RU2004110719A - Зздабиторы протеаз, расщепляющих за пролином - Google Patents

Зздабиторы протеаз, расщепляющих за пролином Download PDF

Info

Publication number
RU2004110719A
RU2004110719A RU2004110719/04A RU2004110719A RU2004110719A RU 2004110719 A RU2004110719 A RU 2004110719A RU 2004110719/04 A RU2004110719/04 A RU 2004110719/04A RU 2004110719 A RU2004110719 A RU 2004110719A RU 2004110719 A RU2004110719 A RU 2004110719A
Authority
RU
Russia
Prior art keywords
alkyl
compound
compound according
general formula
item
Prior art date
Application number
RU2004110719/04A
Other languages
English (en)
Other versions
RU2345065C2 (ru
Inventor
Дейвид Майкл ИВАНЗ (GB)
Дейвид Майкл ИВАНЗ
Дорин Мэри ЭШВОРТ (GB)
Дорин Мэри ЭШВОРТ
Original Assignee
Ферринг Б.В. (NL)
Ферринг Б.В.
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 Ферринг Б.В. (NL), Ферринг Б.В. filed Critical Ферринг Б.В. (NL)
Publication of RU2004110719A publication Critical patent/RU2004110719A/ru
Application granted granted Critical
Publication of RU2345065C2 publication Critical patent/RU2345065C2/ru

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
    • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/335—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/38—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
    • 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
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the 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
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon 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
    • C07D213/60—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
    • 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
    • C07D215/12—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
    • C07D251/40—Nitrogen atoms
    • C07D251/48—Two nitrogen atoms
    • C07D251/50—Two nitrogen atoms with a halogen atom attached to the third ring carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
    • C07D251/40—Nitrogen atoms
    • C07D251/48—Two nitrogen atoms
    • C07D251/52—Two nitrogen atoms with an oxygen or sulfur atom attached to the third ring carbon atom
    • 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
    • C07D277/04—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
    • 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
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/06—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon 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
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D307/81—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 atoms of the carbocyclic ring
    • C07D317/66—Nitrogen atoms not forming part of a nitro radical
    • 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
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Claims (67)

