150727-23-4

Upstream product

• 1878-85-9 (2-methoxyphenoxy)acetic acid 
• 20730-58-9 2-(2-Methoxyphenoxy)propanedioic acid diethyl ester 
• 150727-22-3 5-(o-methoxyphenoxy)-4,6-dihydroxy-pyrimidine 
• 202288-08-2 5-(2-methoxy-phenoxy)-1H-pyrimidine-4,6-dione 
• 150726-89-9 (2-methoxyphenoxy)-malonic acid dimethyl ester 
• 90-05-1 2-methoxy-phenol 

Downstream Products

• 150727-24-5 4-tert-butyl-N-[6-chloro-5-(o-methoxyphenoxy)-4-pyrimidinyl]-benzene sulfonamide 
• 346671-58-7 5-isopropyl-N-[6-chloro-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide 
• 441797-63-3 C₁₈H₁₇ClN₄O₄S 
• 441796-04-9 C₂₀H₂₂N₄O₆S 
• 441796-05-0 C₂₄H₂₃BrN₆O₆S 
• 150727-85-8 4-amino-6-chloro-5-(o-methoxyphenoxy)pyrimidine 
• 346671-59-8 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide 
• 346671-52-1 4-tert.-butyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-benzene sulfonamide 
• 202288-09-3 4-tert-butyl-N-[6-(4-hydroxy-butoxy)-5-(2-methoxy-phenoxy)-pyrimidin-4-yl]-benzenesulfonamide 

Relevant academic research and scientific papers

Phenyl pyrimidinamine anti-tumor compound as well as preparation method and application thereof

The invention belongs to the technical field of medicines, relates to a compound with anti-tumor activity and a specific chemical structure, and particularly relates to a phenyl pyrimidinamine compound as well as a preparation method and application thereof. The structural general formula of the phenyl pyrimidinamine compound is shown in the specification, wherein an R group is a hydrogen atom, a 2-position monosubstituted fluorine atom, or 3-position and 4-position monosubstituted methyl, a fluorine atom, a chlorine atom and a bromine atom. Experimental research shows that the prepared phenyl pyrimidinamine compound shows a good result in an in-vitro anti-tumor activity test, can be used for preparing anti-tumor drugs, and opens up a new way for developing the anti-tumor drugs with an endothelin receptor as a new target. The preparation method provided by the invention is simple and feasible, higher in yield and easy for large-scale production.

The discovery of N -[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy] ethoxy]-4-pyrimidinyl]- N ′-propylsulfamide (macitentan), an orally active, potent dual endothelin receptor antagonist

Starting from the structure of bosentan (1), we embarked on a medicinal chemistry program aiming at the identification of novel potent dual endothelin receptor antagonists with high oral efficacy. This led to the discovery of a novel series of alkyl sulfamide substituted pyrimidines. Among these, compound 17 (macitentan, ACT-064992) emerged as particularly interesting as it is a potent inhibitor of ETA with significant affinity for the ET B receptor and shows excellent pharmacokinetic properties and high in vivo efficacy in hypertensive Dahl salt-sensitive rats. Compound 17 successfully completed a long-term phase III clinical trial for pulmonary arterial hypertension.

The use of sulfonylamido pyrimidines incorporating an unsaturated side chain as endothelin receptor antagonists

A series of compounds structurally related to bosentan 1 featuring an unsaturated side chain at position 6 of the core pyrimidine have been studied for their potential to block the ETA and ETB receptor. Incorporation of a 2-butyne-1,4-diol linker bearing a pyridyl carbamoyl moiety led to in vitro highly potent endothelin receptor antagonists (e.g., 70 and 75). The propargyl derivative 26 significantly reduced blood pressure in in vivo model studies with hypertensive salt-sensitive Dahl rats.

Butyne diol derivatives

The present invention relates to novel butyne diol derivatives of the general formula I and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of the general formula I and especially their use as endothelin receptor antagonists.

6 alkoxy-4-pyrimidinyl bis-sulfonamides

The present invention relates to novel bis-sulfonamides represented, for example, by formula I below and a pure diastereomer, a mixture of diastereomers, a diastereomeric racemate, a mixture of diastereomeric racemates and meso-forms and a pharmaceutically acceptable salt thereof, wherein R1represents aryl; aryl-lower alkyl; aryl-lower alkenyl; heteroaryl; or heteroaryl-lower alkyl; and R2represents lower alkyl; trifluoromethyl; lower alkoxy-lower alkyl; lower alkenyl; lower alkynyl; aryl; aryl-lower alkyl; aryl-lower alkenyl; heterocyclyl; heterocyclyl-lower alkyl; heteroaryl; heteroaryl-lower alkyl; cycloalkyl; or cycloalkyl-lower alkyl. The present invention also relates to a process for manufacturing those compounds, pharmaceutical compositions containing one or more of those compounds as endothelin antagonists, and a method of treating a subject having a disorder involving endothelin with the compounds of the invention.

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

The synthesis and structure-activity relationships of a series of N-pyrimidinyl benzenesulfonamides as ETB selective antagonists are described. N-Isoxazolyl benzenesulfonamide 1a, previously reported, was selected as a lead compound, and isosteric replacement of the isoxazole ring of 1a with a pyrimidine ring led to the discovery of the highly potent ETB selective antagonist 6e with oral bioavailability. Modification of the terminal aldehyde group at the 6-position of the pyrimidine ring was investigated, and malonate 15b and acylhydrazone 16f were found to be equipped to aldehyde 6e. Compound 6e showed ETB antagonistic activity on in vivo evaluation. Copyright

SULFONAMIDES

The novel sulfonamides of formula I, STR1 in which the symbols R. sup.1-R 9, R a, R b, X, Y and n have the significance given in the description and salts thereof can be used for the treatment of circulatory disorders, especially hypertension, ischemia, vasopasms and angina pectoris.