- HETEROCYCLIC KINASE INHIBITORS AND PRODUCTS AND USES THEREOF
-
Compounds are provided having the structure of Formula (I) or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, tautomer, isotope, or salt thereof, wherein A, X, R3, R5, R6, R7, R8, Y
- -
-
-
- Scope and limitations of reductive amination catalyzed by half-sandwich iridium complexes under mild reaction conditions
-
The conversion of aldehydes and ketones to 1° amines could be promoted by half-sandwich iridium complexes using ammonium formate as both the nitrogen and hydride source. To optimize this method for green chemical synthesis, we tested various carbonyl substrates in common polar solvents at physiological temperature (37 °C) and ambient pressure. We found that in methanol, excellent selectivity for the amine over alcohol/amide products could be achieved for a broad assortment of carbonyl-containing compounds. In aqueous media, selective reduction of carbonyls to 1° amines was achieved in the absence of acids. Unfortunately, at Ir catalyst concentrations of 1 mM in water, reductive amination efficiency dropped significantly, which suggest that this catalytic methodology might be not suitable for aqueous applications where very low catalyst concentration is required (e.g., inside living cells).
- Nguyen, Dat P.,Sladek, Rudolph N.,Do, Loi H.
-
supporting information
(2020/07/15)
-
- Nano-Fe3O4@SiO2-SO3H: A magnetic, reusable solid-acid catalyst for solvent-free reduction of oximes to amines with the NaBH3CN/ZrCl4 system
-
In this study, the immobilization of sulfonic acid on silica-layered magnetite was carried out by the reaction of ClSO3H with silica-layered magnetite. The prepared magnetic nanoparticles of Fe3O4@SiO2-SO3H were then characterized using scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometry, and transmission electron microscopy. The sulfonated nanocomposite exhibited excellent catalytic activity and reusability in the reduction of various aldoximes and ketoximes with NaBH3CN in the presence of ZrCl4. All reactions were carried out under solvent-free conditions (r.t. or 75–80°C) within 3–70 min to afford amines in high to excellent yields.
- Sadighnia, Leila,Zeynizadeh, Behzad,Karami, Shiva,Abdollahi, Mohammad
-
p. 535 - 542
(2019/01/04)
-
- Monomeric Octahedral Ruthenium(II) Complex Enabled meta-C-H Nitration of Arenes with Removable Auxiliaries
-
A removable oxime-assisted meta-C-H nitration of arenes is reported. Mechanistic investigations and DFT calculations reveal a new monomeric octahedral ruthenium(II) complex is responsible for the meta-selective nitration. Dioxygen as a cooxidant is crucial for achieving high conversion and good yields. Moreover, the utility of the present reaction protocol is further showcased by the late-stage modification of the clinical CNS drugs Diazepam and Fluvoxamine.
- Fan, Zhoulong,Li, Jie,Lu, Heng,Wang, Dong-Yu,Wang, Chao,Uchiyama, Masanobu,Zhang, Ao
-
supporting information
p. 3199 - 3202
(2017/06/23)
-
- Stereoelectronic effects in the reaction of aromatic substrates catalysed by: Halomonas elongata transaminase and its mutants
-
A transaminase from Halomonas elongata and four mutants generated by an in silico-based design were recombinantly produced in E. coli, purified and applied to the amination of mono-substituted aromatic carbonyl-derivatives. While benzaldehyde derivatives were excellent substrates, only NO2-acetophenones were transformed into the (S)-amine with a high enantioselectivity. The different behaviour of wild-type and mutated transaminases was assessed by in silico substrate binding mode studies.
- Contente, Martina Letizia,Planchestainer, Matteo,Molinari, Francesco,Paradisi, Francesca
-
p. 9306 - 9311
(2016/10/13)
-
- CATALYST COMPOUNDS
-
The present invention relates to an iridium-based catalyst compound for hydrogenating reducible moieties, especially imines and iminiums, the catalyst compounds being defined by the formulas: where ring B is either itself polycyclic, or ring B together with R is polycyclic. The catalysts of the invention are particularly effective in reductive amination procedures 10 which involve the in situ generation of the imine or iminium under reductive hydrogenative conditions.