1. Соединение согласно общей формуле 1 или его фармацевтически приемлемая соль,
Figure 00000001
где либо G1 представляет собой -CH2-X2-(CH2)a-G3, и G2 представляет собой Н, либо G2 представляет собой -CH2-(CH2)a-G3, и G1 представляет собой Н;
G3 выбран из группы согласно общей формуле 2, группы согласно общей формуле 3 и группы согласно общей формуле 4;
Figure 00000002
а равно 0, 1 или 2;
b равно 1 или 2;
X1 выбран из СН2, S, CF2, CHF, СН(СН3), С(СН3)2, СН(CN) и О;
X2 выбран из СН2, О и S, при условии, что если а равно 1, то X2 представляет собой СН2;
X3, X4 и X5 выбраны из N и СН, при условии, что по меньшей мере два из X3, X4 и X5 представляют собой N;
X6 выбран из О и NH;
X7 выбран из СН2, О, S и NH;
R1 выбран из Н и CN;
R2 выбран из Н и алкила;
R3 выбран из Н, Cl, ОН, O-алкила, NH2, NH-алкила и N(алкил)2;
R4, R5, R6, R7 и R8 независимо выбраны из Н, Br, Cl, F, CF3, алкила, ацила, ОН, O-алкила, NH2, NH-алкила, N(алкил)2, NO2, NH-ацила, CO2Н, CO2-алкила, CONH2, CONH-алкила, CON(алкила)2 и CN;
R9 выбран из Н и алкила;
R10, R11, R12, R13 и R14 независимо выбраны из Н, Br, Cl, F, CF3, алкила, ацила, ОН, O-алкила, NH2, NH-алкила, N(алкил)2, NO2, NH-ацила, CO2Н, CO2-алкила, CONH2, CONH-алкила, CON(алкил)2 и CN;
R15 и R16 независимо выбраны из Н, алкила, алкенила, полифторалкила, аралкила, арила и -CH2-L-R17, или R15 и R16 вместе образуют группу согласно общей формуле 5, общей формуле 6 или общей формуле 7;
Figure 00000003
R17 выбран из Н, алкила и арила;
R18 выбран из Н, алкила, арила, ОН, O-алкила, NH2, NH-алкила и N(алкил)2;
R19 выбран из Н, алкила, арила, F, Cl, Br, CF3, ОН, O-алкила, NH2, NH-алкила и N(алкил)2;
L выбран из ковалентной связи, СН=СН, С≡С и -С6Н4-;
d и e выбраны из 0, 1, 2 и 3 так, что d+e равно 3, 4 или 5; и
f выбран из 1, 2 и 3;
при условии что, когда R15 и R16 оба представляют собой Н, и b равно 1, тогда X1 не представляет собой S или СН2.
2. Соединение согласно общей формуле 8 или его фармацевтически приемлемая соль
Figure 00000004
где а равно 0, 1 или 2;
b равно 1 или 2;
X1 выбран из СН3, S, CF3, CHF, СН(СН3), С(СН3)2, CH(CN) и О;
X2 выбран из СН3, О и S, при условии, что если а равно 1, то X2 представляет собой CH2;
X3, X4 и X5 выбраны из N и СН, при условии, что по меньшей мере два из X3, X4 и X5 представляют собой N;
X6 выбран из О и NH;
R1 выбран из Н и CN;
R2 выбран из Н и алкила;
R3 выбран из Н, Cl, ОН, O-алкила, NH2, NH-алкила и N(алкил)2;
R4, R5, R6, R7 и R8 выбраны независимо из Н, Br, Cl, F, CF3, алкила, ацила, ОН, O-алкила, NH2, NH-алкила, N(алкил)2, NO2, NH-ацила, CO2Н, CO2-алкила, CONH2, CONH-алкила, CON(алкил)2 и CN.
3. Соединение по п.2, где R1 представляет собой Н.
4. Соединение по п.2, где R1 представляет собой CN.
5. Соединение по п.2, где X1 представляет собой CH2.
6. Соединение по п.2, где X1 представляет собой S.
7. Соединение по п.2, где b равно 1.
8. Соединение по п.2, где b равно 2.
9. Соединение по п.2, где а равно 1.
10. Соединение по п.2, где а равно 2, и X2 представляет собой СН2.
11. Соединение по п.2, где X3, X4 и X5 все представляют собой N.
12. Соединение согласно общей формуле 9 или его фармацевтически приемлемая соль
Figure 00000005
где а равно 1 или 2;
b равно 1 или 2;
X1 выбран из СН2, S, CF3, CHF, СН(СН3), С(СН3)2, CH(CN) и О;
X3, X4 и X5 выбраны из N и СН, при условии, что по меньшей мере два из X3, X4 и X5 представляют собой N;
X6 выбран из О и NH;
R1 выбран из Н и CN;
R2 выбран из Н и алкила;
R3 выбран из Н, Cl, ОН, O-алкила, NH2, NH-алкила и N(алкил)2;
R4, R5, R6, R7 и R8 выбраны независимо из Н, Br, Cl, F, CF3, алкила, ацила, ОН, O-алкила, NH2, NH-алкила, N(алкил)2, NO2, NH-ацила, CO2Н, CO2-алкила, CONH2, CONH-алкила, CO2-алкил)2 и CN.
13. Соединение по п.12, где R1 представляет собой Н.
14. Соединение по п.12, где R1 представляет собой CN.
15. Соединение по п.12, где X1 представляет собой СН2.
16. Соединение по п.12, где X1 представляет собой S.
17. Соединение по п.12, где b равно 1.
18. Соединение по п.12, где b равно 2.
19. Соединение по п.12, где а равно 1.
20. Соединение по п.12, где X3, X4 и X5 все представляют собой N.
21. Соединение согласно общей формуле 10 или его фармацевтически приемлемая соль
Figure 00000006
где а равно 0, 1 или 2;
b равно 1 или 2;
X1 выбран из СН2, S, CF2, CHF, СН(СН3), С(СН3)2, СН(CN) и О;
X2 выбран из СН2, О и S при условии, что если а равно 1, то X2 представляет собой CH2;
X7 выбран из О, S, СН2 и NH;
R1 выбран из Н и CN;
R9 выбран из Н и алкила;
R10, R11, R12, R13 и R14 выбраны независимо из Н, Br, Cl, F, CF3, алкила, ацила, ОН, O-алкила, NH2, NH-алкила, N(алкил)2, NO2, NH-ацила, CO2Н, CO2-алкила, CONH2, CONH-алкила, CON(алкил)2 и CN, выбран из Н, Cl, ОН, O-алкила, NH2, NH-алкила и N(алкил)2.
22. Соединение по п.21, где R1 представляет собой Н.
23. Соединение по п.21, где R1 представляет собой CN.
24. Соединение по п.21, где X1 представляет собой СН2.
25. Соединение по п.21, где X1 представляет собой S.
26. Соединение по п.21, где b равно 1.
27. Соединение по п.21, где b равно 2.
28. Соединение по п.21, где а равно 1.
29. Соединение по п.21, где а равно 2, и X2 представляет собой СН2.
30. Соединение согласно общей формуле 11 или его фармацевтически приемлемая соль,
Figure 00000007
где а равно 1 или 2;
b равно 1 или 2;
X1 выбран из СН2, S, CF2, CHF, СН(СН3), С(СН3)2, CH(CN) и О;
X7 выбран из О, S, CH2 и NH;
R1 выбран из Н и CN;
R9 выбран из Н и алкила;
R10, R11, R12, R13 и R14 выбраны независимо из Н, Br, Cl, F, CF3, алкила, ацила, ОН, O-алкила, NH2, NH-алкила, N(алкил)2, NO3, NH-ацила, CO2Н, CO2-алкила, CONH2, CONH-алкила, CON(алкил)2 и CN, выбран из Н, Cl, ОН, O-алкила, NH2, NH-алкила и N(алкил)2.
31. Соединение по п.30, где R1 представляет собой Н.
