- Process Optimization, Product Profile Mapping, and Intensification of 1,1-Diamino-2,2-dinitroethylene
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Industrialization of a chemical process needs an understanding of process chemistry, optimal process envelope, and the best choice of operation. 1,1-Diamino-2,2-dinitroethylene (FOX-7) is a new generation, and the highly insensitive compound finds application in high-energy formulations as well as preparation of novel high-energy compounds. The present study highlights efforts made for establishing a continuous process for FOX-7. The intermediates of nitration of 2-methylpyrimidine-4, 6-dione were isolated and characterized by spectroscopic tools. Reaction kinetics was also derived for the formation of intermediates. Product profiles of the reaction were evaluated on deriving expressions for various reactors. The simultaneous effect of heat and reaction was evaluated in a tubular reactor to obtain the runaway reaction condition. The effective reactor scheme was evaluated, designed, and experimented. Process intensification was carried out in a continuous set up comprising various contact patterns. The present study delivered a safe and productive method for FOX-7 processing
- Jadhav, Pandurang M.,Sarangapani, Radhakrishnan,Patil, Rajendra S.,Pandey, Raj K.
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Read Online
- Predicting the impact sensitivity of a polymorphic high explosive: The curious case of FOX-7
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The impact sensitivity (IS) of FOX-7 polymorphs is predicted by phonon up-pumping to decrease as layers of FOX-7 molecules flatten. Experimental validation proved anomalous owing to a phase transition during testing, raising questions regarding impact sensitivity measurement and highlighting the need for models to predict IS of polymorphic energetic materials.
- Michalchuk, Adam A. L.,Morrison, Carole A.,Pulham, Colin R.,Rudi?, Svemir
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supporting information
p. 11213 - 11216
(2021/11/03)
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- Phenyl and Diaryl Ureas with Thiazolo[5,4-d]pyrimidine Scaffold as Angiogenesis Inhibitors: Design, Synthesis and Biological Evaluation
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Angiogenesis is crucial for tumor growth and inhibition of angiogenesis has been regarded as a promising approach for cancer therapy. Vascular endothelial growth factor receptor-2 (VEGFR-2) is an important factor in angiogenesis. In this work, a novel series of thiazolo[5,4-d]pyrimidine derivatives inhibiting angiogenesis were rationally designed and synthesized. Their inhibitory activities against human umbilical vein endothelial cells (HUVEC) were investigated in vitro. 1-(4-Fluorophenyl)-3-{4-[(5-methyl-2-phenyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl)amino]phenyl}urea (19b) and 1-(3-Fluorophenyl)-3-{4-[(5-methyl-2-phenyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl)amino]phenyl}urea (19g) exhibited the most potent inhibitory effect on HUVEC proliferation (IC50=12.8 and 5.3 μm, respectively). Compound 19g could inhibit the migration of human umbilical vein endothelial cells. These results support the further investigation of these compounds as potent anticancer agents.
- Xue, Wen-Jun,Deng, Ya-Hui,Yan, Zhong-Hui,Liu, Ji-Ping,Liu, Yu,Sun, Li-Ping
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- An efficient and convenient synthesis of 4,6-Dichloro-2-methyl-5- nitropyrimidine
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A convenient synthesis of 4, 6-dihydro-2-methyl-pyrimidine can be obtained by cyclization reaction of acetamidine hydrochloride and diethyl malonate in the presence of sodium methoxide for a 91.2 % yield. 4, 6-Dihydro-2-methyl-5- nitropyrimidine can be achieved by nitration under the mixed acids of nitric acid, trichloroacetic acid and acetic acid in an 88.3 % yield and then the chlorination using phosphorus oxytrichloride can afford 4, 6-dichloro-2-methyl- 5-nitropyrimidine with an 82.6 % yield.
- Zhou, Shuwen,Xu, Defeng,Wang, Ziqiao,Zhu, Zhiling,Zha, Zhenyu,Fan, Yu,Su, Hongkui
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p. 3559 - 3561
(2014/08/05)
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- Discovery of triazolopyrimidine-based PDE8B inhibitors: Exceptionally ligand-efficient and lipophilic ligand-efficient compounds for the treatment of diabetes
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PDE8B is a cAMP-specific isoform of the broader class of phosphodiesterases (PDEs). As no selective PDE8B inhibitors had been reported, a high throughput screen was run with the goal of identifying selective tools for exploring the potential therapeutic utility of PDE8B inhibition. Of the numerous hits, one was particularly attractive since it was amenable to rapid deconstruction leading to inhibitors with very high ligand efficiency (LE) and lipophilic ligand efficiency (LLE). These triazolopyrimidines were optimized for potency, selectivity and ADME properties ultimately leading to compound 42. This compound was highly potent and selective with good bioavailability and advanced into pre-clinical development.
