USRE42462E1 - Carboxylic acid derivatives, their preparation and use - Google Patents

Carboxylic acid derivatives, their preparation and use Download PDF

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Publication number
USRE42462E1
USRE42462E1 US12/481,594 US48159497A USRE42462E US RE42462 E1 USRE42462 E1 US RE42462E1 US 48159497 A US48159497 A US 48159497A US RE42462 E USRE42462 E US RE42462E
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phenyl
alkyl
group
alkoxy
alkylthio
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Hartmut Riechers
Dagmar Klinge
Wilhelm Amberg
Andreas Kling
Stefan Muller
Ernst Baumann
Joachim Rheinheimer
Uwe Josef Vogelbacher
Wolfgang Wernet
Liliane Unger
Manfred Raschack
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Royalty Pharma Collection Trust
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Abbott GmbH and Co KG
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Definitions

  • the present invention relates to novel carboxylic acid derivatives, their preparation and use.
  • Endothelin is a peptide which is composed of 21 amino acids and is synthesized and released by the vascular endothelium. Endothelin exists in three isoforms, ET-1, ET-2 and ET-3. In the following text, “endothelin” or “ET” signifies one or all isoforms of endothelin. Endothelin is a potent vasoconstrictor and has a potent effect on vessel tone. It is known that this vasoconstriction is caused by binding of endothelin to its receptor (Nature, 332, (1988) 411-415; FEBS Letters, 231, (1988) 440-444 and Biochem. Biophys. Res. Commun., 154, (1988) 868-875).
  • endothelin causes persistent vasoconstruction in the peripheral, renal and cerebral blood vessels, which may lead to illnesses. It has been reported in the literature that elevated plasma levels of endothelin were found in patients with hypertension, acute myocardial infarct, pulmonary hypertension, Raynaud's syndrome, atherosclerosis and in the airways of asthmatics (Japan J. Hypertension, 12, (1989) 79, J. Vascular Med. Biology 2, (1990) 207, J. Am. Med. Association 264, (1990) 2868).
  • the invention relates to carboxylic acid derivatives of the formula I
  • R is formyl, tetrazole [sic], nitrile [sic], a COOH group —COOH or a radical which can be hydrolyzed to —COOH, and the other substituents have the following meanings:
  • the compounds, and the intermediates for preparing them, such as IV and VI, may have one or more asymmetrical substituted carbon atoms.
  • Such compounds may be in the form of the pure enantiomers or pure diastereomers or a mixture thereof.
  • the use of an enantiomerically pure compound as active substance is preferred.
  • the invention furthermore relates to the use of the above-mentioned carboxylic acid derivatives for producing drugs, in particular for producing endothelin receptor inhibitors.
  • the invention furthermore relates to the preparation of the compounds of the formula IV in enantiomerically pure form.
  • Enantioselective epoxidation of an olefin with two phenyl substituents is known (J. Org. Chem. 59, 1994, 4378-4380).
  • ester groups in these systems permit epoxidation in high optical purity.
  • Carboxylic acid derivatives of the general formula VI can be prepared by reacting the epoxides of the general formula IV (eg. e.g., with R ⁇ ROOR 10 [sic]) with alcohols or thiols of the general formula V where R 6 and Z have the meanings stated in claim 1 .
  • compounds of the general formula IV are heated with compounds of the formula V, in the molar ratio of about 1:1 to 1:7, preferably 1 to 3 mole equivalents, to 50-200° C., preferably 80-150° C.
  • the reaction can also take place in the presence of a diluent. All solvents which are inert toward the reagents used can be used for this purpose.
  • solvents or diluents are water, aliphatic, alicyclic and aromatic hydrocarbons, which may in each case be chlorinated, such as hexane, cyclohexane, petroleum ether, naphtha, benzene, toluene, xylene, methylene chloride, chloroform, carbon tetrachloride, ethyl chloride and trichloroethylene, ethers such as diisopropyl ether, dibutyl ether, methyl tert-butyl ether, propylene oxide, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, alcohols, such as methanol, ethanol, isopropanol, butanol and ethylene glyco
  • the reaction is preferably carried out at a temperature in the range from 0° C. to the boiling point of the solvent or mixture of solvents.
  • Suitable catalysts are strong organic and inorganic acids, and Lewis acids. Examples thereof are, inter alia, sulfuric acid, hydrochloric acid, trifluoroacetic acid, p-toluenesulfonic acid, boron trifluoride etherate and titanium(IV) alcoholates.
  • enantiomerically pure compounds of the formula VI by carrying out a classical racemate resolution on racemic or diastereomeric compounds of the formula VI using suitable enantiomerically pure bases such as brucine, strychnine, quinine, quinidine, chinchonidine [sic], chinchonine [sic], yohimbine, morphine, dehydroabietylamine, ephedrine ( ⁇ ), (+), deoxyephedrine (+), ( ⁇ ), threo-2-amino-1-(p-nitrophenyl)-1,3-propanediol (+), ( ⁇ ), threo-2-(N,N-dimethylamino)-1-(p-nitrophenyl)-1,3-propanediol (+), ( ⁇ ) threo-2-amino-1-phenyl-1,3-propanediol (+), ( ⁇ ), ⁇ -methylbenzylamine (+), ( ⁇ ), ⁇ -(
  • R 15 is halogen or R 16 —SO 2 —
  • R 16 can be C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl or phenyl.
