EP0724573A1 - Pyrimidinones as antiarthritic and anti-inflammatories - Google Patents

Pyrimidinones as antiarthritic and anti-inflammatories

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Publication number
EP0724573A1
EP0724573A1 EP94928624A EP94928624A EP0724573A1 EP 0724573 A1 EP0724573 A1 EP 0724573A1 EP 94928624 A EP94928624 A EP 94928624A EP 94928624 A EP94928624 A EP 94928624A EP 0724573 A1 EP0724573 A1 EP 0724573A1
Authority
EP
European Patent Office
Prior art keywords
phenyl
methyl
oxo
alkyl
dihydro
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.)
Withdrawn
Application number
EP94928624A
Other languages
German (de)
English (en)
French (fr)
Inventor
Richard Allen Nugent
Stephen T. Schlachter
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.)
Pharmacia and Upjohn Co
Original Assignee
Pharmacia and Upjohn Co
Upjohn Co
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 Pharmacia and Upjohn Co, Upjohn Co filed Critical Pharmacia and Upjohn Co
Publication of EP0724573A1 publication Critical patent/EP0724573A1/en
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/34—One oxygen atom
    • C07D239/36—One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
    • 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]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/56—One oxygen atom and one sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6509—Six-membered rings
    • C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3

Definitions

  • the present invention is directed toward pyrimidinones and their pharmaceutically acceptable salts which are characterized by (Formula I) which are useful as anti-inflammatories and antiarthritic agents.
  • the present compounds are useful in humans and lower animals as a safe and effective treatment of chronic inflammatory diseases. These diseases include periodontal disease, rheumatoid arthritis, osteoarthritis, neuritis, bursitis, pneumoconioses, Crohn's disease, chronic inflammatory bowel disease, chronic asthma, atherosclerosis, multiple sclerosis, and sarcoidosis.
  • US Patent 4,746,654 discloses bisphosphonates useful as anti-inflammatory agents
  • Australian Patent A-51534/85 discloses bisphosphonates useful in treating abnormal calcium and phosphorous metabolism and useful in treating arthritis
  • US Patent 3,683,080 discloses polyphosphonates; in particular, diphosphonates useful in inhibiting anomalous deposition and mobilization of calcium phosphate in animal tissue
  • European Patent Application 0 168 262 discloses an intermediate pyrimidine compound, Formula Vila which is similar to the subject compound except that the corresponding R 2 is only hydrogen or a lower alkyl. The compounds are described to be useful for treating hypertension and cerebrovascular disease.
  • the present invention is pyrimidinones or its pharmaceutically acceptable salts which are structurally represented by Formula I
  • R 2 is a) (CH 2 ) n -Y and i) where n is 1 then Y is C r C 6 alkoxy, morpholinyl, piperdinyl, pyrrolidinyl, phenoxy, phenylthio, phenylsulfonyl, phenylsulfinyl, -NHC(O)-C 1 -C 6 carboxylic acid, N 3 , NH 2 , diethylamino, hydrogen (provided R 4 is benzyloxy), halogen (provided R 3 is a C j -Cg alkyl) or CH("EWG") 2 where "EWG" is an electron withdrawing group each individually selected from the group consisting of CO 2 R or
