WO1998027108A2 - Nouveaux composes amide - Google Patents
Nouveaux composes amide Download PDFInfo
- Publication number
- WO1998027108A2 WO1998027108A2 PCT/JP1997/004243 JP9704243W WO9827108A2 WO 1998027108 A2 WO1998027108 A2 WO 1998027108A2 JP 9704243 W JP9704243 W JP 9704243W WO 9827108 A2 WO9827108 A2 WO 9827108A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- preparation
- group
- phenyl
- alkyl
- nmr
- Prior art date
Links
- 0 C*C=C[C@](CC=C*)C(*1)=C(*)N=C1N Chemical compound C*C=C[C@](CC=C*)C(*1)=C(*)N=C1N 0.000 description 4
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/90—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
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- 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
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen 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
Definitions
- TECHNICAL FIELD This invention relates to new amide compounds and pharmaceutically acceptable salts thereof which are useful as medicament.
- This invention relates to new amide compounds.
- One object of this invention is to provide the new and useful amide compounds and pharmaceutically acceptable salts thereof which possess a strong inhibitory activity on the production of nitric oxide (NO).
- Another object of this invention is to provide a process for the preparation of the amide compounds and salts thereof.
- a further object of this invention is to provide a pharmaceutical composition comprising said amide compound or a pharmaceutically acceptable salt thereof.
- Still further object of this invention is to provide a use of said amide compounds or pharmaceutically acceptable salts thereof as a medicament for prophylactic and therapeutic treatment of NO-mediated diseases such as adult respiratory distress syndrome, cardiovascular ischemia, myocarditis, heart failure, synovitis, shock (e.g., septic shock, etc.), diabetes (e.g., insulin-dependent diabetes mellitus, etc.), diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, glomerulonephritis, peptic ulcer, inflammatory bowel disease (e.g., ulcerative colitis, chronic colitis, etc.), cerebral infarction, cerebral ischemia, cerebral hemorrhage, migraine, rheumatoid arthritis, gout, neuritis, postherpetic neuralgia, osteoarthritis, osteoporosis, systemic lupus erythematosus, rejection by organ transplantation, asthma, metastasis, Alzheimer's disease, arthritis, CNS disorders, derma
- R 1 is indolyl which may have a suitable substituent selected from the group consisting of lower alkyl, phenyl, halogen, lower alkoxy, and nitro, benzofuranyl, phenyl which may have one or two suitable substituent(s) selected from the group consisting of amino, acylamino, lower alkylamino, halogen, lower alkoxy and nitro, lower alkyl, quinoxalinyl, quinolyl, pyrrolyl, pyrimidinyl having benzofuranyl, benzimidazolyl, benzothienyl, benzothiazolyl, benzoxazolyl, indolinyl, anilino, phenylcarbaoyl or imidazolyl which may have one or two suitable substituent(s) selected from the group consisting of phenyl, lower alkyl and indolyl;
- R 2 is hydrogen or phenyl(lower)alkyl
- R* is hydrogen, phenyl or pyridyl, each of which may have suitable substituent(s) selected from the group consisting of lower alkyl, lower alkoxy, lower alkylthio, halogen, trihalomethyl, nitro, cyano, imidazolyl, optionally protected hydroxy, acyl, amino, acylamino, diacylamino, di(lower)alkylamino, amino(lower)alkyl, acylamino(lower)alkyl, pyrazolyl, morpholinyl, piperidyl, triazolyl, lower alkoxy(lower)alkoxy, hydroxy(lower)alkyl, lower alkylpiperazinyl, phenyl and carboxy, quinolyl or 3,4-methylenedioxyphenyl;
- R 5 is hydrogen, imidazolyl, phenyl, nitrophenyl, phenyl(lower)alkyl, optionally esterified carboxy or a group of the formula
- R 7 and R 8 are the same or different and each is hydrogen, phenyl, phenyl(lower)alkyl, lower alkyl or lower alkoxy; or
- Y is a group of the formula
- R 3 is hydrogen or a group of the formula -(CH 2 ) consult-R 6 in which R 6 is optionally protected hydroxy, acyl, carboxy, acylamino, lower alkoxy, phenyl(lower)alkoxy, lower alkylthio, phenyl which may have a suitable substituent selected from the group consisting of lower alkoxy, halogen, amino, acylamino, diacylamino and nitro, pyridyl which may have a suitable substituent selected from the group consisting of lower alkoxy and halogen, pyrazinyl, pyrimidinyl, furyl, imidazolyl, naphthyl, N-(lower)- alkylindolyl or 3,4-methylenedioxyphenyl, and n is an integer of 0 to 3, or a group of the formula
- R 11 is phenyl, phenoxy or phenyl(lower)alkoxy; or R 2 and R 3 in combination form a group of the formula
- R 1 ° is hydrogen, lower alkyl or lower alkoxy; or a pharmaceutically acceptable salt thereof, provided that the compound shown below is excluded: a compound of the formula
- R 1 ' is indolyl or benzofuranyl
- R 2 ' is hydrogen, lower alkylthio(lower)alkyl or a group of the formula
- R 5 ' is hydrogen, lower alkoxy or halogen
- R 3 ' is hydrogen, quinolyl or phenyl which may have a suitable substituent selected from the group consisting of lower alkyl, lower alkoxy, lower alkylthio and halogen
- R*' is hydrogen or optionally esterified carboxy
- X' is S or NR 6 ' in which R 6 ' is hydrogen, lower alkyl or a group of the formula - CH2 - ⁇ JT
- R 7 ' is lower alkyl or lower alkoxy, and a pharmaceutically acceptable salt thereof.
- Suitable pharmaceutically acceptable salts of the object compound (I) are conventional non-toxic salts and include, for example, a salt with a base or an acid addition salt such as a salt with an inorganic base, for example, an alkali metal salt (e.g., sodium salt, potassium salt, etc.), an alkaline earth metal salt (e.g., calcium salt, magnesium salt, etc.), an ammonium salt; a salt with an organic base, for example, an organic amine salt (e.g., triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine salt, etc.); an inorganic acid addition salt (e.g., hydrochloride, hydrobromide, sulfate, phosphate, etc.
- an inorganic acid addition salt e.g., hydrochloride, hydrobromide, sulfate, phosphate, etc.
- an organic carboxylic or sulfonic acid addition salt e.g., formate, acetate, trifluoroacetate, maleate, tartrate, citrate, fumarate, methanesulfonate, benzenesulfonate, toluenesulfonate, etc.
- a salt with a basic or acidic amino acid e.g., arginine, aspartic acid, gultamic acid, etc.
- lower is used to intend a group having 1 to 6, preferably 1 to 4, carbon atom(s), unless otherwise provided.
- Suitable "lower alkoxy” and “lower alkoxy moiety" in the terms “lower alkoxy(lower)alkoxy” and “phenyl(lower) lkoxy” include, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, tert-pentyloxy and hexyloxy, in which more preferred one is Ci-C* alkoxy.
- Suitable "halogen” includes, for example, fluorine, bromine, chlorine and iodine.
- Optionally esterified carboxy includes carboxy and esterified carboxy. Suitable examples of said ester include lower alkyl ester (e.g., methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, tert-butyl ester, pentyl ester, tert-pentyl ester, hexyl ester, etc.); lower alkenyl ester (e.g., vinyl ester, allyl ester, etc.); lower alkynyl ester (e.g., ethynyl ester, propynyl ester, etc.); lower alkoxy(lower)alkyl ester (e.g., methoxymethyl ester, ethoxymethyl ester, isopropoxymethyl ester, 1 -methoxyethyl ester, 1 -ethoxyethyl ester, etc.); mono(or
- Suitable "trihalomethyl” includes, for example, trifluoromethyl, trichloromethyl and tribromomethyl, in which preferred one is trifluoromethyl.
- Suitable “amino protective group” includes, for example, acyl and conventional protective group such as mono(or di or tri)aryl(lower)- alkyl, for example, mono(or di or tri)phenyl(lower)alkyl (e.g., benzyl, trityl, etc.).
- acyl and “acyl moiety” in the terms “acylamino”, “diacylamino” and “acylamino(lower)alkyl” include, for example, carbamoyl which may be substituted by suitable substituent(s), aliphatic acyl group and acyl group containing an aromatic ring, which is referred to as aromatic acyl, or a heterocyclic ring, which is referred to as heterocyclic acyl.
- acyl which may be substituted by suitable substituent(s)
- substituent(s) includes a group of the formula
- R 12 and R 13 are the same or different and each is hydrogen, lower alkyl, phenyl which may have a suitable substituent selected from the group consisting of lower alkoxy and halogen, phenyl(lower)- alkyl, pyridyl, pyridyl(lower)alkyl or 3,4-methylenedioxyphenyl; aliphatic acyl such as lower alkanoyl which may be substituted by one to three halogen atoms (e.g., formyl, acetyl, propanoyl, butanoyl, 2- methylpropanoyl, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, trichloroacetyl, trifluoroacetyl, etc.), lower alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, tert- pentyl
- naphthyl(lower)alkanoyl e.g., naphthylacetyl, naphthylpropanoyl, naphthylbutanoyl, etc.
- aryl(lower)alkoxycarbonyl e.g., phenyl(lower)alkoxycarbonyl (e.g., benzyloxycarbonyl, etc.), etc.
- aryloxycarbonyl e.g., phenoxycarbonyl, naphthyloxycarbonyl, etc.
- aryloxy(lower)alkanoyl e.g., phenoxyacetyl, phenoxypropionyl, etc.
- arylsulfonyl e.g., phenylsulfonyl, p-tolylsufonyl, etc.
- heterocyclic acyl such as indolylcarbonyl (e.g., indolylcarbon
- Optionally protected hydroxy includes hydroxy and protected hydroxy.
- Suitable examples of "hydroxy protective group" in the term “protected hydroxy” include acyl (e.g., acetyl, trichloroacetyl, etc.), mono(or di or tri)phenyl(lower)alkyl which may have one or more suitable substituent(s) (e.g., benzyl, 4-methoxybenzyl, trityl, etc.), trisubstituted silyl [e.g., tri(lower)alkylsilyl (e.g., trimethylsilyl, tert-butyldimethylsilyl, etc.), etc.], tetrahydropyranyl and the like.
- acyl e.g., acetyl, trichloroacetyl, etc.
- mono(or di or tri)phenyl(lower)alkyl which may have one or more suitable substituent(s) (
- Suitable "protected carboxy” is carboxy group protected by conventional protective group such as lower alkoxycarbonyl [e.g., methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, sec-butoxycarbonyl, isobutoxycarbonyl, tert- butoxycarbonyl, pentyloxycarbonyl, neopentyloxycarbonyl, hexyloxycarbonyl, etc.], optionally substituted phenyl(lower)- alkoxycarbonyl for example, mono- or di- or triphenyl(lower)- alkoxycarbonyl which may be substituted by nitro [e.g., benzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, benzhydryloxycarbonyl, trityloxycarbonyl, etc.] and the like.
- lower alkoxycarbonyl e.g., methoxycarbonyl,
- Suitable "cyclo(lower)alkyl” includes cycloalkyl having 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, in which more preferred ones are cyclopropyl and cyclobutyl.
- morpholinyl includes 2-morpholinyl, 3-morpholinyl and 4-morpholinyl (i.e. morpholino).
- piperidyl includes 1 -piperidyl (i.e. piperidino), 2- piperidyl, 3-piperidyl and 4-piperidyl.
- the object compound (I) of the present invention can be prepared by the following processes.
