1083088-79-2

Upstream product

• 95644-24-9 3-(3,4-dimethoxyphenyl)-4,4-dimethyl-1H-pyrazol-5(4H)-one 
• 118811-07-7 tert-butyl 4-(tosyloxy)piperidin-1-carboxylate 
• 180695-79-8 tert-butyl 4-bromo-1-piperidinecarboxylate 
• 95644-16-9 methyl 3-(3,4-dimethoxyphenyl)-2,2-dimethyl-3-oxopropanoate 
• 3535-37-3 3,4-dimethoxybenzoic acid chloride 

Downstream Products

• 1083088-53-2 5-(3,4-dimethoxyphenyl)-4,4-dimethyl-2-(piperidin-4-yl)-2,4-dihydro-3H-pyrazol-3-one hydrochloride 
• 1083088-78-1 3-(3,4-dimethoxyphenyl)-4,4-dimethyl-1-(piperidin-4-yl)-1H-pyrazol-5(4H)-one 

Relevant academic research and scientific papers

Lead Optimization of Phthalazinone Phosphodiesterase Inhibitors as Novel Antitrypanosomal Compounds

Human African trypanosomiasis is causing thousands of deaths every year in the rural areas of Africa. In this manuscript we describe the optimization of a family of phtalazinone derivatives. Phosphodiesterases have emerged as attractive molecular targets for a novel treatment for a variety of neglected parasitic diseases. Compound 1 resulted in being a potent TbrPDEB1 inhibitor with interesting activity against T. brucei in a phenotypic screen. Derivative 1 was studied in an acute in vivo mouse disease model but unfortunately showed no efficacy due to low metabolic stability. We report structural modifications to achieve compounds with an improved metabolic stability while maintaining high potency against TbrPDEB1 and T. brucei. Compound 14 presented a good microsomal stability in mouse and human microsomes and provides a good starting point for future efforts.

NOVEL PYRAZOLONE-DERIVATIVES AND THEIR USE AS PD4 INHIBITORS

The compounds of formula (1) wherein R1 represents a phenyl derivative of formulae (a), (b) or (c) R10 is 1-3C-alkyl and R11 is 1-3C-alkyl, or R10 and R11 together with the carbon atom, to which they are bonded, form a spiro-linked 3-, 4-, 5- or 6-membered hydrocarbon ring, A is C(O) or S(O)2, and R12 is phenyl, naphthalenyl, pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl, 1,6-naphthyridinyl, 1,8-naphthyridinyl, indolyl, phenyl substituted by R13, R14, R15 and R16, pyridinyl substituted by R17 and R18, naphthalenyl substituted by R19 and R20, quinolinyl substituted by R21 or indolyl substituted by R22, are novel effective inhibitors of the type 4 phosphodiesterase.