- SUBSTITUTED TRIAZOLE DERIVATIVES AND USES THEREOF
-
The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.
- -
-
Page/Page column 82
(2019/06/05)
-
- A method for the synthesis of pharmaceutical intermediates
-
The invention relates to the field of medical chemistry, in particular relates to the field of pharmaceutical synthesis, and more particularly relates to a synthesis method for a medical intermediate. The synthesis method comprises the following steps: firstly enabling a compound I to react with oxalyl chloride to prepare a compound II; and directly adding a reaction liquid to a compound III through treatment or absence of treatment, so as to obtain a compound IV. The synthesis route provided by the invention is simple in production technology, high in product yield, and simple in purification and treatment; and the product is high in purity after being simply treated, low in preparation cost and suitable for industrialized production.
- -
-
Paragraph 0025-0026; 0029; 0032; 0037; 0042; 0047
(2017/10/11)
-
- Identification of indole inhibitors of human hematopoietic prostaglandin D2 synthase (hH-PGDS)
-
Abstract Human H-PGDS has shown promise as a potential target for anti-allergic and anti-inflammatory drugs. Here we describe the discovery of a novel class of indole inhibitors, identified through focused screening of 42,000 compounds and evaluated using a series of hit validation assays that included fluorescence polarization binding, 1D NMR, ITC and chromogenic enzymatic assays. Compounds with low nanomolar potency, favorable physico-chemical properties and inhibitory activity in human mast cells have been identified. In addition, our studies suggest that the active site of hH-PGDS can accommodate larger structural diversity than previously thought, such as the introduction of polar groups in the inner part of the binding pocket.
- Edfeldt, Fredrik,Even?s, Johan,Lepist?, Matti,Ward, Alison,Petersen, Jens,Wissler, Lisa,Rohman, Mattias,Sivars, Ulf,Svensson, Karin,Perry, Matthew,Feierberg, Isabella,Zhou, Xiao-Hong,Hansson, Thomas,Narjes, Frank
-
p. 2496 - 2500
(2015/06/02)
-
- THIAZOLECARBOXAMIDES AND PYRIDINECARBOXAMIDE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS
-
The present disclosure describes thiazole and pyridine carboxamide derivatives, their compositions and methods of use. The compounds inhibit the activity of the Pim kinases and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases.
- -
-
Paragraph 0820; 0821
(2014/07/23)
-
- Synthesis and biological evaluation of 7-substituted-1-(3-bromophenylamino) isoquinoline-4-carbonitriles as inhibitors of myosin light chain kinase and epidermal growth factor receptor
-
Here we present the synthesis and biological activity of a series of 7-substituted-1-(3-bromophenylamino)isoquinoline-4-carbonitriles as inhibitors of myosin light chain kinase (MLCK) and the epidermal growth factor receptor kinase (EGFR). The inhibitory
- Rode, Haridas B.,Sos, Martin L.,Grütter, Christian,Heynck, Stefanie,Simard, Jeffrey R.,Rauh, Daniel
-
experimental part
p. 429 - 439
(2011/02/27)
-
- Straightforward and facile approach toward the n-derivatization of pyroglutamates through mitsunobu reaction: Synthesis of N-alkyl/N-acyl pyroglutamates
-
Pyroglutamates have been acknowledged as useful chiral synthons for the synthesis of many bioactive natural products, ACE inhibitors, and conformationally constrained peptides. Though the reactivity differences between two differential carbonyl groups have been well exploited, there is still a dearth of publications on the N-alkylation/acylation of native pyroglutamate as such, due to the relatively low reactivity of NH of pyroglutamates. In the present communication, we report for the first time a simple and efficient methodology for the N-alkylation/acylation of pyroglutamate via Mitsunobu reaction. Copyright Taylor & Francis Group, LLC.
- Panday, Sharad Kumar,Prasad, Jagdish,Pathak, Manoher Bhushan
-
experimental part
p. 3654 - 3661
(2011/10/09)
-
- Functionalized pyrrolidine inhibitors of human type II α-mannosidases as anti-cancer agents: Optimizing the fit to the active site
-
Refining the chemical structure of functionalized pyrrolidine-based inhibitors of Golgi α-mannosidase II (GMII) to optimize binding affinity provided a lead molecule that demonstrated nanomolar competitive inhibition of α-mannosidases II and an optimal fit in the active site of Drosophila GMII by X-ray crystallography. Esters of this lead compound also inhibited the growth of human glioblastoma and brain-derived endothelial cells more than the growth of non-tumoral human fibroblasts, suggesting their potential for anti-cancer therapy.