- Deninno, Michael P.,Wright, Stephen W.,Etienne, John B.,Olson, Thanh V.,Rocke, Benjamin N.,Corbett, Jeffrey W.,Kung, Daniel W.,Dirico, Kenneth J.,Andrews, Kim M.,Millham, Michele L.,Parker, Janice C.,Esler, William,Van Volkenburg, Maria,Boyer, David D.,Houseknecht, Karen L.,Doran, Shawn D.
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scheme or table
p. 5721 - 5726
(2012/09/22)
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- NITROGENATED FUSED RING DERIVATIVE, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, AND USE OF THE SAME FOR MEDICAL PURPOSES
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[Purpose] The present invention provides compounds useful as agents for the prevention or treatment of a sex hormone-dependent disease or the like. [Solution] The present invention provides nitrogen-containing fused ring derivatives represented by the following general formula (I) which has a GnRH antagonistic activity, prodrugs, salts, pharmaceutical compositions containing the same, medicinal uses thereof and the like. In the formula (I), rings A and B are independently aryl or heteroaryl; RA and RB are independently halogen, cyano, alkyl, alkylsulfonyl, -OW1, -SW1, -COW2, -NW3W4, -SO2NW3W4, aryl, etc.; RC is H or alkyl; E is oxygen atom, etc.; U is single bond or alkylene; and X is Y, -CO-Y, -SO2-Y -S-(alkylene)-Y, -O-(alkylene)-Y, -SO2-(alkylene)-Y, etc.; Y is Z or amino, etc.; and Z is cycloalkyl, heterocycloalkyl, aryl, heteroaryl, etc.
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Page/Page column 42
(2010/01/29)
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- On the synthesis of 1,1-diamino-2,2-dinitroethene (FOX-7) by nitration of 4,6-dihydroxy-2-methylpyrimidine
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The synthesis of 1,1-diamino-2,2-dinitroethene (FOX-7) by nitration of 4,6-dihydroxy-2-methylpyrimidine and hydrolysis of the resulting intermediate 2-dinitromethylene-5,5-dinitropy-rimidine-4,6-dione has been studied. By varying the reaction parameters the optimal conditions for the synthesis of FOX-7 have been identified and gave a >90% yield of the pure product. The optimised process allowed the spent acid to be recycled without loss of yield, with almost stoichiometric consumption of nitric acid. The purity of the FOX-7 has been determined using a newly developed HPLC method
- Latypov, Nikolaj V.,Johansson, Martin,Holmgren, Erik,Sizova, Ekaterina V.,Sizov, Vladimir V.,Bellamy, Anthony J.
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- Amide compounds and medications containing the same technical field
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The present invention provides to a novel compound having an ACAT inhibiting activity. The present invention relates to compounds represented by formula (I) wherein represents an optionally substituted divalent residue such as benzene, pyridine, cyclohexane or naphthalene, or a group,Het represents a 5- to 8-membered, substituted or unsubstituted heterocyclic group containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, such as a monocyclic group, a polycyclic group or a group of a fused ring,X represents —NH—, an oxygen atom or a sulfur atom,Y represents —NR4—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone,Z represents a single bond or —NR5—,R4 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group,R5 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, andn is integer of from 1 to 15, or salts or solvates thereof, and a pharmaceutical composition containing at one of these compounds.
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Page/Page column 134
(2010/02/10)
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- CRF receptor antagonists and methods relating thereto
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Compounds are disclosed which have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in a warm-blooded animals, including stroke. The compounds of this invention have the following structures: wherein n, m, R, R1, R2, X and Ar are as defined herein, including stereoisomes and pharmaceutically acceptable salts thereof.
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Page column 14
(2010/01/30)
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- 1N-ALKYL-N-ARYLPYRIMIDINAMINES AND DERIVATIVES THEREOF
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The present invention provides novel compounds, compounds and pharmaceutical compositions thereof, and methods of using same in the treatment of affective disorders, anxiety, depression, post-traumatic stress disorders, eating disorders, supranuclear palsy, irritable bowel syndrome, immune suppression, Alzheimer'disease, gastrointestinal diseases, anorexia nervosa, drug and alcohol withdrawal symptoms, drug addiction, inflammatory disorders, or fertility problems. The novel compounds provided by this invention are those of formula: wherein R 1, R 3, R 4, R 5, Z, Y, V, X, X', J, K, L, and M are as defined herein.
