 atomy uhlíku,
A znamená mono- bi-nebo tricyklický heteroaromatický zbytek odvozený od thiofenu, isoxazolu, pyrazolu, pyridinu, pyrimidinu, pyridazinu, indolu, benzoxazolu, benzthiadiazolu, benzimidazolu, indazolu, benztriazolu, chinolinu, isochinolinu, chinazoHn^ chinoxalinu, akridi.nu, ^iazok, pyrazolo [3,4-bj ργτΐά^^ pyrazolo £3,4-dJ -pyrimidinu a purinu, nebo od sloučeniny vzniklé kombinací těchto látek, jakož i odpovídající hydroheteroaromatický zbytek odvozený od těchto sloučenin, přičemž tento zbytek může být napojen na řetězec
-X-Nprostřednictvím uhlíkového atomu v kruhu nebo také dusíkového atomu v kruhu příslušného heterocyklu, nebo v případě, že alespoň jeden ze symbolů R-, R-, R^ a R. nepředstavuje atom vodíku, znamená A rovněž fenylový zbytek, a každý ze symbolů R?, Rg, Rg, R^^ a R-, které mohou být stejné nebo rozdílné, představuje jednovazný nebo dvojvazný substituent vybraný ze skupiny zahrnující atom vodíku, atomy halogenů, aminoskupinu, alkylaminoskupiny s 1 až 6 atomy uhlíku, alkoxyskupiny s 1 až 6 atomy uhlíku, kyanoskupinu, hydroxymethylovou skupinu, alkylové skupiny s 1 až 6 atomy uhlíku, fenylovou skupinu, kyslík a síru, jakož i jejich farmakologicky snášitelné soli.
Protože sloučeniny obecného vzorce I obsahují asymetrické atomy uhlíku, spadají do rozsahu vynálezu rovněž příslušné opticky aktivní formy a racemické směsi těchto sloučenin.
Hydroheteroaromatickými zbytky ve významu symbolu A ve smyslu tohoto vynálezu jsou parciálně hydrogenované deriváty bi- a tricyklických heterocyklů, například indolin, ne však úplně hydrogenované monocyklické heterocykly, jako piperidin.
Přerušované čáry mezi symboly R?, Rg, . Rg, R-^θ a R . . na jedné straně a kruhem A na straně druhé znamenají vždy druhou vazbu v případě, že R?, Rg, Rg, R- nebo R- představuje dvojvazný substituent, jako kyslík nebo síru.
Alkylovými skupinami ve významu symbolů R-, R2, R-, R4· Rg, Rg· R?· Rg· Rg* k^ a R nebo alkylovými částmi alkoxyskupin, fenylalkoxyskupin a alkylaminoskupin, se míní přímé ne'bo rozvětvené alkylové skupiny s I až 6 atomy uhlíku, výhodně s 1 až 4 atomy uhlíku, jako například skupina methylová, ethylová, propylová, isopropylová, butylová, isobutylová, sek.butylová, terč.butylová, n-pentylová nebo n-hexylová. Zvlášř výhodné jsou skupiny methylová, ethylová, propylová, isopropylováRa butylová. .
Halogeny se ve smyslu tohoto vynálezu míní fluor, chlor, brom a jod, zejména fluor, chlor a brom.
Alkylenovými řetězci ve významu symbolu X se míní přímé nebo rozvětvené řetězce se 2 až 6 atomy uhlíku, s výhodou se 2 až 4 atomy uhlíku. Zvlášt výhodné jsou v dané m ohledu ethylenová a propylenová skupina.
Pro odborníka je pochopitelné, že v případech, kdy zbytek A představuje seskupení, které nemůže být substituováno více než 3 nebo 4 zbytky R?, Rg, Rg, R-^θ a R, musí jeden nebo dva ze substituentů R-, Rg, Rg, R10 a R.. odpadnout.
Předmětem vynálezu je způsob výroby sloučenin shora uvedeného obecného vzorce I. Tyto sloučeniny se připravují tak, že se o sobě známým způsobem sloučenina obecného vzorce IV

Claims (1)