32. Соединение по п.30, где R1 представляет собой CN.
33. Соединение по п.30, где X1 представляет собой СН2.
34. Соединение по п.30, где X1 представляет собой S.
35. Соединение по п.30, где b равно 1.
36. Соединение по п.30, где b равно 2.
37. Соединение по п.30, где а равно 1.
38. Соединение согласно общей формуле 12 или его фармацевтически приемлемая соль
Figure 00000008
где а равно 0, 1 или 2;
b равно 1 или 2;
X1 выбран из СН2, S, CF2, CHF, СН(СН3), С(СН3)2, CH(CN) и О;
X2 выбран из CH2, О и S, при условии, что если а равно 1, то X2 представляет собой СН2;
R1 выбран из Н и CN;
R15 и R16 каждый независимо выбран из Н, алкила, алкенила, полифторалкила, аралкила, арила и CH2-L-R17;
или R15 и R16 вместе представляют собой группу согласно общей формуле 5, группу согласно общей формуле 6 или группу согласно общей формуле 7;
Figure 00000009
R17 выбран из Н, алкила и арила;
R18 выбран из Н, алкила, арила, ОН, O-алкила, NH2, NH-алкила и N(алкил)2;
R19 выбран из Н, алкила, арила, F, Cl, Br, CF3, ОН, O-алкила, NH2, NH-алкила и N(алкил)2;
L выбран из ковалентной связи, СН=СН, С≡С и -С6Н4-;
d и e выбраны из 0, 1, 2 и 3 так, что d+e равно 3, 4 или 5; и
f выбран из 1, 2 и 3;
при условии, что когда R15 и R16 оба представляют собой Н, и b равно 1, тогда X1 не представляет собой S или СН2.
39. Соединение по п.38, где R1 представляет собой Н.
40. Соединение по п.38, где R1 представляет собой CN.
41. Соединение по п.38, где X1 представляет собой СН2.
42. Соединение по п.38, где X1 представляет собой S.
43. Соединение по п.38, где b равно 1.
44. Соединение по п.38, где b равно 2.
45. Соединение по п.38, где а равно 1.
46. Соединение по п.38, где а равно 2, и X2 представляет собой СН2.
47. Соединение согласно общей формуле 13 или его фармацевтически приемлемая соль,
Figure 00000010
где а равно 1 или 2;
b равно 1 или 2;
X1 выбран из СН2, S, CF2, CHF, СН(СН3), С(СН3)2, СН(CN) и О;
R1 выбран из Н и CN;
R15 и R16 каждый независимо выбран из Н, алкила, алкенила, полифторалкила, аралкила, арила и CH2-L-R17;
или R15 и R16 вместе представляют собой группу согласно общей формуле 5, группу согласно общей формуле 6 или группу согласно общей формуле 7;
Figure 00000009
R17 выбран из Н, алкила и арила;
R18 выбран из Н, алкила, арила, ОН, O-алкила, NH2, NH-алкила и N(алкил)2;
R19 выбран из Н, алкила, арила, F, Cl, Br, CF3, ОН, O-алкила, NH2, NH-алкила и N(алкил)2;
L выбран из ковалентной связи, СН=СН, С≡С и -С6Н4-;
d и e выбраны из 0, 1, 2 и 3 так, что d+e равно 3, 4 или 5; и
f выбран из 1, 2 и 3.
48. Соединение по п.47, где R1 представляет собой Н.
49. Соединение по п.47, где R1 представляет собой CN.
50. Соединение по п.47, где X1 представляет собой СН2.
51. Соединение по п.47, где X1 представляет собой S.
52. Соединение по п.47, где b равно 1.
53. Соединение по п.47, где b равно 2.
54. Соединение по п.47, где а равно 1.
55. Фармацевтическая композиция, содержащая соединение по любому из пп.1-54.
56. Применение соединения по любому из пп.1-54 в качестве компонента в изготовлении фармацевтической композиции.
57. Способ лечения заболевания у субъекта, являющегося человеком или животным, при котором этому субъекту вводят терапевтически активное количество соединения по любому из пп.1-54.
58. Способ лечения по п.57, где заболевание обусловлено нарушением регуляции протеаз, расщепляющих за пролином, или их эндогенных субстратов.
59. Способ лечения по п.57, где заболевание облегчают ингибированием протеаз, расщепляющих за пролином.
60. Способ лечения по п.57, где заболевание обусловлено нарушением регуляции протеазы, расщепляющей за пролином, или ее эндогенных субстратов, причем эта протеаза является внутриклеточной.
61. Композиция по п.1 или 38, при условии, что когда X1=S; b=1; R1=Н; G2=Н; G1 представляет собой -CH2-X2-(CH2)a-GЗ; а=1, X2=CH2; G3=NR15R16, и один из R15, R16=Н, другой из R15, R16 не представляет собой пиридил, замещенный пиридил, пиразинил или замещенный пиразинил.
62. Композиция по пп.1, 38 или 47, при условии, что когда b=1, R1 представляет собой Н, и X1 представляет собой S; G1=Н; G2 представляет собой -CH2-(CH2)a-G3; а=1; G3 представляет собой NR15R16, и один из R15 и R16 представляет собой Н, другой из R15, R16 не представляет собой пиридил, замещенный пиридил, пиразинил или замещенный пиразинил.
63. Композиция по пп.1, 38 или 47, при условии, что когда b=1, R1 представляет собой CN, и X1 представляет собой СН2; G1=Н; G2 представляет собой -CH2-(CH2)a-G3; а=1; G3 представляет собой NR15R16, и один из R15 и R16 представляет собой Н, другой из R15, R16 не представляет собой пиридил, замещенный пиридил, пиразинил или замещенный пиразинил.
64. Композиция по пп.1, 38 или 47, при условии, что когда G2=Н; G1=-CH2-X2-(CH2)a-G3, X2 представляет собой СН2; а=1; G3=NR15R16, и R15=R16=Н; b не равно 2, когда X1 представляет собой О или СН2, и b не равно 1, когда X1 представляет собой СН2.
65. Способ лечения по п.57, где заболевание обусловлено нарушением регуляции не ассоциированных с мембранами протеаз, расщепляющих за пролином (post-proline cleaving proteases), таких как энзимы QPP, DPP-8 и DPP-9, или их эндогенных субстратов.
66. Способ лечения по п.57, где заболевание облегчают ингибированием не ассоциированных с мембранами протеаз, расщепляющих за пролином, таких как энзимы QPP, DPP-8 и DPP-9, или их эндогенных субстратов.
67. Способ по п.65 или 66, где соединение представляет собой селективный ингибитор не ассоциированных с мембранами протеаз, расщепляющих за пролином.
RU2004110719/04A 2001-10-23 2002-10-23 Ингибиторы протеаз, расщепляющих за пролином RU2345065C2 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0125445.7A GB0125445D0 (en) 2001-10-23 2001-10-23 Protease Inhibitors
GB0125445.7 2001-10-23

