WO1996041803A1 - Derives d'acide piperidineacetique comme inhibiteurs d'agregat de plaquettes sanguines dependant du fibrinogene - Google Patents

Derives d'acide piperidineacetique comme inhibiteurs d'agregat de plaquettes sanguines dependant du fibrinogene Download PDF

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Publication number
WO1996041803A1
WO1996041803A1 PCT/EP1996/002536 EP9602536W WO9641803A1 WO 1996041803 A1 WO1996041803 A1 WO 1996041803A1 EP 9602536 W EP9602536 W EP 9602536W WO 9641803 A1 WO9641803 A1 WO 9641803A1
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WO
WIPO (PCT)
Prior art keywords
formula
compound
piperidin
pharmaceutically acceptable
compounds
Prior art date
Application number
PCT/EP1996/002536
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English (en)
Inventor
Brian David Judkins
Original Assignee
Glaxo Group Limited
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 Glaxo Group Limited filed Critical Glaxo Group Limited
Priority to AU63025/96A priority Critical patent/AU6302596A/en
Publication of WO1996041803A1 publication Critical patent/WO1996041803A1/fr

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Classifications

    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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

Definitions

  • P1per1d1neacet1c add derivatives as Inhibitors of fibrinogen-dependent blood platelet aggregation
  • This invention relates to acetic acid derivatives, to processes for their preparation, to pharmaceutical compositions containing such compounds and to their use in medicine.
  • glycoprotein complex Gp I lb/11 la is the fibrinogen binding site on platelets that mediates the adhesive function required for platelet aggregation and thrombus formation.
  • Gp I lb/11 la is the fibrinogen binding site on platelets that mediates the adhesive function required for platelet aggregation and thrombus formation.
  • the invention further provides a compound of formula (I)
  • pharmaceutically acceptable derivative is meant any pharmaceutically acceptable salt, solvate or ester, or salt or solvate of such ester, of the compounds of formula (I), or any other compound which upon administration to the recipient is capable of providing (directly or indirectly) a compound of formula (I) or an active metabolite or residue thereof.
  • salts referred to above will be the physiologically acceptable salts, but other salts may find use, for example in the preparation of compounds of formula (I) and the physiologically acceptable salts thereof.
  • Suitable physiologically acceptable salts of the compounds of formula (I) include acid addition salts formed with inorganic or organic acids (for example hydrochlorides, hydrobromides, sulphates, phosphates, benzoates, naphthoates, hydroxynaphthoates, p-toluenesulphonates, methanesulphonates, sulphamates, ascorbates, tartrates, salicylates, succinates, lactates, glutarates, glutaconates, acetates, tricarballylates, citrates, fumarates and maleates) and inorganic base salts such as alkali metal salts (for example sodium salts).
  • inorganic or organic acids for example hydrochlorides, hydrobromides, sulphates, phosphates, benzoates, naphthoates, hydroxynaphthoates, p-toluenesulphonates, methanesulphonates, sulphamates, as
  • salts of the compounds of formula (I) include salts formed with trifluoro- acetic acid.
  • compounds of interest include carboxylic acid esters of the compounds of formula (I).
  • esters include C ⁇ _6alkyl esters.
  • carboxylic acid ester derivatives of formula (I) may be useful as intermediates in the preparation of compounds of formula (I), or as pharmaceutically acceptable derivatives of formula (I), or both.
  • the term 'alkyl' as a group or part of a group means a straight or branched chain alkyl group, for example a methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl or t-butyl group.
  • the present invention encompasses all isomers of the compounds of formula (I) and their pharmaceutically acceptable derivatives, including all geometric, tautomeric and optical forms, and mixtures thereof (e.g. racemic mixtures).
  • the present invention provides a compound selected from:
  • a preferred compound of the invention is:
  • the compounds of the present invention are of interest for use in human and veterinary medicine, particularly in the treatment of thrombotic disorders.
  • thrombotic disorders include occlusive vascular diseases such as myocardial infarction, cardiac fatalities, angina, transient ischaemic attacks and thrombotic stroke, arteriosclerosis, vessel wall disease, peripheral vascular disease, nephropathy, retinopathy, postoperative thrombosis, pulmonary embolism, deep vein thrombosis and retinal vein thrombosis.
  • the compounds of the invention are also of interest for use in the prophylactic treatment of peri- and postoperative complications following organ transplantation (particularly cardiac and renal), coronary artery bypass, peripheral artery bypass, angioplasty, thrombolysis and endarterectomy.
  • the compounds of the invention may also be useful for the treatment of other conditions in which the glycoprotein complex Gp llb/llla or other integrin receptors are implicated.
  • the compounds of the invention may potentiate wound healing and be useful in the treatment of bone conditions caused or mediated by increased bone resorption.
  • bone diseases include osteoporosis, hypercalcaemia of malignancy, osteopenia due to bone metastases, periodontal disease, hyperparathyroidism, periarticular erosions in rheumatoid arthritis, Paget's disease, immobilization-induced osteopenia and glucocorticoid treatment.
  • the compounds of the invention may also be useful for the treatment of certain cancerous diseases.
  • compounds of the invention may be of use to prevent or delay metastasis in cancer.