- -
-
Paragraph 0314; 0321
(2015/03/28)
-
- The efficient solvent-free reduction of oximes to amines with NaBH3CN catalyzed by ZrCl4/nano Fe3O4 system
-
Reduction of various aldoximes and ketoximes to the corresponding amines was carried out easily and efficiently with NaBH3CN in the presence of ZrCl4/nano Fe3O4 system. The reactions were carried out under solvent-free conditions at room temperature or 75-80°C to afford amines in high to excellent yields.
- Sadighnia, Leila,Zeynizadeh, Behzad
-
p. 873 - 878
(2015/03/18)
-
- SUBSTITUTED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
-
The present disclosure relates to pyrimidine compounds of formula (I), their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to process of preparation of these pyrimidine compounds, and to pharmaceutical compositions containing them. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases and disorders mediated by epidermal growth factor receptor (EGFR) family kinases.
- -
-
Paragraph 000135
(2015/03/13)
-
- Design, synthesis and biological evaluation of novel inosine 5′-monophosphate dehydrogenase (IMPDH) inhibitors
-
This study is based on our attempts to further explore the structure-activity relationship (SAR) of VX-148 (3) in an attempt to identify inosine 5′-mono-phosphate dehydrogenase (IMPDH) inhibitors superior to mycophenolic acid. A five-point pharmacophore developed using structurally diverse, known IMPDH inhibitors guided further design of novel analogs of 3. Several conventional as well as novel medicinal chemistry strategies were tried. The combined structure- and ligand-based approaches culminated in a few analogs with either retained or slightly higher potency. The compounds which retained the potency were also checked for their ability to inhibit human peripheral blood mononuclear cells proliferation. This study illuminates the stringent structural requirements and strict SAR for IMPDH II inhibition.
- Dunkern, Torsten,Chavan, Sunil,Bankar, Digambar,Patil, Anuja,Kulkarni, Pritee,Kharkar, Prashant S.,Prabhu, Arati,Goebel, Heike,Rolser, Edith,Burckhard-Boer, Waltraud,Arumugam, Premkumar,Makhija, Mahindra T.
-
p. 408 - 419
(2014/06/09)
-
- Primary amines by transfer hydrogenative reductive amination of ketones by using cyclometalated IrIII catalysts
-
Cyclometalated iridium complexes are found to be versatile catalysts for the direct reductive amination (DRA) of carbonyls to give primary amines under transfer-hydrogenation conditions with ammonium formate as both the nitrogen and hydrogen source. These complexes are easy to synthesise and their ligands can be easily tuned. The activity and chemoselectivity of the catalyst towards primary amines is excellent, with a substrate to catalyst ratio (S/C) of 1000 being feasible. Both aromatic and aliphatic primary amines were obtained in high yields. Moreover, a first example of homogeneously catalysed transfer-hydrogenative DRA has been realised for β-keto ethers, leading to the corresponding β-amino ethers. In addition, non-natural α-amino acids could also be obtained in excellent yields with this method. Reduce the work! A broad range of ketones have been successfully aminated to afford primary amines under transfer-hydrogenation conditions by using ammonium formate as the amine source and 0.1 mol % of a cyclometalated IrIII catalyst (see scheme). Copyright
- Talwar, Dinesh,Salguero, Noemi Poyatos,Robertson, Craig M.,Xiao, Jianliang
-
supporting information
p. 245 - 252
(2014/01/17)
-
- CATALYST COMPOUNDS
-
The present invention relates to an iridium-based catalyst compound for hydrogenating reducible moieties, especially imines and iminiums, the catalyst compounds being defined by the formulas: where ring B is either itself polycyclic, or ring B together with R is polycyclic. The catalysts of the invention are particularly effective in reductive amination procedures 10 which involve the in situ generation of the imine or iminium under reductive hydrogenative conditions.
