[go: up one dir, main page]

WO1997034900A1 - Derives azaspiro - Google Patents

Derives azaspiro Download PDF

Info

Publication number
WO1997034900A1
WO1997034900A1 PCT/EP1997/001405 EP9701405W WO9734900A1 WO 1997034900 A1 WO1997034900 A1 WO 1997034900A1 EP 9701405 W EP9701405 W EP 9701405W WO 9734900 A1 WO9734900 A1 WO 9734900A1
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
alkyl
biphenyl
tetrahydrospiro
furo
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/EP1997/001405
Other languages
English (en)
Inventor
Laramie Mary Gaster
Paul Adrian Wyman
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Ltd
Original Assignee
SmithKline Beecham Ltd
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 SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Priority to JP9533158A priority Critical patent/JP2000506877A/ja
Priority to EP97914272A priority patent/EP0888357A1/fr
Publication of WO1997034900A1 publication Critical patent/WO1997034900A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
    • C07D491/20—Spiro-condensed systems
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/22—Anxiolytics
    • 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
    • A61P25/24—Antidepressants
    • 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
    • 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
    • A61P5/00—Drugs for disorders of the endocrine 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
    • 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
    • A61P9/08—Vasodilators for multiple indications
    • 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
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to novel piperidine derivatives, processes for their preparation, and pharmaceutical compositions containing them.
  • EPA 0533266/7/8 disclose a series of benzanilide derivatives which are said to possess 5HT 1D receptor antagonist activity.
  • PCT/EP/95/04889 discloses further 5HT 1D receptor antagonists having a spiropiperidine structure. These compounds are said to be of use in the treatment of various CNS disorders.
  • the 5HT 1D ⁇ receptor has now been reclassif ⁇ ed as the 5HT 1B receptor (P.R Hartig et al Trends in Pharmacological Science, 1996, 17, 103 - 105.
  • the present invention therefore provides a compound of formula (I) or a salt or N-oxide thereof:
  • P is a 5 - to 7-membered carbocyclic or heterocyclic ring containing one to four heteroatoms selected from oxygen, nitrogen or sulphur;
  • R 1 , R 2 and R 3 are independently hydrogen, halogen, C 1-6 alkyl, C 3-6 cycloalkyl,
  • B is oxygen or sulphur
  • D is nitrogen, carbon or a CH group
  • E is oxygen, CR 18 R 19 or NR 20 where R 18 , R 19 and R 20 are independently hydrogen or C 1-6 alkyl or E is S(O) v where v is 0, 1 or 2;
  • C 1-6 alkyl groups may be straight chain or branched.
  • aryl includes phenyl and naphthyl.
  • Heteroaryl groups include thienyl, furyl, pyridyl, pyrimidyl and pyrazinyl groups.
  • Optional substituents for aryl and heteroaryl groups include those groups listed above for R 1 - R 3 .
  • P is a 5- to 7-membered carbocyclic or heterocyclic group containing one to four heteroatoms selected from oxygen, nitrogen or sulphur.
  • suitable groups inlude cyclohexyl, pyridine, pyrimidine, pyrazine, oxazole or thiazole.
  • P is pyrimidine.
  • R 1 , R 2 and R 3 are independently hydrogen, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl, C 1-6 alkoxy, hydroxy C 1-6 alkyl, C 1-6 alkylOC 1-6 alkyl, acyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO 2 R 9 , CONR 10 R 1 1 , NR 10 R 1 1 where R 9 , R 10 and R 11 are independently hydrogen or C 1-6 alkyl or R 2 and R 3 together form a group -(CH 2 ) r -R 14 -(CH 2 ) s - where R 14 is O, S, CH 2 or NR 15 where R 15 is hydrogen or C 1-6 alkyl and r and s are independently 0, 1 or 2.
  • R 2 is
  • R 2 group is ortho with respect to the biphenyl linkage.
  • R 2 is methyl.
  • R 3 is hydrogen.
  • D is nitrogen, carbon or a CH group.
  • D is nitrogen.
  • R 4 is oxygen
  • R 6 together with R 7 forms a group -A- where A is (CR 16 R 17 ) t where t is 2 or 3 and R 16 and R 17 are both hydrogen. Most preferably R 6 together with R 7 forms a (CH 2 ) 2 group.
  • R 8 is hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 2-6 alkenyl or
  • R 8 is C 1-6 alkylC 3-6 cycloalkyl.
  • R 8 is C 1-6 alkyl, most preferably R 8 is methyl.
  • B is oxygen or sulphur, preferably B is oxygen.
  • R 9 and R 10 are independently hydrogen or C 1-6 alkyl. Preferably R 9 and R 10 are both hydrogen.
  • m is 2 forming part of a spiro-piperidine ring,
  • E is oxygen, CR 18 R 19 or NR 20 where R 18 , R 19 and R 20 are independently hydrogen or C 1-6 alkyl or E is S(O) v where v is 0, 1 or 2.
  • E is oxygen.
  • R 21 and R 22 are independently hydrogen or C 1-6 alkyl.