  • the reaction preferably takes place in one of the abovementioned inert diluents with the addition of a suitable base, ie. i.e., of a base which deprotonates the intermediate VI, in a temperature range from room temperature to the boiling point of the solvent.
  • alkali metal or alkaline earth metal hydride such as sodium hydride, potassium hydride or calcium hydride
  • a carbonate such as an alkali metal carbonate, eg. e.g., sodium or potassium carbonate
  • an alkali metal or alkaline earth metal hydroxide such as sodium or potassium hydroxide
  • an organometallic compound such as butyllithium
  • an alkali metal amide such as lithium diisopropylamide.
  • the reaction preferably takes place in one of the above-mentioned inert diluents with the addition of a suitable base, ie. i.e., a base which deprotonates the intermediate IX, in a temperature range from room temperature to the boiling point of the solvent.
  • a suitable base ie. i.e., a base which deprotonates the intermediate IX
  • organic bases such as triethylamine, pyridine, imidazole or diazabicycloundecane [sic].
  • cuprates can be prepared as described in Tetrahedron Letters 23, (1982) 3755.
  • Compounds of the formula I can also be prepared by starting from the corresponding carboxylic acids, ie. i.e., compounds of the formula I where R is COOH, and initially converting these in a conventional manner into an activated form, such as a halide, an anhydride or imidazolide, and then reacting the latter with an appropriate hydroxy compound HOR 10 .
  • This reaction can be carried out in the usual solvents and often requires addition of a base, in which case those mentioned above are suitable.
  • These two steps can also be simplified, for example, by allowing the carboxylic acid to act on the hydroxy compound in the presence of a dehydrating agent such as a carbodiimide.
  • compounds of the formula I can be prepared by starting from the salts of the corresponding carboxylic acids, ie. i.e., from compounds of the formula I where R is COR 1 and R 1 is OM, where M can be an alkali metal cation or the equivalent of an alkaline earth metal cation.
  • salts can be reacted with many compounds of the formula R 1 -A where A is a conventional nucleofugic leaving group, for example halogen such as chlorine, bromine, iodine or aryl- or alkylsulfonyl which is unsubstituted or substituted by halogen, alkyl or haloalkyl, such as toluenesulfonyl and methylsulfonyl, or another equivalent leaving group.
  • A is a conventional nucleofugic leaving group, for example halogen such as chlorine, bromine, iodine or aryl- or alkylsulfonyl which is unsubstituted or substituted by halogen, alkyl or haloalkyl, such as toluenesulfonyl and methylsulfonyl, or another equivalent leaving group.
  • Compounds of the formula R 1 -A with a reactive substituent A are known or can be easily obtained with general expert knowledge
  • R in formula I may vary widely.
  • R is a group
  • R 1 has the following meanings:
  • carboxylic acid derivatives of the general formula I both as pure enantiomers and pure diastereomers or as mixture thereof, are those where the substituents have the following meanings:
  • the ET A receptor-expressing CHO cells were grown in F 12 medium containing 10% fetal calf serum, 1% glutamine, 100 U/ml penicillin and 0.2% streptomycin (Gibco BRL, Gaithersburg, Md., USA).
  • the cells were washed with PBS and incubated with 0.05% trypsin-containing PBS for 5 min. Neutralization was then carried out with F 12 medium, and the cells were collected by centrifugation at 300 ⁇ g. To lyze lyse the cells, the pellet was briefly washed with lysis buffer (5 mM Tris-IICl, pII 7.4 with 10% glycerol) and then incubated at a concentration of 107 cells/ml of lysis buffer at 4° C. for 30 min. The membranes were centrifuged at 20,000 ⁇ g for 10 min, and the pellet was stored in liquid nitrogen.
  • lysis buffer 5 mM Tris-IICl, pII 7.4 with 10% glycerol
  • Guinea pig cerebella were homogenized in a Potter-Elvejhem homogenizer and [lacuna] obtained by differential centrifugation at 1000 ⁇ g for 10 min and repeated centrifugation of the supernatant at 20,000 ⁇ g for 10 min.
  • the membranes were suspended in incubation buffer (50 mM Tris-HCl, pH 7.4 with 5 mM MnCl 2 , 40 ⁇ g/ml bacitracin and 0.2% BSA) at a concentration of 50 ⁇ g of protein per assay mixture and incubated with 25 pM [125I] [ 125 I]-ET 1 (ET A receptor assay) or 25 pM [125I] [ 125 I]-RZ 3 (ET B receptor assay) in the presence and absence of test substance at 25° C.
  • the nonspecific binding was determined using 10 --7 10 ⁇ 7 M ET 1 .
  • the free and bound radioligand were separated by filtration through GF/B glass fiber filters (Whatman, England) on a Skatron cell collector (Skatron, Lier, Norway) and the filters were washed with ice-cold Tris-HCl buffer, pH 7.4 with 0.2% BSA. The radioactivity collected on the filters was quantified using a Packard 2200 CA liquid scintillation counter.
  • This assay system is a functional, cell-based assay for endothelin receptors.
  • endothelin 1 When certain cells are stimulated with endothelin 1 (ET1) they show an increase in the intracellular calcium concentration. This increase can be measured in intact cells loaded with calcium-sensitive dyes.
  • test animals received an i.v. injection of the test compounds (1 ml/kg) 5 min before the administration of ET1.