Publications (2)

Publication Number Publication Date
RU2004110719A true RU2004110719A (ru) 2005-10-20
RU2345065C2 RU2345065C2 (ru) 2009-01-27

Family

ID=9924375

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2004110719/04A RU2345065C2 (ru) 2001-10-23 2002-10-23 Ингибиторы протеаз, расщепляющих за пролином

Country Status (17)

Country Link
US (2) US7335677B2 (ru)
EP (1) EP1446116A1 (ru)
JP (1) JP2005511541A (ru)
KR (1) KR20040047943A (ru)
CN (1) CN1571667A (ru)
AU (1) AU2002336190B2 (ru)
CA (1) CA2464254A1 (ru)
GB (1) GB0125445D0 (ru)
HU (1) HUP0401738A2 (ru)
IL (1) IL161191A0 (ru)
MX (1) MXPA04003829A (ru)
NO (1) NO20042080L (ru)
NZ (1) NZ532048A (ru)
PL (1) PL370220A1 (ru)
RU (1) RU2345065C2 (ru)
WO (1) WO2003035057A1 (ru)
ZA (1) ZA200402501B (ru)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2507213C2 (ru) * 2005-10-04 2014-02-20 Солидженикс, Инк., Новые пептиды для лечения и профилактики иммунопатологических заболеваний, включая лечение и профилактику инфекции посредством модулирования врожденного иммунитета

