HUP0301501A2 - Glucagon antagonists/inverse agonists, pharmaceutical compositions containing them and their use for preparation of pharmaceutical compositions - Google Patents

Glucagon antagonists/inverse agonists, pharmaceutical compositions containing them and their use for preparation of pharmaceutical compositions

Info

Publication number
HUP0301501A2
HUP0301501A2 HU0301501A HUP0301501A HUP0301501A2 HU P0301501 A2 HUP0301501 A2 HU P0301501A2 HU 0301501 A HU0301501 A HU 0301501A HU P0301501 A HUP0301501 A HU P0301501A HU P0301501 A2 HUP0301501 A2 HU P0301501A2
Authority
HU
Hungary
Prior art keywords
general formula
group
pharmaceutical compositions
compounds
substituted
Prior art date
Application number
HU0301501A
Other languages
Hungarian (hu)
Inventor
Carsten Behrens
Inge Thoger Christensen
Anker Steen Jorgensen
Janos Tibor Kodra
Jesper Lau
Peter Madsen
Christian Sams
Original Assignee
Novo Nordisk A/S
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 Novo Nordisk A/S filed Critical Novo Nordisk A/S
Publication of HUP0301501A2 publication Critical patent/HUP0301501A2/en

Links

Classifications

    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/04—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms
    • C07C275/20—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
    • C07C275/24—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/30—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/32—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
    • C07C275/34—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C317/34—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring
    • C07C317/38—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atom of at least one amino group being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfones
    • C07C317/42—Y being a hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
    • C07C323/43—Y being a hetero atom
    • C07C323/44—X or Y being nitrogen atoms
    • 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
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • 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
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/40—Acylated substituent nitrogen atom
    • 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
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D263/57—Aryl or substituted aryl radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/28—Radicals substituted by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
    • C07D277/66—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2 with aromatic rings or ring systems directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/68—Benzothiazoles 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 in position 2
    • C07D277/82—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom 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
    • C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
    • C07D319/08—1,3-Dioxanes; Hydrogenated 1,3-dioxanes condensed with carbocyclic rings or ring systems
    • 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
    • C07D333/06—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
    • 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
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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 hetero ring
    • C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Abstract

A találmány tárgyát az (I) általános képletű vegyületek és ezekettartalmazó gyógyászati készítmények képezik; a találmány tárgyáhoztartozik ezen kívül az (I) általános képletű vegyületek alkalmazásagyógyászati készítmények előállítására. Az (I) általános képletűvegyületek eredményesen alkalmazhatók glükagon antagonista hatásukkövetkeztében a magas vércukorszint csökkentésére, az I-es típusú, aII-típusú diabetes, valamint elhízottság és a lipid metabolizmusrendellenességeinek kezelésére. Az (I) általános képletben aszubsztituensek jelentése igen sokféle, így például R1, R2, R3, R4 ésR5 jelentése egymástól függetlenül hidrogénatom vagy alkilcsoport; Ajelentése -C(O)-, -CH(OR6)- vagy -CHF-, ahol a képletben R6 jelentésehidrogénatom vagy alkilcsoport, Z jelentése ariléncsoport vagy 5- vagy6 tagú kétértékű heteroaromás gyűrű, amelyben egy vagy két heteroatomvan jelen, ahol a heteroaromás gyűrű adott esetben szubsztituálvalehet, X jelentése adott esetben az alkil részen szubsztituált ésnitrogénatommal megszakított alkil-karbonilcsoport; D jelentésetöbbszörösen szubsztituált fenil- vagy öt vagy hattagú nitrogén- vagyoxigénatomot tartalmazó heterogyűrűvel kondenzált fenilcsoport. Ejelentése szubsztituált hattagú telített vagy telítetlen mono vagybiciklusos csoport. ÓThe subject of the invention is the compounds of general formula (I) and medicinal preparations containing them; the subject of the invention also includes the use of the compounds of general formula (I) for the production of pharmaceutical preparations. Due to their glucagon antagonist effect, the compounds of general formula (I) can be effectively used to reduce high blood sugar levels, to treat type I and type II diabetes, as well as obesity and lipid metabolism disorders. The meanings of substituents in the general formula (I) are very diverse, so for example R1, R2, R3, R4 and R5 are independently a hydrogen atom or an alkyl group; It means -C(O)-, -CH(OR6)- or -CHF-, where R6 in the formula is a hydrogen atom or an alkyl group, Z is an arylene group or a 5- or 6-membered bivalent heteroaromatic ring in which one or two heteroatoms are present, where the heteroaromatic ring may optionally be substituted, X is optionally substituted on the alkyl part and interrupted by a nitrogen atom alkylcarbonyl group; D is a polysubstituted phenyl group or a phenyl group fused with a heteroring containing five or six membered nitrogen or oxygen atoms. It means a substituted six-membered saturated or unsaturated mono- or bicyclic group. HE

