WO2000027842A1 - Composes - Google Patents

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Publication number
WO2000027842A1
WO2000027842A1 PCT/SE1999/001988 SE9901988W WO0027842A1 WO 2000027842 A1 WO2000027842 A1 WO 2000027842A1 SE 9901988 W SE9901988 W SE 9901988W WO 0027842 A1 WO0027842 A1 WO 0027842A1
Authority
WO
WIPO (PCT)
Prior art keywords
methoxy
pyridinamine
piperidinyl
formula
compound
Prior art date
Application number
PCT/SE1999/001988
Other languages
English (en)
Inventor
Anthony Cook
Peter Hamley
Alan Tinker
Original Assignee
Astrazeneca Ab
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab
Priority to EP99971807A priority Critical patent/EP1124821A1/fr
Priority to AU14345/00A priority patent/AU1434500A/en
Priority to JP2000581020A priority patent/JP2002529463A/ja
Publication of WO2000027842A1 publication Critical patent/WO2000027842A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • 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
    • 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
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • 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
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • the compounds of the present invention are clearly distinguished from those of the prior art by virtue of the nature of the particular substituents attached to the 2-aminopyridine ring.
  • R represents hydr ⁇ gen or one or more substituents selected independently from Cl to 6
  • R independently represent hydrogen or Cl to 4 alkyl; 2 4 or R and R are joined together and represent -[CH2] m -;
  • Y represents hydrogen or Cl to 4 alkyl
  • the compounds of formula (I) and their pharmaceutically acceptable salts, enantiomers, racemates and tautomers have the advantage that they are inhibitors of the enzyme nitric oxide synthase (NOS).
  • NOS nitric oxide synthase
  • the compounds of formula (I) and their pharmaceutically acceptable salts, enantiomers, racemates and tautomers have the advantage that they are inhibitors of the inducible isoform of the enzyme nitric oxide synthase (iNOS).
  • a more particular aspect of the invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt, enantiomer, racemate or tautomer thereof, in the manufacture of a medicament, for the treatment or prophylaxis of inflammatory disease.
  • a method of treating, or reducing the risk of, inflammatory disease in a person suffering from or at risk of, said disease comprises administering to the person a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, enantiomer, racemate or tautomer thereof.
  • a method of treating, or reducing the risk of, inflammation, inflammatory disease and inflammatory related disorders in a person suffering from or at risk of, said disease or condition comprises administering to the person a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, enantiomer, racemate or tautomer thereof in combination with a COX-2 inhibitor.
  • Q in formula (I) represents hydrogen, halogen or cyano.
  • Particular compounds of the invention include:
  • Cl to 6 alkyl denotes a straight or branched chain alkyl group having from 1 to 6 carbon atoms or a cyclic alkyl group having from 3 to 6 carbon atoms. Examples of such groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopentyl and cyclohexyl.
  • Cl to 6 alkoxy denotes a straight or branched chain alkoxy group having from 1 to 6 carbon atoms. Examples of such groups include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy and t-butoxy.
  • alkylthio are to be interpreted similarly.
  • Examples of a five membered aromatic heterocyclic ring containing one to three heteroatoms selected independently from O, S or N, or a six membered aromatic azacyclic ring containing one or two nitrogen atoms include furan, thiophene, pyrrole, thiazole, oxazole, imidazole, triazole, thiadiazole, pyridine, pyrimidine, pyrazine and pyridazine.
  • bicyclic aromatic heterocyclic ring system containing one to three heteroatoms independently selected from O, S or N examples include quinoline, isoquinoline, benzofuran, benzothiophene, benzothiazole, indole and benzotriazole.
  • R , R , R , R , X, Y and Z are as defined above with an acyl derivative of formula (HI)
  • Q and A are as defined above and L represents a leaving group
  • R , R , R ' A, Q, X, Y and Z are as defined above;
