- Nitrogen-containing ring derivative inhibitor as well as preparation method and application thereof
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The invention relates to a nitrogen-containing ring derivative inhibitor as well as a preparation method and an application thereof. In particular, the present invention relates to a compound represented by general formula (I), a preparation method thereof, a pharmaceutical composition containing the compound, and uses of the compound as a P2X3 inhibitor in treatment of P2X3 receptor dysfunction diseases, especially in treatment of neurogenic diseases.
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Paragraph 0759-0765
(2021/05/12)
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- Identification of diphenylalkylisoxazol-5-amine scaffold as novel activator of cardiac myosin
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To identify novel potent cardiac myosin activator, a series of diphenylalkylisoxazol-5-amine compounds 4–7 have been synthesized and evaluated for cardiac myosin ATPase activation. Among the 37 compounds, 4a (CMA at 10 μM = 81.6%), 4w (CMA at 10 μM = 71.2%) and 6b (CMA at 10 μM = 67.4%) showed potent cardiac myosin activation at a single concentration of 10 μM. These results suggested that the introduction of the amino-isoxazole ring as a bioisostere for urea group is acceptable for the cardiac myosin activation. Additional structure–activity relationship (SAR) studies were conducted. Para substitution (-Cl, –OCH3, -SO2N(CH3)2) to the phenyl rings or replacement of a phenyl ring with a heterocycle (pyridine, piperidine and tetrahydropyran) appeared to attenuate cardiac myosin activation at 10 μM. Additional hydrogen bonding acceptor next to the amino group of the isoxazoles did not enhance the activity. The potent isoxazole compounds showed selectivity for cardiac myosin activation over skeletal and smooth muscle myosin, and therefore these potent and selective isoxazole compounds could be considered as a new series of cardiac myosin ATPase activators for the treatment of systolic heart failure.
- Boggu, Pulla Reddy,Venkateswararao, Eeda,Manickam, Manoj,Sharma, Niti,Kang, Jong Seong,Jung, Sang-Hun
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- NOVEL PYRAZOLO-PYRROLO-PYRIMIDINE-DIONE DERIVATIVES AS P2X3 INHIBITORS
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The present invention covers substituted Pyrazolo-pyrrolo-pyrimidine-dione (PPPD) compounds of general formula (I): in which R1, R2 and R3 are as defined herein, methods of preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of neurogenic diseases, as a sole agent or in combination with other active ingredients.
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Page/Page column 100
(2019/05/15)
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- A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones
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The acylation of the acetonitrile anion with lactones and esters in ethereal solvents was successfully exploited using inexpensive KOt-Bu to obtain a variety of β-ketonitriles and trifunctionalized building blocks, including useful O-unprotected diols. It was discovered that lactones react to produce the corresponding derivatized cyclic hemiketals. Furthermore, the addition of a catalytic amount of isopropanol, or 18-crown-6, was necessary to facilitate the reaction and to reduce side-product formation under ambient conditions.
- Pienaar, Daniel P.,Butsi, Kamogelo R.,Rousseau, Amanda L.,Brady, Dean
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supporting information
p. 2930 - 2935
(2019/12/23)
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- Preparation of 3,4-Substituted-5-Aminopyrazoles and 4-Substituted-2-Aminothiazoles
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3,4-Substituted-5-aminopyrazoles and 4-substituted-2-aminothiazoles are frequently used intermediates in medicinal chemistry and drug discovery projects. We report an expedient flexible synthesis of 3,4-substituted-5-aminopyrazoles (35 examples), based on palladium-mediated α-arylation of β-ketonitriles with aryl bromides. A library of 4-substituted-2-aminothiazoles (21 examples) was assembled by a sequence employing Suzuki coupling of newly prepared, properly protected pinacol ester and MIDA ester of 4-boronic acid-2-aminothiazole with (hetero)aryl halides.
- Havel, Stepan,Khirsariya, Prashant,Akavaram, Naresh,Paruch, Kamil,Carbain, Benoit
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p. 15380 - 15405
(2019/01/04)
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- One-pot dichlorinative deamidation of primary β-ketoamides
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An approach to the dichlorinative deamidation of primary β-ketoamides through ketonic cleavage is described, and a series of α,α-dichloroketones were furnished mostly in the presence of TEMPO. Based on control experiments, a mechanism involving tandem dichlorination and deamidation is proposed to interpret the observed reactivity.
- Zheng, Congke,Zhang, Xiaohui,Ijaz Hussain, Muhammad,Huang, Mingming,Liu, Qing,Xiong, Yan,Zhu, Xiangming
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supporting information
p. 574 - 577
(2017/01/16)
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- Umpolung Strategy for Synthesis of β-Ketonitriles through Hypervalent Iodine-Promoted Cyanation of Silyl Enol Ethers
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An efficient method to synthesize β-ketonitriles from silyl enol ethers by an umploung hypervalent iodine(III)-CN species generated in situ from PhIO/BF3·Et2O/TMSCN has been developed for the first time. This method can be applied to structurally diverse aromatic and aliphatic substrates and further extended to preparation of bioactive compounds like 5-aminopyrazole and 5-aminoisoxazole.