  • G is CH 2 .
  • X and Y are independently CR 9 R 10 where R 9 and R 10 are as defined above.
  • R 9 and R 10 are as defined above.
  • X and Y are both CH 2 .
  • Particularly preferred compounds of the invention include:
  • Preferred salts of the compounds of formula (I) are pharmaceutically acceptable salts. These include acid addition salts such as hydrochlorides, hydrobromides, phosphates, acetates, fumarates, maleates, tartrates, citrates, oxalates, methanesulphonates and p-toluenesulphonates.
  • acid addition salts such as hydrochlorides, hydrobromides, phosphates, acetates, fumarates, maleates, tartrates, citrates, oxalates, methanesulphonates and p-toluenesulphonates.
  • Certain compounds of formula (I) are capable of existing in stereoisomeric forms.
  • the present invention provides a process for the preparation of a compound of formula (I) which comprises:
  • R 1 , R 2 , R 3 and R 4 are groups as defined in formula (I) or protected derivatives thereof and L is a leaving group
  • R 6 , R 7 , R 8 , R 9 , R 10 , E, G, X, Y, and m are groups as defined in formula (I) or protected derivatives thereof and optionally thereafter in any order:
  • Suitable activated carboxylic acid derivatives of formula (II) include acyl halides and acid anhydrides. Activated compounds of formula (II) can also be prepared by reaction of the corresponding carboxylic acid with a coupling reagent such as
  • L is an ester forming group such that the resulting esters of formula (II) can be reacted with compounds of formula (in) in the presence of an organo- aluminium reagent such as trimethylaluminium.
  • an organo- aluminium reagent such as trimethylaluminium.
  • Such a reaction is typically carried out in the presence of an inert solvent such as toluene.
  • Intermediate compounds of formula (II) and (Ill) can be prepared using standard procedures known in the art. Certain intermediate compounds of formula (II) and (Ill) are novel and form a further aspect of the invention. It will be appreciated to those skilled in the art that it may be necessary to protect certain reactive substituents during some of the above procedures. Standard protection and deprotection techniques can be used such as those described in Greene T.W. 'Protective groups in organic synthesis' New York, Wiley (1981). For example, primary amines can be protected as phthalimide, benzyl, benzyloxycarbonyl or trityl derivatives.
  • Carboxylic acid groups can be protected as esters. .Aldehyde or ketone groups can be protected as acetals, ketals, thioacetals or thioketals. Deprotection is achieved using standard conditions.
  • 5HT 1B receptor antagonists are useful in the treatment of CNS disorders such as mood disorders, including depression, seasonal affective disorder and dysthymia; anxiety disorders, including generalised anxiety, panic disorder, agoraphobia, social phobia, obsessive compulsive disorder and post-traumatic stress disorder; memory disorders, including dementia, amnestic disorders and age-associated memory impairment; and disorders of eating behaviours, including anorexia nervosa and bulimia nervosa.
  • Other CNS disorders include motor disorders such as Parkinson's disease, dementia in Parkinson's disease, neuroleptic- induced Parkinsonism and tardive dyskinesias, as well as other psychiatric disorders.
  • 5HT 1B receptor antagonists may also be of use in the treatment of endocrine disorders such as hyperprolactinaemia, in the treatment of vasospasm (particularly in the cerebral vasculature) and hypertension, as well as disorders in the gastrointestinal tract where changes in motility and secretion are involved. They may also be of use in the treatment of sexual dysfunction and
  • the present invention provides a compound of general formula (I) or a physiologically acceptable salt or solvate thereof for use in therapy.
  • the present invention also provides a compound of general formula (I) or a physiologically acceptable salt or solvate thereof for use in the treatment of the
  • the invention provides the use of a compound of general formula (I) or a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment of the aforementioned disorders.
  • the invention provides a method of treating the aforementioned disorders which comprises administering an effective amount to a patient in need of such treatment of a compound of general formula (I) or a pharmaceutically acceptable salt or solvate thereof.
  • a compound of general formula (I) or a physiologically acceptable salt or solvate thereof for use in the treatment or prophylaxis of depression.
  • the compounds according to the invention may advantageously be used in conjunction with one or more other therapeutic agents, for instance, different antidepressant agents.