  • R , R , R , A, Q, X, Y and Z are as defined above;
  • the present invention includes compounds of formula (I) in the form of salts, in particular acid addition salts.
  • Suitable salts include those formed with both organic and inorganic acids.
  • Such acid addition salts will normally be pharmaceutically acceptable although salts of non-pharmaceutically acceptable acids may be of utility in the preparation and purification of the compound in question.
  • preferred salts include those formed from hydrochloric, hydrobromic, sulphuric, phosphoric, citric, tartaric, lactic, pyruvic, acetic, succinic, fumaric, maleic, methanesulphonic and benzenesulphonic acids.
  • the preparation of compounds of formula (II) may be achieved by reaction of a compound of formula (IV) with a compound of formula (VET)
  • the preparation of compounds of formula (II) may be achieved by reaction of a compound of formula (VI) with a compound of formula (IX) using the methodology of process (c) above.
  • Intermediate compounds may also exist in enantiomeric forms and may be used as purified enantiomers, diastereomers, racemates or mixtures.
  • the compounds of formula (I) may exist in alternative tautomeric forms.
  • Compounds of formula (I) are provided in another tautomeric form or as a mixture thereof.
  • the compounds of formula (I), and their pharmaceutically acceptable salts, enantiomers, racemates and tautomers, are useful because they possess pharmacological activity in animals.
  • the compounds are active as inhibitors of the enzyme nitric oxide synthase. More particularly, they are inhibitors of the inducible isoform of the enzyme nitric oxide synthase and as such are predicted to be useful in therapy, for example, as anti-inflammatory agents. They may also have utility as inhibitors of the neuronal isoform of the enzyme nitric oxide synthase.
  • the compounds and their pharmaceutically acceptable salts, enantiomers, racemates and tautomers are indicated for use in the treatment or prophylaxis of diseases or conditions in which synthesis or oversynthesis of nitric oxide synthase forms a contributory part.
  • the compounds are indicated for use in the treatment of inflammatory conditions in mammals including man.
  • Conditions that may be specifically mentioned are: osteoarthritis, rheumatoid arthritis, rheumatoid spondylitis, gouty arthritis and other arthritic conditions, inflamed joints; eczema, psoriasis, dermatitis or other inflammatory skin conditions such as sunburn; inflammatory eye conditions including uveitis and conjunctivitis; lung disorders in which inflammation is involved, for example, asthma, bronchitis, chronic obstructive pulmonary disease, pigeon fancier's disease, farmer's lung, acute respiratory distress syndrome; bacteraemia, endotoxaemia (septic shock), aphthous ulcers, gingivitis, pyresis, pain, meningitis and pancreatitis; conditions of the gastrointestinal tract including inflammatory bowel disease, Crohn's disease, atrophic gastritis, gastritis varialoforme, ulcerative colitis, coeliac disease, regional ileit
  • the compounds will also be useful in the treatment and alleviation of acute pain or persistent inflammatory pain or neuropathic pain or pain of a central origin.
  • the compounds of formula (I) and their pharmaceutically acceptable salts, enantiomers, racemates and tautomers may also be useful in the treatment or prophylaxis of diseases or conditions in addition to those mentioned above.
  • the compounds may be useful in the treatment of atherosclerosis, glaucoma, cystic fibrosis, hypotension associated with septic and/or toxic shock, in the treatment of dysfunction of the immune system, as an adjuvant to short-term immunosuppression in organ transplant therapy, in the control of onset of diabetes, in the maintenance of pancreatic function in diabetes, in the treatment of vascular complications associated with diabetes and in cotherapy with cytokines, for example TNF or interleukins.
  • cytokines for example TNF or interleukins.