- R 1 , R 2 , R ft , R 5 , R 7 , R 8 , R 9 , X, Y, m and n are each as l 7 defined above,
- R 1 * is amino protective group
- R 15 is hydrogen or lower alkyl
- R 16 is acyl
- R 1 is acylamino or diacylamino
- R 18 is carboxy or lower alkoxycarbonyl
- R 19 is esterified carboxy
- R 20 is acylamino or diacylamino
- R 21 is carbamoyl which may be substituted by suitable substituent(s)
- R 22 is hydroxy protective group
- R 23 is acyl
- R 2 * is lower alkyl
- R 25 is protected carboxy
- R 26 is esterified carboxy
- R 27 is carbamoyl which may be substituted by suitable substituent(s)
- R 28 is acylamino or diacylamino
- R 29 is acyl
- R 30 is esterified carboxy.
- the starting compounds can be prepared by the method of Preparation mentioned below or by a process known in the art for preparing their structually analogous compounds.
- the compound (I) or a salt thereof can be prepared by reacting the compound (II) or its reactive derivative at the amino group, or a salt thereof with the compound (III) or its reactive derivative at the
- Suitable reactive derivative of the compound (II) includes Schiff's base type imino or its tautomeric enamine type isomer formed by the reaction of the compound (II) with a carbonyl compound such as aldehyde, ketone or the like; a silyl derivative formed by the reaction of the compound (II) with a silyl compound such as N,0- bis(trimethylsilyl)acetamide, N-trimethylsilylacetamide or the like; a derivative formed by the reaction of the compound (II) with phosphorus trichloride or phosgene.
- Suitable reactive derivative of the compound (III) includes an acid halide, an acid anhydride and an activated ester.
- the suitable example may be an acid chloride; an acid azide; a mixed acid anhydride with an acid such as substituted phosphoric acid (e.g., dialkylphosphoric acid, phenylphosphoric acid, diphenylphosphoric acid, dibenzylphosphoric acid, halogenated phosphoric acid, etc.), dialkylphosphorous acid, sulfurous acid, thiosulfuric acid, alkanesulfonic acid (e.g., methanesulfonic acid, ethanesulfonic acid, etc.), sulfuric acid, alkylcarbonic acid, aliphatic carboxylic acid (e.g., pivalic acid, pentanoic acid, isopentanoic acid, 2-ethylbutyric acid, trichloroacetic acid, etc.); aromatic carboxylic acid (e.g., benzoic acid, etc.
- the reaction is usually carried out in a conventional solvent such as water, acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N,N- dimethylformamide, pyridine or any other organic solvents which do not adversely affect the reaction, or the mixture thereof.
- a conventional solvent such as water, acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N,N- dimethylformamide, pyridine or any other organic solvents which do not adversely affect the reaction, or the mixture thereof.
- the reaction is preferably carried out in the presence of a conventional condensing agent such as N,N'- dicyclohexylcarbodiimide; N-cyclohexyl-N' -morpholinoethylcarbodiimide; N-cyclohexyl-N' -(4-diethylaminocyclohexyl)carbodiimide; N,N' - diisopropylcarbodiimide; N-ethyl-N' -(3-dimethylaminopropyl)- carbodiimide; N,N-carbonyl-bis-(2-methylimidazole) ; pentamethylene- ketene-N-cyclohexylimine; diphenylketene-N-cyclohexylimine; ethoxyacetylene; 1 -alkoxy-1 -chloroethylene; trialkyl pho
- the reaction may also be carried out in the presence of an organic or inorganic base such as an alkali metal bicarbonate, tri(lower)alkylamine, pyridine, N-(lower)alkylmorpholine, N,N- di(lower)alkylbenzylamine, or the like.
- an organic or inorganic base such as an alkali metal bicarbonate, tri(lower)alkylamine, pyridine, N-(lower)alkylmorpholine, N,N- di(lower)alkylbenzylamine, or the like.
- the reaction temperature is not critical, and the reaction is usually carried out under cooling to heating.
- the compound (I)-1 or a salt thereof can be prepared by reacting the compound (II) or a salt thereof with the compound (IV).
- the reaction can be carried out in the same manner as in or a manner similar to Example 27.
- the compound (I)-2 or a salt thereof can be prepared by subjecting the compound (V) or a salt thereof to elimination reaction of the amino protective group.
- Suitable method of this elimination reaction includes conventional one such as hydrolysis, reduction and the like, (i) For hydrolysis :
- the hydrolysis is preferably carried out in the presence of a base or an acid including Lewis acid.
- Suitable base includes an inorganic base and an organic base such as an alkali metal [e.g., sodium, potassium, etc.], an alkaline earth metal [e.g., magnesium, calcium, etc.], the hydroxide or carbonate or hydrogencarbonate thereof, trialkylamine [e.g., trimethylamine, triethylamine, etc.], picoline, 1 ,5-diazabicyclo[ .3.0]non-5-one, or the like.
- an alkali metal e.g., sodium, potassium, etc.
- an alkaline earth metal e.g., magnesium, calcium, etc.
- trialkylamine e.g., trimethylamine, triethylamine, etc.
- picoline 1 ,5-diazabicyclo[ .3.0]non-5-one, or the like.
- Suitable acid includes an organic acid [e.g., formic acid, acetic acid, propionic acid, trichloroacetic acid, trifluoroacetic acid, etc.], and an inorganic acid [e.g. , hydrochloric acid, hydrobromic acid, sulfuric acid, hydrogen chloride, hydrogen bromide, etc.].
- organic acid e.g., formic acid, acetic acid, propionic acid, trichloroacetic acid, trifluoroacetic acid, etc.
- an inorganic acid e.g. , hydrochloric acid, hydrobromic acid, sulfuric acid, hydrogen chloride, hydrogen bromide, etc.
- Lewis acid such as trihaloacetic acid [e.g., trichloroacetic acid, trifluoroacetic acid, etc.], or the like is preferably carried out in the presence of cation trapping agents [e.g., anisole, phenol, etc.]. This reaction is usually carried out without solvent.
- the reaction may be carried out in a conventional solvent such as water, alcohol (e.g., methanol, ethanol, isopropyl alcohol, etc.), tetrahydrofuran, dioxane, toluene, methylene chloride, ethylene dichloride, chloroform, N,N-dimethylformamide, N,N-dimethylacetamide or any other organic solvents which do not adversely affect the reaction, or a mixture thereof.
- a conventional solvent such as water, alcohol (e.g., methanol, ethanol, isopropyl alcohol, etc.), tetrahydrofuran, dioxane, toluene, methylene chloride, ethylene dichloride, chloroform, N,N-dimethylformamide, N,N-dimethylacetamide or any other organic solvents which do not adversely affect the reaction, or a mixture thereof.
- reaction temperature is not critical and the reaction is usually carried out under cooling to warming, (ii) For reduction :
- Reduction is carried out in a conventional manner, including chemical reduction and catalytic reduction.
- Suitable reducing reagent to be used in chemical reduction are hydrides (e.g., hydrogen iodide, hydrogen sulfide, lithium aluminum hydride, sodium borohydride, sodium cyanoborohydride, etc.), or a combination of a metal (e.g., tin, zinc, iron, etc.) or metallic compound (e.g., chromium chloride, chromium acetate, etc.) and an organic acid or inorganic acid (e.g., formic acid, acetic acid, propionic acid, trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid, hydrobromic acid, etc.).
- a metal e.g., tin, zinc, iron, etc.
- metallic compound e.g., chromium chloride, chromium acetate, etc.
- organic acid or inorganic acid e.g., formic acid, acetic acid, propionic acid,
- Suitable catalysts to be used in catalytic reduction are conventional ones such as platinum catalysts (e.g., platinum plate, spongy platinum, platinum black, colloidal platinum, platinum oxide, platinum wire, etc.), palladium catalysts (e.g., spongy palladium, palladium black, palladium oxide, palladium on carbon, palladium hydroxide on carbon, colloidal palladium, palladium on barium sulfate, palladium on barium carbonate, etc.
- platinum catalysts e.g., platinum plate, spongy platinum, platinum black, colloidal platinum, platinum oxide, platinum wire, etc.
- palladium catalysts e.g., spongy palladium, palladium black, palladium oxide, palladium on carbon, palladium hydroxide on carbon, colloidal palladium, palladium on barium sulfate, palladium on barium carbonate, etc.
- nickel catalysts e.g., reduced nickel, nickel oxide, Raney nickel, etc.
- cobalt catalysts e.g., reduced cobalt, Raney cobalt, etc.
- iron catalysts e.g., reduced iron, Raney iron, Ullman iron, etc.
- the reduction is usually carried out in a conventional solvent such as water, alcohol (e.g., methanol, ethanol, isopropyl alcohol, etc.), tetrahydrofuran, dioxane, toluene, methylene chloride, ethylene dichloride, chloroform, N,N-dimethylformamide, N,N-dimethylacetamide or any other organic solvents which do not adversely affect the reaction, or a mixture thereof.
- a solvent such as water, alcohol (e.g., methanol, ethanol, isopropyl alcohol, etc.), tetrahydrofuran, dioxane, toluene, methylene chloride, ethylene dichloride, chloroform, N,N-dimethylformamide, N,N-dimethylacetamide or any other organic solvents which do not adversely affect the reaction, or a mixture thereof.
- alcohol e.g., methanol, ethanol, isopropyl alcohol, etc.
- reaction temperature of this reduction is not critical and the reaction is usually carried out under cooling to warming.
- the compound (I)-4 or a salt thereof can be prepared by reacting the compound (I) ⁇ 3 or its reactive derivative at the amino group, or a salt thereof with the compound (VI) or its reactive derivative at the carboxy group, or a salt thereof.
- This reaction can be carried out in a similar manner to the reaction in the aforementioned Process (1 ) , and therefore the reagents to be used and the reaction conditions (e.g., solvent, reaction temperature, etc.) can be referred to those of the Process ⁇ .
- the reaction conditions e.g., solvent, reaction temperature, etc.
- the compound (I)-6 or a salt thereof can be prepared by subjecting the compound (I)-5 or a salt thereof to reduction.
- the reduction can be carried out in the same manner as in or a manner similar to Example 60.
- the compound (I)-7 or a salt thereof can be prepared by subjecting the compound (I)-6 or a salt thereof to acylation.
- the acylation can be carried out in the same manner as in or a manner similar to Example 61.
- the compound (I)-9 or a salt thereof can be prepared by subjecting the compound (I)-8 or a salt thereof to reduction.
- the reduction can be carried out in the same manner as in or a manner similar to Example 111.
- the compound (I)-10 or a salt thereof can be prepared by subjecting the compound (I)-9 or a salt thereof to oxidation.
- the oxidation can be carried out in the same manner as in or a manner similar to Example 112.
- the compound (I)-12 or a salt thereof can be prepared by subjecting the compound (I)-11 or a salt thereof to hydrolysis.
- the hydrolysis can be carried out in the same manner as in or a manner similar to Example 113.
- the compound (I)-14 or a salt thereof can be prepared by subjecting the compound (I)-13 or a salt thereof to reduction.
- the reduction can be carried out in the same manner as in or a manner similar to Example 123.
- the compound (I)-15 or a salt thereof can be prepared by subjecting the compound (I)-14 or a salt thereof to acylation.
- the acylation can be carried out in the same manner as in or a manner similar to Example 124.
- the compound (I)-16 or a salt thereof can be prepared by subjecting the compound (I)-12 or a salt thereof to amidation.
- the compound (I)-18 or a salt thereof can be prepared by subjecting the compound (I)-17 or a salt thereof to elimination reaction of the hydroxy protective group.
- This reaction can be carried out in a similar manner to the reaction in the aforementioned Process (3) , and therefore the reagents to be used and the reaction conditions (e.g., solvent, reaction temperature, etc. ) can be referred to those of the Process (3).