  • R 3 is hydrogen or C j -C 8 alkyl
  • R 4 is hydrogen, hydroxyl, C j -C 8 alkyl, alkoxy, benzyloxy or phenoxy
  • R 5 is hydrogen, halogen, C j -C 8 alkyl, C j -C 8 alkoxy, phenoxy, C j -C 8 alkylthio, thiophenyl, NH 2 , Aryl (except that R 5 is other than phenyl when R 4 and Y are both hydrogen) or Heteroaryl;
  • R 6 is H, C j -C 8 alkyl, benzyl, phenyl, phenyl substituted with one to five F, Cl, Br, I, NO 2 , OCH 3 or C r C 4 alkyl;
  • R 7 is H, C j -C alkyl, benzyl, phenyl, phenyl substituted with one to five F, Cl, Br, I, NO 2 , OCH g or C j -C ⁇ alkyl, or where both R 7 's are taken together to form a CH 2 - CH , CH 2 -CH 2 -CH 2 or CH 2 -C(CH 3 ) 2 -CH 2 whereby a heterocyclic ring containing the bonded P atom and the two O atoms is formed.
  • the present invention comprises the use of these compounds in humans and lower animals as a safe and effective treatment of chronic inflammatory diseases.
  • the invention is a method for treating inflammation by administering to a patient (animals, including humans) in need of such treatment an anti-inflammatory effective amount of a compound of Formula I.
  • routes of administration include oral, intramuscular, intravenous, transdermal, intra-articular, subcutaneous, or intraperitoneal.
  • An effective amount is an amount whereby the symptoms of inflammation or arthritis such as pain and discomfort are relieved or reduced or mobility of the affected area is increased.
  • a typical dosage is about 0.001 mg to 1.0 gram with dose determined by the particular mode of administration, use and frequency of administration.
  • the present invention comprises pyrimidinones and their pharmaceutically acceptable salts which are characterized by (Formula I, above) and which are useful as anti-inflammatories and anti-arthritic agents. These compounds are particularly useful in the treatment of arthritis and its associated symptoms such as inflammation and excessive bone growth or remodelling.
  • Formula I the variable designations are further defined as follows.
  • C-C j defines the number of carbon atoms present from the integer "i" to the integer "j” inclusive.
  • C j -C 8 alkyl refers to alkyl of 1-3 carbon atoms, inclusive, or methyl, ethyl, propyl, and isopropyl.
  • C j -C 8 alkyl is methyl, ethyl, propyl, butyl, pentyl, hexyl, and isomeric forms thereof.
  • aAryl means phenyl or naphthyl.
  • Heteroaryl means morpholinyl, piperazinyl, piperidinyl, imidazolidinyl, pyrazolidinyl, isoxazolyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl.
  • halogen includes fluoro, chloro, bromo and iodo.
  • Pharmaceutically acceptable salts means salts useful for administering the compounds of this invention or useful forms the compounds may take in vitro or in vivo and include potassium, sodium, hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, acetate, propionate, lactate, mesylate, maleate, malonate, succinate, tartrate, citric acid and the like. These salts may be in hydrated form.
  • pyrimidinones and derivatives (Formula I) useful as anti-inflammatories and antiarthritics are prepared as shown in Examples 1-35 and in Table 1, below.