  1. Během pokusu, při němž se zvířata udržují v bdělém stavu, se průběžně snímá arteriální krevní tlak prostřednictvím katetru a elektromechanického převaděče tlaku. Kromě toho se pomocí manometru, který byl zaveden do ventrikulárního katetru a posunut do srdce, průběžně měří tlak v levé komoře a z něho se určí derivace podle času dp/dt .... Srdeční frekvence шах (fCOj.) se zjistí spočtením srdečních tepů při rychlém posunu papíru v určitých časových úsecích.
    Testované látky se podávají infusí v dávce 0,25 pg/kg/min po dobu 60 minut, načež následuje třičetiminutové sledování. V případě některých látek se dávky zdesetinásobí nebo se injikují déle v logaritmickém odstupňování, aby se docílilo co největšího odstupu dávek.
    Z logaritmu dávky podané v určitém čase a účinku na'popřípadě frekvenci (íCor> se vypočte lineární regrese. Z ní pak lze vypočítat dávky % a de +5q * (pggkg), které zvyšují výchozí hodnoty dp/dtjax, popřípadě fcor-o 30 %, popřípadě o 50 % (příklad viz v tabulce 1).
    Výsledky dosažené při aplikaci srovnávacích látek a sloučenin podle vynálezu jsou shrnuty v tabulce 2. Z těchto výsledků vyplývá, že srovnávací látka A, tj. l-fenoxy-3-(2-(2,t-dimethflfynalam0ne(hthylam0np]oranan~0lOl (příklad 7 DCS č. 28 44 497) má sice dobrý kardiotonický účinek (vzestup dp/dtmax), ve stejné dávce však rovněž zvyšuje frekvenci, což je v zásadě nežádoucí jev, protože v takovémto případě je srdce silně'zatěžováno.
    Jako míra účinnosti testovaných látek se nejdříve hledá dávka, která zvyšuje sílu srdečního stavu (dp/dt) a srdeční frekvenci (f...) o 30, resp. 50 %. Pokud se vydělí шаХ COl hodnoty ED+30 %foor hodnotami ed+3q % dp/dť jsou zvlášt cenné ty látky, které mají tento podíl'vysoký, protože u těchto látek v určité dávce je zvýšení síly 'srdečního stahu větší než zvýšení srdeční frekvence.
    Cím je tedy shora uvedený podíl vyšší, tím lepší je příslušná sloučenina. Naproti tomu však obecně nelze pokládat nízké dávky za kriterium zvlášt příznivého účinku - záleží totiž na poměru účinku na srdeční frekvenci ke kontraktilitě.
    Srovnávací látka B, tj. . l-fenoxy-3-|*2-(l,3-dimethylpyrimidin-2,4-dion-6-ylamino)ethylaminolpropan-2-ól (příklad 1 z'DCS č. 28 19 629) nevykazuje žádný kardiotonický účinek.
    Tabulka 1 test kardiotonického účinku na bdících psech
    pa f cor dp/dt = střední arteriální krevní tlak (mm Hg) = srdeční frekvence (tepy/min) = rychlost vzestupu tlaku v levé komoře (mm Hg/s)
    popř. DEt5Q % = dávka způsobující zvýšení (pq/kg) výchozích hodnot o 30 % resp. 50
    slou- měřená výchozí počet minut < od začátku infuse DE +•30 % DE+50 % regresní čeni- veličina hodnota dávka testované látky (ug/kg) rovnice na 5 10 15 30 45 60 1,25 2,5 3,75 7,5 11,25 15,0 AX> pa 96 97 99 98 98 105 105 f 92 93 115 108 123 141 149 4,5 10,9 y=53 log X + 95,5 cor dp/dt 2,15 2,05 2,48 2,60 2,90 3, 68 3,48 4,4 8,8 y=67 log X + 86,5 I pa 98 97 106 100 105 106 102 f 55 57 77 63 65 85 103 3,81 8,55 y=57 log X + 96,9 cor dp/dt 2,30 3,20 3,30 3,40 3,80 4, 40 4,80 1,55 2,74 y=81 log X + 114,4
    Legenda:
    x> l-fenoxy-3-[2-(2,6~áunethylfenylamino')ethylaminojpropan-2-ol (příklad 7 z DOS č. 28 44 497)
    V následující tabulce 2 jsou uvedeny hodnoty pro další sloučeniny, získané analogickým
    způsobem jako hodnoty v tabulce 1. Tabulka 2 sloučenina DE+30 (ug/kg) dp/dt % ^cor fcor dp/dt DE+50 % (ju/kg) dP/dt fCor fcor dp/dt AX) 4,4 ’ 4,5 1,0 8,8 10,9 1,2 BXXc 7150 >150 - >150 >150 - I 1,55 3,81 2,46 2,74 8,55 3,15 II 22,6 >150 >6,6 47,1 >150 >3,2 III 45,4 311 6,9 155 669 4,3 IV 21,2 70,8 3,3 85,1 742 8,7 V 9,7 18,7 1,9 36,8 75,5 2,1 VI 236 2 734 11,6 589 8 979 15,2 VII 72,7 160 2,20 110 348 3,16 VIII 27,7 82,8 2,99 39,0 135 3,46
    Legenda:
CS821080A 1980-06-23 1981-06-16 Production method of aryloxypropanolamines CS244670B2 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19803023369 DE3023369A1 (de) 1980-06-23 1980-06-23 Aryloxypropanolamine, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel

Publications (2)

Publication Number Publication Date
CS108082A2 CS108082A2 (en) 1985-09-17
CS244670B2 true CS244670B2 (en) 1986-08-14

Family

ID=6105194

Family Applications (2)

Application Number Title Priority Date Filing Date
CS821080A CS244670B2 (en) 1980-06-23 1981-06-16 Production method of aryloxypropanolamines
CS814492A CS244661B2 (en) 1980-06-23 1981-06-16 Production method of aryloxypropanol amides

Family Applications After (1)

Application Number Title Priority Date Filing Date
CS814492A CS244661B2 (en) 1980-06-23 1981-06-16 Production method of aryloxypropanol amides

Country Status (15)

Country Link
US (3) US4438128A (cs)
EP (2) EP0042593B1 (cs)
JP (2) JPS5732269A (cs)
AT (2) ATE12492T1 (cs)
AU (1) AU540425B2 (cs)
CA (1) CA1184188A (cs)
CS (2) CS244670B2 (cs)
DD (1) DD159771A5 (cs)
DE (3) DE3023369A1 (cs)
ES (1) ES8204725A1 (cs)
FI (1) FI80681C (cs)
HU (1) HU189514B (cs)
IL (1) IL63104A (cs)
SU (2) SU1287748A3 (cs)
ZA (1) ZA814112B (cs)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3023369A1 (de) * 1980-06-23 1982-01-14 Boehringer Mannheim Gmbh, 6800 Mannheim Aryloxypropanolamine, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE3048487A1 (de) * 1980-12-22 1982-07-29 Cassella Ag, 6000 Frankfurt Basisch substituierte pyridazine, ihre herstellung und ihre verwendung
DE3131146A1 (de) * 1981-08-06 1983-02-24 Boehringer Mannheim Gmbh, 6800 Mannheim Neue heteroaryloxypropanolamine, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
JPS58159466A (ja) * 1982-03-17 1983-09-21 Asahi Chem Ind Co Ltd 新規な３位に枝別れ側鎖を有するインダゾ−ル誘導体およびその製造法
DE3277694D1 (en) * 1982-06-23 1987-12-23 Teikoku Hormone Mfg Co Ltd Hydrazinopyridazine compound, process for production thereof, and use thereof as medicament
US4624958A (en) * 1983-04-14 1986-11-25 Pfizer Inc. Antiprotozoal 1,4-di(p-amidinophenyl)imidazoles
US4556668A (en) * 1983-07-15 1985-12-03 American Hospital Supply Corporation Ethylenediamine derivatives of aryloxypropanolamine aryl esters having various medicinal properties
US5334601A (en) * 1984-03-14 1994-08-02 Bodor Nicholas S Soft β-adrenergic blocking agents
US5202347A (en) * 1984-03-14 1993-04-13 Bodor Nicholas S Soft β-adrenergic blocking agents
DE3428526A1 (de) * 1984-08-02 1986-02-13 Boehringer Mannheim Gmbh, 6800 Mannheim Neue aminoalkohole, verfahren zu deren herstellung sowie diese verbindung enthaltende arzneimittel
DE3428525A1 (de) * 1984-08-02 1986-02-13 Boehringer Mannheim Gmbh, 6800 Mannheim Verwendung von alkylendiamin-derivaten zur behandlung von durchblutungsstoerungen sowie arzneimittel, die diese verbindung enthalten
JPH0629254B2 (ja) * 1986-09-08 1994-04-20 帝国臓器製薬株式会社 ピリダジノン誘導体
US4851536A (en) * 1987-05-07 1989-07-25 American Home Products Corporation Cyclohexylquinolines as inhibitors of interleukin 1
US4920134A (en) * 1987-08-07 1990-04-24 Takeda Chemical Industries, Ltd. 2-O-pyrimidinyl glycerol derivatives
US5149698A (en) * 1987-08-11 1992-09-22 Glaxo Group Limited Chloroaniline derivatives
US5051423A (en) * 1988-07-13 1991-09-24 Schering Ag Derivatized alkanolamines as cardiovascular agents
IT1229118B (it) * 1988-07-29 1991-07-22 Simes Composti attivi sul sistema cardiovascolare che presentano sia la struttura dei beta-bloccanti sia una porzione calcio-antagonista
DE3934436A1 (de) * 1989-06-01 1991-04-18 Thomae Gmbh Dr K 2-hydroxy-n-propylamine, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