- the reaction conditions e.g., solvent, reaction temperature, etc.
- the compound (I)-19 or a salt thereof can be prepared by subjecting the compound (I)-18 or a salt thereof to esterification.
- the esterification can be carried out in the same manner as in or a manner similar to Example 133.
- the compound (I)-20 or a salt thereof can be prepared by subjecting the compound (I)-18 or a salt thereof to 0-alkylation.
- the 0-alkylation can be carried out in the same manner as in or a manner similar to Example 135.
- the compound (I)-22 or a salt thereof can be prepared by subjecting the compound (I)-21 or a salt thereof to elimination reaction of the carboxy protective group.
- This reaction can be carried out in a similar manner to the reaction in the aforementioned Process (3) , and therefore the reagents to be used and the reaction conditions (e.g., solvent, reaction temperature, etc.) can be referred to those of the Process (3).
- the reaction conditions e.g., solvent, reaction temperature, etc.
- the compound (I)-23 or a salt thereof can be prepared by subjecting the compound (I)-22 or a salt thereof to esterification.
- the esterification can be carried out in the same manner as in or a manner similar to Example 74.
- the compound (I)-24 or a salt thereof can be prepared by subjecting the compound (I)-22 or a salt thereof to amidation.
- the amidation can be carried out in the same manner as in or a manner similar to Example 95.
- the compound (I)-26 or a salt thereof can be prepared by subjecting the compound (I)-25 or a salt thereof to reduction.
- the reduction can be carried out in the same manner as in or a manner similar to Example 119.
- the compound (I)-27 or a salt thereof can be prepared by subjecting the compound (I)-26 or a salt thereof to acylation.
- the acylation can be carried out in the same manner as in or a manner similar to Example 120.
- the compound (I)-29 or a salt thereof can be prepared by subjecting the compound (I)-28 or a salt thereof to esterification.
- the esterification can be carried out in the same manner as in or a manner similar to Example 138.
- the compound (I)-31 or a salt thereof can be prepared by subjecting the compound (I)-30 or a salt thereof to hydrolysis.
- the hydrolysis can be carried out in the same manner as in or a manner similar to Example 168.
- the compound (I)-32 or a salt thereof can be prepared by reacting the compound (I)-31 or its reactive derivative at the carboxy group, or a salt thereof with the compound (VII) or its reactive derivative at the amino group, or a salt thereof.
- This reaction can be carried out in a similar manner to the reaction in the aforementioned Process (1 ) , and therefore the reagents to be used and the reaction conditions (e.g., solvent, reaction temperature, etc.) can be referred to those of the Process
- the compound (I)-33 can be prepared by reacting the compound (VIII) with the compound (IX) in the presence of an acid.
- This reaction can be carried out in the same manner as in or a manner similar to Example 178.
- Suitable salts of the starting compounds and their reactive derivatives in Process (1) can be referred to the ones as exemplified for the compound (I).
- the compounds obtained by the above process can be isolated and purified by a conventional method such as pulverization, recrystallization, column chromatography, reprecipitation, or the like.
- the compound (I) and the other compounds may include one or more stereoisomer(s) such as optical isomer(s) and geometrical isomer(s) due to asymmetric carbon atom(s) and double bond(s), and all of such isomers and mixtures thereof are included within the scope of this invention.
- the object compounds (I) and pharmaceutically acceptable salts thereof include solvates [e.g., enclosure compounds (e.g., hydrate, etc.)].
- the object compounds (I) and pharmaceutically acceptable salts thereof possess a strong inhibitory activity on the production of nitric oxide (NO).
- the object compounds (I) and pharmaceutically acceptable salts thereof are expected to possess a nitric oxide synthase (NOS)-inhibitory activity or a NOS-production inhibitory activity.
- NOS nitric oxide synthase
- NO-mediated diseases such as adult respiratory distress syndrome, cardiovascular ischemia, myocarditis, heart failure, synovitis, shock (e.g., septic shock, etc.), diabetes (e.g., insulin-dependent diabetes mellitus, etc.), diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, glomerulonephritis, peptic ulcer, inflammatory bowel disease (e.g., ulcerative colitis, chronic colitis, etc.), cerebral infarction, cerebral ischemia, cerebral hemorrhage, migraine, rheumatoid arthritis, gout, neuritis, postherpetic neuralgia, osteoarthritis, osteoporosis, systemic lupus erythematosus, rejection by organ transplantation, asthma, metastasis, Alzheimer's disease, arthritis, CNS disorders, dermatitis, hepatitis, liver cirrhosis, multiple sclerosis, pancrea
- test Compounds In order to illustrate the usefulness of the object compound (I) , the pharmacological test result of the representative compound of the compound (I) is shown in the following. Test Compounds :
- RAW264.7 American Type Culture Collection, No. TTB71
- DMEM Dulbecco's modified Eagle's medium
- penicillin, streptomycin and 10$ heat-inactivated fetal bovine serum were removed from culture flasks by rubber cell scraper and were centrifuged and resuspended in DMEM without phenol red. They were plated in 96-well microtiter plates (10 5 cells per well) and allowed to adhere over 2 hours.
- test samples were added and the cells were preincubated for 1 hour. Thereafter the cells were activated with both of lipopolysaccharide (LPS) (1/zg/ml) and interferon ⁇ (INF ) (3 u/ml) for 18-24 hours.
- LPS lipopolysaccharide
- INF interferon ⁇
- An equal volume of Griess reagent ( ] % sulfanilamide/0.1/ ⁇ N-naphthylethylenediamine dihydrochloride/2.5% H3PO1*) was added and the cells were incubated at room temperature for 10 minutes. The absorbance was read at 570 nm using microplate reader and NO ⁇ " was measured using NaNO ⁇ as a standard.
- the object compound (I) of the present invention and pharmaceutically acceptable salts thereof are used in the form of a conventional pharmaceutical preparation in admixture with a conventional pharmaceutically acceptable carrier such as an organic or inorganic solid or liquid excipient which is suitable for oral, parenteral or external administration.
- a conventional pharmaceutically acceptable carrier such as an organic or inorganic solid or liquid excipient which is suitable for oral, parenteral or external administration.
- the pharmaceutical preparation may be compounded in a solid form such as granule, capsule, tablet, dragee, suppository or ointment, or in a liquid form such as solution, suspension or emulsion for injection, intravenous drip, ingestion, eye drop, etc.
- auxiliary substance such as stabilizing agent, wetting or emulsifying agent, buffer or any other commonly used additives.
- the effective ingredient may usually be administered in a unit dose of 0.001 mg/kg to 500 mg/kg, preferably 0.01 mg/kg to 10 mg/kg, 1 to 4 times a day.
- the above dosage may be increased or decreased according to age, body weight and conditions of the patient or administering method.
- R 1 is indolyl which may have a suitable substituent selected from the group consisting of lower alkyl, phenyl, halogen, lower alkoxy, and nitro, benzofuranyl, phenyl which may have one or two
- R 2 is hydrogen or phenyl(lower)alkyl
- R* is phenyl or pyridyl, each of which has suitable substituent(s) selected from the group consisting of trihalomethyl, nitro, cyano, imidazolyl, optionally protected hydroxy, acyl, amino, acylamino, diacylamino, di(lower)alkylamino, amino(lower)alkyl, acylamino(lower)alkyl, pyrazoly1, morpholinyl, piperidyl, triazolyl, lower alkoxy(lower)alkoxy, hydroxy(lower)alkyl, lower alkylpiperazinyl, phenyl and carboxy, or 3, -methylenedioxyphenyl;
- R 5 is hydrogen, imidazolyl, phenyl, nitrophenyl, phenyl(lower)alkyl, optionally esterified carboxy or a group of the formula
- R 7 and R 8 are the same or different and each is hydrogen, phenyl, phenyl(lower)alkyl, lower alkyl or lower alkoxy; or
- Y is a group of the formula
- R 6 is optionally protected hydroxy, acyl, carboxy, acylamino, lower alkoxy, phenyl(lower) lkoxy, lower alkylthio, phenyl which may have a suitable substituent selected from the group consisting of lower alkoxy, halogen, amino, acylamino, diacylamino and nitro, pyridyl which may have a suitable substituent selected from the group consisting of lower alkoxy and halogen, pyrazinyl, pyrimidinyl, furyl, imidazolyl, naphthyl, N-(lower)- alkylindolyl or 3,4-methylenedioxyphenyl, and n is an integer of 0 to 3, or a group of the formula
- R 1 ' is phenyl, phenoxy or phenyl(lower)alkoxy; or R 2 and R 3 in combination form a group of the formula
- R 1 ° is hydrogen, lower alkyl or lower alkoxy; or a pharmaceutically acceptable salt thereof.
- R 1 is indolyl which has a suitable substituent selected from the group consisting of lower alkyl, phenyl, halogen, lower alkoxy, and nitro, phenyl which may have one or two suitable substituent(s) selected from the group consisting of amino, acylamino, lower alkylamino, halogen, lower alkoxy and nitro, lower alkyl, quinoxalinyl, quinolyl, pyrrolyl, pyrimidinyl having benzofuranyl, benzimidazolyl, benzothienyl, benzothiazolyl, benzoxazolyl, indolinyl, anilino, phenylcarbamoyl or imidazolyl which may have one or two suitable substituent(s) selected from the group consisting of phenyl, lower alkyl and indolyl;
- R 2 is hydrogen or phenyl(lower)alkyl
- R ft is hydrogen, phenyl or pyridyl, each of which may have suitable substituent(s) selected from the group consisting of lower alkyl, lower alkoxy, lower alkylthio and halogen or quinolyl;
- R 5 is hydrogen, imidazolyl, phenyl, nitrophenyl, phenyl(lower)alkyl, optionally esterified carboxy or a group of the formula
- R 7 and R 8 are the same or different and each is hydrogen, phenyl, phenyl(lower)alkyl, lower alkyl or lower alkoxy; or
- Y is a group of the formula
- R 6 is optionally protected hydroxy, acyl, carboxy, acylamino, lower alkoxy, phenyl(lower)alkoxy, lower alkylthio, phenyl which may have a suitable substituent selected from the group consisting of lower alkoxy, halogen, amino, acylamino, diacylamino and nitro, pyridyl which may have a suitable substituent selected from the group consisting of lower alkoxy and halogen, pyrazinyl, pyrimidinyl, furyl, imidazolyl, naphthyl, N-(lower)- alkylindolyl or 3,4-methylenedioxyphenyl, and n is an integer of 0 to 3, or a group of the formula
- R 1 ' is phenyl, phenoxy or phenyl(lower)alkoxy; or R 2 and R 3 in combination form a group of the formula
- R 1 ° is hydrogen, lower alkyl or lower alkoxy; or a pharmaceutically acceptable salt thereof.
- R 1 is indolyl or benzofuranyl
- R 2 is hydrogen or phenyl(lower) lkyl
- R* is hydrogen, phenyl or pyridyl, each of which may have suitable substituent(s) selected from the group consisting of lower alkyl, lower alkoxy, lower alkylthio and halogen or quinolyl;
- R 5 is hydrogen, imidazolyl, phenyl, nitrophenyl, phenyl(lower)alkyl, optionally esterified carboxy or a group of the formula
- R 7 and R 8 are the same or different and each is hydrogen, phenyl, phenyl(lower)alkyl, lower alkyl or lower alkoxy; or
- Y is a group of the formula
- R 3 is a group of the formula in which R 6 is optionally protected hydroxy, acyl, carboxy, acylamino, lower alkoxy, phenyl(lower)alkoxy, phenyl which has a suitable substituent selected from the group consisting of amino, acylamino, diacylamino and nitro, pyridyl which may have a suitable substituent selected from the group consisting of lower alkoxy and halogen, pyrazinyl, pyrimidinyl, furyl, imidazolyl, naphthyl, N-(lower)- alkylindolyl or 3,4-methylenedioxyphenyl, and n is an integer of 0 to 3, or a group of the formula
- R 11 is phenyl, phenoxy or phenyl(lower)alkoxy; or R 2 and R 3 in combination form a group of the formula
- R 1 ° is hydrogen, lower alkyl or lower alkoxy; or a pharmaceutically acceptable salt thereof.
