701977-68-6

Upstream product

• 1088496-50-7 C₁₃H₁₄ClNO₄ 
• 591-19-5 m-Bromoaniline 
• 220731-02-2 ethyl 3-(2-chloropyridin-3-yl)-3-oxopropionate 
• 122-51-0 orthoformic acid triethyl ester 
• 49609-84-9 2-Chloronicotinoyl chloride 

Downstream Products

• 477251-79-9 N-Isopropyl-1-(3-bromophenyl)-1,4-dihydro[1,8]naphthyridin-4-one-3-carboxamide 
• 477251-78-8 1-(3-Bromophenyl)-1,4-dihydro[1,8]naphthyridin-4-one-3-carboxylic Acid 
• 500355-51-1 N-isopropyl-1-[3-(3-hydroxy-3-phenylbut-1-ynyl)phenyl]-1,4-dihydro[1,8]naphthyridin-4-one-3-carboxamide 
• 500355-37-3 N-isopropyl-1-[(3-phenylethynyl)phenyl]-1,4-dihydro[1,8]naphthyridin-4-one-3-carboxamide 
• 477251-77-7 ethyl 1-(3-bromophenyl)-1,4-dihydro[1,8]naphthyridin-4-one-3-carboxylate 

Relevant academic research and scientific papers

Alternative Forms of the Phosphodiesterase-4 Inhibitor N-Cyclopropyl-1--4-Oxo-1,4-Dihydro-1,8-Naphthyridine-3-Carboxyamide

The present invention is directed to alternative forms of the title phosphodiesterase 4 inhibitor which has the structural formula shown immediately below:

Discovery of MK-0952, a selective PDE4 inhibitor for the treatment of long-term memory loss and mild cognitive impairment

The structure-activity relationship of a novel series of 8-biarylnaphthyridinones acting as type 4 phosphodiesterase (PDE4) inhibitors for the treatment of long-term memory loss and mild cognitive impairment is described herein. The manuscript describes a new paradigm for the development of PDE4 inhibitor targeting CNS indications. This effort led to the discovery of the clinical candidate MK-0952, an intrinsically potent inhibitor (IC 50 = 0.6 nM) displaying limited whole blood activity (IC50 = 555 nM). Supporting in vivo results in two preclinical efficacy tests and one test assessing adverse effects are also reported. The comparative profiles of MK-0952 and two other Merck compounds are described to validate the proposed hypothesis.

Optimization and structure-activity relationship of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides: Identification of MK-0873, a potent and effective PDE4 inhibitor

A SAR study of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides is described. Optimization of the series was based on in vitro potency against PDE4, inhibition of the LPS-induced production of TNF-α in human whole blood and minimizing affinity f

4-OXO-1-(3-SUBSTITUTED PHENYL-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-3-CARBOXAMIDE PHOSPHODIESTERASE-4 INHIBITORS

Compounds represented by Formula (I):or a pharmaceutically acceptable salt thereof, are phosphodiesterase 4 inhibitors useful in the treatment of asthma and inflammation and useful for the enhancement of cognition.

METHOD OF PREPARING INHIBITORS OF PHOSPHODIESTERASE-4

In one aspect, the present invention is directed to a one pot method of preparing intermediates of Formula V, which are useful in making inhibitors of phosphodiesterase-4: The present invention is also directed to a method of preparing phosphodiesterase inhibitors comprising the Formula

1-biaryl-1,8-naphthyridin-4-one phosphodiesterase-4 inhibitors

Compounds represented by Formula (I): or a pharmaceutically acceptable salt thereof, are phosphodiesterrase 4 inhibitors useful in the treatment of asthma and inflammation.

Alkyne-aryl phosphodiesterase-4 inhibitors

Compounds represented by Formula (I): or a pharmaceutically acceptable salt thereof, are phosphodiesterase 4 inhibitors useful in the treatment of asthma and inflammation.