HU0301501A 2000-06-23 2001-06-21 Glucagon antagonists/inverse agonists, pharmaceutical compositions containing them and their use for preparation of pharmaceutical compositions HUP0301501A2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DKPA200000984 2000-06-23
DKPA200001734 2000-11-17
PCT/DK2001/000435 WO2002000612A1 (en) 2000-06-23 2001-06-21 Glucagon antagonists/inverse agonists

Publications (1)

Publication Number Publication Date
HUP0301501A2 true HUP0301501A2 (en) 2003-08-28

Family

ID=26068842

Family Applications (1)

Application Number Title Priority Date Filing Date
HU0301501A HUP0301501A2 (en) 2000-06-23 2001-06-21 Glucagon antagonists/inverse agonists, pharmaceutical compositions containing them and their use for preparation of pharmaceutical compositions

Country Status (14)

Country Link
EP (1) EP1296942A1 (en)
JP (1) JP2004501897A (en)
KR (1) KR20030029061A (en)
CN (1) CN1437581A (en)
AU (1) AU2001265834A1 (en)
BR (1) BR0111908A (en)
CA (1) CA2411552A1 (en)
CZ (1) CZ20024105A3 (en)
HU (1) HUP0301501A2 (en)
IL (1) IL153181A0 (en)
MX (1) MXPA02012273A (en)
NO (1) NO20026149L (en)
PL (1) PL359619A1 (en)
WO (1) WO2002000612A1 (en)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030203946A1 (en) * 2000-11-17 2003-10-30 Carsten Behrens Glucagon antagonists/inverse agonists
US6881746B2 (en) 2001-12-03 2005-04-19 Novo Nordick A/S Glucagon antagonists/inverse agonists
EP1463715A1 (en) * 2001-12-03 2004-10-06 Novo Nordisk A/S Novel glucagon antagonists
US6762318B2 (en) 2001-12-03 2004-07-13 Novo Nordisk A/S Glucagon antagonists
US7081473B2 (en) 2002-05-22 2006-07-25 Sanwa Kagaku Kenkyusho Co., Ltd. Agent for preventing/ameliorating obesity comprising methylidene hydrizide compound as active ingredient
WO2004002480A1 (en) * 2002-06-27 2004-01-08 Novo Nordisk A/S Novel glucagon antagonists/inverse agonists
WO2004056763A2 (en) * 2002-12-20 2004-07-08 Novo Nordisk A/S Novel glucagon antagonists
WO2004063147A1 (en) * 2003-01-10 2004-07-29 Novo Nordisk A/S Salts and solvates of glucagon antagonists
ATE490244T1 (en) 2003-01-27 2010-12-15 Merck Sharp & Dohme SUBSTITUTED PYRAZOLES, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF USE
JP2007503453A (en) * 2003-05-14 2007-02-22 ノボ　ノルディスク　アクティーゼルスカブ Novel compounds for treating obesity
SI1656139T1 (en) * 2003-07-21 2011-12-30 Merck Serono Sa Aryl dicarboxamides
EP1689707A1 (en) * 2003-11-25 2006-08-16 Novo Nordisk A/S Novel compounds for the treatment of obesity
WO2005058845A2 (en) * 2003-12-19 2005-06-30 Novo Nordisk A/S Novel glucagon antagonists/inverse agonists