  • the rise in blood pressure in the test animals was compared with that in the control animals.
  • the principle of the test is the inhibition of the sudden heart death caused in mice by endothelin, which is probably induced by constriction of the coronary vessels, by pretreatment with endothelin receptor antagonists.
  • Intravenous injection of 10 nmol/kg endothelin in a volume of 5 ml/kg of body weight results in death of the animals within a few minutes.
  • the lethal endothelin-1 dose is checked in each case on a small group of animals. If the test substance is administered intravenously, the endothelin-1 injection which was lethal in the reference group usually takes place 5 min thereafter. With other modes of administration, the times before administration are extended, where appropriate up to several hours.
  • the survival rate is recorded, and effective doses which protect 50% of the animals (ED 50) from endothelin-induced heart death for 24 h or longer are determined.
  • Segments of rabbit aorta are, after an initial tension of 2 g and a relaxation time of 1 h in Krebs-Henseleit solution at 37° C. and pH 7.3-7.4, first induced to contract with K + . After washing out, an endothelin dose-effect plot up to the maximum is constructed.
  • Potential endothelin antagonists are administered to other preparations of the same vessel 15 min before starting the endothelin dose-effect plot.
  • the effects of the endothelin are calibrated as a % of the K + -induced contraction. Effective endothelin antagonists result in a shift to the right in the endothelin dose-effect plot.
  • the compounds according to the invention can be administered orally or parenterally (subcutaneously, intravenously, intramuscularly, intraperotoneally intraperitoneally) in a conventional way. Administration can also take place with vapors or sprays through the nasopharyngeal space.
  • the dosage depends on the age, condition and weight of the patient and on the mode of administration.
  • the daily dose of active substance is, as a rule, about 0.5-50 mg/kg of body weight on oral administration and about 0.1-10 mg/kg of body weight on parenteral administration.
  • 91.11 g (0.5 mol) of benzophenone and 45.92 g (0.85 mol) of sodium methoxide were suspended in 150 ml of methyl tert-butyl ether (MTB) at room temperature. After cooling to ⁇ 100° C., 92.24 g (0.85 mol) of methyl chloroacetate were added in such a way that the internal temperature rose to 40° C. while continuing to cool in a bath at ⁇ 10° C. The mixture was then stirred without cooling at the autogenous temperature for one hour. After addition of 250 ml of water and brief stirring, the aqueous phase was separated off. The MTB phase was washed with 250 ml of dilute sodium chloride solution.
  • MTB methyl tert-butyl ether
  • the residue was suspended in 500 ml of water and 350 ml of MTB and then the pH was adjusted to 1.2 with concentrated hydrochloric acid at room temperature, and, after stirring and phase separation, the aqueous phase was separated off and extracted with 150 ml of MTB.
  • the combined organic phases were extracted with 100 ml of water. 370 ml of MTB were distilled out and then 390 ml of n-heptane were added under reflux, and the mixture was slowly cooled to room temperature while the product crystallized.
  • the contents of the flask were diluted with about 600 ml of H 2 O and cautiously acidified with concentrated HCl, and 250 ml of ethyl acetate were added. 31.4 g of pure product precipitated and were filtered off.
  • the ethyl acetate phase was separated from the mother liquor, the aqueous phase was extracted again with ethyl acetate, and the combined organic phases were concentrated.
  • reaction mixture was stirred at ⁇ 10° C. for about 2 h, then poured into water and extracted several times with ethyl acetate. The combined organic phases were dried over Na 2 SO 4 and concentrated, and the residue was purified by chromatography on silica gel (n-heptane/ethyl acetate).
  • Electrospray-MS 435 (M+H + ) 1 H-NMR (CDCl 3 ): ⁇ (ppm) 3.28 (s, 3H), 3.85 (s, 6H), 5.75 (s, 1H), 7.25-7.40 (m, 10H), 7.50 (s, 1H).
  • Receptor binding data were measured by the binding assay described above for the compounds listed below. The results are shown in Table 2 [sic].