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- Some specific features of acid nitration of 2-substituted 4,6-dihydroxypyrimidines. Nucleophilic cleavage of the nitration products
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The nitration of 2-substituted 4,6-dihydroxypyrimidines in concentrated sulfuric acid yields the corresponding 5,5-dinitro derivatives. When the substituent in position 2 is an alkyl group, the nitration occurs both at position 5 and at the α-carbon atom of the side chain. Hydrolysis of 2-substituted 4,6-dihydroxy-5,5-dinitropyrimidines leads to formation of 1,1-diamino-2-R-2-nitroethylene derivatives. 1,1-Diamino-2,2-dinitroethylene was obtained by nitration of 4,6-dihydroxy-2-methylpyrimidine and subsequent hydrolysis of 4,6-dihydroxy-5,5-dinitro-2-(dinitromethylene)-2,5-dihydropyrimidine.
- Astrat'ev,Dashko,Mershin,Stepanov,Urazgil'deev
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p. 729 - 733
(2007/10/03)
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- Heterocyclyl-substituted ring-fused pyridines and pyrimidines as corticotropin releasing hormone(CRH) antagonists, useful for treating CNS and stress-related disorders
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Corticotropin releasing factor (CRF) antagonists of Formula (I): and their use in treating psychiatric disorders and neurological diseases, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in mammals.
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- Compounds and methods which modulate feeding behavior and related diseases
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There are provided compounds, compositions and methods of use thereof in the modulation of feeding behavior, obesity, diabetes, cancer (tumor), inflammatory disorders, depression, stress related disorders, Alzheimer's disease and other disease conditions.
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- Structure-activity relationships of a series of pyrrolo[3,2-d]pyrimidine derivatives and related compounds as neuropeptide Y5 receptor antagonists
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Neuropeptide Y (NPY) has been shown to play an important role in the regulation of food intake and energy balance. Pharmacological data suggests that the Y5 receptor subtype contributes to the effects of NPY on appetite, and therefore a Y5 antagonist might be a useful therapeutic agent for the treatment of obesity. In attempts to identify potential Y5 antagonists, a series of pyrrolo[3,2-d]pyrimidine derivatives was prepared and evaluated for their ability to bind to Y5 receptors in vitro. We report here the synthesis and initial structure-activity relationship investigations for this class of compounds. The target compounds were prepared by a variety of synthetic routes designed to modify both the substitution and the heterocyclic core of the pyrrolo[3,2-d]pyrimidine lead 1. In addition to identifying several potent Y5 antagonists for evaluation as potential antiobesity agents, a pharmacophore model for the human Y5 receptor is presented.
- Norman,Chen,Chen,Fotsch,Hale,Han,Hurt,Jenkins,Kincaid,Liu,Lu,Moreno,Santora,Sonnenberg,Karbon
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p. 4288 - 4312
(2007/10/03)
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- Arylamino fused pyrimidines
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Corticotropin releasing factor (CRF) antagonists of formula I or formula II: and their use in treating anxiety, depression, and other psychiatric and neurological disorders.
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- Purin-8-ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists
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A series of purin-8-ones was prepared and discovered to have excellent binding affinity to the CRH-R1 receptor. Structure-activity studies focused on amine side-chain optimization, urea substitution and pyridyl isostere incorporation. Thus, the highly potent purin-8-ones show promise as a new class of potential anxiolytics and/or antidepressants.
- Beck, James P.,Arvanitis, Argyrios G.,Curry, Matt A.,Rescinito, Joseph T.,Fitzgerald, Larry W.,Gilligan, Paul J.,Zaczek, Robert,Trainor, George L.
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p. 967 - 972
(2007/10/03)
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- Pyrimidine derivatives
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The present invention relates to novel 5-(ω-substituted amino-alkanoyl amino)pyrimidine derivatives, processes for producing the derivatives, and pharmaceutical compositions containing said derivatives. The compounds in the present invention have potent effects of inhibiting ACAT activity and lowering serum cholesterol. The compounds of the present invention are extremely useful for the treatment and/or prevention of arteriosclerosis or hyperlipidemia.
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