35824-91-0

Usage

Uses

Used in Pharmaceutical Synthesis:
1,3-Dicyclohexylbarbituric Acid is used as an intermediate in the synthesis of Daprodustat (D193368), a novel HIF (Hypoxia inducible factor)-prolyl hydroxylase inhibitor. This application is significant because Daprodustat has potential therapeutic benefits in treating anemia and other conditions related to hypoxia.
In the pharmaceutical industry, 1,3-Dicyclohexylbarbituric Acid plays a vital role in the development of new drugs targeting hypoxia-related diseases. Its unique structure allows for the creation of compounds with specific biological activities, making it a valuable asset in the field of medicinal chemistry.

InChI:InChI=1/C16H24N2O3/c19-14-11-15(20)18(13-9-5-2-6-10-13)16(21)17(14)12-7-3-1-4-8-12/h12-13H,1-11H2

Upstream product

• 64-17-5 ethanol 
• 116418-82-7 1,3-dicyclohexyl-5-diazopyrimidine-2,4,6(1H,3H,5H)-trione 
• 71-43-2 benzene 
• 2387-23-7 1,3-Dicyclohexylurea 
• 1663-67-8 malonoyl dichloride 
• 141-82-2 malonic acid 
• 538-75-0 dicyclohexyl-carbodiimide 
• 108-91-8 cyclohexylamine 

Downstream Products

• 84941-34-4 5-Aminomethylen-1,3-dicyclohexylbarbitursaeure 
• 144535-34-2 1,3-Dicyclohexyl-6,8-dimethyl-1H,8H-1,3,6,8,9-pentaaza-anthracene-2,4,5,7-tetraone 
• 129750-86-3 ethyl ester of 2-methyl-2-(1,3-dicyclohexyl-2,4,6-trioxo-perhydropyrimidin-5-yl) acetic acid 
• 144535-30-8 1,3-Dicyclohexyl-1H-pyrimido[4,5-b]quinoline-2,4-dione 
• 93660-26-5 N-{4-[N'-(1,3-Dicyclohexyl-2,4,6-trioxo-tetrahydro-pyrimidin-5-ylidene)-hydrazino]-2-methyl-5-phenyl-2H-pyrazol-3-yl}-benzamide 
• 66400-18-8 6-chloro-1,3-dicyclohexyl-1H-pyrimidine-2,4-dione 
• 72820-31-6 1,3-dicyclohexyl-6-hydrazino-1H-pyrimidine-2,4-dione 
• 129750-90-9 2-methyl-2-(1,3-dicyclohexyl-2,4,6-trioxo-5-methyl-perihydropyrimidin-5-yl) acetic acid 
• 129750-87-4 2-methyl-2-(1,3-dicyclohexyl-2,4,6-trioxo-perhydropyrimidin-5-yl) acetic acid 
• 129750-91-0 2-methyl-2-(1,3-dicyclohexyl-2,4,6-trioxo-5-morpholinomethyl-perihydropyrimidin-5-yl) acetic acid 
• 129750-92-1 2-methyl-2-<1,3-dicyclohexyl-2,4,6-trioxo-5-(N-methyl-N-piperazinomethyl)-perihydropyrimidin-5-yl> acetic acid 
• 129750-88-5 ethyl ester of 2-methyl-2-(1,3-dicyclohexyl-2,4,6-trioxo-5-morpholinomethyl-perihydropyrimidin-5-yl) acetic acid 
• 129750-89-6 ethyl ester of 2-methyl-2-<1,3-dicyclohexyl-2,4,6-trioxo-5-(N-methyl-N-piperazinomethyl)-perihydropyrimidin-5-yl> acetic acid 
• 1070801-99-8 (Z)-5-[(anilino)(mercapto)methylidene]-1,3-dicyclohexylpyrimidine-2,4,6(1H,3H,5H)-trione 

Relevant academic research and scientific papers

Dehydration of an Insoluble Urea Byproduct Enables the Condensation of DCC and Malonic Acid in Flow

A procedure for the preparation of N,N′-dicyclohexylbarbituric acid from DCC and malonic acid is described. Addition of phosphorus oxychloride to the reaction mixture facilitates dehydration of the insoluble byproduct N,N′-dicyclohexyl urea, enabling operation in continuous flow. A development approach based on in situ monitoring of batch reactions was used, which supported screening and determination of reaction conditions at small scale prior to scaleup in flow. Additional mechanistic understanding and control of impurity formation are presented.