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Families Citing this family (68)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19533023B4 (de) * 1994-10-14 2007-05-16 Basf Ag Neue Carbonsäurederivate, ihre Herstellung und Verwendung
DE19536891A1 (de) * 1995-10-04 1997-04-10 Basf Ag Neue Aminosäurederivate, ihre Herstellung und Verwendung
DE19614533A1 (de) * 1996-04-12 1997-10-16 Basf Ag Neue alpha-Hydroxysäurederivate, ihre Herstellung und Verwendung
DE19614534A1 (de) * 1996-04-12 1997-10-16 Basf Ag Neue Carbonsäurederivate, ihre Herstellung und Verwendung
DE19636046A1 (de) * 1996-09-05 1998-03-12 Basf Ag Neue Carbonsäurederivate, ihre Herstellung und Verwendung als gemischte ET¶A¶/ET¶B¶-Rezeptorantagonisten
HUP0000553A3 (en) 1996-12-18 2001-08-28 Abbott Gmbh & Co Kg Sixmembered nitrogencontained heteroaromatic carboxylic acid derivatives, pharmaceutical compositions containing them, and their use for producing pharmaceutical compositions
US6030975A (en) * 1997-03-14 2000-02-29 Basf Aktiengesellschaft Carboxylic acid derivatives, their preparation and use in treating cancer
WO1999011629A1 (de) * 1997-09-04 1999-03-11 Basf Aktiengesellschaft Neue carbonsäurederivate, ihre herstellung und verwendung als gemischte eta/etb-endothelin-rezeptorantagonisten
DE59810600D1 (de) * 1997-09-26 2004-02-19 Abbott Gmbh & Co Kg Endothelin antagonist und renin-angiotensin system hemmer als kombinationspräparate
DE19743142A1 (de) * 1997-09-30 1999-04-01 Knoll Ag Pharmazeutische Kombinationspräparate
DE19743143A1 (de) * 1997-09-30 1999-04-01 Knoll Ag Pharmazeutische Kombinationspräparate
DE19743681A1 (de) * 1997-10-02 1999-04-08 Knoll Ag Methode zur Verhinderung der Transplantatabstoßung
CA2307770A1 (en) * 1997-10-31 1999-05-14 Basf Aktiengesellschaft Novel carboxylic acid derivatives which carry amide side chains, production of said carboxylic acid derivatives and their use as endothelin receptor antagonists
DE19750529A1 (de) 1997-11-14 1999-05-20 Basf Ag Neue heterocyclisch substituierte alpha-Hydroxycarbonsäurederivate, ihre Herstellung und Verwendung als Endothelinrezeptorantagonisten
DE19806438A1 (de) * 1998-02-17 1999-08-19 Basf Ag Neue Carbonsäurederivate mit 5-substituiertem Pyrimidinring, ihre Herstellung und Verwendung
DE19809635A1 (de) 1998-03-06 1999-09-09 Basf Ag Verfahren zur Darstellung von Endothelinrezeptorantagonisten vom Sulfanyltyp
DE19850301A1 (de) * 1998-10-30 2000-05-04 Basf Ag Verfahren zur Racematspaltung von 2-Hydroxypropionsäuren
US7566452B1 (en) 1999-05-04 2009-07-28 New York University Cancer treatment with endothelin receptor antagonists
DE10002393A1 (de) 2000-01-20 2001-07-26 Basf Ag Verfahren zur enantioselektiven Herstellung von 3,3-Diphenyl-2,3-epoxypropionsäureestern
US8168616B1 (en) 2000-11-17 2012-05-01 Novartis Ag Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension
DE10064797A1 (de) * 2000-12-22 2002-06-27 Knoll Ag Orale und parenterale pharmazeutische Formulierung, umfassend eine niedermolekulare Thrombininhibitor-Pro-Pharmakon
WO2002064573A1 (de) * 2001-02-14 2002-08-22 Abbott Gmbh & Co. Kg Neue carbonsäurederivate mit alkylsubstituierten triazinen, ihre herstellung und verwendung als endothelin-rezeptorantagonisten
EP1243262B1 (en) 2001-03-20 2006-05-31 Schwarz Pharma Ag Novel use of a peptide class of compound for treating non-neuropathic inflammatory pain
PT1243263E (pt) 2001-03-21 2003-03-31 Sanol Arznei Schwarz Gmbh Nova utilizacao de uma classe peptidica de composto para o tratamento de alodinia ou de outros tipos diferentes de dor cronica ou fantasma
US6772708B2 (en) * 2001-10-30 2004-08-10 The Procter And Gamble Company Wetness indicator having improved colorant retention
DE10259382A1 (de) * 2002-12-18 2004-07-01 Abbott Gmbh & Co. Kg 3-Substituierte 3,4-Dihydro-thieno[2,3-d]pyrimidin-4-on-Derivate, ihre Herstellung und Verwendung
US20040204422A1 (en) * 2003-04-14 2004-10-14 Abbott Gmbh & Co. Kg. N-[(Piperazinyl)hetaryl]arylsulfonamide compounds
GB0327839D0 (en) 2003-12-01 2003-12-31 Novartis Ag Organic compounds
TW200605867A (en) 2004-03-17 2006-02-16 Novartis Ag Use of organic compounds
CN1950101B (zh) 2004-04-16 2011-03-30 舒沃茨药物股份公司 肽化合物用于预防和治疗慢性头痛的用途