  • a compound of formula (I) or a pharmaceutically acceptable derivative thereof for use in human or veterinary medicine, particularly for use in the treatment of thrombotic disorders.
  • a compound of formula (I) or a pharmaceutically acceptable derivative thereof for use in the treatment of a condition which is mediated through the Glycoprotein complex Gpllb/llla or other integrin receptor.
  • a method of treating a human or animal subject suffering from a condition which is mediated through the Glycoprotein complex Gpllb/llla or other integrin receptor which comprises administering to said subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable derivative.
  • a method of treating a human or animal subject suffering from a thrombotic disorder comprises administering to said subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable derivative thereof.
  • the compounds of the invention may advantageously be used in conjunction with one or more other therapeutic agents.
  • suitable agents for adjunctive therapy include thrombolytic agents or any other compound stimulating thrombolysis or fibrinolysis and cytotoxic drugs.
  • thrombolytic agents or any other compound stimulating thrombolysis or fibrinolysis and cytotoxic drugs.
  • present invention covers the use of a compound of formula (I) or a pharmaceutically acceptable derivative thereof in combination with one or more other therapeutic agents.
  • compositions comprising a compound of formula (I) or a pharmaceutically acceptable derivative thereof adapted for use in human or veterinary medicine.
  • Such compositions may conveniently be presented for use in conventional manner in admixture with one or more physiologically acceptable carriers or excipients.
  • the compounds according to the invention may be formulated for administration in any suitable manner.
  • the compounds may, for example, be formulated for topical administration or administration by inhalation or, more preferably, for oral, transdermal or parenteral administration.
  • the pharmaceutical composition may take the form of, for example, tablets, capsules, powders, solutions, syrups or suspensions prepared by conventional means with acceptable excipients.
  • the pharmaceutical composition may be given in the form of a transdermal patch, such as a transdermal iontophoretic patch.
  • a transdermal patch such as a transdermal iontophoretic patch.
  • the pharmaceutical composition may be given as an injection or a continuous infusion (e.g. intravenously, intravascularly or subcutaneously).
  • the compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles and may contain formulatory agents such as suspending, stabilising and/or dispersing agents.
  • For administration by injection these may take the form of a unit dose presentation or as a multidose presentation preferably with an added preservative.
  • the active ingredient may be in powder form for reconstitution with a suitable vehicle.
  • the compounds of the invention may also be formulated as a depot preparation.
  • Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection.
  • the compounds of the invention may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.
  • the compounds of the invention may also be used in combination with other therapeutic agents.
  • the invention thus provides, in a further aspect, a combination comprising a compound of formula (I) or a pharmaceutically acceptable derivative thereof together with a further therapeutic agent, in particular a thrombolytic agent.
  • compositions comprising a combination as defined above together with a pharmaceutically acceptable carrier or excipient comprise a further aspect of the invention.
  • the individual components of such combinations may be administered either sequentially or simultaneously in separate or combined pharmaceutical formulations.
  • a proposed daily dosage of a compound of formula (I) for the treatment of man is 0.01 mg/kg to 30 mg/kg, which may be conveniently administered in 1 to 4 doses.
  • the precise dose employed will depend on the age and condition of the patient and on the route of administration.
  • a daily dose of 0.1 mg/kg to 10mg/kg may be suitable for systemic administration.
  • X is defined as in formula (I) above unless otherwise stated and R represents a chlorine, bromine or iodine atom, or a -OSO 2 CF 3 group.
  • compounds of formula (I) may be prepared by reacting a compound of formula (II)
  • Suitable transition metal catalysts include palladium catalysts, such as a palladium triarylphosphine catalyst.
  • Suitable temperatures are from about 50 to about 200°C, such as 80 to 120°C, or the reflux temperature of the solvent.
  • the reaction is effected in the presence of a base, such as a tertiary amine; a palladium catalyst, for example a palladium triarylphosphine catalyst; a solvent, such as a polar solvent, for example ⁇ /./V-dimethylfoimamide; and at elevated temperature, for example from about 50 to 200°C, such as at 80 to 120°C, or the reflux temperature of the solvent reflux.
  • a base such as a tertiary amine
  • a palladium catalyst for example a palladium triarylphosphine catalyst
  • a solvent such as a polar solvent, for example ⁇ /./V-dimethylfoimamide
  • elevated temperature for example from about 50 to 200°C, such as at 80 to 120°C, or the reflux temperature of the solvent reflux.
  • compounds of formula (I) may be prepared by interconversion, utilising other compounds of formula (I) as precursors.
  • the hydrogenation may be effected in the presence of a transition metal catalyst, such as Raney Nickel, or a palladium, platinum or rhodium catalyst.
  • a transition metal catalyst such as Raney Nickel
  • a palladium, platinum or rhodium catalyst effected in a solvent, such as an alcohol (e.g. ethanol).