Selective Inhibitors of a Human Prolyl Hydroxylase (OGFOD1) Involved in Ribosomal Decoding

Human prolyl hydroxylases are involved in the modification of transcription factors, procollagen, and ribosomal proteins, and are current medicinal chemistry targets. To date, there are few reports on inhibitors selective for the different types of prolyl hydroxylases. We report a structurally informed template-based strategy for the development of inhibitors selective for the human ribosomal prolyl hydroxylase OGFOD1. These inhibitors did not target the other human oxygenases tested, including the structurally similar hypoxia-inducible transcription factor prolyl hydroxylase, PHD2.

Substituted pyrimidinetrione compound, composition containing same and application of substituted pyrimidinetrione compound

The invention provides a substituted pyrimidinetrione compound, a composition containing the same and application of the substituted pyrimidinetrione compound. The invention discloses the pyrimidinetrione compound as shown in formula (I) or the crystal form, pharmaceutically acceptable salt, prodrug, stereisomer, hydrate or solvent compound thereof. The pyrimidinetrione compound and the composition containing the same can be used for regulating hypoxia-inducible factors (HIF) and/or erythropoietin (EPO) and can be used for preparing medicine for regulating and controlling human body anemia.

4-hydroxy-2-quinolones 199*. Use of N,N'-dicyclohexylcarbodiimide in the synthesis of ethyl 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylates

A novel method has been developed for the synthesis of 4-hydroxy-2-oxo-1,2- dihydroquinoline-3-carboxylic acids esters based on the use of monoethyl malonate as an acylating agent in the presence of N,N'-dicyclohexylcarbodiimide and characterized by high yields and purity for the final products. Practical recommendations are given for the removal of specific admixtures.

Pyrimidine-2,4,6-trione derivatives and their inhibition of mutant SOD1-dependent protein aggregation. Toward a treatment for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, leading to muscle weakness, paralysis, and death, most often from respiratory failure. The only FDA-approved drug for the treatment of ALS, riluzole, only extends the median survival in patients by 2-3 months. There is an urgent need for novel therapeutic strategies for this devastating disease. Using a high-throughput screening assay targeting an ALS cultured cell model (PC12-G93A-YFP cell line), we previously identified three chemotypes that were neuroprotective. We present a further detailed analysis of one promising scaffold from that group, pyrimidine-2,4,6-triones (PYTs), characterizing a number of PYT analogues using SAR and ADME. The PYT compounds show good potency, superior ADME data, low toxicity, brain penetration, and excellent oral bioavailability. Compounds from this series show 100% efficacy in the protection assay with a good correlation in activity between the protection and protein aggregation assays. The modifications of the PYT scaffold presented here suggest that this chemical structure may be a novel drug candidate scaffold for use in clinical trials in ALS.

PROLYL HYDROXYLASE INHIBITORS

The invention described herein relates to certain pyrimidinetrione N-substituted glycine derivatives of formula (I), (I) which are antagonists of HIF prolyl hydroxylases and are useful for treating diseases benefiting from the inhibition of this enzyme, anemia being one example.

Pyrimidine derivatives, method for preparation thereof and pharmaceutical composition having said derivatives as active elements

The invention provides i), pyrimidine derivatives of the following formula (I), their pharmaceutically acceptable salt and method for preparation thereof. (R1 and R2 represent independently hydrogen atom, linear or branched alkyl group, substituted or non-substituted phenyl or cyclohexyl group; and R3 represents linear or branched lower alkyl or alkoxy group; represents both stereo isomers.); and ii), Pharmaceutical compositions having the pyrimidine derivatives of formula (I) or pharmaceutically acceptable salts thereof, particularly anti-inflammatory agents, agents for treating respiratory tract disorders or agents for treating cerebrovascular diseases.