EP1604656A1 (en) 2004-06-09 2005-12-14 Schwarz Pharma Ag Novel use of peptide compounds for treating amyotrophic lateral sclerosis (ALS)
NZ552651A (en) 2004-08-27 2010-07-30 Sanol Arznei Schwarz Gmbh Novel use of peptide compounds for treating bone cancer pain, chemotherapy-and nucleoside-induced pain
DE102005025161A1 (de) * 2005-06-01 2006-12-07 Phenion Gmbh & Co. Kg Derivate des Pyrimidins und Triazins und deren Verwendung
CA2637897A1 (en) * 2006-01-20 2007-07-26 Schering Corporation Carbocyclic and heterocyclic arylsulfones as gamma secretase inhibitors
US20100022568A1 (en) * 2006-04-13 2010-01-28 Actelion Pharmaceeuticals Ltd. Endothelin receptor antagonists for early stage idiopathic pulmonary fibrosis
AU2007260207B2 (en) 2006-06-15 2012-11-08 Ucb Pharma Gmbh Pharmaceutical composition with synergistic anticonvulsant effect
DK2101777T3 (en) 2006-12-12 2015-08-17 Gilead Sciences Inc COMPOSITION FOR TREATMENT OF PULMONAL HYPERTENSION
WO2008097468A2 (en) 2007-02-02 2008-08-14 Concert Pharmaceuticals, Inc. Selective endothelin type-a antagonists
CN101801936B (zh) * 2007-07-31 2012-10-03 吉利德科罗拉多公司 安立生坦的代谢物和衍生物
US20090069353A1 (en) * 2007-09-12 2009-03-12 Protia, Llc Deuterium-enriched ambrisentan
DE102008037324A1 (de) 2008-08-11 2010-02-18 Ratiopharm Gmbh Pharmazeutische Formulierung zur pulmonalen Blutdrucksenkung
US8404840B2 (en) * 2008-11-05 2013-03-26 Msn Laboratories Limited Process for the preparation of endothelin receptor antagonists
WO2010091877A2 (en) 2009-02-13 2010-08-19 Ratiopharm Gmbh Process for producing ambrisentan
DE202009009917U1 (de) 2009-07-21 2010-02-11 Ratiopharm Gmbh Ambrisentan in spezifischer kristalliner Form
WO2011004402A2 (en) 2009-07-10 2011-01-13 Cadila Healthcare Limited Improved process for the preparation of ambrisentan and novel intermediates thereof
WO2011022694A2 (en) * 2009-08-20 2011-02-24 University Of Tennessee Research Foundation, The Furanopyrimidine cannabinoid compounds and related methods of use
IN2012DN05025A (zh) * 2009-12-07 2015-10-23 Univ Johns Hopkins
AU2010328230B2 (en) 2009-12-07 2016-06-02 Cardioxyl Pharmaceuticals, Inc. Bis-acylated hydroxylamine derivatives
EP2547663A1 (en) 2010-03-15 2013-01-23 Natco Pharma Limited A process for the preparation of highly pure ambrisentan
US20130184490A1 (en) * 2010-08-04 2013-07-18 Natco Pharma Limited Process to prepare s-2-hydroxy-3-methoxy-3,3-diphenyl propionic acid
EP2637664B1 (en) 2010-10-15 2017-03-29 Gilead Sciences, Inc. Compositions and methods of treating pulmonary hypertension
EP2476670A1 (en) 2011-01-07 2012-07-18 Zentiva, K.S. Stable solid salts of ambrisentan
CN102276536B (zh) 2011-06-10 2015-04-29 中国科学院化学研究所 一种光学纯的(+)-安倍生坦和光学纯的(+)-达芦生坦的制备方法
CN103012280B (zh) * 2011-09-22 2015-04-29 江苏康缘药业股份有限公司 一种制备安立生坦的方法
KR101855506B1 (ko) 2011-10-13 2018-05-08 주식회사 동진쎄미켐 방향족 고리 함유 고분자 및 이를 포함하는 레지스트 하층막 조성물
IN2014MN00850A (zh) 2011-10-19 2015-04-17 Cipla Ltd
EP2867214B1 (en) 2012-06-29 2016-08-10 Kern Pharma, S.L. Preparation process of carboxylic acid derivatives and intermediates thereof
CN103524424A (zh) * 2012-07-04 2014-01-22 天津药物研究院 一种安立生坦的晶型vi及其制备方法和应用
CN103524425A (zh) * 2012-07-04 2014-01-22 天津药物研究院 一种安立生坦的晶型v及其制备方法和应用
CN104098462B (zh) * 2013-04-12 2017-11-17 江苏豪森药业集团有限公司 2‑羟基‑3‑甲氧基‑3,3‑二苯基丙酸消旋物的拆分方法
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WO2024092240A1 (en) 2022-10-28 2024-05-02 Chinook Therapeutics, Inc. Treatment of iga nephropathy using an endothelin receptor antagonist and an april binding antibody

Citations (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS514135A (zh) 1974-06-25 1976-01-14 Hasegawa T Co Ltd
EP0347811A1 (en) 1988-06-20 1989-12-27 Kumiai Chemical Industry Co., Ltd. Alkanoic acid derivatives and herbicidal compositions
EP0400741A1 (en) 1989-06-02 1990-12-05 Shell Internationale Researchmaatschappij B.V. Herbicidal compounds
EP0409368A2 (de) 1989-07-19 1991-01-23 Schering Aktiengesellschaft Substituierte alfa-Pyrimidinyloxy-carbonsäurederivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Mittel mit herbizider, fungizider und pflanzenwachstumsregulierender Wirkung
JPH0331266A (ja) 1989-06-27 1991-02-12 Nissan Chem Ind Ltd ピリミジン誘導体及び除草剤
JPH03240777A (ja) 1990-02-20 1991-10-28 Ube Ind Ltd 脂肪酸誘導体、その製造法及び除草剤