  • hydrogenation may be effected using diimide.
  • diimide is generated in situ from a suitable salt, such as diazenedicarboxylic acid, dipotassium salt, and the reaction is effected in the presence of an acid, such as acetic acid, and a solvent, such as an alcohol (e.g. methanol).
  • a suitable salt such as diazenedicarboxylic acid, dipotassium salt
  • the reaction is effected in the presence of an acid, such as acetic acid, and a solvent, such as an alcohol (e.g. methanol).
  • an alcohol e.g. methanol
  • Another process (C) for preparing compounds of formula (I) thus comprises deprotecting protected derivatives of compounds of formula (I).
  • compounds of formula (I) may be prepared from protected carboxyl derivatives of compounds of formula (I).
  • compounds of formula (I) may be prepared from protected amino derivatives of compounds of formula (I).
  • the protecting groups used in the preparation of compounds of formula (I) may be used in conventional manner. See, for example, those described in 'Protective Groups in Organic Synthesis' by Theodora W. Green, second edition, (John Wiley and Sons, 1991), which also describes methods for the removal of such groups.
  • carboxyl protecting groups include, for example, carboxylic acid ester groups such as carboxylic acid alkyl or aralkyl esters, for example where the alkyl or aralkyl portion of the ester function is methyl, ethyl, tert-butyl, methoxymethyl, benzyl, diphenylmethyl, triphenylmethyl or p-nitrobenzyl.
  • carboxylic acid ester groups such as carboxylic acid alkyl or aralkyl esters, for example where the alkyl or aralkyl portion of the ester function is methyl, ethyl, tert-butyl, methoxymethyl, benzyl, diphenylmethyl, triphenylmethyl or p-nitrobenzyl.
  • ester is an unbranched alkyl (e.g. methyl) ester deprotection may be effected under conditions of either basic hydrolysis, for example using lithium hydroxide, or acidic hydrolysis, for example using hydroch
  • Tert-butyl and triphenylmethyl ester groups may be removed under conditions of acid hydrolysis, for example using formic or trifluoroacetic acid at room temperature or using hydrochloric acid in acetic acid.
  • Benzyl, diphenylmethyl and nitrobenzyl ester groups may be removed by hydrogenolysis in the presence of a metal catalyst (e.g. palladium).
  • Particular amino protecting groups include, for example, aralkyl groups such as benzyl, diphenylmethyl or triphenylmethyl groups; and acyl groups such as N- benzyloxycarbonyl, t-butoxycarbonyl or trifluoroacetyl groups.
  • the required isomer may conveniently be separated using preparative high performance liquid chromatography (h.p.l.c.) applied to the final title compounds of processes (A) to (C) above or applied prior to any final deprotection step in said processes.
  • preparative high performance liquid chromatography h.p.l.c.
  • the intermediates formed by coupling a protected derivative of a compound of formula (II) with a protected derivative of formula (III) are also an important aspect of the present invention and include 4- ⁇ 2-[1-(1-tert-butoxycarbonylmethyl-piperidin-4-yl)-1H- indazol-5-yl]-(E)-vinyl ⁇ -piperidine-1 -carboxylic acid, tert-butyl ester.
  • acids of the invention are isolated following work-up as acid addition salts, e.g. trifluoroacetate or hydrochloride salts.
  • Pharmaceutically acceptable acid addition salts of the compounds of the invention may be prepared from the corresponding trifluoroacetate salts by exchange of ion using conventional means, for example by neutralisation of the trifluoroacetate salt using a base such as aqueous sodium hydroxide, followed by addition of a suitable organic or inorganic acid, for example, hydrochloric acid.
  • pharmaceutically acceptable acid addition salts may be prepared directly by effecting deprotection with the appropriate organic or inorganic acid, for example, hydrochloric acid.
  • Inorganic base salts of the compounds of the invention may also be prepared from the corresponding trifluoroacetate salts by addition of a suitable strong base such as sodium hydroxide.
  • Solvates (e.g. hydrates) of a compound of the invention may be formed during the work-up procedure of one of the aforementioned process steps.
  • 5-bromo-1 H indazole may be prepared as follows:
  • 1,4-dioxan (250ml) and 2N aqueous sodium hydroxide (200ml) was treated portionwise, over 15min, with di-tert-butyl dicarbonate (95.4g, 0.437mol) at 25°.
  • Inhibition of platelet aggregation by compounds of the invention was determined according to the following procedure. Citrated whole blood (1 part 3.8% w/v trisodium citrate; 9 parts blood) was obtained from human volunteers, free of medication for at least 10 days prior to donation. The blood was treated with aspirin (0.1 mM) and prostacyclin (0.06 ⁇ M) prior to centrifugation (1400g, 4 minutes, 20°C). The supernatant platelet-rich plasma (PRP) was isolated and further centrifuged (1400g, 10 minutes, 20°C) to sediment the platelets.
  • Human citrated whole blood (1 part 3.8% w/v trisodium citrate: 9 parts blood) was obtained from human volunteers who had been free of medication for at least 10 days prior to donation.
  • the blood was incubated with test compound for 5 minutes at 37°C in a shaking waterbath.
  • a single platelet count was obtained using a Sysmex K-1000 haematological analyser and then platelet aggregation was induced by the addition of 1 ⁇ M U-46619 (a stable thromboxane A2 mimetic). After a further 5 minute incubation in a shaking waterbath (37°C), another single platelet count was taken. The degree of platelet aggregation was assessed from the fall in single platelet count and the ability of the test compounds to inhibit this was determined. The ICso value was then calculated.
  • Example 4 when tested in this screen, had an IC5 0 value of 87nm.