  • the compounds of formula (I) may also be useful in the treatment of hypoxia, for example in cases of cardiac arrest and stroke, neurodegenerative disorders including nerve degeneration and/or nerve necrosis in disorders such as ischaemia, hypoxia, hypoglycaemia, epilepsy, and in external wounds (such as spinal cord and head injury), hyperbaric oxygen convulsions and toxicity, dementia, for example pre-senile dementia, Alzheimer's disease and ADDS-related dementia, Sydenham's chorea, Parkinson's disease, Tourette's Syndrome, Huntington's disease, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Korsakoffs disease, imbecility relating to a cerebral vessel disorder, sleeping disorders, schizophrenia, depression, pain, autism, seasonal affective disorder, jet-lag, depression or other symptoms associated with Premenstrual Syndrome (PMS), anxiety and septic shock.
  • PMS Premenstrual Syndrome
  • Compounds of formula (I) may also be expected to show activity in the prevention and reversal of tolerance to opiates and diazepines, treatment of drug addiction, treatment of migraine and other vascular headaches, neurogenic inflammation, in the treatment of gastrointestinal motility disorders, cancer and in the induction of labour.
  • Prophylaxis is expected to be particularly relevant to the treatment of persons who have suffered a previous episode of, or are otherwise considered to be at increased risk of, the disease or condition in question.
  • Persons at risk of developing a particular disease or condition generally include those having a family history of the disease or condition, or those who have been identified by genetic testing or screening to be particularly susceptible to developing the disease or condition.
  • the dosage administered will, of course, vary with the compound employed, the mode of administration and the treatment desired. However, in general, satisfactory results are obtained when the compounds are administered at a dosage of the solid form of between 1 mg and 2000 mg per day.
  • the compounds of formula (I), and pharmaceutically acceptable derivatives thereof may be used on their own, or in the form of appropriate pharmaceutical compositions in which the compound or derivative is in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier.
  • Administration may be by, but is not limited to, enteral (including oral, sublingual or rectal), intranasal, intravenous, topical or other parenteral routes.
  • enteral including oral, sublingual or rectal
  • intranasal intranasal
  • intravenous topical or other parenteral routes.
  • Conventional procedures for the selection and preparation of suitable pharmaceutical formulations are described in, for example, "Pharmaceuticals - The Science of Dosage Form Designs", M. E. Aulton, Churchill Livingstone, 1988.
  • the pharmaceutical composition preferably comprises less than 80% and more preferably less than 50% of a compound of formula (I), or a pharmaceutically acceptable salt, enantiomer, racemate or tautomer thereof.
  • the compounds of formula (I), and pharmaceutically acceptable derivatives thereof, may also be advantageously used in combination with a COX-2 inhibitor.
  • COX-2 inhibitors are Celecoxib and MK-966.
  • the NOS inhibitor and the COX-2 inhibitor may either be formulated together within the same pharmaceutical composition for administration in a single dosage unit, or each component may be individually formulated such that separate dosages may be administered either simultaneously or sequentially.
  • Methyl phosphonium bromide (7.1 g, 0.02 mol) was suspended in tetrahydrofuran (75 ml) and 2M butyl lithium (10 ml in hexane, 0.02 mol) added at 0 °C. After 1 h at room temperature the solution was added dropwise over 30 min. to a solution of l-(4-chlorobenzoyl)-4-piperidone (2.38 g, 0.01 mol) in tetrahydrofuran (75 ml). After 16 h, water was added, followed by extraction with ether three times. The extracts were combined, dried over magnesium sulphate and evaporated. The residue was purified by flash column chromatography eluting with 30% ethyl acetate in hexane to yield the title compound as an oil. MS (+EI) m /z 236/238 (M + ).
  • N-ri-(3-FuranylcarbonylV4-piperidinyll-4-methyl-2-pyridinamine A mixture of 4-methyl-N-(4-piperidinyl)-2-pyridinamine (0.19 g, 1 mmol) (Intermediate B), 3-furancarboxylic acid (0.12 g, 1.1 mmol), bromo-tris-pyrrolidinophosphonium hexafluorophosphate (0.7 g, 1.5 mmol) and Hunig's base (0.52 ml, 3 mmol) was stirred in dichloromethane for 20 h. The solution was diluted with water, separated and the organic layer dried (magnesium sulphate) and evaporated.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