  • the present invention also provides a pharmaceutical composition, which comprises a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • a pharmaceutical composition of the invention which may be prepared by admixture, suitably at ambient temperature and atmospheric pressure, is usually adapted for oral, parenteral or rectal administration and, as such, may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable or infusible solutions or suspensions or suppositories. Orally administrable compositions are generally preferred.
  • Tablets and capsules for oral administration may be in unit dose form, and may contain conventional excipients, such as binding agents, fillers, tabletting lubricants, disintegrants and acceptable wetting agents.
  • the tablets may be coated according to methods well known in normal pharmaceutical practice.
  • Oral liquid preparations may be in the form of, for example, aqueous or oily suspension, solutions, emulsions, syrups or elixirs, or may be in the form of a dry product for reconstitution with water or other suitable vehicle before use.
  • Such liquid preparations may contain conventional additives such as suspending agents, emulsifying agents, non-aqueous vehicles (which may include edible oils), preservatives, and, if desired, conventional flavourings or colorants.
  • fluid unit dosage forms are prepared utilising a compound of the invention or pharmaceutically acceptable salt thereof and a sterile vehicle.
  • the compound depending on the vehicle and concentration used, can be either suspended or dissolved in the vehicle.
  • the compound can be dissolved for injection and filter sterilised before filling into a suitable vial or ampoule and sealing.
  • adjuvants such as a local anaesthetic, preservatives and buffering agents are dissolved in the vehicle.
  • the composition can be frozen after filling into the vial and the water removed under vacuum.
  • Parenteral suspensions are prepared in substantially the same manner, except that the compound is suspended in the vehicle instead of being dissolved, and sterilisation cannot be
  • the compound can be sterilised by exposure to ethylene oxide before suspension in a sterile vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound.
  • composition may contain from 0.1% to 99% by weight, preferably from 10 to 60% by weight, of the active material, depending on the method of administration.
  • suitable unit doses may be 0.05 to 1000 mg, more suitably 1.0 to 200 mg, and such unit doses may be administered more than once a day, for example two or three a day. Such therapy may extend for a number of weeks or months.
  • the title compound was prepared from 3-chloropyridazine (106 mg; 0.92 mmol) and methyl 4'-amino-2'-methylbiphenyl-4-carboxylate (D2, 223 mg; 0.92 mmol) using a method similar to Description 3, as a brown oil which crystallised to a yellow foam (35 mg, 12%).
  • the title compound was prepared from 4-bromopyridine (407 mg; 0.0025 mol) and methyl 4'-amino-2'-methylbiphenyl-4-carboxylate (D2, 619 mg; 0.0025 mol) using a method similar to that of Description 3 to give the title compound as an off-white solid (169 mg, 21%).
  • the title compound was prepared from methyl 2'-methyl-4'-(pyrimidin-2-yloxy)biphenyl-4- carboxylate (D6, 69 mg; 0.215 mmol) and 1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3- f]indole-3,4'-piperidine] (Description 8, WO 96/19477) (53 mg; 0.215 mmol) following the procedure outlined in Example 1, as a pale lemon/white powder (49 mg, 40%).
  • the title compound was prepared from methyl 2'-methyl-4'-(pyridazin-3-ylamino)biphenyl- 4-carboxylate (D8, 35 mg; 0.109 mmol) and 1'-methyl-2,3,6,7-tetrahydrospiro [furo[2,3- f]indole-3,4'- ⁇ iperidine] (Description 8, WO 96/19477) (27 mg; 0.109 mmol) following the procedure outlined in Example 1, as an off-white solid (11 mg, 19%).
  • the title compound was prepared from methyl 2 , -methyl-4'-(pyridin-4-ylamino)biphenyl-4- carboxylate (D9, 149 mg; 0.468 mmol) and l'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3- fjindole-3,4'-piperidine] (Description 8, WO 96/19477) (114 mg; 0.468 mmol) following the procedure outlined in Example 1, as a white solid (147 mg, 60%).
  • the title compound was prepared from 2'-methyl-4'-(pyridine-2-carbonyl)biphenyl-4- carboxylic acid (Dl l, 395 mg, 1.246 mmol) and l'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3- f]indole-3,4'- ⁇ iperidine] (Description 8, WO 96/19477) (304 mg, 1.246 mmol) following a similar procedure to that outlined in Example 3, as a beige solid.
  • the crude product was purified by chromatography on silica gel, eluting with 0-5% methanol/dichloromethane. .After evaporation the title compound was afforded as a dull yellow solid (92 mg, 14%).