DE4029648A1 (de) 1990-09-19 1992-03-26 Hoechst Ag 4-anilino-pyrimidine, verfahren zu ihrer herstellung, sie enthaltende mittel und ihre verwendung als fungizide
EP0481512A1 (en) 1990-10-19 1992-04-22 Ube Industries, Ltd. 3-Alkoxyalkanoic acid derivative, process for preparing the same and herbicide using the same
DE4035758A1 (de) 1990-11-08 1992-05-14 Schering Ag Substituierte (alpha)-pyrimidinyloxy(thio)- und (alpha)-triazinyloxy(thio)-carbonsaeurederivate, verfahren zu ihrer herstellung und ihre verwendung als mittel mit herbizider, fungizider und pflanzenwachstumsregulierender wirkung
EP0517215A1 (en) 1991-06-07 1992-12-09 Ube Industries, Ltd. Pyrimidine or triazine derivative, process for preparing the same and herbicide using the same
DE4123469A1 (de) 1991-07-16 1993-01-21 Basf Ag Herbizide mittel, die n-dichloracetyl-diazacycloalkane als antagonistische verbindungen enthalten
EP0548710A1 (de) 1991-12-21 1993-06-30 BASF Aktiengesellschaft Glykolaldehyd- und Milchsäurederivate, deren Herstellung und herbizide Verwendung
DE4201875A1 (de) 1992-01-24 1993-07-29 Basf Ag Thiocarbonsaeurederivate, verfahren und zwischenprodukte zu ihrer herstellung
EP0567014A1 (en) 1992-04-17 1993-10-27 Ube Industries, Ltd. Sulfonamide derivative, process for preparing the same and herbicide using the same
US5270289A (en) 1989-07-19 1993-12-14 Schering Aktiengesellschaft Herbicidal dimethoxy pyrimidinyloxy-fluorinated acids and salts
WO1994000987A2 (en) 1992-07-08 1994-01-20 Ciba-Geigy Ag Selective herbicidal composition
EP0581184A1 (en) 1992-07-21 1994-02-02 Ube Industries, Ltd. 3-Alkoxy-N-cycloalkylsulfonylalkanoic amide derivative, process for preparing the same and herbicide using the same
DE4313412A1 (de) 1993-04-23 1994-10-27 Basf Ag 3-(Het)aryl-Carbonsäurederivate, Verfahren und Zwischenprodukte zu ihrer Herstellung
DE4313413A1 (de) 1993-04-23 1994-10-27 Basf Ag 3-(Het)aryloxy(thio)-Carbonsäurederivate, Verfahren und Zwischenprodukte zu ihrer Herstellung
DE4335950A1 (de) 1993-10-21 1995-04-27 Basf Ag Derivate von 3-Hydroxycarbonsäuren, deren Herstellung und Verwendung
DE4411225A1 (de) 1994-03-31 1995-10-05 Basf Ag Verwendung von Carbonsäurederivaten als Arzneimittel
WO1996000219A1 (en) 1994-06-27 1996-01-04 Ciba-Geigy Ag Pyrimidinyl- and triazinyl-oxy and thio-3-haloalkyl-propionic acid derivatives as herbicides
US5541148A (en) 1992-07-08 1996-07-30 Ciba-Geigy Corporation Selective safened herbicidal composition comprising 2-ethoxycarbonyl-3-(4,6-dimethoxypyrimidine-2-yl) oxy-pyridine and an acylsulfamoylphenyl-urea safener
JP2730021B2 (ja) 1991-05-31 1998-03-25 宇部興産株式会社 ３−ベンジルオキシアルカン酸誘導体、その製造法及び除草剤
US5969134A (en) 1994-10-14 1999-10-19 Basf Aktiengesellschaft Carboxylic acid derivatives, their preparation and use
US6030975A (en) 1997-03-14 2000-02-29 Basf Aktiengesellschaft Carboxylic acid derivatives, their preparation and use in treating cancer
US6197780B1 (en) 1997-12-05 2001-03-06 Knoll Aktiengesellschaft Method for combating obesity
US6329384B1 (en) 1997-09-26 2001-12-11 Abbott Laboratories Endothelin antagonist and renin-angiotensin system inhibitor as a combined preparation
US6352992B1 (en) 1997-09-30 2002-03-05 Abbott Laboratories Endothelin antagonist and beta receptor blocking agent as combined preparations
US6559338B1 (en) 1998-10-30 2003-05-06 Basf Aktiengesellschaft Method for racemate splitting of 2-hydroxypropionic acids
US6677465B2 (en) 2000-01-20 2004-01-13 Abbott Gmbh & Co. Kg Method for the enantioselective preparation of 3,3-diphenyl-2,3-epoxy propionic acid esters
WO2009017777A2 (en) 2007-07-31 2009-02-05 Gilead Colorado, Inc. Metabolites and derivatives of ambrisentan

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE403578C (de) 1924-10-02 Walter Beige Verfahren zum Innen-Emaillieren von Roehren
JP2771604B2 (ja) * 1988-06-20 1998-07-02 クミアイ化学工業株式会社 除草剤及びその有効成分となる新規なアルカン酸誘導体
FR2650365B1 (fr) 1989-07-28 1991-11-22 Caillau Ets Raccord rapide
JPH05125058A (ja) * 1990-10-19 1993-05-21 Ube Ind Ltd ３−アルコキシアルカン酸化合物、その中間体、その製造法及び除草剤
JP2730022B2 (ja) * 1991-06-07 1998-03-25 宇部興産株式会社 ３−アルコキシブチリルイミダゾール誘導体、その製造法及び除草剤
CA2125570A1 (en) * 1991-12-10 1993-06-24 Frank Zurmuhlen Pyrimidinyl- or triazinyl-oxy(or thio)aldehyde derivatives and their use as herbicides or plant-growth regulators