  • the Formula I compounds of this invention have been tested in a Delayed Type Hypersensitivity Granuloma Assay (DTH GRA) model for inflammation.
  • DTH GRA Delayed Type Hypersensitivity Granuloma Assay
  • mice have a DTH granuloma (DTH GRA) lesion induced by subcutaneously implanting a mBSA-soaked filter which is excised after nine days.
  • DTH GRA DTH granuloma
  • Compounds are administered to the mice to determine their effect on the lesions. The results are recorded as percent inhibition. The larger the inhibition, the more effective the compound. Inhibition of 10 to 20% is considered to indicate anti- granuloma activity. Greater than 30% inhibition is good activity.
  • the DTH GRA data obtained from the compounds of Formula 1 are shown in the Table 2, below. The compounds are scored as having anti-inflammatory activity at 10-20% inhibition and good activity at greater than 30% inhibition.
  • Example 2 Made by the same method of Example 2 were Examples 3-6, whose compounds are identified below.
  • EXAMPLE 3 4(3H)-Pyrimidinone, 3-methyl-6-phenyl-2-[(phenylthio)methyl]-
  • EXAMPLE 4 Phosphonic acid, [2-(l,6-dihydro-l-methyl-6-oxo-4-phenyl-2- pyrimidinyl) ethylidene]bis-, tetraethyl ester
  • R 3 is methyl
  • R 4 is hydrogen
  • R 5 is phenyl
  • R 2 is -CH 2 -CH-(PO(OEt) 2 ) 2 , mp 86-88°C.
  • EXAMPLE 5 Propanedioic acid, [(l,6-dihydro-l-methyl-6-oxo-4-phenyl-2- pyrimidinyl)methyl]-, diethyl ester
  • R 3 is methyl
  • R 4 is hydrogen
  • R 5 is phenyl
  • R 2 is -CH 2 -CH-(CO 2 Et) 2 , mp 102-103°C.
  • EXAMPLE 6 2-Pyrimidinepropanoicacid,.alpha.-(diethoxyphosphinyl)-l,6- dihydro-1- methyl-6-oxo-4-phenyl-, ethyl ester
  • R 3 is methyl
  • R 4 is hydrogen
  • R 5 is phenyl
  • R 2 is -CH 2 -CH(CO 2 Et)(PO(OEt) 2 ), mp 119°C.
  • Example 7 Made by the same method of Example 7, the title compound was prepared, mp 133-134°C.
  • Example 7 Made by the same method of Example 7, the title compound was prepared, mp 84-85°C.
  • EXAMPLE 12 4(3H)-Pyrimidinone, 2-(aziodomethyl)-3-methyl-6-phenyl- 4(3H)-Pyrimidinone, 2-(iodomethyl)-3-methyl-6-phenyl- (4.06 g, 12.4 mmol) was treated with sodium azide (1.62 g, 24.9 mmol) and acetonitrile (25 ml) and stirred at 22°C for 60 hours then concentrated in vacuo. The residue was dissolved in methylene chloride, washed with saturated NaHCO 3 , 3x IM NaHSO 3 , saturated NaCl, dried with MgSO 4 , and concentrated in vacuo (40%), mp 111-112°C.
  • EXAMPLE 15 Butanoic acid, 4-[[(l,6-dihydro-l-methyl-6-oxo-4-phenyl-2- pyrimidinyl) methyl] amino]-4-oxo- 4(3H)-Pyrimidinone, 2-(aminomethyl)-3-methyl-6-phenyl- (304 mg, 1.41 mmol) dissolved in chloroform (5 ml) was treated with succinic anhydride (141 mg, 1.41 mmol) then heated to reflux for 1 hour. The resultant solid was filtered, washed with chloroform and dried: 0.377 g, (1.20 mmol, 85%), mp 200-201°C.
  • Example 15 In a similar to Example 15 manner the title compound was prepared: from glutaric anhydride (62%), mp 181-182°C.
  • Benzenesulfinic acid, sodium salt (0.346 g, 2.1 mmol) was slurried in toluene (5 ml), then treated with 4(3H)-Pyrimidinone, 2-(iodomethyl)-3-methyl-6-phenyl- (0.517 g, 1.6 mmol) and heated to 70°C for 20 hours. The reaction was cooled to room temperature and most of the solvent was removed in vacuo. The residue was dissolved in methylene chloride, washed thrice with saturated NaHCO g and IM NaHSO g , dried with MgSO 4 , and concentrated in vacuo.