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Endocrinology (AREA)
  • Psychiatry (AREA)
  • Reproductive Health (AREA)
  • Diabetes (AREA)
  • Psychology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention concerne des composés de la formule (I), où P est un noyau carbocyclique ou hétérocyclique de 5 à 7 éléments, contenant un à quatre hétéroatomes sélectionnés parmi de l'oxygène, de l'azote ou du souffre; R4 est O, S, CH¿2?, C=O, NR?5¿CO ou NR5; D est de l'azote ou du carbone; E est O, CR?18R19, NR20¿, ces composés présentant une activité antagoniste du récepteur 5HT1B.
PCT/EP1997/001405 1996-03-21 1997-03-19 Derives azaspiro Ceased WO1997034900A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP9533158A JP2000506877A (ja) 1996-03-21 1997-03-19 アザスピロ誘導体
EP97914272A EP0888357A1 (fr) 1996-03-21 1997-03-19 Derives azaspiro

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9605945.6A GB9605945D0 (en) 1996-03-21 1996-03-21 Novel compounds
GB9605945.6 1996-03-21

Publications (1)

Publication Number Publication Date
WO1997034900A1 true WO1997034900A1 (fr) 1997-09-25

Family

ID=10790780

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1997/001405 Ceased WO1997034900A1 (fr) 1996-03-21 1997-03-19 Derives azaspiro

Country Status (4)

Country Link
EP (1) EP0888357A1 (fr)
JP (1) JP2000506877A (fr)
GB (1) GB9605945D0 (fr)
WO (1) WO1997034900A1 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7144911B2 (en) 2002-12-31 2006-12-05 Deciphera Pharmaceuticals Llc Anti-inflammatory medicaments
US7202257B2 (en) 2003-12-24 2007-04-10 Deciphera Pharmaceuticals, Llc Anti-inflammatory medicaments
US7279576B2 (en) 2002-12-31 2007-10-09 Deciphera Pharmaceuticals, Llc Anti-cancer medicaments
US8143293B2 (en) 2007-04-20 2012-03-27 Deciphera Pharmaceuticals, Llc Kinase inhibitors useful for the treatment of myleoprolific diseases and other proliferative diseases
US8940756B2 (en) 2012-06-07 2015-01-27 Deciphera Pharmaceuticals, Llc Dihydronaphthyridines and related compounds useful as kinase inhibitors for the treatment of proliferative diseases
US9241942B2 (en) 2007-06-08 2016-01-26 Mannkind Corporation IRE-1α inhibitors
US10966966B2 (en) 2019-08-12 2021-04-06 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11185535B2 (en) 2019-12-30 2021-11-30 Deciphera Pharmaceuticals, Llc Amorphous kinase inhibitor formulations and methods of use thereof
US11266635B2 (en) 2019-08-12 2022-03-08 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11395818B2 (en) 2019-12-30 2022-07-26 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea
US11779572B1 (en) 2022-09-02 2023-10-10 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11986463B2 (en) 2018-01-31 2024-05-21 Deciphera Pharmaceuticals, Llc Combination therapy for the treatment of gastrointestinal stromal tumor
US12102620B2 (en) 2018-01-31 2024-10-01 Deciphera Pharmaceuticals, Llc Combination therapy for the treatment of mastocytosis