CA2110500A1 (en) * 1992-06-17 1993-12-23 Christoph Luthy Pyrimidinyl- and tetrazinyl compounds with herbicidal activity
EP0627472B1 (en) * 1993-06-03 2000-03-08 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha Curable composition
CA2202919A1 (en) 1994-10-21 1996-05-02 Michiel M. Van Oort Medicament carrier for dry powder inhalator and process for forming the same
CN101491028A (zh) 2006-07-12 2009-07-22 华为技术有限公司 用于控制拥塞的方法

Patent Citations (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS514135A (zh) 1974-06-25 1976-01-14 Hasegawa T Co Ltd
EP0347811A1 (en) 1988-06-20 1989-12-27 Kumiai Chemical Industry Co., Ltd. Alkanoic acid derivatives and herbicidal compositions
EP0400741A1 (en) 1989-06-02 1990-12-05 Shell Internationale Researchmaatschappij B.V. Herbicidal compounds
JPH0331266A (ja) 1989-06-27 1991-02-12 Nissan Chem Ind Ltd ピリミジン誘導体及び除草剤
EP0409368A2 (de) 1989-07-19 1991-01-23 Schering Aktiengesellschaft Substituierte alfa-Pyrimidinyloxy-carbonsäurederivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Mittel mit herbizider, fungizider und pflanzenwachstumsregulierender Wirkung
US5270289A (en) 1989-07-19 1993-12-14 Schering Aktiengesellschaft Herbicidal dimethoxy pyrimidinyloxy-fluorinated acids and salts
JPH03240777A (ja) 1990-02-20 1991-10-28 Ube Ind Ltd 脂肪酸誘導体、その製造法及び除草剤
DE4029648A1 (de) 1990-09-19 1992-03-26 Hoechst Ag 4-anilino-pyrimidine, verfahren zu ihrer herstellung, sie enthaltende mittel und ihre verwendung als fungizide
EP0481512A1 (en) 1990-10-19 1992-04-22 Ube Industries, Ltd. 3-Alkoxyalkanoic acid derivative, process for preparing the same and herbicide using the same
US5178663A (en) 1990-10-19 1993-01-12 Ube Industries, Ltd. 3-alkoxyalkanoic acid derivative, process for preparing the same and herbicide using the same
DE4035758A1 (de) 1990-11-08 1992-05-14 Schering Ag Substituierte (alpha)-pyrimidinyloxy(thio)- und (alpha)-triazinyloxy(thio)-carbonsaeurederivate, verfahren zu ihrer herstellung und ihre verwendung als mittel mit herbizider, fungizider und pflanzenwachstumsregulierender wirkung
JP2730021B2 (ja) 1991-05-31 1998-03-25 宇部興産株式会社 ３−ベンジルオキシアルカン酸誘導体、その製造法及び除草剤
EP0517215A1 (en) 1991-06-07 1992-12-09 Ube Industries, Ltd. Pyrimidine or triazine derivative, process for preparing the same and herbicide using the same
US5387575A (en) 1991-06-07 1995-02-07 Ube Industries, Ltd. Pyrimidine derivatives, process for preparing the same and herbicide using the same
DE4123469A1 (de) 1991-07-16 1993-01-21 Basf Ag Herbizide mittel, die n-dichloracetyl-diazacycloalkane als antagonistische verbindungen enthalten
EP0548710A1 (de) 1991-12-21 1993-06-30 BASF Aktiengesellschaft Glykolaldehyd- und Milchsäurederivate, deren Herstellung und herbizide Verwendung
US5326744A (en) 1991-12-21 1994-07-05 Basf Aktiengesellschaft Glycol aldehyde and lactic acid derivatives and the preparation and use thereof
DE4201875A1 (de) 1992-01-24 1993-07-29 Basf Ag Thiocarbonsaeurederivate, verfahren und zwischenprodukte zu ihrer herstellung
US5318945A (en) 1992-01-24 1994-06-07 Basf Aktiengesellschaft Thiocarboxylic acid derivatives
EP0567014A1 (en) 1992-04-17 1993-10-27 Ube Industries, Ltd. Sulfonamide derivative, process for preparing the same and herbicide using the same
US5376620A (en) 1992-04-17 1994-12-27 Ube Industries, Ltd. Sulfonamide derivative, process for preparing the same and herbicide using the same
WO1994000987A2 (en) 1992-07-08 1994-01-20 Ciba-Geigy Ag Selective herbicidal composition
US5541148A (en) 1992-07-08 1996-07-30 Ciba-Geigy Corporation Selective safened herbicidal composition comprising 2-ethoxycarbonyl-3-(4,6-dimethoxypyrimidine-2-yl) oxy-pyridine and an acylsulfamoylphenyl-urea safener
US5389601A (en) 1992-07-21 1995-02-14 Ube Industries, Ltd. 3-alkoxy-N-cycloalkylsulfonyalkanoic amide derivative and herbicide using the same
EP0581184A1 (en) 1992-07-21 1994-02-02 Ube Industries, Ltd. 3-Alkoxy-N-cycloalkylsulfonylalkanoic amide derivative, process for preparing the same and herbicide using the same
DE4313413A1 (de) 1993-04-23 1994-10-27 Basf Ag 3-(Het)aryloxy(thio)-Carbonsäurederivate, Verfahren und Zwischenprodukte zu ihrer Herstellung