ES2337596T3 (en) * 2004-06-14 2010-04-27 Eli Lilly And Company ANTIGONISTS OF THE RECEIVER OF GLUCATION, PREPARATION AND THERAPEUTIC USES.
CN101146762A (en) 2005-03-21 2008-03-19 默克公司 Substituted aryl and heteroaryl derivatives
EP1868985A4 (en) 2005-03-30 2010-05-05 Merck Sharp & Dohme Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
US7709658B2 (en) 2005-07-26 2010-05-04 Merck Sharp & Dohme Corp. Process for synthesizing a substituted pyrazole
TW200745031A (en) 2005-10-13 2007-12-16 Merck & Co Inc Acyl indoles, compositions containing such compounds and methods of use
SI1957484T1 (en) * 2005-11-23 2010-07-30 Lilly Co Eli Glucagon receptor antagonists, preparation and therapeutic uses
WO2007111864A2 (en) 2006-03-23 2007-10-04 Merck & Co., Inc. Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
JP2009537525A (en) 2006-05-16 2009-10-29 メルク エンド カムパニー インコーポレーテッド Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
TW200821284A (en) 2006-10-03 2008-05-16 Merck & Co Inc Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
ES2720430T3 (en) 2007-02-09 2019-07-22 Metabasis Therapeutics Inc Novel glucagon receptor antagonists
EP2291358B1 (en) 2008-05-16 2018-03-28 Merck Sharp & Dohme Corp. Glucagon receptor antagonists, compositions, and methods for their use
WO2010019830A1 (en) 2008-08-13 2010-02-18 Metabasis Therapeutics, Inc. Glucagon antagonists
NZ611529A (en) 2010-12-23 2015-06-26 Pfizer Glucagon receptor modulators
HUE030364T2 (en) 2011-02-08 2017-04-28 Pfizer Glucagon receptor modulator
KR20140023441A (en) 2011-07-22 2014-02-26 화이자 인코포레이티드 Quinolinyl glucagon receptor modulators
WO2013138753A1 (en) 2012-03-16 2013-09-19 Fox Chase Chemical Diversity Center, Inc. Prodrugs of riluzole and their method of use
EP3065736B1 (en) 2013-11-04 2018-11-14 Merck Sharp & Dohme Corp. Glucagon receptor antagonist compounds, compositions thereof, and methods of use
EP3154956A4 (en) 2014-06-12 2018-01-17 Ligand Pharmaceuticals, Inc. Glucagon antagonists
WO2023283425A1 (en) 2021-07-09 2023-01-12 Plexium, Inc. Aryl compounds and pharmaceutical compositions that modulate ikzf2

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6174905B1 (en) * 1996-09-30 2001-01-16 Mitsui Chemicals, Inc. Cell differentiation inducer
BR9810378A (en) * 1997-07-01 2000-08-29 Novo Nordisk As Compound, use of the same, pharmaceutical composition, and, processes of treating type i or type ii diabetes, of treating hyperglycemia, and of decreasing blood glucose in a mammal
US6613942B1 (en) * 1997-07-01 2003-09-02 Novo Nordisk A/S Glucagon antagonists/inverse agonists
EP1183229B1 (en) * 1999-05-17 2005-10-26 Novo Nordisk A/S Glucagon antagonists/inverse agonists