Families Citing this family (79)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6258597B1 (en) * 1997-09-29 2001-07-10 Point Therapeutics, Inc. Stimulation of hematopoietic cells in vitro
US6979697B1 (en) * 1998-08-21 2005-12-27 Point Therapeutics, Inc. Regulation of substrate activity
US6890904B1 (en) 1999-05-25 2005-05-10 Point Therapeutics, Inc. Anti-tumor agents
WO2004076434A1 (en) * 2003-02-28 2004-09-10 Aic Dipeptidyl peptidase inhibitors
WO2004076433A1 (en) * 2003-02-28 2004-09-10 Aic Dipeptidyl peptidase inhibitors
US20040242566A1 (en) * 2003-03-25 2004-12-02 Syrrx, Inc. Dipeptidyl peptidase inhibitors
JP4806628B2 (ja) 2003-05-05 2011-11-02 プロビオドルグ エージー グルタミニルシクラーゼ阻害剤
US7169926B1 (en) 2003-08-13 2007-01-30 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
US7678909B1 (en) 2003-08-13 2010-03-16 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
US7579357B2 (en) * 2003-08-13 2009-08-25 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
WO2005026148A1 (en) * 2003-09-08 2005-03-24 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
US20050065144A1 (en) * 2003-09-08 2005-03-24 Syrrx, Inc. Dipeptidyl peptidase inhibitors
JP2007509898A (ja) 2003-11-03 2007-04-19 プロビオドルグ エージー 神経障害治療に有用な組合せ
KR20180050427A (ko) 2003-11-17 2018-05-14 노파르티스 아게 디펩티딜 펩티다제 ⅳ 억제제의 용도
ES2940341T3 (es) 2004-01-20 2023-05-05 Novartis Ag Formulación y proceso de compresión directa
EP1713780B1 (en) 2004-02-05 2012-01-18 Probiodrug AG Novel inhibitors of glutaminyl cyclase
US7732446B1 (en) 2004-03-11 2010-06-08 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
BRPI0418639B8 (pt) * 2004-03-15 2021-05-25 Takeda Pharmaceutical compostos inibidores de dipeptidil peptidase, assim como composição farmacêutica contendo os mesmos
EP2305352A1 (en) 2004-04-02 2011-04-06 Merck Sharp & Dohme Corp. 5-alpha-reductase inhibitors for use in the treatment of men with metabolic and anthropometric disorders
EP1753748B1 (en) 2004-05-12 2009-07-29 Pfizer Products Inc. Proline derivatives and their use as dipeptidyl peptidase iv inhibitors
US7687638B2 (en) * 2004-06-04 2010-03-30 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
WO2006019965A2 (en) 2004-07-16 2006-02-23 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
JP2008507541A (ja) 2004-07-23 2008-03-13 ロイヤルティ，スーザン・マリー ペプチダーゼ阻害剤
US20060063719A1 (en) * 2004-09-21 2006-03-23 Point Therapeutics, Inc. Methods for treating diabetes
EP1828192B1 (en) * 2004-12-21 2014-12-03 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
DOP2006000008A (es) 2005-01-10 2006-08-31 Arena Pharm Inc Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1
MX2007011453A (es) * 2005-04-22 2008-02-12 Alantos Pharmaceuticals Holding Inc Inhibidores de la dipeptidil peptidasa-iv.
MY152185A (en) 2005-06-10 2014-08-29 Novartis Ag Modified release 1-[(3-hydroxy-adamant-1-ylamino)-acetyl]-pyrrolidine-2(s)-carbonitrile formulation
AU2006278039B2 (en) * 2005-08-11 2010-10-21 F. Hoffmann-La Roche Ag Pharmaceutical composition comprising a DPP-lV inhibitor
HRP20140091T4 (hr) * 2005-09-14 2021-12-24 Takeda Pharmaceutical Company Limited Davanje inhibitora dipeptidil peptidaze
CN101374523B (zh) * 2005-09-14 2012-04-11 武田药品工业株式会社 用于治疗糖尿病的二肽基肽酶抑制剂
TW200745080A (en) * 2005-09-16 2007-12-16 Takeda Pharmaceuticals Co Polymorphs of tartrate salt of 2-[2-(3-(R)-amino-piperidin-1-yl)-5-fluoro-6-oxo-6H-pyrimidin-1-ylmethyl]-benzonitrile and methods of use therefor
JP5122462B2 (ja) 2005-09-16 2013-01-16 武田薬品工業株式会社 ジペプチジルペプチダーゼ阻害剤
TW200745079A (en) * 2005-09-16 2007-12-16 Takeda Pharmaceuticals Co Polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile and methods of use therefor
GB0526291D0 (en) 2005-12-23 2006-02-01 Prosidion Ltd Therapeutic method
WO2007112347A1 (en) 2006-03-28 2007-10-04 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
JP2009531456A (ja) * 2006-03-28 2009-09-03 武田薬品工業株式会社 （ｒ）−３−アミノピペリジン二塩酸塩の調製
PE20071221A1 (es) 2006-04-11 2007-12-14 Arena Pharm Inc Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas
EA200802054A1 (ru) 2006-04-12 2009-04-28 Пробиодруг Аг Ингибиторы фермента