- R 1 is indolyl which may have a suitable substituent selected from the group consisting of lower alkyl, phenyl, halogen, lower alkoxy, and nitro or benzofuranyl;
- R 2 is hydrogen
- R" is phenyl which may have suitable substituent(s) selected from the group consisting of trihalomethyl, nitro, cyano, imidazolyl, optionally protected hydroxy, acyl, amino, acylamino, diacylamino, di(lower)alkylamino, amino(lower)alkyl, acylamino(lower)alkyl, pyrazolyl, morpholinyl, piperidyl, triazolyl, lower alkoxy(lower)alkoxy, hydroxy(lower)alkyl, lower alkylpiperazinyl, phenyl and carboxy;
- R 5 is hydrogen
- Y is a group of the formula
- R 6 is pyridyl which may have a suitable substituent selected from the group consisting of lower alkoxy and halogen, and n is an integer of 0 to 3; m is 0 or 1 ; and X is NR 9 in which R 9 is hydrogen, lower alkyl, cyclo(lower)alkyl or a group of the formula
- R 1 ° is hydrogen, lower alkyl or lower alkoxy; or a pharmaceutically acceptable salt thereof.
- the starting compound (430 mg) was dissolved in trifluoroacetic acid (1.5 ml) and the mixture was stirred at room temperature for 1 hour. The mixture was concentrated, made basic with 1N sodium hydroxide solution and extracted three times with chloroform. The organic layer was dried over magnesium sulfate and filtered. Evaporation of the solvent gave the object compound as an oil (314 mg).
- the starting compound (600 mg) was heated at 40°C for 2 hours in methyl iodide (10 ml). The reaction mixture was evaporated, and the residue was suspended in an aqueous sodium carbonate solution. The mixture was extracted with chloroform. The organic layer was washed successively with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel with a chloroform-methanol (20:1) as eluent to give the object compound as a pale yellow oily solid (376.5 mg). mp : 116-119°C MASS (ESI) (m/z) : 302 (M+H) +
- the object compound was obtained according to a similar manner to that of Preparation 3 except that a mixutre of trifluoroacetic acid and dichloromethane was used instead of trifluoroacetic acid.
- MASS 322 (M+1)
- the object compound was obtained according to a similar manner to that of Preparation 5.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- the object compound was obtained according to a similar manner to that of Preparation 5.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- the object compound was obtained according to a similar manner to that of Preparation 5.
- the object compound was obtained according to a similar manner to that of Preparation 5.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- a solution of potassium tert-butoxide (4.2 g) in anhydrous tetrahydrofuran (70 ml) was cooled under nitrogen atmosphere to -70°C, and a solution of the starting compound (10 g) in anhydrous tetrahydrofuran (35 ml) was added while maintaining the reaction temperature at -70°C. After 30 minutes, this solution was added dropwise to a solution of 4-bromobenzoyl chloride (8.21 g) in anhydrous tetrahydrofuran (24 ml) with stirring while cooling at -70°C on a cooling bath. The reaction mixture was stirred at -70°C for 1 hour and quenched with 3N-hydrochloric acid (100 ml).
- the cooling bath was removed and the reaction mixture was concentrated to dryness under reduced pressure.
- the residue was dissolved in water (15 ml) and extracted with diethyl ether (twice).
- the aqueous layer was concentrated in vaciio , and the residue was dissolved in anhydrous methanol.
- the precipitated white solid (KCl) was removed by filtration.
- the object compound was obtained according to a similar manner to that of Preparation 5.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- the object compound was obtained according to a similar manner to that of Preparation 5.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- the object compound was obtained according to a similar manner to that of Preparation 5.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- the object compound was obtained according to a similar manner to that of Preparation 5.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- the object compound was obtained according to a similar manner to that of Preparation 5.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- the object compound was obtained according to a similar manner to that of Preparation 91.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- the object compound was obtained according to a similar manner to that of Preparation 5.
- the object compound was obtained according to a similar manner to that of Preparation 2.
- the object compound was obtained according to a similar manner to that of Preparation 5 except that a mixture of dichloromethane and dimethylformamide was used instead of dichloromethane.
Abstract
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP52752898A JP2001505585A (ja) | 1996-12-16 | 1997-11-20 | 新規アミド化合物およびそれらの一酸化窒素シンターゼ阻害剤としての用途 |
AU49680/97A AU4968097A (en) | 1996-12-16 | 1997-11-20 | New amide compounds |
EP97912529A EP0946587A2 (fr) | 1996-12-16 | 1997-11-20 | Nouveaux composes amide |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AUPO4219 | 1996-12-16 | ||
AUPO4219A AUPO421996A0 (en) | 1996-12-16 | 1996-12-16 | New amide compounds |
AUPO5929A AUPO592997A0 (en) | 1997-04-01 | 1997-04-01 | New amide compounds |
AUPO5929 | 1997-04-01 | ||
AUPO9030A AUPO903097A0 (en) | 1997-09-09 | 1997-09-09 | New amide compounds |
AUPO9030 | 1997-09-09 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1998027108A2 true WO1998027108A2 (fr) | 1998-06-25 |
WO1998027108A3 WO1998027108A3 (fr) | 1998-07-30 |
Family
ID=27157969
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1997/004243 WO1998027108A2 (fr) | 1996-12-16 | 1997-11-20 | Nouveaux composes amide |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0946587A2 (fr) |
JP (1) | JP2001505585A (fr) |
WO (1) | WO1998027108A2 (fr) |
Cited By (84)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999051215A2 (fr) * | 1998-04-06 | 1999-10-14 | Fujisawa Pharmaceutical Co., Ltd. | Nouvelle utilisation |
WO1999054314A1 (fr) * | 1998-04-17 | 1999-10-28 | Boehringer Ingelheim Pharma Kg | Nouveaux heterocycles a 5 noyaux a substitution diphenyle, leur procede de preparation et leur utilisation comme medicaments |
WO1999057114A1 (fr) * | 1998-05-04 | 1999-11-11 | Fujisawa Pharmaceutical Co., Ltd. | Derives de carboxamide heterocycliques utilisees comme inhibiteurs de la production de monoxyde d'azote |
WO2000049015A1 (fr) * | 1999-02-17 | 2000-08-24 | Fujisawa Pharmaceutical Co., Ltd. | Composes pyridine et leur utilisation pharmaceutique |
WO2001002387A1 (fr) * | 1999-07-05 | 2001-01-11 | Fujisawa Pharmaceutical Co., Ltd. | N-imidazolylmethyl-carboxamides utilises comme inhibiteurs de la production d'oxyde nitrique |
WO2001026656A2 (fr) * | 1999-10-11 | 2001-04-19 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Derives d'heterocycles a 5 chainons et leur application comme inhibiteurs de monoamine oxydase |
FR2812546A1 (fr) * | 2000-08-01 | 2002-02-08 | Sod Conseils Rech Applic | Derives d'heterocycles a 5 chainons, leur preparation et leur application a titre de medicaments |
JP2002508323A (ja) * | 1997-12-17 | 2002-03-19 | メルク エンド カムパニー インコーポレーテッド | インテグリン受容体拮抗薬 |
WO2003074517A1 (fr) * | 2002-03-06 | 2003-09-12 | Astrazeneca Ab | Derives d'amido-indole possedant une activite d'inhibition de la glycogene phosphorylase |
JP2003528871A (ja) * | 2000-03-27 | 2003-09-30 | シエーリング アクチエンゲゼルシャフト | Nosインヒビターとしてのn−複素環式誘導体 |
EP1387680A1 (fr) * | 2001-03-05 | 2004-02-11 | TransTech Pharma Inc. | Agents th rapeutiques base de d riv s benzimidazole |
EP1444204A1 (fr) * | 2001-10-22 | 2004-08-11 | The Research Foundation Of State University Of New York | Inhibiteurs de proteines kinases et de proteines phosphatases, methodes d'identification et methodes d'utilisation associees |
JP2004531526A (ja) * | 2001-04-10 | 2004-10-14 | ソシエテ・ド・コンセイユ・ド・ルシエルシエ・エ・ダアツプリカーション・シヤンテイフイツク・(エス.セー.エール.アー.エス) | 5員複素間誘導体、その製造法及びその医薬としての使用 |
EP1487796A1 (fr) * | 2002-03-28 | 2004-12-22 | Neurogen Corporation | Biarylamides substitues en tant que modulateurs du recepteur c5a |
US6852725B1 (en) * | 1998-06-12 | 2005-02-08 | Societe De Conseils De Recherches Et D'applications Scientifiques, S. A. S. | Imidazolyl derivatives |
WO2006004924A2 (fr) * | 2004-06-28 | 2006-01-12 | Amgen Sf, Llc | Composes imidazolo, compositions et leurs methodes d'utilisation |
US7057051B2 (en) | 2001-07-20 | 2006-06-06 | Merck & Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
US7115648B2 (en) | 2002-03-06 | 2006-10-03 | Astrazeneca Ab | Indole-amide derivatives and their use as glycogen phosphorylase inhibitors |
US7122567B2 (en) | 2002-03-06 | 2006-10-17 | Astrazeneca Ab | Heterocyclic amide derivatives having glycogen phosphorylase inhibitory activity |
AU2002224797B2 (en) * | 2000-10-30 | 2006-10-26 | Janssen Pharmaceutica N.V. | Tripeptidyl peptidase inhibitors |
US7129249B2 (en) | 2002-03-06 | 2006-10-31 | Astrazeneca Ab | Heterocyclic amide derivatives as inhibitors of glycogen phoshorylase |
US7138415B2 (en) | 2002-03-06 | 2006-11-21 | Astrazeneca Ab | Indolamid derivatives which possess glycogenphosphorylase inhibitory activity |
US7148225B2 (en) | 2002-03-28 | 2006-12-12 | Neurogen Corporation | Substituted biaryl amides as C5A receptor modulators |
US7169927B2 (en) | 2002-03-06 | 2007-01-30 | Astrazeneca Ab | Indole-amide derivatives and their use as glycogen phosphorylase inhibitors |