Abstract

La présente invention se rapporte à des composés de formule (I) ainsi qu'à leurs sels, leurs solvates et leurs esters, aux sels et aux solvates desdits esters, ainsi qu'à des dérivés pharmaceutiquement acceptables de composés de formule (I), dans laquelle X représente CH2-CH2 ou CH=CH. L'invention se rapporte également aux procédés de préparation desdits composés de formule (I), aux compositions pharmaceutiques les contenant et leur utilisation en médecine, particulièrement dans le traitement des thromboses.
PCT/EP1996/002536 1995-06-13 1996-06-10 Derives d'acide piperidineacetique comme inhibiteurs d'agregat de plaquettes sanguines dependant du fibrinogene WO1996041803A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU63025/96A AU6302596A (en) 1995-06-13 1996-06-10 Piperidineacetic acid derivatives as inhibitors of fibrinoge n-dependent blood platelet aggregation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9511989.7A GB9511989D0 (en) 1995-06-13 1995-06-13 Chemical compounds
GB9511989.7 1995-06-13

Publications (1)

Publication Number Publication Date
WO1996041803A1 true WO1996041803A1 (fr) 1996-12-27

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AU (1) AU6302596A (fr)
GB (1) GB9511989D0 (fr)
WO (1) WO1996041803A1 (fr)
ZA (1) ZA964968B (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997049382A1 (fr) * 1996-06-21 1997-12-31 Glaxo Group Limited Dispositifs d'administration iontophoretique d'antagonistes de glycoproteine iib/iiia
WO2000035488A2 (fr) * 1998-12-18 2000-06-22 Du Pont Pharmaceuticals Company Medicaments antagonistes du recepteur de la vitronectine
US6511648B2 (en) 1998-12-18 2003-01-28 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US6511649B1 (en) 1998-12-18 2003-01-28 Thomas D. Harris Vitronectin receptor antagonist pharmaceuticals
US6524553B2 (en) 1998-03-31 2003-02-25 Bristol-Myers Squibb Pharma Company Quinolone vitronectin receptor antagonist pharmaceuticals
US6537520B1 (en) 1998-03-31 2003-03-25 Bristol-Myers Squibb Pharma Company Pharmaceuticals for the imaging of angiogenic disorders
US6548663B1 (en) 1998-03-31 2003-04-15 Bristol-Myers Squibb Pharma Company Benzodiazepine vitronectin receptor antagonist pharmaceuticals
US6558649B1 (en) 1998-12-18 2003-05-06 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US6569402B1 (en) 1998-12-18 2003-05-27 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US6794518B1 (en) 1998-12-18 2004-09-21 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
WO2013154109A1 (fr) * 2012-04-10 2013-10-17 大日本住友製薬株式会社 Nouveau dérivé indazole substitué en position 1
JP2015096495A (ja) * 2013-10-08 2015-05-21 大日本住友製薬株式会社 新規１位置換インダゾール誘導体からなる医薬