- Shen, Hang,Li, Jiaqiang,Liu, Qing,Pan, Jing,Huang, Ruofeng,Xiong, Yan
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p. 7212 - 7218
(2015/07/28)
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- Chemo- And stereoselective reduction of β-keto-α-oximino nitriles by using baker's yeast
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The baker's yeast mediated reduction of β-keto-α-oximino nitriles 3 at 20 ° C gave β-hydroxy-α-oximino nitriles 4 in high yields with high enantiomeric purity [enantiomeric excess (ee) values >99%]. At room temperature, the same reaction afforded the product in a slightly lower yield. The β-hydroxy-α-oximino nitriles 4 were obtained as single stereoisomers according to chiral GC-MS analyses and the 1H and 19F NMR spectra of the corresponding Mosher esters. The abso-lute stereochemistry of alcohol 4a was determined by hydrolysis of its oximino nitrile group followed by conversion into its corresponding α-hydroxy ester. The β-hydroxy-α-oximino nitrile products were further submitted to oxime- and nitrileselective transformations. This chemo- and stereoselective reduction can be used to generate important chiral building blocks.
- Mo, Kilwoong,Kang, Soon Bang,Kim, Youseung,Lee, Yong Sup,Lee, Jae Wook,Keum, Gyochang
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p. 1137 - 1143
(2015/02/19)
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- AURORA KINASE INHIBITORS
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Disclosed herein inter alia are compositions and methods useful in the treatment of cancer and for modulating the activity of Aurora A kinase and/or a Myc family protein.
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Paragraph 0265
(2014/12/12)
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- PYRIDO PYRIMIDINES
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Compounds of formula and pharmaceutically acceptable salts thereof are described, as well as the pharmaceutical compositions containing said compounds and their pharmaceutically acceptable salts, and the use of said compounds and pharmaceutical compositions for the treatment, control or amelioration of proliferative diseases, including cancer, Down syndrome or early onset Alzheimer's disease.
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Page/Page column 112
(2012/07/28)
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- Biocatalytic strategy toward asymmetric β-hydroxy nitriles and γ-amino alcohols
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A library of 20 bakers' yeast reductases, that are overexpressed in Escherichia coli, were screened against a variety of β-keto nitriles. Enzymes from the aldose reductase and the short chain dehydrogenase family displayed activity toward these substrates. All of the seven substrates were reduced with high enantioselectivities and in some cases both antipodes could be synthesized in high ees. These whole-cell reactions afforded gram quantities of asymmetric compounds that could ultimately lead to scaleable and simple synthesis to new drug analogs of serotonin reuptake inhibitors and β-adrenergic blocking agents.
- Nowill, Randall W.,Patel, Trisha J.,Beasley, David L.,Alvarez, Jose A.,Jackson III, Elizah,Hizer, Todd J.,Ghiviriga, Ion,Mateer, Scott C.,Feske, Brent D.
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supporting information; experimental part
p. 2440 - 2442
(2011/05/16)
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- INHIBITORS OF AKT ACTIVITY
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Invented are novel 1 H-imidazo[4,5-c]pyridin-2-yl compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
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Page/Page column 123-124
(2008/06/13)
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- ARALKYL AMINES AS CANNABINOID RECEPTOR MODULATORS
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Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson’s disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, including alcohol and nicotine addiction, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.
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Page/Page column 102
(2010/02/11)
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- Nitrogen-containing bicyclic compounds and drugs containing the same as the active ingredient
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A nitrogen-containing bicyclic compound of formula (I) or a pharmaceutically acceptable salt thereof (wherein the symbols have the same meanings as described in the specification). The compound of formula (I) has an inhibitory activity against PDE7 and it
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Page/Page column 121
(2010/02/14)
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- 3,4 Dihydroisoquinoline derivative compounds and drugs containing these compounds as the active ingredient
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A 3,4-dihydroisoquinoline derivative compound of formula (I) or a non-toxic salt thereof and a pharmaceutical agent comprising it as active ingredient (wherein all symbols have the same meaning as described in the specification). The compound of formula (
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- Synthesis and Hypocholesterolemic Activity of 6,7-Dihydro-4H-pyrazolopyrrolopyrimidine-5,8-diones, Novel Inhibitors of AcylCoA:Cholesterol O-Acyltransferase
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A novel series of 6,7-dihydro-4H-pyrazolopyrrolopyrimidine-5,8-dione inhibitors of the enzyme acylCoA:cholesterol O-acyltransferase is described.A number of these derivatives were found to be potent modulators of serum lipoprotein levels in
- Larsen, Scott D.,Spilman, Charles H.,Bell, Frank P.,Dinh, Dac M.,Martinborough, Esther,Wilson, Gracella J.
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p. 1721 - 1727
(2007/10/02)
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- The Syntheses of 5-Amino-3-t-butylisothiazole and 3-Amino-5-t-butylisothiazole
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A general synthesis of 3-amino-3-alkylpropenenitriles is described.These intermediates are further transformed to 5-amino-3-alkylisothiazoles.Also described is the synthesis of the novel isomer, 3-amino-5-t-butylisothiazole.
- Hackler, Ronald E.,Burow, Kenneth W.,Kaster, Sylvester V.,Wickiser, David I.
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p. 1575 - 1578
(2007/10/02)
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