WO2007052073A2 (fr) * | 2005-10-31 | 2007-05-10 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Derives d'amide de soufre et d'amide a heterocycle substitue utilises en tant qu'inhibiteurs d'histone desacetylase (hdac) |
US7241790B2 (en) * | 2002-07-30 | 2007-07-10 | University Of Virginia Patent Foundation | Compounds active in spinigosine 1-phosphate signaling |
WO2008011557A2 (fr) * | 2006-07-20 | 2008-01-24 | Borchardt Allen J | Inhibiteurs hétéroaryliques de la kinase rho |
KR100822085B1 (ko) * | 1999-10-11 | 2008-04-15 | 소시에떼 드 꽁세이으 드 르세르세 에 따블리까시옹 시앙띠피끄 (에스.세.에르.아.에스.) | 5-원 헤테로사이클 유도체, 이의 제조 방법 및의약으로서의 이의 용도 |
US7381736B2 (en) | 2004-09-02 | 2008-06-03 | Metabasis Therapeutics, Inc. | Thiazole and thiadiazole inhibitors of tyrosine phosphatases |
US7453002B2 (en) | 2004-06-15 | 2008-11-18 | Bristol-Myers Squibb Company | Five-membered heterocycles useful as serine protease inhibitors |
US7566734B2 (en) | 2000-08-01 | 2009-07-28 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. | Imidazolyl derivatives |
US7576221B2 (en) | 2004-06-18 | 2009-08-18 | Novartis Vaccines And Diagnostics, Inc. | Substituted imidazole derivatives |
US7626040B2 (en) | 2005-08-09 | 2009-12-01 | Novartis Vaccines And Diagnostics, Inc. | Substituted imidazole compounds as KSP inhibitors |
US7626039B2 (en) | 2005-12-14 | 2009-12-01 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, ayrlpropynamide, or arylmethylurea analogs as factor XIa inhibitors |
EP2188274A1 (fr) * | 2007-08-03 | 2010-05-26 | Boehringer Ingelheim International GmbH | Inhibiteurs de polymerase virale |
DE10332560B4 (de) * | 2003-07-11 | 2010-07-08 | Chiracon Gmbh | Verfahren zur Herstellung von ß- Heteroaryl-2-alanin-Verbindungen über 2-Amino-2-(heteroarylmethyl)-carbonsäure-Verbindungen |
US7772216B2 (en) | 2001-10-22 | 2010-08-10 | The Research Foundation Of State University Of New York | Protein kinase and phosphatase inhibitors and methods for designing them |
US7820646B2 (en) | 2007-01-05 | 2010-10-26 | Novartis Vaccines And Diagnostics, Inc. | Cyclized derivatives as Eg-5 inhibitors |
US7863294B2 (en) * | 2004-12-10 | 2011-01-04 | Instituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Heterocycle derivatives as histone deacetylase (HDAC) inhibitors |
US7884120B2 (en) | 2002-08-19 | 2011-02-08 | Lorus Therapeutics Inc. | 2,4,5-trisubstituted imidazoles and their use as anti-microbial agents |
US7901894B2 (en) | 1999-01-13 | 2011-03-08 | The Research Foundation Of State University Of New York | Kinase inhibitors |
WO2011084642A1 (fr) * | 2009-12-16 | 2011-07-14 | Neuropore Therapies, Inc. | Composé approprié pour le traitement de synucléopathies |
US8148392B2 (en) | 2005-05-25 | 2012-04-03 | Lorus Therapeutics Inc. | 2-indolyl imidazo [4,5-d] phenanthroline derivatives and their use in the treatment of cancer |
US8227462B2 (en) | 2008-09-10 | 2012-07-24 | Novartis Ag | Pyrrolidine-1,2-dicarboxamide derivatives |
US8293753B2 (en) | 2009-07-02 | 2012-10-23 | Novartis Ag | Substituted 2-carboxamide cycloamino ureas |
US8354397B2 (en) | 2001-07-27 | 2013-01-15 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
EP2546231A1 (fr) * | 2010-03-04 | 2013-01-16 | Ajinomoto Co., Inc. | Dérivé d'alkylamine |
US8404684B2 (en) | 2003-05-02 | 2013-03-26 | Novartis Ag | Inhibitors of phosphatidylinositol 3-kinase |
US8431575B2 (en) | 2010-02-18 | 2013-04-30 | Transtech Pharma, Inc. | Phenyl-heteroaryl derivatives and methods of use thereof |
US8476257B2 (en) | 2007-12-19 | 2013-07-02 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US8580833B2 (en) | 2009-09-30 | 2013-11-12 | Transtech Pharma, Inc. | Substituted imidazole derivatives and methods of use thereof |
US8940771B2 (en) | 2007-12-20 | 2015-01-27 | Novartis Ag | Organic compounds |
US8969372B2 (en) | 2003-11-14 | 2015-03-03 | Aptose Boisciences Inc. | Aryl imidazoles and their use as anti-cancer agents |
WO2015142001A3 (fr) * | 2014-03-21 | 2015-12-03 | 충남대학교산학협력단 | Composé doté d'une action cardiotonique et composition pharmaceutique permettant de prévenir ou de traiter l'insuffisance cardiaque et contenant ledit composé |
WO2016024587A1 (fr) * | 2014-08-13 | 2016-02-18 | 日本曹達株式会社 | Composé de diarylimidazole et agent de lutte antiparasitaire |
CN105473575A (zh) * | 2013-08-09 | 2016-04-06 | 埃科特莱茵药品有限公司 | 作为alx受体激动剂的苯并咪唑基-甲基脲衍生物 |
US9309247B2 (en) | 2013-03-20 | 2016-04-12 | Lorus Therapeutics Inc. | 2-substituted imidazo[4,5-D]phenanthroline derivatives and their use in the treatment of cancer |
WO2017104741A1 (fr) | 2015-12-16 | 2017-06-22 | 日本曹達株式会社 | Composé de type arylazole et agent de lutte contre les organismes nuisibles |
WO2017068089A3 (fr) * | 2015-10-23 | 2017-07-27 | Vifor (International) Ag | Nouveaux inhibiteurs de la ferroportine |
WO2018192973A1 (fr) | 2017-04-18 | 2018-10-25 | Vifor (International) Ag | Sels inhibiteurs de ferroportine |
US20190270729A1 (en) * | 2016-06-21 | 2019-09-05 | Shifa Biomedical Corporation | Anti-Proprotein Convertase Subtilisin Kexin Type 9 (Anti-PCSK9) Compounds and Methods of Using the Same in the Treatment and/or Prevention of Cardiovascular Diseases |
US10618916B2 (en) | 2018-05-11 | 2020-04-14 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US10669271B2 (en) | 2018-03-30 | 2020-06-02 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US10793565B2 (en) | 2016-12-22 | 2020-10-06 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US10800768B2 (en) | 2016-12-22 | 2020-10-13 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US10806785B2 (en) | 2016-12-22 | 2020-10-20 | Incyte Corporation | Immunomodulator compounds and methods of use |
US11104957B2 (en) | 2013-10-04 | 2021-08-31 | Aptose Biosciences, Inc. | Compositions and methods for treating cancers |
US11149047B2 (en) | 2017-10-30 | 2021-10-19 | Aptose Biosciences, Inc. | Aryl imidazoles for treatment of cancer |
CN113683598A (zh) * | 2020-05-18 | 2021-11-23 | 成都先导药物开发股份有限公司 | 一种免疫调节剂 |
US11401279B2 (en) | 2019-09-30 | 2022-08-02 | Incyte Corporation | Pyrido[3,2-d]pyrimidine compounds as immunomodulators |
US11407749B2 (en) | 2015-10-19 | 2022-08-09 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11465981B2 (en) | 2016-12-22 | 2022-10-11 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11535615B2 (en) | 2015-12-22 | 2022-12-27 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11572366B2 (en) | 2015-11-19 | 2023-02-07 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11608337B2 (en) | 2016-05-06 | 2023-03-21 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11613536B2 (en) | 2016-08-29 | 2023-03-28 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11673883B2 (en) | 2016-05-26 | 2023-06-13 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11718605B2 (en) | 2016-07-14 | 2023-08-08 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11753406B2 (en) | 2019-08-09 | 2023-09-12 | Incyte Corporation | Salts of a PD-1/PD-L1 inhibitor |
US11760756B2 (en) | 2020-11-06 | 2023-09-19 | Incyte Corporation | Crystalline form of a PD-1/PD-L1 inhibitor |
US11780836B2 (en) | 2020-11-06 | 2023-10-10 | Incyte Corporation | Process of preparing a PD-1/PD-L1 inhibitor |
US11866451B2 (en) | 2019-11-11 | 2024-01-09 | Incyte Corporation | Salts and crystalline forms of a PD-1/PD-L1 inhibitor |
US11866434B2 (en) | 2020-11-06 | 2024-01-09 | Incyte Corporation | Process for making a PD-1/PD-L1 inhibitor and salts and crystalline forms thereof |
US11873309B2 (en) | 2016-06-20 | 2024-01-16 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008521853A (ja) * | 2004-12-02 | 2008-06-26 | プロビオドルグ エージー | 神経疾患治療用の新規化合物 |
JP2008007405A (ja) * | 2004-12-07 | 2008-01-17 | Takeda Chem Ind Ltd | カルボキサミド誘導体 |
US8329159B2 (en) * | 2006-08-11 | 2012-12-11 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US7659270B2 (en) * | 2006-08-11 | 2010-02-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US7759495B2 (en) * | 2006-08-11 | 2010-07-20 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US7990335B2 (en) | 2007-12-05 | 2011-08-02 | Antennas Direct, Inc. | Antenna assemblies with antenna elements and reflectors |
US8093243B2 (en) * | 2008-02-12 | 2012-01-10 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
USD883265S1 (en) | 2008-02-29 | 2020-05-05 | Antennas Direct, Inc. | Antenna |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0491525A1 (fr) * | 1990-12-18 | 1992-06-24 | Eli Lilly And Company | Benzamides et sulfonamides comme agents hypoglycémiques |
WO1996016981A2 (fr) * | 1994-12-02 | 1996-06-06 | Fujisawa Pharmaceutical Co., Ltd. | Composes peptidiques pour la prevention et/ou le traitement de maladies induites par no |
-
1997
- 1997-11-20 EP EP97912529A patent/EP0946587A2/fr not_active Withdrawn
- 1997-11-20 WO PCT/JP1997/004243 patent/WO1998027108A2/fr not_active Application Discontinuation
- 1997-11-20 JP JP52752898A patent/JP2001505585A/ja active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0491525A1 (fr) * | 1990-12-18 | 1992-06-24 | Eli Lilly And Company | Benzamides et sulfonamides comme agents hypoglycémiques |
WO1996016981A2 (fr) * | 1994-12-02 | 1996-06-06 | Fujisawa Pharmaceutical Co., Ltd. | Composes peptidiques pour la prevention et/ou le traitement de maladies induites par no |
Non-Patent Citations (23)
Title |
---|
CHEMICAL ABSTRACTS, vol. 81, no. 7, 19 August 1974 Columbus, Ohio, US; abstract no. 37511r, HEINISCH G ET AL: "2-Dialkylaminoacylaminoimidazoles as potential local anesthetics." page 385; column 1; XP002057314 & SCI. PHARM., vol. 42, no. 1, 1974, pages 19-33, * |