  • title compound was prepared from glutaric anhydride (26%), mp 170-171°C.
  • EXAMPLE 22 Phosphonic acid, [(l,6-dihydro-l-methyl-6-oxo-4-phenyl-2- pyrimidinyl)cyclopropylidene]bis-,tetraethyl ester
  • EXAMPLE 25 Propanedioic acid, [2-(l,6-dihydro-l-methyl-6-oxo-4-phenyl-2- pyrimidinyDethyl]-, bis(l,l-dimethylethyl) ester 4(3H)-Pyrimidmone, 2,3-dimethyl-6-phenyl (0.744 g, 3.72 mmol) was dissolved in THF (37 ml), cooled to -78°C, then treated with lithium bis(trimethylsilyl)amide (4.1 ml, 4.1 mmol).
  • the ester (22.10 g, 0.113 mol) was dissolved in THF (5 ml) and added slowly to a -78°C solution of LiHMDS (1 M in THF, 230 ml, 0.230 mol). After stirring for 45 minutes, benzoyl chloride (13.1 ml, 0.113 mol) was added and the reaction warmed to room temperature for 45 minutes. It was quenched with 1 N HC1, extracted thrice with methyl t-butyl ether, dried with MgSO 4 , and stripped: 45.68 g (0.153 mol).
  • the crude material, acetamidine hydrochloride (28.95 g, 0.306 mol), and 25% sodium methoxide/methanol (77 ml, 0.336 mol) were combined and heated to reflux for 36 hours. It was cooled, diluted with water, and pH adjusted to 7 with concentrated HC1. The precipitate was collected, washed with cold ether, and air dried: 20.45 g (70.00 mmol, 62%), mp 168°C.
  • the pyrimidinone (5.84 g, 20.0 mmol), K g CO g (3.20 g, 23 mmol), and methyl iodide (3.7 ml, 60 mmol) were heated in refluxing methanol (50 ml) overnight. The reaction was cooled and seeded. The precipitate was collected, washed with water and dried in the oven: 5.052 g (16.49 mmol, 82%), mp 118-119°C.
  • EXAMPLE 28 Phosphonic acid, [3-(l,6-dihydro-5-hydroxy-l-methyl-6-oxo-4- phenyl-2-pyrimidinyl)propylidene]bis-, tetraethyl ester Phosphonic acid, [3-[l,6-dihydro-l-methyl-6-oxo-4-phenyl-5-(phenylmethoxy)-2- pyrimidinyl]propylidene]bis-, tetraethyl ester (1.60 g, 2.64 mmol) in ethanol (50 ml) was treated with 10% Pd/C (320 mg) and ammonium formate (4.00 g), then heated to reflux for 2 hours.
  • the catalyst was removed by filtering through Celite and stripped. The residue was dissolved in methylene chloride, filtered through a short pad of silica gel and the pad was washed well with acetone. After concentration, the crude material was recrystallized from methyl t-butyl ether: 884 mg (1.71 mmol, 65%), mp 138-139°C.
  • Hydrogen chloride gas (2.0 g, 55 mmol) was slowly bubbled into acetonitrile (7.5 ml).
  • EXAMPLE 31 4(3H)-Pyrimidinone,2,3-dimethyl-6-phenylthio- Sodium hydride (0.36 g, 7.5 mmol) slurried in dimethyl formamide (25 ml) was treated with thiophenol (0.73 ml, 7.12 mmol) and 6-chloro-2,3-dimethyl-4(3H)- pyrimidinone (1.13 g, 7.13 mmol). The mixture was stirred at 22°C for 24 hours then diluted with H 2 O (70 ml).
  • EXAMPLE 32 4(3H)-Pyrimidinone, 2,3-dimethyl-6-piperidinyl 4(3H)-Pyrimidinone, 6-chloro-2,3-dimethyl- (0.778 g, 4.90 mmol) was slurried in piperidine (15 ml) and the solution was heated to reflux for 1 hour, then at 60°C for 18 hours. The reaction mixture was filtered through Celite and concentrated in vacuo. The residue was dissolved in methylene chloride and washed with 6% NaHCO 3 , 2 x H 2 O, then dried with MgSO 4 .