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0533268A1 (fr) * 1991-09-18 1993-03-24 Glaxo Group Limited Dérivés de benzanilide comme 5-HT1D antagonistes
WO1995017401A1 (fr) * 1993-12-21 1995-06-29 Smithkline Beecham Plc Carboxamides de dihydrobenzofuranyle-biphenyle presentant une activite antagoniste du 5ht¿1d?
WO1996011934A1 (fr) * 1994-10-18 1996-04-25 Smithkline Beecham Plc Composes spiro tricycliques, leur procede de preparation et leur utilisation en tant qu'antagonistes du recepteur de 5ht1d

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0533268A1 (fr) * 1991-09-18 1993-03-24 Glaxo Group Limited Dérivés de benzanilide comme 5-HT1D antagonistes
WO1995017401A1 (fr) * 1993-12-21 1995-06-29 Smithkline Beecham Plc Carboxamides de dihydrobenzofuranyle-biphenyle presentant une activite antagoniste du 5ht¿1d?
WO1996011934A1 (fr) * 1994-10-18 1996-04-25 Smithkline Beecham Plc Composes spiro tricycliques, leur procede de preparation et leur utilisation en tant qu'antagonistes du recepteur de 5ht1d

Cited By (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7144911B2 (en) 2002-12-31 2006-12-05 Deciphera Pharmaceuticals Llc Anti-inflammatory medicaments
US7279576B2 (en) 2002-12-31 2007-10-09 Deciphera Pharmaceuticals, Llc Anti-cancer medicaments
US7342037B2 (en) 2002-12-31 2008-03-11 Deciphera Pharmaceuticals, Llc Anti-inflammatory medicaments
US7666895B2 (en) 2002-12-31 2010-02-23 Deciphera Pharmaceuticals, Llc Anti-inflammatory medicaments
US7737283B2 (en) 2002-12-31 2010-06-15 Deciphera Pharmaceuticals, Llc Anti-inflammatory medicaments
US7202257B2 (en) 2003-12-24 2007-04-10 Deciphera Pharmaceuticals, Llc Anti-inflammatory medicaments
US8143293B2 (en) 2007-04-20 2012-03-27 Deciphera Pharmaceuticals, Llc Kinase inhibitors useful for the treatment of myleoprolific diseases and other proliferative diseases
US9241942B2 (en) 2007-06-08 2016-01-26 Mannkind Corporation IRE-1α inhibitors
US9546149B2 (en) 2007-06-08 2017-01-17 Mannkind Corporation IRE-1α inhibitors
US9981901B2 (en) 2007-06-08 2018-05-29 Fosun Orinove Pharmatech, Inc. IRE-1α inhibitors
US8940756B2 (en) 2012-06-07 2015-01-27 Deciphera Pharmaceuticals, Llc Dihydronaphthyridines and related compounds useful as kinase inhibitors for the treatment of proliferative diseases
USRE48731E1 (en) 2012-06-07 2021-09-14 Deciphera Pharmaceuticals, Llc Dihydronaphthyridines and related compounds useful as kinase inhibitors for the treatment of proliferative diseases
US12102620B2 (en) 2018-01-31 2024-10-01 Deciphera Pharmaceuticals, Llc Combination therapy for the treatment of mastocytosis
US11986463B2 (en) 2018-01-31 2024-05-21 Deciphera Pharmaceuticals, Llc Combination therapy for the treatment of gastrointestinal stromal tumor
US12023326B2 (en) 2019-08-12 2024-07-02 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11344536B1 (en) 2019-08-12 2022-05-31 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US12318373B2 (en) 2019-08-12 2025-06-03 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11426390B2 (en) 2019-08-12 2022-08-30 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11433056B1 (en) 2019-08-12 2022-09-06 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11529336B2 (en) 2019-08-12 2022-12-20 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11534432B2 (en) 2019-08-12 2022-12-27 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11576904B2 (en) 2019-08-12 2023-02-14 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US12295944B2 (en) 2019-08-12 2025-05-13 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US10966966B2 (en) 2019-08-12 2021-04-06 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US12059410B2 (en) 2019-08-12 2024-08-13 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US12059411B2 (en) 2019-08-12 2024-08-13 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US12023327B2 (en) 2019-08-12 2024-07-02 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11813251B2 (en) 2019-08-12 2023-11-14 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US12023325B2 (en) 2019-08-12 2024-07-02 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11266635B2 (en) 2019-08-12 2022-03-08 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11969414B2 (en) 2019-08-12 2024-04-30 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors
US11911370B1 (en) 2019-12-30 2024-02-27 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US11793795B2 (en) 2019-12-30 2023-10-24 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea
US11896585B2 (en) 2019-12-30 2024-02-13 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea
US11918564B1 (en) 2019-12-30 2024-03-05 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US11850241B1 (en) 2019-12-30 2023-12-26 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US11969415B1 (en) 2019-12-30 2024-04-30 Deciphera Pharmaceuticals, Llc (methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US11850240B1 (en) 2019-12-30 2023-12-26 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US11844788B1 (en) 2019-12-30 2023-12-19 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US12023328B2 (en) 2019-12-30 2024-07-02 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US11185535B2 (en) 2019-12-30 2021-11-30 Deciphera Pharmaceuticals, Llc Amorphous kinase inhibitor formulations and methods of use thereof
US11801237B2 (en) 2019-12-30 2023-10-31 Deciphera Pharmaceuticals, Llc Amorphous kinase inhibitor formulations and methods of use thereof
US11903933B2 (en) 2019-12-30 2024-02-20 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US11395818B2 (en) 2019-12-30 2022-07-26 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea
US12064422B2 (en) 2019-12-30 2024-08-20 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US11612591B2 (en) 2019-12-30 2023-03-28 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea
US12213967B2 (en) 2019-12-30 2025-02-04 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US12213968B2 (en) 2019-12-30 2025-02-04 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US12226406B2 (en) 2019-12-30 2025-02-18 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US11576903B2 (en) 2019-12-30 2023-02-14 Deciphera Pharmaceuticals, Llc Amorphous kinase inhibitor formulations and methods of use thereof
US12318374B2 (en) 2019-12-30 2025-06-03 Deciphera Pharmaceuticals, Llc Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoropheyl)-3-phenylurea
US11779572B1 (en) 2022-09-02 2023-10-10 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors

Also Published As

Publication number Publication date
JP2000506877A (ja) 2000-06-06
EP0888357A1 (fr) 1999-01-07
GB9605945D0 (en) 1996-05-22

Similar Documents

Publication Publication Date Title
US5905080A (en) Amide and urea derivatives as 5HT1D receptor antagonists
US5919932A (en) Biphenylamide derivatives as 5HT1D antagonists
KR101108722B1 (ko) 데아자퓨린 및 이의 용도
EP0736025B1 (fr) Carboxamides de dihydrobenzofuranyle-biphenyle presentant une activite antagoniste du 5ht1d
US5834471A (en) Amide derivatives as 5HT1D receptor antagonists
US5696122A (en) Indole and indoline derivatives as 5HT1D receptor antagonists
EP0788499A1 (fr) Derives de pyridinyluree actifs dans le traitement des troubles du systeme nerveux central
JPH11505236A (ja) フェニルジヒドロベンゾフラン
WO1997034900A1 (fr) Derives azaspiro
WO1998042666A1 (fr) Derives 3,4-dialcoxyphenyle et leur utilisation
EP0777650B1 (fr) Derives biphenylamide en tant qu'antagonistes du 5ht 1d
US5889022A (en) Indole, indoline and quinoline derivatives with 5HT1D (anti-depressive) activity
US6066644A (en) Azaspiro derivatives with 5HT1B activity
EP0752982B1 (fr) Derives biphenyles en tant qu'antagonistes du 5ht1d
AU718597B2 (en) Indoline derivatives useful as 5-HT-2C receptor antagonists
WO1998050343A2 (fr) Derives (hetero)aryle carboxamides, leur procede de preparation et leur utilisation dans les desordres cns
JPWO2006082872A1 (ja) １−（ピペリジン−４−イル）−１ｈ−インドール誘導体
US6166034A (en) Spiro piperidine derivatives as 5HT1D receptor antagonists
EP0889893A1 (fr) Derives azaspiro
EP0889892A1 (fr) Derives azaspiro
CA2238162A1 (fr) Composes spiro tricycliques en tant qu'antagonistes recepteurs 5ht1d
KR19990026029A (ko) 신규 화합물
KR20030055769A (ko) 신규한 카테콜 벤즈아미드 유도체 및 그의 제조방법

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US

AL Designated countries for regional patents

Kind code of ref document: A1

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
WWE Wipo information: entry into national phase

Ref document number: 1997914272

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1997914272

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1997914272

Country of ref document: EP