CROSS D F W ET AL: "Peptides. Part XIV. Thiazoleamino-acids, Degradation Products of Thiostrepton." JOURNAL OF THE CHEMICAL SOCIETY., April 1963, LETCHWORTH GB, pages 2143-2150, XP002057308 * |
DATABASE CROSSFIRE Beilstein Informationssysteme GmbH Franfurt DE, XP002057315 & REV. ROUM. CHIM. , vol. 10, 1965, pages 617-620, * |
DATABASE CROSSFIRE Beilstein Informationssysteme GmbH Frankfurt DE, XP002057316 & STUD. UNIV. BABES-BOLYAI CHEM., vol. 1, 1960, page 155 * |
DATABASE CROSSFIRE Beilstein Informationssysteme GmbH Frankfurt DE, XP002057317 & AM. CHEM. J., vol. 47, 1912, pages 234-236, * |
DATABASE CROSSFIRE Beilstein Informationssysteme GmbH Frankfurt DE, XP002057318 & TETRAHEDRON., vol. 30, 1974, OXFORD GB, pages 3859-3864, * |
DATABASE CROSSFIRE Beilstein Informationssysteme GmbH Frankfurt DE, XP002057319 & ARCH. PHARM., vol. 312, 1979, pages 198-205, * |
DATABASE CROSSFIRE Beilstein Informationssysteme GmbH Frankfurt DE, XP002057320 & CHEM. HETEROCYCL. COMPD. (ENGL. TRANSL.), vol. 6, 1970, pages 486-488, * |
DATABASE CROSSFIRE Beilstein Informationssysteme GmbH Frankfurt DE, XP002057321 & CHEM. PHARM. BULL., vol. 17, 1969, page 2381 * |
DATABASE CROSSFIRE Beilstein Informationssysteme GmbH Frankfurt DE, XP002057322 & SYNTH. COMMUN., vol. 18, no. 7, 1988, pages 651-658, * |
DATABASE CROSSFIRE Beilstein Informationssysteme GmbH Frankfurt DE, XP002057323 & UKR. KHIM. ZH. (RUSS. ED.), vol. 21, 1955, pages 726-729, * |
GERBERT U ET AL: "Model reactions for enzymic catalysis. IV. Structure-activity relationship of new transaminators with imidazole, thiazole, and benzimidazole skeletons" JUSTUS LIEBIGS ANN. CHEM. , no. 4, 1974, pages 644-654, XP002057306 * |
GORDON T D ET AL: "Synthetic Approaches to the 'Azole' Peptide Mimetics" TETRAHEDRON LETTERS., vol. 34, no. 12, 19 March 1993, OXFORD GB, pages 1901-1904, XP002038851 * |
HAMADA Y ET AL: "New methods and reagents in organic synthesis. 67. A general synthesis of derivatives of optically pure 2-(1-aminoalkyl)thiazole-4 -carboxylic acids" J. ORG. CHEM. , vol. 52, no. 7, 3 April 1987, pages 1252-1255, XP002057304 * |
LI G ET AL: "Synthesis of a Directly Connected Thiazole-Oxazole Ring System Present in Microcin B17" J. ORG. CHEM. , vol. 61, no. 2, 26 January 1996, pages 778-780, XP002057303 * |
LIEBSCHER J ET AL: "Formylation Products of Thioamides; Part 12. Synthesis of Thiazoles by the Reaction of S-Alkylated Thioamides or Thioureas with Acid Derivatives" SYNTHESIS., no. 4, April 1985, STUTTGART DE, pages 414-417, XP002057313 * |
MOFFETT R B ET AL: "Antiulcer Agents. p-Aminobenzamido Aromatic Compounds" JOURNAL OF MEDICINAL CHEMISTRY., vol. 14, no. 10, October 1971, WASHINGTON US, pages 963-968, XP002057311 * |
NAIR V ET AL: "Regioselective [4+2] and [2+2] Cycloadditions of 1-Azirines to Heterocumulenes. Formation and Rearrangements of the Cycloadducts" JOURNAL OF ORGANIC CHEMISTRY., vol. 39, no. 25, 13 December 1974, EASTON US, pages 3763-3767, XP002057312 * |
PETTIT G R ET AL: "Antineoplastic agents. 109. Structural biochemistry. 24. Synthesis of the cyclo-Ä(gly)Thz-(R)- and (S)-(gln)Thz-L-Val-L-Leu-L -ProÜ isomers of dolastatin 3" J. ORG. CHEM. , vol. 50, no. 15, 26 July 1985, pages 2654-2659, XP002057305 * |
PYL T ET AL: "Zur Darstellung von 7-Benzoylamino-pyrrolo[2.1-bÜthiazolen" JUSTUS LIEBIGS ANNALEN DER CHEMIE., vol. 676, 1964, WEINHEIM DE, pages 141-150, XP002057309 * |
PYL T ET AL: "Zur Kenntnis der Imidazo[5.1-bÜthiazole" JUSTUS LIEBIGS ANNALEN DER CHEMIE., vol. 679, 1964, WEINHEIM DE, pages 144-150, XP002057310 * |
See also references of EP0946587A2 * |
SETO Y ET AL: "Unusual amino acids and their peptides. V. Synthesis and the absolute configuration of.beta.-(2-thiazolyl)-.beta.-alanine present in bottromycin" BULL. CHEM. SOC. JAP. , vol. 47, no. 1, January 1974, pages 151-155, XP002057307 * |
Cited By (172)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002508323A (ja) * | 1997-12-17 | 2002-03-19 | メルク エンド カムパニー インコーポレーテッド | インテグリン受容体拮抗薬 |
WO1999051215A3 (fr) * | 1998-04-06 | 2000-03-09 | Fujisawa Pharmaceutical Co | Nouvelle utilisation |
WO1999051215A2 (fr) * | 1998-04-06 | 1999-10-14 | Fujisawa Pharmaceutical Co., Ltd. | Nouvelle utilisation |
WO1999054314A1 (fr) * | 1998-04-17 | 1999-10-28 | Boehringer Ingelheim Pharma Kg | Nouveaux heterocycles a 5 noyaux a substitution diphenyle, leur procede de preparation et leur utilisation comme medicaments |
WO1999057114A1 (fr) * | 1998-05-04 | 1999-11-11 | Fujisawa Pharmaceutical Co., Ltd. | Derives de carboxamide heterocycliques utilisees comme inhibiteurs de la production de monoxyde d'azote |
US6852725B1 (en) * | 1998-06-12 | 2005-02-08 | Societe De Conseils De Recherches Et D'applications Scientifiques, S. A. S. | Imidazolyl derivatives |
US7238695B2 (en) | 1998-06-12 | 2007-07-03 | Societe De Conseils De Recherches Et D'applications Scientifiques, Sas | Imidazolyl derivatives |
US7901894B2 (en) | 1999-01-13 | 2011-03-08 | The Research Foundation Of State University Of New York | Kinase inhibitors |
US6521643B1 (en) | 1999-02-17 | 2003-02-18 | Fujisawa Pharmaceutical Co., Ltd. | Pyridine compounds and their pharmaceutical use |
WO2000049015A1 (fr) * | 1999-02-17 | 2000-08-24 | Fujisawa Pharmaceutical Co., Ltd. | Composes pyridine et leur utilisation pharmaceutique |
WO2001002387A1 (fr) * | 1999-07-05 | 2001-01-11 | Fujisawa Pharmaceutical Co., Ltd. | N-imidazolylmethyl-carboxamides utilises comme inhibiteurs de la production d'oxyde nitrique |
EP1228760A2 (fr) * | 1999-10-11 | 2002-08-07 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Dérivés d'hétérocycles à 5 chaínons, leur préparation et leur application à titre de médicaments |
JP2003511416A (ja) * | 1999-10-11 | 2003-03-25 | ソシエテ・ド・コンセイユ・ド・ルシエルシエ・エ・ダアツプリカーション・シヤンテイフイツク・(エス.セー.エール.アー.エス) | 5員複素環誘導体、その製造方法及びその医薬としての使用 |
AU783129B2 (en) * | 1999-10-11 | 2005-09-29 | Ipsen Pharma S.A.S. | 5-membered heterocycle derivatives, production thereof and use thereof as medicaments |
JP4972263B2 (ja) * | 1999-10-11 | 2012-07-11 | イプセン ファルマ ソシエテ パール アクシオン サンプリフィエ | 5員複素環誘導体、その製造方法及びその医薬としての使用 |
EP1228760A3 (fr) * | 1999-10-11 | 2004-01-28 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Dérivés d'hétérocycles à 5 chaínons, leur préparation et leur application à titre de médicaments |
WO2001026656A3 (fr) * | 1999-10-11 | 2002-04-18 | Sod Conseils Rech Applic | Derives d'heterocycles a 5 chainons et leur application comme inhibiteurs de monoamine oxydase |
KR100822085B1 (ko) * | 1999-10-11 | 2008-04-15 | 소시에떼 드 꽁세이으 드 르세르세 에 따블리까시옹 시앙띠피끄 (에스.세.에르.아.에스.) | 5-원 헤테로사이클 유도체, 이의 제조 방법 및의약으로서의 이의 용도 |
EP1589007A2 (fr) | 1999-10-11 | 2005-10-26 | Societe de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S) SAS | Dérivés d'hétérocycles à 5 chainons, leur préparation et leur application comme médicaments |
CZ304331B6 (cs) * | 1999-10-11 | 2014-03-05 | Ipsen Pharma, S.A.S. | Použití thiazolových derivátů pro přípravu léčiva |
WO2001026656A2 (fr) * | 1999-10-11 | 2001-04-19 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Derives d'heterocycles a 5 chainons et leur application comme inhibiteurs de monoamine oxydase |
JP2003528871A (ja) * | 2000-03-27 | 2003-09-30 | シエーリング アクチエンゲゼルシャフト | Nosインヒビターとしてのn−複素環式誘導体 |
US7566734B2 (en) | 2000-08-01 | 2009-07-28 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. | Imidazolyl derivatives |
US7638546B1 (en) | 2000-08-01 | 2009-12-29 | Ipsen Pharma S.A.S. | Imidazolyl derivatives |
FR2812546A1 (fr) * | 2000-08-01 | 2002-02-08 | Sod Conseils Rech Applic | Derives d'heterocycles a 5 chainons, leur preparation et leur application a titre de medicaments |
EP1392291B1 (fr) * | 2000-10-30 | 2007-05-30 | Janssen Pharmaceutica N.V. | Inhibiteurs de tripeptidyl peptidase |
AU2002224797B2 (en) * | 2000-10-30 | 2006-10-26 | Janssen Pharmaceutica N.V. | Tripeptidyl peptidase inhibitors |
US7329684B2 (en) | 2001-03-05 | 2008-02-12 | Transtech Pharma, Inc. | Benzimidazole derivatives as therapeutic agents |
EP1387680A1 (fr) * | 2001-03-05 | 2004-02-11 | TransTech Pharma Inc. | Agents th rapeutiques base de d riv s benzimidazole |
EP1387680A4 (fr) * | 2001-03-05 | 2010-01-13 | Transtech Pharma Inc | Agents th rapeutiques base de d riv s benzimidazole |
US7087632B2 (en) * | 2001-03-05 | 2006-08-08 | Transtech Pharma, Inc. | Benzimidazole derivatives as therapeutic agents |
CZ304550B6 (cs) * | 2001-04-10 | 2014-07-02 | Ipsen Pharma, S.A.S. | Deriváty heterocyklů s 5 atomy kruhu, jejich příprava a jejich použití jako léčiv |
JP2004531526A (ja) * | 2001-04-10 | 2004-10-14 | ソシエテ・ド・コンセイユ・ド・ルシエルシエ・エ・ダアツプリカーション・シヤンテイフイツク・(エス.セー.エール.アー.エス) | 5員複素間誘導体、その製造法及びその医薬としての使用 |
US7057051B2 (en) | 2001-07-20 | 2006-06-06 | Merck & Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
US7572785B2 (en) | 2001-07-20 | 2009-08-11 | Merck & Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
US8354397B2 (en) | 2001-07-27 | 2013-01-15 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
US8772275B2 (en) | 2001-07-27 | 2014-07-08 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
US8088768B2 (en) | 2001-10-22 | 2012-01-03 | The Research Foundation Of The State University Of New York | Protein kinase and phosphatase inhibitors |
EP1444204A1 (fr) * | 2001-10-22 | 2004-08-11 | The Research Foundation Of State University Of New York | Inhibiteurs de proteines kinases et de proteines phosphatases, methodes d'identification et methodes d'utilisation associees |
US7427608B2 (en) | 2001-10-22 | 2008-09-23 | The Research Foundation Of State University Of New York | Protection against and treatment of hearing loss |
