- MRGPRX2 ANTAGONISTS FOR THE TREATMENT OF INFLAMMATORY DISORDERS
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The present disclosure is directed to use of MrgprX2 antagonists in the treatment of inflammatory disorders, e.g., inflammatory disorders of the skin. This invention is also directed to pharmaceutical compositions comprising a MrgprX2 antagonist and a pha
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Paragraph 00115; 00224
(2021/05/15)
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- Investigations on substituted (2-aminothiazol-5-yl)(imidazo[1,2-a]pyridin-3-yl)methanones for the treatment of Alzheimer's disease
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Alzheimer's disease (AD) is a neurodegenerative disease majorly affecting old age populations. Various factors that affect the progression of the disease include, amyloid plaque formation, neurofibrillary tangles, inflammation, oxidative stress, etc. Here
- Sagar, Sneha R.,Singh, Devendra Pratap,Das, Rajesh D.,Panchal, Nirupa B.,Sudarsanam, Vasudevan,Nivsarkar, Manish,Vasu, Kamala K.
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- Oxazole-based drug molecule for hospital sterilization, and preparation method thereof
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The invention discloses an oxazole-based drug molecule for hospital sterilization, and a preparation method thereof, and belongs to the technical field of synthesis of antibacterial drugs. According to the technical scheme, the oxazole-based drug molecule
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Paragraph 0033; 0034; 0035; 0036; 0037; 0038; 0038
(2019/10/01)
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- Pharmacological investigation of quinoxaline-bisthiazoles as multitarget-directed ligands for the treatment of Alzheimer's disease
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Alzheimer's disease (AD) is the most prevalent disease of old age leading to dementia. Complex AD pathogenesis involves multiple factors viz. amyloid plaque formation, neurofibrillary tangles and inflammation. Herein we report of a new series of quinoxaline-bisthiazoles as multitarget-directed ligands (MTDLs) targeting BACE-1 and inflammation concurrently. Virtual screening of a library of novel quinoxaline-bisthiazoles was performed by docking studies. The most active molecules from the docking library were taken up for synthesis and characterized by spectral data. Compounds 8a-8n showed BACE-1 inhibition in micro molar range. One of the compounds, 8n showed BACE-1 inhibition at IC50 of 3 ± 0.07 μM. Rat paw edema inhibition in acute and chronic models of inflammation were obtained at 69 ± 0.45% and 55 ± 0.7%, respectively. Compound 8n also showed noteworthy results in AlCl3 induced AD model. The treated rats exhibited excellent antiamnesic, antiamyloid, antioxidant, and neuroprotective properties. Behavioural parameters suggested improved cognitive functions which further validates the testimony of present study. Moreover, compound 8n was found to have inherent gastrointestinal safety. This new string of quinoxaline-bisthiazoles were identified as effective lead for the generation of potent MTDLs and compound 8n was found to showcase qualities to tackle AD pathogenesis.
- Sagar, Sneha R.,Singh, Devendra Pratap,Das, Rajesh D.,Panchal, Nirupa B.,Sudarsanam, Vasudevan,Nivsarkar, Manish,Vasu, Kamala K.
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- Discovery, Development, and SAR of Aminothiazoles as LIMK Inhibitors with Cellular Anti-Invasive Properties
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As part of a program to develop a small molecule inhibitor of LIMK, a series of aminothiazole inhibitors were discovered by high throughput screening. Scaffold hopping and subsequent SAR directed development led to a series of low nanomolar inhibitors of LIMK1 and LIMK2 that also inhibited the direct biomarker p-cofilin in cells and inhibited the invasion of MDA MB-231-luc cells in a matrigel inverse invasion assay.
- Charles, Mark D.,Brookfield, Joanna L.,Ekwuru, Tennyson C.,Stockley, Martin,Dunn, John,Riddick, Michelle,Hammonds, Tim,Trivier, Elisabeth,Greenland, Gavin,Wong, Ai Ching,Cheasty, Anne,Boyd, Susan,Crighton, Diane,Olson, Michael F.
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supporting information
p. 8309 - 8313
(2015/11/09)
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- Efficient synthesis of new tetradentate ligands with potential applications for 64Cu PET-imaging
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We wish to report the synthesis of new tetradentate ligands in less than 3 h in good to excellent yields from a commercially available compound using microwave-assisted technology. First tests of complexation showed a high ability of these ligands to chel
- Bodio, Ewen,Julienne, Karine,Gouin, Sébastien G.,Faivre-Chauvet, Alain,Deniaud, David
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body text
p. 924 - 927
(2011/03/20)
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- Utilization of a nitrogen-sulfur nonbonding interaction in the design of new 2-aminothiazol-5-yl-pyrimidines as p38α MAP kinase inhibitors
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The design, synthesis, and structure-activity relationships (SAR) of a series of 2-aminothiazol-5-yl-pyrimidines as novel p38α MAP kinase inhibitors are described. These efforts led to the identification of 41 as a potent p38α inhibitor that utilizes a un
- Lin, Shuqun,Wrobleski, Stephen T.,Hynes Jr., John,Pitt, Sidney,Zhang, Rosemary,Fan, Yi,Doweyko, Arthur M.,Kish, Kevin F.,Sack, John S.,Malley, Mary F.,Kiefer, Susan E.,Newitt, John A.,McKinnon, Murray,Trzaskos, James,Barrish, Joel C.,Dodd, John H.,Schieven, Gary L.,Leftheris, Katerina
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scheme or table
p. 5864 - 5868
(2010/11/18)
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- Synthesis of nitrogen bicyclic scaffolds: Pyrimido[1,2-a]pyrimidine-2,6- diones
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The multi-step synthesis of 1,3,7-trisubstituted pyrimido[1,2-a] pyrimidinediones starting from isothiocyanates is described. These nitrogen bicycles were prepared by an iterative sequence of functionalization/ cyclocondensation reactions. [4+2] Cycloaddition reactions took place between diazadienic chains and various acyl chlorides providing sophisticated heterobicycles.