US5703017A (en) 1993-04-23 1997-12-30 Basf Aktiengesellschaft 3-(Het) arylcarboxylic acid derivatives, their preparation and intermediates for their preparation
EP0695295B1 (de) 1993-04-23 2002-03-06 Basf Aktiengesellschaft 3-(het)aryl-carbonsäurederivate, verfahren und zwischenprodukte zu ihrer herstellung
EP0695296A1 (de) 1993-04-23 1996-02-07 Basf Aktiengesellschaft 3-(het)aryloxy(thio)-carbonsäurederivate, verfahren und zwischenprodukte zu ihrer herstellung
DE4313412A1 (de) 1993-04-23 1994-10-27 Basf Ag 3-(Het)aryl-Carbonsäurederivate, Verfahren und Zwischenprodukte zu ihrer Herstellung
US5661106A (en) 1993-04-23 1997-08-26 Basf Aktiengesellschaft 3-(Het)aryloxy(thio)carboxylic acid derivatives, their preparation and intermediates for their preparation
DE4335950A1 (de) 1993-10-21 1995-04-27 Basf Ag Derivate von 3-Hydroxycarbonsäuren, deren Herstellung und Verwendung
WO1995026716A1 (de) 1994-03-31 1995-10-12 Basf Aktiengesellschaft Pyrimidin- oder triazincarbonsäurederivate zur verwendung als arzneimittel
DE4411225A1 (de) 1994-03-31 1995-10-05 Basf Ag Verwendung von Carbonsäurederivaten als Arzneimittel
US5840722A (en) 1994-03-31 1998-11-24 Basf Aktiengesellschaft Use of carboxylic acid derivatives as drugs
WO1996000219A1 (en) 1994-06-27 1996-01-04 Ciba-Geigy Ag Pyrimidinyl- and triazinyl-oxy and thio-3-haloalkyl-propionic acid derivatives as herbicides
US7109205B2 (en) 1994-10-14 2006-09-19 Abbott Gmbh & Co. Kg Carboxylic acid derivatives, their preparation and use
US6600043B2 (en) 1994-10-14 2003-07-29 Basf Aktiengesellschaft Carboxylic acid derivatives, their preparation and use
US20070203338A1 (en) 1994-10-14 2007-08-30 Hartmut Riechers Novel carboxylic acid derivatives, their preparation and use
US6197958B1 (en) 1994-10-14 2001-03-06 Basf Aktiengesellschaft Carboxylic acid derivatives, their preparation and use
US20060276474A1 (en) 1994-10-14 2006-12-07 Abbott Gmbh & Co. Kg. Novel carboxylic acid derivatives, their preparation and use
US7119097B2 (en) 1994-10-14 2006-10-10 Abbott Gmbh & Co. Kg Carboxylic acid derivatives, their preparation and their use
US5969134A (en) 1994-10-14 1999-10-19 Basf Aktiengesellschaft Carboxylic acid derivatives, their preparation and use
US6030975A (en) 1997-03-14 2000-02-29 Basf Aktiengesellschaft Carboxylic acid derivatives, their preparation and use in treating cancer
US6329384B1 (en) 1997-09-26 2001-12-11 Abbott Laboratories Endothelin antagonist and renin-angiotensin system inhibitor as a combined preparation
US6352992B1 (en) 1997-09-30 2002-03-05 Abbott Laboratories Endothelin antagonist and beta receptor blocking agent as combined preparations
US6197780B1 (en) 1997-12-05 2001-03-06 Knoll Aktiengesellschaft Method for combating obesity
US6559338B1 (en) 1998-10-30 2003-05-06 Basf Aktiengesellschaft Method for racemate splitting of 2-hydroxypropionic acids
US6677465B2 (en) 2000-01-20 2004-01-13 Abbott Gmbh & Co. Kg Method for the enantioselective preparation of 3,3-diphenyl-2,3-epoxy propionic acid esters
WO2009017777A2 (en) 2007-07-31 2009-02-05 Gilead Colorado, Inc. Metabolites and derivatives of ambrisentan

Non-Patent Citations (14)

* Cited by examiner, † Cited by third party
Title
Advanced Organic Chem., Third Ed., Jerry Mar. 1985, pp. 750, 863.
Agr. Biol. Chem., 40(5), 993-1000, 1976, on the Sterochemistry . . . Kogure et al.
Chung, Vo Van et al., "Photochemical Reaction of Ethyl 3-Methyl-3-phenylgycidate in Methanol and Ether Solvents", Bulletin of the Chemical Society of Japan, vol. 49(1), 341-342 (1976).
Ciba-Geigy AG "Neue Selektiv-herbizide Mittel" Research Disclosure Journal (1994).
Hirata et al., Biochem. Biophys. Res. Commun., 154:868-875 (1988).
J. Vascular Med. Biology, 2:207 (1990).
Japan J. Hypertension 12:79 (1989).
Kanno et al., J. Am. Med. Association, 264, 2868b (1990).
Raschack et al. (J. Cardiovasc. Pharmacol. (1995), 26 (Suppl. 3), S397-S399.
Raschack et al., Journal of Cardiovascular Pharmacology (1995), 26 (Suppl. 3), S397-S399.
Riechers et al. (J. Med. Chem. (1996), 39(11), 2123-8).
Riechers et al., Journal of Medicinal Chemistry (1996), 39(11), 2123-8.
Yanagisawa et al., FEBS Letters, 231-440-444 (1988).
Yanagisawa et al., Nature, 332:411-415 (1988).

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