EP1444204A4 (fr) * | 2001-10-22 | 2009-11-04 | Univ New York State Res Found | Inhibiteurs de proteines kinases et de proteines phosphatases, methodes d'identification et methodes d'utilisation associees |
US7129225B2 (en) | 2001-10-22 | 2006-10-31 | The Research Foundation Of State University Of New York | Protection against and treatment of hearing loss |
US7772216B2 (en) | 2001-10-22 | 2010-08-10 | The Research Foundation Of State University Of New York | Protein kinase and phosphatase inhibitors and methods for designing them |
US7166636B2 (en) | 2002-03-06 | 2007-01-23 | Astrazeneca Ab | Indole-amid derivatives which possess glycogen phosphorylase inhibitory activity |
US7122567B2 (en) | 2002-03-06 | 2006-10-17 | Astrazeneca Ab | Heterocyclic amide derivatives having glycogen phosphorylase inhibitory activity |
US7332515B2 (en) | 2002-03-06 | 2008-02-19 | Astrazeneca Ab | Indole-amid derivatives which possess glycogen phosphorylase inhibitory activity |
US7169927B2 (en) | 2002-03-06 | 2007-01-30 | Astrazeneca Ab | Indole-amide derivatives and their use as glycogen phosphorylase inhibitors |
WO2003074517A1 (fr) * | 2002-03-06 | 2003-09-12 | Astrazeneca Ab | Derives d'amido-indole possedant une activite d'inhibition de la glycogene phosphorylase |
US7129249B2 (en) | 2002-03-06 | 2006-10-31 | Astrazeneca Ab | Heterocyclic amide derivatives as inhibitors of glycogen phoshorylase |
US7115648B2 (en) | 2002-03-06 | 2006-10-03 | Astrazeneca Ab | Indole-amide derivatives and their use as glycogen phosphorylase inhibitors |
US7138415B2 (en) | 2002-03-06 | 2006-11-21 | Astrazeneca Ab | Indolamid derivatives which possess glycogenphosphorylase inhibitory activity |
EP1487796A4 (fr) * | 2002-03-28 | 2005-11-16 | Neurogen Corp | Biarylamides substitues en tant que modulateurs du recepteur c5a |
EP1487796A1 (fr) * | 2002-03-28 | 2004-12-22 | Neurogen Corporation | Biarylamides substitues en tant que modulateurs du recepteur c5a |
US7148225B2 (en) | 2002-03-28 | 2006-12-12 | Neurogen Corporation | Substituted biaryl amides as C5A receptor modulators |
US7241790B2 (en) * | 2002-07-30 | 2007-07-10 | University Of Virginia Patent Foundation | Compounds active in spinigosine 1-phosphate signaling |
US8394815B2 (en) | 2002-08-19 | 2013-03-12 | Lorus Therapeutics Inc. | 2,4,5-trisubstituted imidazoles and their use as anti-microbial agents |
US7884120B2 (en) | 2002-08-19 | 2011-02-08 | Lorus Therapeutics Inc. | 2,4,5-trisubstituted imidazoles and their use as anti-microbial agents |
US8987305B2 (en) | 2002-08-19 | 2015-03-24 | Aptose Biosciences Inc. | 2,4,5-trisubstituted imidazoles and their use as anti-microbial agents |
US8404684B2 (en) | 2003-05-02 | 2013-03-26 | Novartis Ag | Inhibitors of phosphatidylinositol 3-kinase |
DE10332560B4 (de) * | 2003-07-11 | 2010-07-08 | Chiracon Gmbh | Verfahren zur Herstellung von ß- Heteroaryl-2-alanin-Verbindungen über 2-Amino-2-(heteroarylmethyl)-carbonsäure-Verbindungen |
US8969372B2 (en) | 2003-11-14 | 2015-03-03 | Aptose Boisciences Inc. | Aryl imidazoles and their use as anti-cancer agents |
US10080739B2 (en) | 2003-11-14 | 2018-09-25 | Aptose Biosciences Inc. | Aryl imidazoles and their use as anti-cancer agents |
US8716492B2 (en) | 2004-06-15 | 2014-05-06 | Bristol-Myers Squibb Company | Five-membered heterocycles useful as serine protease inhibitors |
US7453002B2 (en) | 2004-06-15 | 2008-11-18 | Bristol-Myers Squibb Company | Five-membered heterocycles useful as serine protease inhibitors |
US9617224B2 (en) | 2004-06-15 | 2017-04-11 | Bristol-Myers Squibb Company | Five-membered heterocycles useful as serine protease inhibitors |
US8101778B2 (en) | 2004-06-15 | 2012-01-24 | Bristol-Myers Squibb Company | Five-membered heterocycles useful as serine protease inhibitors |
US10112936B2 (en) | 2004-06-15 | 2018-10-30 | Bristol-Myers Squibb Company | Five-membered heterocycles useful as serine protease inhibitors |
US9079860B2 (en) | 2004-06-15 | 2015-07-14 | Bristol-Myers Squibb Company | Five-membered heterocycles useful as serine protease inhibitors |
US8318791B2 (en) | 2004-06-18 | 2012-11-27 | Novartis Vaccines And Diagnostics, Inc. | Substituted imidazole derivatives |
US8735599B2 (en) | 2004-06-18 | 2014-05-27 | Novartis Vaccines And Diagnostics, Inc. | Substituted imidazole derivates |
US7576221B2 (en) | 2004-06-18 | 2009-08-18 | Novartis Vaccines And Diagnostics, Inc. | Substituted imidazole derivatives |
WO2006004924A2 (fr) * | 2004-06-28 | 2006-01-12 | Amgen Sf, Llc | Composes imidazolo, compositions et leurs methodes d'utilisation |
US7271271B2 (en) | 2004-06-28 | 2007-09-18 | Amgen Sf, Llc | Imidazolo-related compounds, compositions and methods for their use |
WO2006004924A3 (fr) * | 2004-06-28 | 2006-03-09 | Amgen Sf Llc | Composes imidazolo, compositions et leurs methodes d'utilisation |
US7381736B2 (en) | 2004-09-02 | 2008-06-03 | Metabasis Therapeutics, Inc. | Thiazole and thiadiazole inhibitors of tyrosine phosphatases |
US7863294B2 (en) * | 2004-12-10 | 2011-01-04 | Instituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Heterocycle derivatives as histone deacetylase (HDAC) inhibitors |
US8148392B2 (en) | 2005-05-25 | 2012-04-03 | Lorus Therapeutics Inc. | 2-indolyl imidazo [4,5-d] phenanthroline derivatives and their use in the treatment of cancer |
US7626040B2 (en) | 2005-08-09 | 2009-12-01 | Novartis Vaccines And Diagnostics, Inc. | Substituted imidazole compounds as KSP inhibitors |
WO2007052073A3 (fr) * | 2005-10-31 | 2007-08-02 | Angeletti P Ist Richerche Bio | Derives d'amide de soufre et d'amide a heterocycle substitue utilises en tant qu'inhibiteurs d'histone desacetylase (hdac) |
AU2006310257B2 (en) * | 2005-10-31 | 2012-04-26 | Msd Italia S.R.L. | Heterocycle substituted amide and sulfur amide derivatives as histone deacetylase (HDAC) inhibitors |
US8080573B2 (en) | 2005-10-31 | 2011-12-20 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Heterocycle substituted amide and sulfur amide derivatives as histone deacetylase (hdac) inhibitors |
WO2007052073A2 (fr) * | 2005-10-31 | 2007-05-10 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Derives d'amide de soufre et d'amide a heterocycle substitue utilises en tant qu'inhibiteurs d'histone desacetylase (hdac) |
US7626039B2 (en) | 2005-12-14 | 2009-12-01 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, ayrlpropynamide, or arylmethylurea analogs as factor XIa inhibitors |
US8252830B2 (en) | 2005-12-14 | 2012-08-28 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor XIa inhibitors |
US7842708B2 (en) * | 2005-12-14 | 2010-11-30 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor XIa inhibitors |
US8604056B2 (en) | 2005-12-14 | 2013-12-10 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor XIa inhibitors |
WO2008011557A3 (fr) * | 2006-07-20 | 2008-07-31 | Allen J Borchardt | Inhibiteurs hétéroaryliques de la kinase rho |
WO2008011557A2 (fr) * | 2006-07-20 | 2008-01-24 | Borchardt Allen J | Inhibiteurs hétéroaryliques de la kinase rho |
US7820646B2 (en) | 2007-01-05 | 2010-10-26 | Novartis Vaccines And Diagnostics, Inc. | Cyclized derivatives as Eg-5 inhibitors |
EP2188274A1 (fr) * | 2007-08-03 | 2010-05-26 | Boehringer Ingelheim International GmbH | Inhibiteurs de polymerase virale |
US8242140B2 (en) | 2007-08-03 | 2012-08-14 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
EP2188274A4 (fr) * | 2007-08-03 | 2011-05-25 | Boehringer Ingelheim Int | Inhibiteurs de polymerase virale |
US8541402B2 (en) | 2007-12-19 | 2013-09-24 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US8476257B2 (en) | 2007-12-19 | 2013-07-02 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US8912182B2 (en) | 2007-12-19 | 2014-12-16 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US8940771B2 (en) | 2007-12-20 | 2015-01-27 | Novartis Ag | Organic compounds |
US8476268B2 (en) | 2008-09-10 | 2013-07-02 | Novartis Ag | Pyrrolidine-1,2-dicarboxamide derivatives |
US8710085B2 (en) | 2008-09-10 | 2014-04-29 | Novartis Ag | Pyrrolidine-1,2-dicarboxamide derivatives |
US8227462B2 (en) | 2008-09-10 | 2012-07-24 | Novartis Ag | Pyrrolidine-1,2-dicarboxamide derivatives |
US8293753B2 (en) | 2009-07-02 | 2012-10-23 | Novartis Ag | Substituted 2-carboxamide cycloamino ureas |
US10363241B2 (en) | 2009-09-30 | 2019-07-30 | Vtv Therapeutics Llc | Substituted imidazole derivatives and methods of use thereof |
US8580833B2 (en) | 2009-09-30 | 2013-11-12 | Transtech Pharma, Inc. | Substituted imidazole derivatives and methods of use thereof |
US9598375B2 (en) | 2009-09-30 | 2017-03-21 | Vtv Therapeutics Llc | Substituted imidazole derivatives and methods of use thereof |
US8846682B2 (en) | 2009-12-16 | 2014-09-30 | Neuropore Therapies, Inc. | Compound suitable for the treatment of synucleopathies |
WO2011084642A1 (fr) * | 2009-12-16 | 2011-07-14 | Neuropore Therapies, Inc. | Composé approprié pour le traitement de synucléopathies |
US9045461B2 (en) | 2010-02-18 | 2015-06-02 | Transtech Pharma, Llc | Phenyl-heteroaryl derivatives and methods of use thereof |
US8431575B2 (en) | 2010-02-18 | 2013-04-30 | Transtech Pharma, Inc. | Phenyl-heteroaryl derivatives and methods of use thereof |
US8741900B2 (en) | 2010-02-18 | 2014-06-03 | Transtech Pharma, Llc | Phenyl-heteroaryl derivatives and methods of use thereof |
EP2546231A1 (fr) * | 2010-03-04 | 2013-01-16 | Ajinomoto Co., Inc. | Dérivé d'alkylamine |
US9561216B2 (en) | 2010-03-04 | 2017-02-07 | Ea Pharma Co., Ltd. | Alkylamine derivative |
US9253997B2 (en) | 2010-03-04 | 2016-02-09 | Ajinomoto Co., Inc. | Alkylamine derivative |
EP2546231A4 (fr) * | 2010-03-04 | 2014-04-30 | Ajinomoto Kk | Dérivé d'alkylamine |