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Rheumatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pain & Pain Management (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP94928624A 1993-10-20 1994-09-21 Pyrimidinones as antiarthritic and anti-inflammatories Withdrawn EP0724573A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US161676 1988-02-29
US13907893A 1993-10-20 1993-10-20
US139078 1993-10-20
US16167693A 1993-12-03 1993-12-03
PCT/US1994/010571 WO1995011235A1 (en) 1993-10-20 1994-09-21 Pyrimidinones as antiarthritic and anti-inflammatories

Publications (1)

Publication Number Publication Date
EP0724573A1 true EP0724573A1 (en) 1996-08-07

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EP94928624A Withdrawn EP0724573A1 (en) 1993-10-20 1994-09-21 Pyrimidinones as antiarthritic and anti-inflammatories

Country Status (4)

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EP (1) EP0724573A1 (ja)
JP (1) JPH09504010A (ja)
AU (1) AU7798994A (ja)
WO (1) WO1995011235A1 (ja)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2269681A1 (en) * 1996-12-12 1998-06-18 Pharmacia & Upjohn Company Llc Use of a 6-aryl pyrimidine compound for treating multiple sclerosis
DK1483247T3 (da) 2002-03-13 2009-08-17 Euro Celtique Sa Arylsubstituerede pyrimidiner og anvendelsen deraf
US7166595B2 (en) * 2002-05-09 2007-01-23 Cytokinetics, Inc. Compounds, methods and compositions
AU2003231799A1 (en) * 2002-05-23 2003-12-12 Merck & Co., Inc. Mitotic kinesin inhibitors
US20070167621A1 (en) 2003-04-03 2007-07-19 Pharmacia Corporation Substituted pyrimidinones
US7183287B2 (en) * 2003-04-03 2007-02-27 Pharmacia Corporation Substituted pyrimidinones
CA2547209A1 (en) 2003-12-19 2005-07-07 Merck & Co., Inc. Mitotic kinesin inhibitors
MX2007004514A (es) 2004-10-13 2007-05-09 Pharmacia & Upjohn Co Llc Formas cristalinas de 3-[5-cloro-4-[(2,4-difluorobencil)oxi]-6 oxopirimidin-1(6h)-il]-n-(2-hidroxetil)-4-metilbenzamida.
GB201111705D0 (en) * 2011-07-07 2011-08-24 Takeda Pharmaceutical Compounds and their use
JO3115B1 (ar) 2011-08-22 2017-09-20 Takeda Pharmaceuticals Co مركبات بيريدازينون واستخدامها كمثبطات daao
UA111861C2 (uk) 2011-11-15 2016-06-24 Такеда Фармасьютікал Компані Лімітед Ароматична гетероциклічна сполука дигідрокси
ES2716008T3 (es) 2012-07-18 2019-06-07 Sunshine Lake Pharma Co Ltd Derivados heterocíclicos nitrogenados y su aplicación en fármacos
GB201222711D0 (en) 2012-12-17 2013-01-30 Takeda Pharmaceutical Novel compounds
WO2015036563A1 (de) 2013-09-16 2015-03-19 Bayer Pharma Aktiengesellschaft Disubstituierte trifluormethylpyrimidinone und ihre verwendung als ccr2 antagonisten
CA2929394C (en) 2013-12-19 2021-11-16 Sunshine Lake Pharma Co., Ltd. Nitrogenous heterocyclic derivatives and their application in drugs
WO2016113205A1 (de) 2015-01-13 2016-07-21 Bayer Pharma Aktiengesellschaft Substituierte pentafluorethylpyrimidinone und ihre verwendung
AU2020412853A1 (en) * 2019-12-23 2022-05-26 Sitryx Therapeutics Limited Carboxy derivatives with antiinflammatory properties

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0521622B1 (en) * 1991-07-03 1997-08-13 PHARMACIA & UPJOHN COMPANY Pyrazolopyrimidine and pyrimidinyl bisphosphonic esters as anti-inflammatories
US5298481A (en) * 1992-07-17 1994-03-29 Rohm And Haas Company 6-arylpyrimidines and herbicidal use

Non-Patent Citations (1)

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Title
See references of WO9511235A1 *

Also Published As

Publication number Publication date
AU7798994A (en) 1995-05-08
WO1995011235A1 (en) 1995-04-27
JPH09504010A (ja) 1997-04-22

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