L'invention concerne: de nouveaux composés de la formule (I), dans laquelle R?1, R2, R3, R4, R5¿, A, Q, X, Y et Z sont définis dans les pièces descriptives de la demande ; et des sels pharmaceutiquement acceptables de ces derniers ; des énantiomères et des tautomères de ces derniers ; des procédés pour les préparer, des compositions les contenant et leur utilisation à des fins thérapeutiques. Ces composés sont des inhibiteurs de l'oxyde nitrique synthase et sont de ce fait, particulièrement utiles dans le traitement ou la prévention de maladies inflammatoires et de la douleur.
PCT/SE1999/001988 1998-11-05 1999-11-03 Composes WO2000027842A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP99971807A EP1124821A1 (fr) 1998-11-05 1999-11-03 Composes
AU14345/00A AU1434500A (en) 1998-11-05 1999-11-03 Compounds
JP2000581020A JP2002529463A (ja) 1998-11-05 1999-11-03 化合物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9803773A SE9803773D0 (sv) 1998-11-05 1998-11-05 Compounds
SE9803773-2 1998-11-05

Publications (1)

Publication Number Publication Date
WO2000027842A1 true WO2000027842A1 (fr) 2000-05-18

Family

ID=20413181

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE1999/001988 WO2000027842A1 (fr) 1998-11-05 1999-11-03 Composes

Country Status (5)

Country Link
EP (1) EP1124821A1 (fr)
JP (1) JP2002529463A (fr)
AU (1) AU1434500A (fr)
SE (1) SE9803773D0 (fr)
WO (1) WO2000027842A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001002387A1 (fr) * 1999-07-05 2001-01-11 Fujisawa Pharmaceutical Co., Ltd. N-imidazolylmethyl-carboxamides utilises comme inhibiteurs de la production d'oxyde nitrique
WO2002090332A2 (fr) * 2001-05-08 2002-11-14 Astrazeneca Ab Nouveaux derives d'aryl heteroalkyl amines
US6887871B2 (en) 2000-02-23 2005-05-03 Astrazeneca Ab Use of phenylheteroakylamine derivatives
US6900243B2 (en) 2000-02-23 2005-05-31 Astrazeneca Ab Phenylheteroalkylamine derivatives
US6953797B2 (en) 2000-02-23 2005-10-11 Astrazeneca Ab Use of phenylheteroalkylamine derivatives
EP1627869A1 (fr) * 2003-05-20 2006-02-22 Ajinomoto Co., Inc. Derive d'amide
US7223794B2 (en) 2001-07-31 2007-05-29 Astrazeneca Ab Arylheteroalkylamine derivatives and their use as inhibitors of nitric oxide synthase
US7776861B2 (en) 2003-07-24 2010-08-17 Purdue Pharma L.P. Therapeutic agents useful for treating pain
US7897627B2 (en) * 2007-12-21 2011-03-01 Hoffmann-La Roche Inc. Heteroaryl derivatives as orexin receptor antagonists
US7923450B2 (en) 2008-01-11 2011-04-12 Hoffmann-La Roche Inc. Modulators for amyloid beta
US8288403B2 (en) 2008-11-10 2012-10-16 Hoffmann-La Roche Inc. Heterocyclic gamma secretase modulators
US8389717B2 (en) 2008-10-09 2013-03-05 Hoffmann-La Roche Inc. Modulators for amyloid beta
US8486967B2 (en) 2010-02-17 2013-07-16 Hoffmann-La Roche Inc. Heteroaryl substituted piperidines
US8962834B2 (en) 2008-02-22 2015-02-24 Hoffmann-La Roche Inc. Modulators of amyloid beta

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996018628A1 (fr) * 1994-12-13 1996-06-20 Pharmacia & Upjohn Company Composes de piperadinyle et piperazinyle anti-sida a substitution alkyle
WO1996018617A1 (fr) * 1994-12-12 1996-06-20 Merck & Co., Inc. Pyridines 2-acylaminees substitutees utilisees comme inhibiteurs de synthase d'oxyde d'azote
WO1997024124A1 (fr) * 1995-12-29 1997-07-10 Smithkline Beecham Corporation Antagonistes du recepteur de la vitronectine
WO1997037655A1 (fr) * 1996-04-10 1997-10-16 Merck & Co., Inc. ANTAGONISTES DU RECEPTEUR αvβ3
EP0870765A1 (fr) * 1995-05-18 1998-10-14 Zeria Pharmaceutical Co., Ltd. Derives d'aminothiazole, medicament contenant ces derives et produit intermediaire obtenu durant la production des composes