USRE49569E1 (en) | 2010-03-04 | 2023-07-04 | Ea Pharma Co., Ltd. | Alkylamine derivative |
KR20150002891A (ko) * | 2010-03-04 | 2015-01-07 | 아지노모토 가부시키가이샤 | 알킬아민 유도체 |
US9309247B2 (en) | 2013-03-20 | 2016-04-12 | Lorus Therapeutics Inc. | 2-substituted imidazo[4,5-D]phenanthroline derivatives and their use in the treatment of cancer |
CN105473575A (zh) * | 2013-08-09 | 2016-04-06 | 埃科特莱茵药品有限公司 | 作为alx受体激动剂的苯并咪唑基-甲基脲衍生物 |
CN105473575B (zh) * | 2013-08-09 | 2017-11-24 | 爱杜西亚药品有限公司 | 作为alx受体激动剂的苯并咪唑基‑甲基脲衍生物 |
US11104957B2 (en) | 2013-10-04 | 2021-08-31 | Aptose Biosciences, Inc. | Compositions and methods for treating cancers |
WO2015142001A3 (fr) * | 2014-03-21 | 2015-12-03 | 충남대학교산학협력단 | Composé doté d'une action cardiotonique et composition pharmaceutique permettant de prévenir ou de traiter l'insuffisance cardiaque et contenant ledit composé |
JP2020114827A (ja) * | 2014-08-13 | 2020-07-30 | 日本曹達株式会社 | ジアリールイミダゾール化合物および有害生物防除剤 |
EP3766871A1 (fr) | 2014-08-13 | 2021-01-20 | Nippon Soda Co., Ltd. | Composé de diarylimidazole et agent de lutte antiparasitaire |
KR102447094B1 (ko) * | 2014-08-13 | 2022-09-23 | 닛뽕소다 가부시키가이샤 | 디아릴이미다졸 화합물 및 유해 생물 방제제 |
WO2016024587A1 (fr) * | 2014-08-13 | 2016-02-18 | 日本曹達株式会社 | Composé de diarylimidazole et agent de lutte antiparasitaire |
US10021880B2 (en) | 2014-08-13 | 2018-07-17 | Nippon Soda Co., Ltd. | Diarylimidazole compound and harmful organism control agent |
CN106573894A (zh) * | 2014-08-13 | 2017-04-19 | 日本曹达株式会社 | 二芳基咪唑化合物和有害生物防除剂 |
JPWO2016024587A1 (ja) * | 2014-08-13 | 2017-05-25 | 日本曹達株式会社 | ジアリールイミダゾール化合物および有害生物防除剤 |
KR20170040243A (ko) | 2014-08-13 | 2017-04-12 | 닛뽕소다 가부시키가이샤 | 디아릴이미다졸 화합물 및 유해 생물 방제제 |
US11407749B2 (en) | 2015-10-19 | 2022-08-09 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
WO2017068089A3 (fr) * | 2015-10-23 | 2017-07-27 | Vifor (International) Ag | Nouveaux inhibiteurs de la ferroportine |
US10738041B2 (en) | 2015-10-23 | 2020-08-11 | Vifor (International) Ag | Ferroportin inhibitors |
US11066399B2 (en) | 2015-10-23 | 2021-07-20 | Vifor (International) Ag | Ferroportin inhibitors |
US11001579B2 (en) | 2015-10-23 | 2021-05-11 | Vifor (International) Ag | Ferroportin inhibitors |
US11572366B2 (en) | 2015-11-19 | 2023-02-07 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11884633B2 (en) | 2015-12-16 | 2024-01-30 | Nippon Soda Co., Ltd. | Arylazole compound and pest control agent |
KR20210094161A (ko) | 2015-12-16 | 2021-07-28 | 닛뽕소다 가부시키가이샤 | 아릴아졸 화합물 및 유해 생물 방제제 |
US11180456B2 (en) | 2015-12-16 | 2021-11-23 | Nippon Soda Co., Ltd. | Arylazole compound and pest control agent |
WO2017104741A1 (fr) | 2015-12-16 | 2017-06-22 | 日本曹達株式会社 | Composé de type arylazole et agent de lutte contre les organismes nuisibles |
KR20180095813A (ko) | 2015-12-16 | 2018-08-28 | 닛뽕소다 가부시키가이샤 | 아릴아졸 화합물 및 유해 생물 방제제 |
EP3872068A1 (fr) | 2015-12-16 | 2021-09-01 | Nippon Soda Co., Ltd. | Composé de type arylazole et agent de lutte contre les organismes nuisibles |
US11535615B2 (en) | 2015-12-22 | 2022-12-27 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11866435B2 (en) | 2015-12-22 | 2024-01-09 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11608337B2 (en) | 2016-05-06 | 2023-03-21 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11673883B2 (en) | 2016-05-26 | 2023-06-13 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11873309B2 (en) | 2016-06-20 | 2024-01-16 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US20200262822A1 (en) * | 2016-06-21 | 2020-08-20 | Shifa Biomedical Corporation | Anti-Proprotein Convertase Subtilisin Kexin Type 9 (Anti-PCSK9) Compounds and Methods of Using the Same in the Treatment and/or Prevention of Cardiovascular Diseases |
US10947220B2 (en) * | 2016-06-21 | 2021-03-16 | Shifa Biomedical Corporation | Anti-proprotein convertase subtilisin kexin type 9 (anti-PCSK9) compounds and methods of using the same in the treatment and/or prevention of cardiovascular diseases |
US20190270729A1 (en) * | 2016-06-21 | 2019-09-05 | Shifa Biomedical Corporation | Anti-Proprotein Convertase Subtilisin Kexin Type 9 (Anti-PCSK9) Compounds and Methods of Using the Same in the Treatment and/or Prevention of Cardiovascular Diseases |
US10899748B2 (en) * | 2016-06-21 | 2021-01-26 | Shifa Biomedical Corporation | Anti-proprotein convertase subtilisin kexin type 9 (anti-PCSK9) compounds and methods of using the same in the treatment and/or prevention of cardiovascular diseases |
US11718605B2 (en) | 2016-07-14 | 2023-08-08 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11613536B2 (en) | 2016-08-29 | 2023-03-28 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US10806785B2 (en) | 2016-12-22 | 2020-10-20 | Incyte Corporation | Immunomodulator compounds and methods of use |
US11787793B2 (en) | 2016-12-22 | 2023-10-17 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US10793565B2 (en) | 2016-12-22 | 2020-10-06 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US10800768B2 (en) | 2016-12-22 | 2020-10-13 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11465981B2 (en) | 2016-12-22 | 2022-10-11 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11339149B2 (en) | 2016-12-22 | 2022-05-24 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11129820B2 (en) | 2017-04-18 | 2021-09-28 | Vifor (International) Ag | Ferroportin-inhibitor salts |
WO2018192973A1 (fr) | 2017-04-18 | 2018-10-25 | Vifor (International) Ag | Sels inhibiteurs de ferroportine |
US11149047B2 (en) | 2017-10-30 | 2021-10-19 | Aptose Biosciences, Inc. | Aryl imidazoles for treatment of cancer |
US10669271B2 (en) | 2018-03-30 | 2020-06-02 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11124511B2 (en) | 2018-03-30 | 2021-09-21 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US10618916B2 (en) | 2018-05-11 | 2020-04-14 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11414433B2 (en) | 2018-05-11 | 2022-08-16 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US10906920B2 (en) | 2018-05-11 | 2021-02-02 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
US11753406B2 (en) | 2019-08-09 | 2023-09-12 | Incyte Corporation | Salts of a PD-1/PD-L1 inhibitor |
US11401279B2 (en) | 2019-09-30 | 2022-08-02 | Incyte Corporation | Pyrido[3,2-d]pyrimidine compounds as immunomodulators |
US11866451B2 (en) | 2019-11-11 | 2024-01-09 | Incyte Corporation | Salts and crystalline forms of a PD-1/PD-L1 inhibitor |
CN113683598B (zh) * | 2020-05-18 | 2022-10-14 | 成都先导药物开发股份有限公司 | 一种免疫调节剂 |
CN113683598A (zh) * | 2020-05-18 | 2021-11-23 | 成都先导药物开发股份有限公司 | 一种免疫调节剂 |
US11760756B2 (en) | 2020-11-06 | 2023-09-19 | Incyte Corporation | Crystalline form of a PD-1/PD-L1 inhibitor |
US11780836B2 (en) | 2020-11-06 | 2023-10-10 | Incyte Corporation | Process of preparing a PD-1/PD-L1 inhibitor |
US11866434B2 (en) | 2020-11-06 | 2024-01-09 | Incyte Corporation | Process for making a PD-1/PD-L1 inhibitor and salts and crystalline forms thereof |
Also Published As
Publication number | Publication date |
---|---|
JP2001505585A (ja) | 2001-04-24 |
WO1998027108A3 (fr) | 1998-07-30 |
EP0946587A2 (fr) | 1999-10-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO1998027108A2 (fr) | Nouveaux composes amide | |
JP7352662B2 (ja) | ベンゾイソオキサゾールスルホンアミド誘導体 | |
CN114269735B (zh) | 二氢或四氢喹唑啉类化合物及其中间体、制备方法和应用 | |
EP1720864B1 (fr) | Derives de thiophene a substitution benzimidazole a activite sur ikk3 | |
US7265120B2 (en) | Pyrazine derivatives and pharmaceutical use thereof | |
JP4625969B2 (ja) | ベンズアミド誘導体 | |
AU2018236290B2 (en) | MK2 inhibitors, synthesis thereof, and intermediates thereto | |
EP0596406A1 (fr) | Imidazo (1,2-a) pyridines comme antagonistes de la bradykinine | |
AU2014244555A1 (en) | DNA-PK inhibitors | |
WO1997045425A1 (fr) | Nouveaux carboxamides d'indolyle et de benzofuranyle utilises comme inhibiteurs de la production d'oxyde nitrique | |
EP2788349A1 (fr) | Inhibiteurs de kinases | |
EP2297112A1 (fr) | Composés de pyrazole comme antagonistes de ccr1 | |
AU2007207671A1 (en) | Compounds for the treatment of inflammatory disorders | |
CN114423751B (zh) | 用作选择性aurora a抑制剂的新型杂环化合物 | |
WO2006059164A2 (fr) | Amides d'acide pyrrolopyridine-2-carboxylique | |
CN112673001A (zh) | 作为激酶抑制剂的吲唑甲酰胺 | |
US8765739B2 (en) | Azetidine compound and pharmaceutical use thereof | |
WO2006056815A1 (fr) | Amides d'acide indole-2-carboxylique | |
EP1075475B1 (fr) | Derives de carboxamides heterocycliques en tant que inhibiteurs de la production du monoxyde d'azote | |
EP2459551B1 (fr) | Dihydrobenzoindazoles | |
JP2003503489A (ja) | 一酸化窒素産生阻害剤としてのn−イミダゾリルメチルカルボキサミド | |
JPH1045751A (ja) | 新規ピペラジン化合物 | |
JPH1081671A (ja) | 新規ペプチド化合物 | |
CN117561262A (zh) | 大环tak1抑制剂 | |
WO1997017349A1 (fr) | Derives heterocycliques fusionnes pentagonaux d'azepine et leur emploi pharmaceutique |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AU CA CN HU IL JP KR MX US AM AZ BY KG KZ MD RU TJ TM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
AK | Designated states |
Kind code of ref document: A3 Designated state(s): AU CA CN HU IL JP KR MX US AM AZ BY KG KZ MD RU TJ TM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A3 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
ENP | Entry into the national phase in: |
Ref country code: JP Ref document number: 1998 527528 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 09319914 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1997912529 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1997912529 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1997912529 Country of ref document: EP |