Also Published As

Publication number Publication date
IL153181A0 (en) 2003-06-24
PL359619A1 (en) 2004-08-23
NO20026149D0 (en) 2002-12-20
WO2002000612A1 (en) 2002-01-03
KR20030029061A (en) 2003-04-11
CZ20024105A3 (en) 2003-05-14
NO20026149L (en) 2003-02-21
BR0111908A (en) 2003-04-01
MXPA02012273A (en) 2003-04-25
AU2001265834A1 (en) 2002-01-08
JP2004501897A (en) 2004-01-22
CN1437581A (en) 2003-08-20
EP1296942A1 (en) 2003-04-02
CA2411552A1 (en) 2002-01-03

Similar Documents

Publication Publication Date Title
HUP0301501A2 (en) Glucagon antagonists/inverse agonists, pharmaceutical compositions containing them and their use for preparation of pharmaceutical compositions
HUP0300565A2 (en) 8-quinolinxanthine and 8-isoquinolinxanthine derivatives as pde 5 inhibitors, their use, process for their preparation and pharmaceutical compositions containing them
HUP0000562A2 (en) Fused pyrazole derivatives, process for their preparation, their use and pharmaceutical compositions containing them
NZ528851A (en) N-aroyl cyclic amines
HUP0100348A2 (en) Bicycles containing a six menbered ring with one or two nitrogen atoms, process for their preparation, use of them, pharmaceutical compositions containing the same and intermediates
HUP0302480A2 (en) Pyridinone derivatives for treatment of atherosclerosis, process for preparation thereof and pharmaceutical compositions containing the same
HUP0302367A2 (en) Aza and polyaza-naphthalenyl carboxamides useful as hiv integrase inhibitors and pharmaceutical compositions containing them
HUP0102102A2 (en) Pyrazoline derivatives, their preparation, pharmaceutical compositions containing them and their use
HUP0302474A2 (en) Therapeutically effective tropane derivatives, process for their preparation pharmaceutical compositions containing them and their use
HUP0401982A2 (en) Indolizine derivates, process for their preparation and pharmaceutical compositions containing the compounds
HUP0402352A2 (en) Pyrimidine derivatives for use as phosphodiesterase (pde)7 inhibitors and pharmaceutical compositions containing them
HUP0300350A2 (en) Pharmaceutical compositions containing 3-amino-azetidine derivatives, novel derivatives and preparation thereof
HUP0204170A2 (en) 5-thia-omega-substituted phenyl-prostaglandin e derivatives, process for producing the same and drugs containing the same as the active ingredient
HUP0401638A2 (en) Thiopene-amides, thiazolesulfonamides as antineoplastic agents, and pharmaceutical composition containing the same
HUP0301117A2 (en) Imidazole derivatives kinase inhibitors, their use, process for their preparation and pharmaceutical compositions containing them
HUP0401083A2 (en) 4-amino-6-phenyl-pyrrolo [2,3-d] pyrimidine derivatives, pharmaceutical compositions containing them and process for the preparation of the compounds
HUP0300920A1 (en) Substituted benzoic acid amides and use thereof as pharmaceutical composition
HUP0002050A2 (en) Substituted imidazole compounds, process for producing them, pharmaceutical compositions containing them and their use
HUP0202049A2 (en) Indole derivatives and their use for the treatment of osteoporosis amongst other applications
HUP0300140A2 (en) 8,8a-dihydro-indeno[1,2-d]thiazole derivatives, substituted in position 8a, a method for their production and their use as medicaments
HUP0203245A2 (en) Imidazopyridine derivatives as phosphodiesterase vii inhibitors and pharmaceutical compositions containing them
HUP0203422A2 (en) Imidazole derivatives as phosphodiesterase vii inhibitors, process for their preparation and pharmaceutical compositions containing them
HUP0400653A2 (en) Benzyl(idene)-lactams and their use as 5ht1-receptor ligands and pharmaceutical compositions containing them
HUP0204154A2 (en) Novel benzothiadiazine derivatives, preparation method and pharmaceutical compositions containing same
ATE485822T1 (en) PHENYLAMINOPYRIDINES AND PHENYLAMINOPYRAZINE

Legal Events

Date Code Title Description
FD9A Lapse of provisional protection due to non-payment of fees