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996018617A1 (fr) * 1994-12-12 1996-06-20 Merck & Co., Inc. Pyridines 2-acylaminees substitutees utilisees comme inhibiteurs de synthase d'oxyde d'azote
WO1996018628A1 (fr) * 1994-12-13 1996-06-20 Pharmacia & Upjohn Company Composes de piperadinyle et piperazinyle anti-sida a substitution alkyle
EP0870765A1 (fr) * 1995-05-18 1998-10-14 Zeria Pharmaceutical Co., Ltd. Derives d'aminothiazole, medicament contenant ces derives et produit intermediaire obtenu durant la production des composes
WO1997024124A1 (fr) * 1995-12-29 1997-07-10 Smithkline Beecham Corporation Antagonistes du recepteur de la vitronectine
WO1997037655A1 (fr) * 1996-04-10 1997-10-16 Merck & Co., Inc. ANTAGONISTES DU RECEPTEUR αvβ3

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001002387A1 (fr) * 1999-07-05 2001-01-11 Fujisawa Pharmaceutical Co., Ltd. N-imidazolylmethyl-carboxamides utilises comme inhibiteurs de la production d'oxyde nitrique
US6887871B2 (en) 2000-02-23 2005-05-03 Astrazeneca Ab Use of phenylheteroakylamine derivatives
US6900243B2 (en) 2000-02-23 2005-05-31 Astrazeneca Ab Phenylheteroalkylamine derivatives
US6953797B2 (en) 2000-02-23 2005-10-11 Astrazeneca Ab Use of phenylheteroalkylamine derivatives
WO2002090332A3 (fr) * 2001-05-08 2007-11-01 Astrazeneca Ab Nouveaux derives d'aryl heteroalkyl amines
WO2002090332A2 (fr) * 2001-05-08 2002-11-14 Astrazeneca Ab Nouveaux derives d'aryl heteroalkyl amines
AU2002306039B2 (en) * 2001-05-08 2008-05-29 Astrazeneca Ab Novel arylheteroalkylamine derivatives
CN100340548C (zh) * 2001-05-08 2007-10-03 阿斯利康(瑞典)有限公司 新型芳杂烷基胺衍生物
US7223794B2 (en) 2001-07-31 2007-05-29 Astrazeneca Ab Arylheteroalkylamine derivatives and their use as inhibitors of nitric oxide synthase
EP1627869A1 (fr) * 2003-05-20 2006-02-22 Ajinomoto Co., Inc. Derive d'amide
US7572815B2 (en) 2003-05-20 2009-08-11 Ajinomoto Co., Inc. Amide derivative
EP1627869A4 (fr) * 2003-05-20 2006-10-18 Ajinomoto Kk Derive d'amide
US8168827B2 (en) 2003-05-20 2012-05-01 Ajinomoto Co., Inc. Amide derivative
US8637548B2 (en) 2003-07-24 2014-01-28 Purdue Pharma L.P. Therapeutic agents useful for treating pain
US7776861B2 (en) 2003-07-24 2010-08-17 Purdue Pharma L.P. Therapeutic agents useful for treating pain
US9301953B2 (en) 2003-07-24 2016-04-05 Purdue Pharma L.P. Therapeutic agents useful for treating pain
US8178560B2 (en) 2003-07-24 2012-05-15 Purdue Pharma L.P. Therapeutic agents useful for treating pain
US7897627B2 (en) * 2007-12-21 2011-03-01 Hoffmann-La Roche Inc. Heteroaryl derivatives as orexin receptor antagonists
US7923450B2 (en) 2008-01-11 2011-04-12 Hoffmann-La Roche Inc. Modulators for amyloid beta
US8962834B2 (en) 2008-02-22 2015-02-24 Hoffmann-La Roche Inc. Modulators of amyloid beta
US8389717B2 (en) 2008-10-09 2013-03-05 Hoffmann-La Roche Inc. Modulators for amyloid beta
US8288403B2 (en) 2008-11-10 2012-10-16 Hoffmann-La Roche Inc. Heterocyclic gamma secretase modulators
US8486967B2 (en) 2010-02-17 2013-07-16 Hoffmann-La Roche Inc. Heteroaryl substituted piperidines

Also Published As

Publication number Publication date
AU1434500A (en) 2000-05-29
SE9803773D0 (sv) 1998-11-05
EP1124821A1 (fr) 2001-08-22
JP2002529463A (ja) 2002-09-10

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