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0542363A2 (fr) * 1991-11-14 1993-05-19 Glaxo Group Limited Dérivés de l'acide piperidine-acétique comme inhibiteurs de l'agrégation des plaquettes sanguines fibrinogen-dépendants

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0542363A2 (fr) * 1991-11-14 1993-05-19 Glaxo Group Limited Dérivés de l'acide piperidine-acétique comme inhibiteurs de l'agrégation des plaquettes sanguines fibrinogen-dépendants

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997049382A1 (fr) * 1996-06-21 1997-12-31 Glaxo Group Limited Dispositifs d'administration iontophoretique d'antagonistes de glycoproteine iib/iiia
US6524553B2 (en) 1998-03-31 2003-02-25 Bristol-Myers Squibb Pharma Company Quinolone vitronectin receptor antagonist pharmaceuticals
US7052673B2 (en) 1998-03-31 2006-05-30 Bristol-Myers Squibb Pharma Company Pharmaceuticals for the imaging of angiogenic disorders
US6548663B1 (en) 1998-03-31 2003-04-15 Bristol-Myers Squibb Pharma Company Benzodiazepine vitronectin receptor antagonist pharmaceuticals
US6537520B1 (en) 1998-03-31 2003-03-25 Bristol-Myers Squibb Pharma Company Pharmaceuticals for the imaging of angiogenic disorders
US6743412B2 (en) 1998-12-18 2004-06-01 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
WO2000035488A2 (fr) * 1998-12-18 2000-06-22 Du Pont Pharmaceuticals Company Medicaments antagonistes du recepteur de la vitronectine
US6511648B2 (en) 1998-12-18 2003-01-28 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US6558649B1 (en) 1998-12-18 2003-05-06 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US6569402B1 (en) 1998-12-18 2003-05-27 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US6683163B2 (en) 1998-12-18 2004-01-27 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US6689337B2 (en) 1998-12-18 2004-02-10 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
WO2000035488A3 (fr) * 1998-12-18 2000-11-09 Du Pont Pharm Co Medicaments antagonistes du recepteur de la vitronectine
US6794518B1 (en) 1998-12-18 2004-09-21 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US6818201B2 (en) 1998-12-18 2004-11-16 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US7018611B2 (en) 1998-12-18 2006-03-28 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US6511649B1 (en) 1998-12-18 2003-01-28 Thomas D. Harris Vitronectin receptor antagonist pharmaceuticals
US7090828B2 (en) 1998-12-18 2006-08-15 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US7321045B2 (en) 1998-12-18 2008-01-22 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
US7332149B1 (en) 1998-12-18 2008-02-19 Bristol-Myers Squibb Pharma Company Vitronectin receptor antagonist pharmaceuticals
WO2013154109A1 (fr) * 2012-04-10 2013-10-17 大日本住友製薬株式会社 Nouveau dérivé indazole substitué en position 1
US8765786B2 (en) 2012-04-10 2014-07-01 Dainippon Sumitomo Pharma Co., Ltd. 1-substituted indazole derivative
CN104395292A (zh) * 2012-04-10 2015-03-04 大日本住友制药株式会社 新的1-取代的吲唑衍生物
US9051295B2 (en) 2012-04-10 2015-06-09 Sumitomo Dainippon Pharma Co., Ltd. 1-substituted indazole derivative
JPWO2013154109A1 (ja) * 2012-04-10 2015-12-17 大日本住友製薬株式会社 新規１位置換インダゾール誘導体
US9309221B2 (en) 2012-04-10 2016-04-12 Sumitomo Dainippon Pharma Co., Ltd. 1-substituted indazole derivative
JP2015096495A (ja) * 2013-10-08 2015-05-21 大日本住友製薬株式会社 新規１位置換インダゾール誘導体からなる医薬

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Publication number Publication date
ZA964968B (en) 1997-01-29
GB9511989D0 (en) 1995-08-09
AU6302596A (en) 1997-01-09

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