- Fiaux, Helene,Kuntz, Douglas A.,Hoffman, Daniela,Janzer, Robert C.,Gerber-Lemaire, Sandrine,Rose, David R.,Juillerat-Jeanneret, Lucienne
-
p. 7337 - 7346
(2008/12/23)
-
- An enantioselective total synthesis of (-)-stemoamide
-
An enantioselective synthesis of (-)-stemoamide has been achieved in 14 steps starting from pyroglutamyl alcohol in ca. 7% overall yield. The key steps in the strategy are a conjugate addition of a vinyl copper reagent and a ring closing metathesis (RCM) reaction to form the seven-membered ring.
- Sibi, Mukund P.,Subramanian, Thangaiah
-
p. 1211 - 1214
(2007/10/03)
-
- Total synthesis of (+)-calyculin A and (-)-calyculin B: Cyanotetraene construction, asymmetric synthesis of the C(26-37) oxazole, fragment assembly, and final elaboration
-
A convergent total synthesis leading to (+)-calyculin A and (-)-calyculin B (1 and 2), antipodes of the potent, highly selective and remarkably cell-permeable phosphatase inhibitors calyculins A and B, has been achieved. In the preceding paper we outlined the asymmetric synthesis of the C(9-25) spiroketal dipropionate subunit (+)-BC; herein we describe construction of the C(1-8) cyanotetraene, an asymmetric synthesis of the C(26-37) oxazole, fragment assembly and final elaboration to (+)-1 and (-)-2. Highlights of the synthesis include: application of a one-pot three-component Suzuki reaction for the construction of phosphonate A, a bifunctional triene precursor of the light sensitive C(1-8) cyanotetraene subunit, an asymmetric synthesis of the C(26-32) oxazole (-)-D, exploiting the Silks-Odom 77Se NMR protocol to assess enantiomeric purity, construction of the C(33-37) subtarget (-)-E in a highly stereocontrolled fashion via an acyliminium ion, and a concise, highly efficient sequence for fragment assembly and elaboration to (+)-calyculin A and (-)-calyculin B. The synthesis of (-)-2 also confirms the structure of calyculin B, previously based only on spectral comparison with calyculin A.
- Smith III, Amos B.,Friestad, Gregory K.,Barbosa, Joseph,Bertounesque, Emmanuel,Duan, James J.-W.,Hull, Kenneth G.,Iwashima, Makoto,Qiu, Yuping,Spoors, P. Grant,Salvatore, Brian A.
-
p. 10478 - 10486
(2007/10/03)
-
- A formal synthesis of (-)-α-kainic acid
-
The formal synthesis of (-)-α-kainic acid was achieved from L-pyroglutamic acid. The C-4 substituent of the pyrrolidine ring was introduced by using a ketyl radical cyclization on an enecarbamate.
- Cossy, Janine,Cases, Manuel,Gomez Pardo, Domingo
-
p. 507 - 509
(2007/10/03)
-
- Synthesis of aza-muricatacin : An analogue of the bioactive muricatacin an acetogenin of annonaceae
-
Muricatacin is a hydroxy butanolide extracted from Annona muricata, and has shown cytotoxic activity. The threo and erythro aza-analogues, namely the hydroxy pyrrolidones have been synthesized through two different routes.
- Baussanne, Isabelle,Schwardt, Oliver,Royer, Jacques,Pichon, Marianne,Figadere, Bruno,Cave, Andre
-
p. 2259 - 2262
(2007/10/03)
-
- Study of the structure-activity relationships of the acetogenin of annonaceae, muricatacin and analogues
-
A study of the structure-cytotoxic activity of the acetogenin of Annonaceae, muricatacin 1, is reported. indeed, muricatacin 1 has shown promising antitumoral activity. Therefore several 5-hydroxy-4-alkcanolides were prepared and then tested against KB and VERO cell lines. A few other analogues were synthesized and tested against both cell lines. Thus this work allowed us to better determine the pharmacophore of the molecule and to propose muricatacin 1 instead of a more complicated acetogenin of Annonaceae as a lead compound in the search for new antineoplastic agents.
- Cave,Chaboche,Figadere,Harmange,Laurens,Peyrat,Pichon,Szlosek,Cotte-Lafitte,Quero
-
p. 617 - 623
(2007/10/03)
-
- Studies on pyrrolidones. An improved synthesis of pyroglutamoyl chloride
-
The reaction of trimethylsilyl pyroglutamate with oxalyl chloride at room temperature easily yields pyroglutamoyl chloride. This unstable compound, obtained with difficulty by other methods, is suitable for the preparation of pyroglutamic esters and amides.
- Rigo,El Ghammarti,Gautret,Couturier
-
p. 2597 - 2607
(2007/10/02)
-