US8324383B2 (en) 2006-09-13 2012-12-04 Takeda Pharmaceutical Company Limited Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
JP5379692B2 (ja) 2006-11-09 2013-12-25 プロビオドルグ エージー 潰瘍、癌及び他の疾患の治療のためのグルタミニルシクラーゼの阻害薬としての３−ヒドロキシ−１，５−ジヒドロ−ピロール−２−オン誘導体
TW200838536A (en) 2006-11-29 2008-10-01 Takeda Pharmaceutical Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
US9126987B2 (en) 2006-11-30 2015-09-08 Probiodrug Ag Inhibitors of glutaminyl cyclase
US8093236B2 (en) 2007-03-13 2012-01-10 Takeda Pharmaceuticals Company Limited Weekly administration of dipeptidyl peptidase inhibitors
WO2008120813A1 (ja) 2007-04-03 2008-10-09 Mitsubishi Tanabe Pharma Corporation ジペプチジルペプチダーゼ４阻害化合物と甘味料との併用
CN101279955B (zh) * 2007-04-03 2012-11-28 北京摩力克科技有限公司 作为二肽肽激酶-iv抑制剂的n-取代硫吗啉衍生物及其医药用途
DK2142514T3 (da) 2007-04-18 2015-03-23 Probiodrug Ag Thioureaderivater som glutaminylcyclase-inhibitorer
CN101357921B (zh) * 2007-08-02 2011-01-12 山东轩竹医药科技有限公司 新的二肽酶-iv抑制剂化合物
CL2008003653A1 (es) 2008-01-17 2010-03-05 Mitsubishi Tanabe Pharma Corp Uso de un inhibidor de sglt derivado de glucopiranosilo y un inhibidor de dppiv seleccionado para tratar la diabetes; y composicion farmaceutica.
EP2108960A1 (en) 2008-04-07 2009-10-14 Arena Pharmaceuticals, Inc. Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditons modulated by PYY
CN101723947B (zh) * 2008-10-21 2012-05-30 山东轩竹医药科技有限公司 二肽酶-ⅳ抑制剂化合物
CN102596904B (zh) * 2009-06-26 2015-01-28 佛罗里达大学研究基金会公司 蛋白酶抑制剂、组合物及使用方法
AR077642A1 (es) 2009-07-09 2011-09-14 Arena Pharm Inc Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo
JP5934645B2 (ja) 2009-09-11 2016-06-15 プロビオドルグ エージー グルタミニルシクラーゼ阻害剤としてのヘテロ環式誘導体
JP6026284B2 (ja) 2010-03-03 2016-11-16 プロビオドルグ エージー グルタミニルシクラーゼの阻害剤
CN102791704B (zh) 2010-03-10 2015-11-25 前体生物药物股份公司 谷氨酰胺酰环化酶(qc, ec 2.3.2.5)的杂环抑制剂
BR112012025592A2 (pt) 2010-04-06 2019-09-24 Arena Pharm Inc moduladores do receptor de gpr119 e o tratamento de distúrbios relacionados com os mesmos
EP2560953B1 (en) 2010-04-21 2016-01-06 Probiodrug AG Inhibitors of glutaminyl cyclase
PE20131371A1 (es) 2010-09-22 2013-11-25 Arena Pharm Inc Moduladores del receptor gpr119 y el tratamiento de trastornos relacionados con este
CN102453001B (zh) * 2010-10-22 2016-06-01 中国医学科学院药物研究所 硫代吗啉类化合物及其制备方法和用途
JP6050264B2 (ja) 2011-03-16 2016-12-21 プロビオドルグ エージー グルタミニルシクラーゼの阻害剤としてのベンゾイミダゾール誘導体
WO2012135570A1 (en) 2011-04-01 2012-10-04 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2012145361A1 (en) 2011-04-19 2012-10-26 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2012145604A1 (en) 2011-04-22 2012-10-26 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2012145603A1 (en) 2011-04-22 2012-10-26 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2012170702A1 (en) 2011-06-08 2012-12-13 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2013055910A1 (en) 2011-10-12 2013-04-18 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
CN102532009B (zh) * 2012-01-12 2014-11-05 浙江大学 一种抑制二肽激肽酶的化合物及制备方法和用途
TWI500613B (zh) 2012-10-17 2015-09-21 Cadila Healthcare Ltd 新穎之雜環化合物
WO2014074668A1 (en) 2012-11-08 2014-05-15 Arena Pharmaceuticals, Inc. Modulators of gpr119 and the treatment of disorders related thereto
CN105085359A (zh) * 2014-05-07 2015-11-25 中国医学科学院药物研究所 含氮杂环取代的吡咯烷甲酰基硫代吗啉类dpp-iv抑制剂
CN105085358A (zh) * 2014-05-07 2015-11-25 中国医学科学院药物研究所 4-取代吡咯烷甲酰基硫代吗啉类dpp-iv抑制剂
GB201415598D0 (en) 2014-09-03 2014-10-15 Univ Birmingham Elavated Itercranial Pressure Treatment
CN104513188A (zh) * 2014-10-22 2015-04-15 广东药学院 一种氰基吡咯烷类衍生物及其制备方法和应用
WO2016144862A1 (en) 2015-03-09 2016-09-15 Intekrin Therapeutics, Inc. Methods for the treatment of nonalcoholic fatty liver disease and/or lipodystrophy
WO2018162722A1 (en) 2017-03-09 2018-09-13 Deutsches Institut Für Ernährungsforschung Potsdam-Rehbrücke Dpp-4 inhibitors for use in treating bone fractures
EP3606527A1 (en) 2017-04-03 2020-02-12 Coherus Biosciences, Inc. Ppar-gamma agonist for treatment of progressive supranuclear palsy
DK3461819T3 (da) 2017-09-29 2020-08-10 Probiodrug Ag Inhibitorer af glutaminylcyklase
US20240101549A1 (en) 2020-12-17 2024-03-28 Astrazeneca Ab N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamides

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0490379A3 (de) * 1990-12-13 1992-06-24 BERLIN-CHEMIE Aktiengesellschaft Diaminosäurederivate und pharmazeutische Zusammensetzungen
DE4344648A1 (de) * 1993-12-24 1995-06-29 Dresden Arzneimittel Neue Aminocarbonsäureamide, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
DE69526969T2 (de) 1994-12-14 2003-03-20 Mitsui Du Pont Polychemical Thermoplastische harzzusammensetzung und seine verwendung
US6011155A (en) * 1996-11-07 2000-01-04 Novartis Ag N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
US6107317A (en) * 1999-06-24 2000-08-22 Novartis Ag N-(substituted glycyl)-thiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
GB0010188D0 (en) * 2000-04-26 2000-06-14 Ferring Bv Inhibitors of dipeptidyl peptidase IV
TWI243162B (en) * 2000-11-10 2005-11-11 Taisho Pharmaceutical Co Ltd Cyanopyrrolidine derivatives
JPWO2002051836A1 (ja) * 2000-12-27 2004-04-22 協和醗酵工業株式会社 ジペプチジルペプチダーゼ−ｉｖ阻害剤
JP2002265439A (ja) * 2001-03-08 2002-09-18 Mitsubishi Pharma Corp シアノピロリジン誘導体およびその医薬用途
GB0109146D0 (en) * 2001-04-11 2001-05-30 Ferring Bv Treatment of type 2 diabetes
US6861440B2 (en) * 2001-10-26 2005-03-01 Hoffmann-La Roche Inc. DPP IV inhibitors

