Synthesis and structure–activity relationships of potent and orally active sulfonamide ETB selective antagonists

Kanda, Yoichi; Kawanishi, Yuji; Oda, Katsuo; Sakata, Takako; Mihara, Shuichi; Asakura, Kouichi; Kanemasa, Toshiyuki; Ninomiya, Mitsuyoshi; Fujimoto, Masafumi; Konoike, Toshiro

doi:10.1016/s0968-0896(00)00305-9

Cited by 44 publications

(20 citation statements)

References 21 publications

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“…Some improvements have also been shown in patients with PAH WHO functional class II [3]. The drug is also indicated to reduce a number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease [3–5]. …”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a UHPLC UV Method for the In-Process Control of Bosentan Monohydrate Synthesis

et al. 2016

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Bosentan monohydrate (4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl) pyrimidin-4-yl]benzene-1-sulfonamide monohydrate) is a dual endothelin receptor antagonist (ERA) applied in the treatment of pulmonary arterial hypertension. To achieve effective process control of the bosentan monohydrate synthesis, it was necessary to develop a selective and not highly time-consuming method for ultra-high performance liquid chromatography (UHPLC). The method is characterized by adequate sensitivity, reproducibility and selectivity for the determination of bosentan monohydrate and related compounds from all synthetic stages. The UHPLC separation was carried out by reversed phase chromatography on the Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 µm) with a mobile phase composed of solvent A (0.1 %, v/v, acetic acid in water) and solvent B (methanol), in the gradient mode at the flow rate of 0.4 mL min−1. Limits of detection and quantification for the compounds were ≤0.1 µg mL−1 and 0.3 µg mL−1, respectively. The linearity for all related compounds was investigated as in the range for the active pharmaceutical ingredient (API) and as in the range for the in-process control. The developed method was validated according to the current guidelines, proving the suitability of the method for its intended purpose.

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Section: Introductionmentioning

confidence: 99%

Development and Validation of a UHPLC UV Method for the In-Process Control of Bosentan Monohydrate Synthesis

et al. 2016

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“…The formic acid serves as both a proton source for the catalysis as well as a trap for the 1,3-diol produced upon hydrolysis. 42 Application of these conditions to substrate 54 led quantitatively to aldehyde 55 .…”

Section: Resultsmentioning

confidence: 96%

Organometallic Enantiomeric Scaffolding: A Strategy for the Enantiocontrolled Construction of Regio- and Stereodivergent Trisubstituted Piperidines from a Common Precursor

2011

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Reported herein is a general and efficient method to construct 2,3,6-trisubstituted piperidines in a substituent-independent fashion. From the high enantiopurity organometallic scaffold (−)-Tp(CO)2[(η-2,3,4)-(1S, 2S)-1-benzyloxycarbonyl-5-oxo-5,6-dihydro-2H-pyridin-2-yl)molybdenum (Tp = hydridotrispyrazolylborato), a variety of TpMo(CO)2-based 2,3,6-trifunctionalized complexes of the (η-3,4,5-dihydropyridinyl) ligand were easily obtained in 5 steps through a sequence of highly regio- and stereospecific metal-influenced transformations (15 examples). From the 2,3,6-trifunctionalized molybdenum complexes, either 2,6-cis-3-trans or 2,3,6-cis systems were selectively obtained through the choice of an appropriate stereodivergent demetalation protocol. The potential of this strategy in synthetic chemistry was demonstrated by the short total synthesis of four natural and one non-natural alkaloids: indolizidines (±)-209I and (±)-8-epi-219F in the racemic series, and enantiocontrolled syntheses of (−)-indolizidine 251N, (−)-quinolizidine 251AA, and (−)-dehydroindolizidine 233E.

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“…Sulfonamides were the principally remedies fundamentally engaged and progressively castoff for petition and chemotherapeutic vehicles intimidating to an variety of maladies [1]. More than thirty drugs obligating this functionality are in assessable apply, entering antiseptic [2,3], and extra biological activities [4][5][6][7][8].…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of the co-crystalline adduct 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide - acetic acid (1/1), C₂₁H₂₄N₄O₄S ⋅ C₂H₄O₂

Ghorab

Alsaid

Al-Dosari

et al. 2017

Zeitschrift Für Kristallographie - New Crystal Structures

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C 23 H 28 N4O 6 S, triclinic, P1 (no. 2), a = 7.3612(3) Å, CCDC no.: 1468856The asymmetric unit of the title crystal structure is shown in the figure. Tables 1 and 2 contain details on crystal structure and measurement conditions and a list of the atoms including atomic coordinates and displacement parameters. Source of material2-((Dimethylamino)methylene)-5,5-dimethylcyclohexane-1,3-dione (1.95 g, 0.01 mol) and 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (2.78 g, 0.01 mol) was added

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Synthesis and structure–activity relationships of potent and orally active sulfonamide ETB selective antagonists

Cited by 44 publications

References 21 publications

Development and Validation of a UHPLC UV Method for the In-Process Control of Bosentan Monohydrate Synthesis

Development and Validation of a UHPLC UV Method for the In-Process Control of Bosentan Monohydrate Synthesis

Organometallic Enantiomeric Scaffolding: A Strategy for the Enantiocontrolled Construction of Regio- and Stereodivergent Trisubstituted Piperidines from a Common Precursor

Crystal structure of the co-crystalline adduct 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide - acetic acid (1/1), C₂₁H₂₄N₄O₄S ⋅ C₂H₄O₂

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Synthesis and structure–activity relationships of potent and orally active sulfonamide ETB selective antagonists

Cited by 44 publications

References 21 publications

Development and Validation of a UHPLC UV Method for the In-Process Control of Bosentan Monohydrate Synthesis

Development and Validation of a UHPLC UV Method for the In-Process Control of Bosentan Monohydrate Synthesis

Organometallic Enantiomeric Scaffolding: A Strategy for the Enantiocontrolled Construction of Regio- and Stereodivergent Trisubstituted Piperidines from a Common Precursor

Crystal structure of the co-crystalline adduct 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide - acetic acid (1/1), C21H24N4O4S ⋅ C2H4O2

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Crystal structure of the co-crystalline adduct 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide - acetic acid (1/1), C₂₁H₂₄N₄O₄S ⋅ C₂H₄O₂