329923-71-9

Upstream product

• 3473-63-0 formamidine acetic acid 
• 29148-27-4 diethyl 2-(4-methylphenyl)propane-1,3-dioate 
• 6313-33-3 formamidine hydrochloride 
• 622-47-9 4-tolylacetic acid 
• 14062-19-2 p-tolylacetic acid ethyl ester 

Downstream Products

• 146533-43-9 4,6-dichloro-5-(4-methylphenyl)pyrimidine 
• 346671-54-3 4,6-dichloro-2-(pyridin-4-yl)-5-(p-tolyl)-pyrimidine 
• 245118-94-9 N-(6-chloro-5-(4-methylphenyl)-4-pyrimidinyl)-4-(2-hydroxy-1,1-dimethylethyl)benzenesulfonamide 
• 169677-18-3 C₂₃H₂₇N₃O₅S 
• 441797-33-7 C₁₈H₁₇ClN₄O₂S 
• 169679-53-2 N-[6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-5-(4-methylphenyl)-4-pyrimidinyl]-4-(2-hydroxy-1,1-dimethylethyl)-benzenesulfonamide 
• 1393813-58-5 C₂₄H₂₃BrN₆O₄S 
• 926008-70-0 [4-(6-chloro-5-(p-tolyl)pyrimidin-4-ylethynyl)phenyl]dimethylamine 

Relevant academic research and scientific papers

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.

4-Amino-5-aryl-6-arylethynylpyrimidines: Structure-activity relationships of non-nucleoside adenosine kinase inhibitors

A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT-702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-ylpyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed.

Arylalkane-sulfonamides having endothelin-antagonist activity

The invention relates to novel aryl-alkane-sulfonamides 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 of those compounds and especially their use as endothelin receptor antagonists.

Novel arylethene-sulfonamides

The invention relates to novel aryl-ethene-sulfonamides 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 of those compounds and especially their use as endothelin receptor antagonists.

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.