NZ234087A (en) * 1989-06-19 1991-08-27 Teikoku Hormone Mfg Co Ltd 2-(3-aryloxy(2-hydroxy-propylamino))-2-methylpropyl- aminophenyl pyridazine derivatives
US5221674A (en) * 1989-06-19 1993-06-22 Teikoku Hormone Mfg. Co., Ltd. Pyridazinone derivatives
US5204463A (en) * 1989-08-10 1993-04-20 Glaxo Inc. Substituted methoxyphenyl-4,5 dihydro-3(2H)-pridazinones having cardiotonic and beta blocking activities
US5096904A (en) * 1989-09-01 1992-03-17 Glaxo Inc. Pyridazinones having cardiotonic and beta blocking activities
US5153209A (en) * 1989-09-22 1992-10-06 Glaxo Inc. Pyridone nitriles useful in treating cardiovascular disease
US5051431A (en) * 1989-09-22 1991-09-24 Glaxo Inc. Pyridone nitriles useful in treating cardiovascular disease
US5304554A (en) * 1990-04-27 1994-04-19 Emory University 4-[(alkyl or dialkyl)amino]quinolines and their method of preparation
JP2592962Y2 (ja) * 1992-07-01 1999-03-31 横河プレシジョン株式会社 アクチュエータ
US5321036A (en) * 1993-02-10 1994-06-14 Bristol-Myers Squibb Company Thiazole and oxazole-based β3 adrenergic receptor agonists
US5677310A (en) * 1993-08-19 1997-10-14 Janssen Pharmaceutica N.V. Vasoconstrictive substituted aryloxyalkyl diamines
SE510074C2 (sv) * 1997-04-04 1999-04-19 Robovalve Ab Membranventil av flervägstyp
JP2006509790A (ja) * 2002-11-27 2006-03-23 アルテシアン セラピューティック，インコーポレイティド 心不全の治療のための混合されたＰＤＥ阻害およびβアドレナリン拮抗薬活性または部分的作用薬活性を有する化合物
AU2003300297A1 (en) * 2002-12-23 2004-07-22 Artesian Therapeutics, Inc. CARDIOTONIC COMPOUNDS WITH INHIBITORY ACTIVITY AGAINST Beta-ADRENERGIC RECEPTORS AND PHOSPHODIESTERASE
EP1833480A2 (en) * 2004-11-30 2007-09-19 Artesian Therapeutics, Inc. Cardiotonic compounds with inhibitory activity against beta-adrenergic receptors and phosphodiesterase
CA2588949A1 (en) * 2004-11-30 2006-06-08 Artesian Therapeutics, Inc. Compounds with mixed pde-inhibitory and .beta.-adrenergic antagonist or partial agonist activity for treatment of heart failure
EP1991527A2 (en) * 2006-06-28 2008-11-19 Teva Pharmaceutical Industries Ltd Polymorphous forms of carvedilol phosphate
GB2442238B (en) * 2006-09-29 2008-10-01 Rolls Royce Plc Sheet metal blank
CA2693032A1 (en) * 2007-06-29 2009-01-08 Emory University Nmda receptor antagonists for neuroprotection
US9796661B2 (en) * 2014-02-07 2017-10-24 Sika Technology Ag Amine for low-emission epoxy resin products
CN105777653A (zh) * 2014-12-26 2016-07-20 中国科学院上海药物研究所 用作Lp-PLA2抑制剂的嘧啶酮类化合物及其药物组合物
SI3097102T1 (en) 2015-03-04 2018-02-28 Gilead Sciences, Inc. A TOOL RECEPTOR MODULING 4,6-DIAMINO-PYRIDO (3,2-D) PYRIMIDINE COMPOUNDS
JP6731427B2 (ja) * 2015-06-30 2020-07-29 ネウラッド リミテッドＮｅｕｒａｄ Ｌｔｄ． 新規の呼吸制御調節化合物、およびこれを製造し、かつ使用する方法
EP3454845A4 (en) * 2016-05-13 2020-04-22 The Board of Trustees of the Leland Stanford Junior University ADRENERGIC RECEPTOR MODULATION COMPOUNDS AND METHODS OF USE THEREOF
ES2826748T3 (es) 2016-09-02 2021-05-19 Gilead Sciences Inc Derivados de 4,6-diamino-pirido[3,2-d]pirimidina como moduladores de receptores de tipo Toll
US10370342B2 (en) 2016-09-02 2019-08-06 Gilead Sciences, Inc. Toll like receptor modulator compounds
TWI751517B (zh) 2019-04-17 2022-01-01 美商基利科學股份有限公司 類鐸受體調節劑之固體形式
TWI751516B (zh) 2019-04-17 2022-01-01 美商基利科學股份有限公司 類鐸受體調節劑之固體形式
TW202115056A (zh) 2019-06-28 2021-04-16 美商基利科學股份有限公司 類鐸受體調節劑化合物的製備方法