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2507213C2 (ru) * 2005-10-04 2014-02-20 Солидженикс, Инк., Новые пептиды для лечения и профилактики иммунопатологических заболеваний, включая лечение и профилактику инфекции посредством модулирования врожденного иммунитета

Also Published As

Publication number Publication date
CN1571667A (zh) 2005-01-26
US7335677B2 (en) 2008-02-26
ZA200402501B (en) 2005-01-13
NZ532048A (en) 2004-10-29
NO20042080L (no) 2004-07-16
WO2003035057A1 (en) 2003-05-01
IL161191A0 (en) 2004-08-31
GB0125445D0 (en) 2001-12-12
AU2002336190B2 (en) 2006-11-30
EP1446116A1 (en) 2004-08-18
KR20040047943A (ko) 2004-06-05
PL370220A1 (en) 2005-05-16
RU2345065C2 (ru) 2009-01-27
MXPA04003829A (es) 2004-07-16
JP2005511541A (ja) 2005-04-28
US20050043299A1 (en) 2005-02-24
US20080255126A1 (en) 2008-10-16
HUP0401738A2 (hu) 2004-12-28
CA2464254A1 (en) 2003-05-01

Similar Documents

Publication Publication Date Title
RU2004110719A (ru) Зздабиторы протеаз, расщепляющих за пролином
DE60114994D1 (de) Blutplättchen-adp-rezeptor-inhibitoren
MXPA02012034A (es) Derivados de tiofeno utiles como agentes anticancerosos.
EA200400432A1 (ru) Производные мочевины
NO20013367L (no) Colchinolderivater som vaskulorskadende midler
CY1111951T1 (el) Φαινυλο-καρβοξαμιδικες ενωσεις χρησιμες για την αντιμετωπιση πονου
BG66085B1 (bg) Фенилаланинови производни
WO2005056524A3 (en) Therapeutic agents useful for treating pain
MXPA05013587A (es) Agentes terapeuticos utiles para el tratamiento del dolor.
EA200100971A1 (ru) Новые соединения и композиции в качестве ингибиторов протеазы
MXPA03005464A (es) Agentes antivirales.
RS20050469A (en) Pyrrolopyrimidine derivatives
WO2005037860A3 (en) Inhibitors of serine proteases, particularly hcv ns3-ns4a protease
EA200501098A1 (ru) Антибактериальные агенты
LU91145I2 (fr) FIROCOXIB facultativement sous forme d'un sel pharmaceutiquement acceptable (PREVICOX).
TNSN04165A1 (en) Substituted hydroxyethylamines
WO2000049007A8 (en) Acetamido acetonitrile derivatives as inhibitors of cathepsin l and/or cathepsin s
HK1069339A1 (en) Substituted diketopiperazines as oxytocin antagonists
EA200100983A1 (ru) Производные 13-метилэритромицина
DK0715623T3 (da) Blodpladeaggregationsinhibitorer
ATE460394T1 (de) 5-asa-derivate mit entzündungshemmender und antibiotischer wirkung und verfahren zur behandlung von krankheiten mit diesen derivaten
WO2005030753A3 (en) Therapeutic agents useful for treating pain
RS50046B (sr) Farmaceutske kompozicije tizoksanida i nitazoksanida
ATE161017T1 (de) Inhibitoren gegen die aggregation von blutplättchen
DE69330601D1 (de) Serotoninergische ergolin derivate

Legal Events

Date Code Title Description
MM4A The patent is invalid due to non-payment of fees

Effective date: 20091024