- Grosjean, Sylvain,Triki, Smail,Meslin, Jean-Claude,Julienne, Karine,Deniaud, David
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scheme or table
p. 9912 - 9924
(2011/02/22)
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- A convenient synthesis of di- and trisubstituted 2-aminoimidazoles from 1-amidino-3-trityl-thioureas
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Convenient synthesis of 2-amino-1,5-disubstituted and 2-amino-1,4,5-trisubstituted imidazoles has been reported using readily available starting materials and simple reagents under mild conditions. Guanylation of 1-amidino-3-trityl-thioureas 1 and 7 using
- Kaila, Jitendra C.,Baraiya, Arshi B.,Pandya, Amit N.,Jalani, Hitesh B.,Vasu, Kamala K.,Sudarsanam
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scheme or table
p. 3955 - 3958
(2009/10/11)
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- A novel, simple cyclocondensation reaction towards glycosyl triazines
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Sugars bearing an isothiocyanate moiety at C-1 react with diazadienium iodide to afford glycosyl triazines that represent, through an easy cyclocondensation reaction step, a flexible entry to different nucleoside analogues. We herein demonstrate that this [4+2] cycloaddition reaction occurs with total regiocontrol and good yields. Subsequent transformation of the thiocarbonyl into a carbonyl, and nucleophilic substitution of the methylsulfanyl group by ammonia, yields the 5-azacytidine analogues. All compounds were fully characterised by IR, HRMS, and 13C and 1H NMR (COSY, HMBC and HMQC). Georg Thieme Verlag.
- Kikelj, Vincent,Julienne, Karine,Janvier, Pascal,Meslin, Jean-Claude,Deniaud, David
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experimental part
p. 3453 - 3460
(2009/05/26)
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- Orthoamides. LIV. Contributions to the chemistry of azavinylogous orthoformic acid amide derivatives
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The azavinylogous aminalester 3 reacts with primary amines to give amidines 5 and 6. In the reaction of 3 with aniline the azavinylogous amidine 7 is produced additionally to the amidine 5c. Ethylendiamine is formylated at both aminogroups, the bis-amidine 8 thus formed is transformed to the salts 9a,b. Benzoxazole and benzimidazole can be prepared from 3 and o-aminophenol and o-phenylenediamine, resp. Carboxylic acid amides, urea, thiourea, aromatic acid hydrazides 17 and the sulfonylhydrazide 19 are formylated by 3 at nitrogen to give N-acylated formamidines 14, 16, 18, 20. From 3 and aliphatic acid hydrazides 17 and alkylhydrazines, resp., can be obtained 1,2,4-triazole 21 and 1-alkyl-1,2,4-triazoles 22a,b, resp. N.N-Dimethylcyanacetamide (32) reacts with 3 and the orthoamide 4a, resp., to give a mixture of the formylated compound 34 and the amidine 33. The reaction conditions are of low influence on the ratio in which 33 and 34 are formed. The orthoamide 4b and 32 react to afford a mixture of the amidine 35 and the enamine 36. Hydrogen-sulfide acts on 3 giving N,N-dimethylthioformamide (37). From 3 and 1-alkynes 41 can be prepared the amidines 42. Hydrolysis of 42b affords phenylpropiolaldehyde (43). The alkylation of the aminalester 3 gives rise to the formation of vinylogous amidinium salts 1c and 1d, resp., additionally is formed the amide acetal 2a. The salt 1d can also be prepared from 3 and borontrifluoride-ether. Iodide reacts with N,N-dimethylformamide acetals 12a,b in an unclear, complicated manner giving orthoesters 53, N,N-dimethylformamide, alkyliodides, alcohols, ammonium iodides 46 and carbondioxide. The action of halogens on 3 affords the salts 1a,b,c,e,f depending on the chosen stoichiometric ratio. Aromatic aldehydes are suited for trapping azavinylogous carbenes formed on thermolysis of 3; 1,3-oxazoles 69 are the reaction products. From 3 and propionaldehyde the amidine 65 can be obtained with low yield. Carbondisulfide transforms 3 to the azavinylogous salt 66. The preparation of the azavinylogous orthoamide 4a is described. The thermolysis of 3 and 4a, resp., gives rise to the formation of the triaminopyrimidine 67. Treatment of 1a with lithium diisopropylamide affords the triaminopyrazine 68, which can also be obtained by thermolysis of 3 in the presence of sodium hydride. Azavinylogous carbenes are thought to be the intermediates. Wiley-VCH Verlag GmbH, 2000.
- Kantlehner, Willi,Hauber, Michael,Haug, Erwin,Schallenmueller, Claus,Regele, Claudia
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p. 682 - 699
(2007/10/03)
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