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE657039A (cs) * 1963-12-13
US3615506A (en) * 1970-02-09 1971-10-26 Eastman Kodak Co Silver halide emulsions containing 3-cyclicamino-5-pyrazolone color couplers
NL7200508A (cs) * 1971-01-18 1972-07-20
BE787103A (fr) 1971-08-04 1973-02-02 Pfizer Nouveaux derives de propanolamine et composition pharmaceutiqueles contenant
US4020071A (en) * 1973-12-20 1977-04-26 Cassella Farbwerke Mainkur Aktiengesellschaft Derivatives of 1-phenoxy-3-amino-propan-2-ol
US4088764A (en) * 1973-12-27 1978-05-09 Cassella Farbwerke Mainkur Aktiengesellschaft Pharmaceutically active derivatives of 1-phenoxy-3-amino-propan-2-ol
US4204998A (en) * 1974-03-28 1980-05-27 Siegfried Aktiengesellschaft N-Amino indole derivatives having pharmacological activity
DE2619164C2 (de) 1976-04-30 1985-07-11 Boehringer Mannheim Gmbh, 6800 Mannheim Indazolyl-(4)-oxy-propanolamine, Verfahren zu ihrer Herstellung und deren Verwendung
GB1583372A (en) * 1977-04-04 1981-01-28 Degussa 1-(3-(3,4,5-trimethoxyphenoxy)-2-hydroxypropyl)-4-aryl piperazine derivatives
LU77339A1 (cs) 1977-05-16 1979-01-19
DD146749A3 (de) * 1977-12-01 1981-03-04 Dieter Lehmann Verfahren zur herstellung von phenoxyalkanolamin-derivaten
DE2833140A1 (de) * 1978-07-28 1980-02-07 Boehringer Sohn Ingelheim Neue n-substituierte heterocyclen
DE3023369A1 (de) * 1980-06-23 1982-01-14 Boehringer Mannheim Gmbh, 6800 Mannheim Aryloxypropanolamine, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE3048487A1 (de) * 1980-12-22 1982-07-29 Cassella Ag, 6000 Frankfurt Basisch substituierte pyridazine, ihre herstellung und ihre verwendung

Also Published As

Publication number Publication date
ATE11535T1 (de) 1985-02-15
AU540425B2 (en) 1984-11-15
DD159771A5 (de) 1983-04-06
IL63104A (en) 1987-07-31
CS449281A2 (en) 1985-09-17
ATE12492T1 (de) 1985-04-15
AU7187981A (en) 1982-01-07
DE3168611D1 (en) 1985-03-14
ZA814112B (en) 1982-07-28
US4438128A (en) 1984-03-20
FI80681B (fi) 1990-03-30
CS244661B2 (en) 1986-08-14
EP0042592B1 (de) 1985-01-30
DE3023369A1 (de) 1982-01-14
ES503175A0 (es) 1982-06-01
CS108082A2 (en) 1985-09-17
SU1287748A3 (ru) 1987-01-30
HU189514B (en) 1986-07-28
US4507488A (en) 1985-03-26
DE3169658D1 (en) 1985-05-09
IL63104A0 (en) 1981-09-13
JPS5745144A (en) 1982-03-13
CA1184188A (en) 1985-03-19
EP0042592A1 (de) 1981-12-30
EP0042593A1 (de) 1981-12-30
ES8204725A1 (es) 1982-06-01
EP0042593B1 (de) 1985-04-03
FI811897L (fi) 1981-12-24
FI80681C (fi) 1990-07-10
US4608383A (en) 1986-08-26
SU1272976A3 (ru) 1986-11-23
JPS5732269A (en) 1982-02-20
JPH023778B2 (cs) 1990-01-24

Similar Documents

Publication Publication Date Title
CS244670B2 (en) Production method of aryloxypropanolamines
RU2413727C2 (ru) Производные пиразола и их применение в качестве ингибиторов рецепторных тирозинкиназ
JPS5671074A (en) 1,2-disubstituted-4-halogenoimidazole-5-acetic acid derivative
KR900004333A (ko) 맥관 형성 억제제
BRPI0918268A2 (pt) inibores de cinase e métodos para uso dos mesmos
KR940005566A (ko) 퀴놀린 화합물
IE902721A1 (en) &#34;Intraocular pressure reducing 11-acyl prostaglandins&#34;
Voronkov et al. Antitumor Activity of Silatranes (A Review).
CN111526877B (zh) 用于ire1抑制的化合物和组合物
EP0268229A2 (en) Imidazolidinone compounds, processes for preparation thereof, compositions comprising such compounds, and the use of such compounds for the manufacture of medicaments having therapeutic value
WO2002076438A2 (en) Flt-1 ligands and their uses in the treatment of diseases regulatable by angiogenesis
EP0285219B1 (en) Method of improving sleep
AU2008256922B2 (en) Raf inhibitors for the treatment of thyroid cancer
EP0226099A3 (en) N-(pyrrol-1-yl)pyridinamines, a process for their preparation and their use as medicaments
US20040110757A1 (en) Flt-1 ligands and their uses in the treatment of diseases regulatable by angiogenesis
SU990761A1 (ru) Гидрохлориды производных 4-дифенилметилен-1-гидроксибензилпиперидина,обладающие свойством улучшать кровообращение
DE102005052102A1 (de) Neue Beta-Agonisten, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel
GB1472718A (en) Anthelmintically active 2-carbalkoxy-amino-5-6-phenyl sulphonyl oxy benzimidazoles and process for their manufacture
KR930000516A (ko) 레닌-억제 특성을 갖는 헤테로사이클릭 화합물, 이의 제조방법 및 이의 용도
GB1354451A (en) Halogen-substituted phenyl-alkylamines and their derivatives
US3845205A (en) 2-loweralkylthioadenosines
IL41664A (en) 2,6-Diamino-dihydropyridines and their pharmaceutical preparations
NO162017C (no) Analogifremgangsmaate for fremstilling av terapeutisk aktive alfa-aryl-alfa-pyridylalkansyrederivater.
WO2015054117A1 (en) Functionalized furan-2-sulfonamides exhibiting endothelial lipase inhibition
KR19980702845A (ko) 췌장염 치료제