- -
-
Paragraph 00163; 00170
(2013/11/05)
-
- A new and convenient method for reduction of oximes to amines with NaBH3CN in the presence of MoCl5/NaHSO4? H2O system
-
Various aldoximes and ketoximes were efficiently reduced to their corresponding amines with NaBH3CN in the presence of MoCl 5/NaHSO4?H2O system. Reduction reactions were carried out in refluxing EtOH or DMF within 0.3-3.8 h to afford the amines in high to excellent yields.
- Kouhkan, Mehri,Zeynizadeh, Behzad
-
experimental part
p. 3323 - 3326
(2012/02/04)
-
- Discovery of 2-(α-methylbenzylamino) pyrazines as potent Type II inhibitors of FMS
-
A series of 2-(α-methylbenzylamino) pyrazines have shown to be potent inhibitors of the FMS tyrosine receptor kinase. Details of SAR studies, modeling and synthesis of compounds within this series are reported.
- Burns, Christopher J.,Harte, Michael F.,Bu, Xianyong,Fantino, Emmanuelle,Giarrusso, Marilena,Joffe, Max,Kurek, Margarita,Legge, Fiona S.,Razzino, Pasquale,Su, Stephen,Treutlein, Herbert,Wan, Soo San,Zeng, Jun,Wilks, Andrew F.
-
scheme or table
p. 1206 - 1209
(2009/08/07)
-
- INHIBITORS OF KINASE ACTIVITY
-
The present invention relates to pyridines or pyrazines that inhibit kinases. In particular the compounds of the invention inhibit members of the class III PTK receptor family such as FMS (CSF-IR), c-KIT, PDGFRβ, PDGFRα or FLT3 and KDR, SRC, EphA2, EphA3, EphA8, FLTl, FLT4, HCK, LCK, PTK5 (FRK), SYK, DDRl and DDR2 and RET. The compounds of the invention are useful in the treatment of kinase associated diseases such as immunological and inflammatory diseases; hyperproliferative diseases including cancer and diseases involving neo-angiogenesis; renal and kidney diseases; bone remodeling diseases; metabolic diseases; and vascular diseases.
- -
-
Page/Page column 91
(2008/12/05)
-
- Enantiomerically enriched 1-phenylethylamines
-
Production of enantiomerically enriched 1-(mono-, di- or trinitro-phenyl)-ethylamine derivatives (I) comprises reacting a nitro-acetophenone derivative (III) with a hydroxylamine compound (IV), reducing the obtained oxime compound (V) using a complex borohydride and an acid in organic solvent to give (I) in racemic form and enantiomerically enriching using an enantiomerically enriched acid. Production of enantiomerically enriched 1-(mono-, di- or trinitro-phenyl)-ethylamine derivatives of formula (I) comprises: (1) reacting an acetophenone derivative of formula (III) with a hydroxylamine compound of formula R5>ONH2.aHX (IV) to give an oxime of formula (V); (2) reducing (V) using a complex borohydride and an acid in organic solvent to give (I) in racemic form, and (3) enantiomerically enriching the product using an enantiomerically enriched acid. [Image] n : 1-3; m : 0 to (5-n); R1>1-12C alkyl, 1-12C alkoxy, 1-12C alkylthio, 5-14C aryl, 5-14C aryloxy, 6-15C aralkyl, 6-15C aralkoxy, F, Cl, CN, optionally protected CHO, optionally protected OH, optionally protected SH, 1-12C haloalkyl, 1-12C haloalkoxy, 1-12C haloalkylthio, A-B'-C(O)-E or A-E; A : a direct bond, 1-8C alkylene, 1-8C alkenylene or 1-8C haloalkylene; B' : a direct bond, O, S or NR2>; R2>H, 1-8C alkyl, 6-15C aralkyl or 5-14C aryl; E : OR3> or N(R4>)2; R3>1-8C alkyl, 6-15C aralkyl or 5-14C aryl; R4>H, 1-8C alkyl, 6-15C aralkyl or 5-14C aryl, or N(R4>)24-12C cyclic amino; a : 0 or 1; R5>H or 1-12C alkyl, and X : anion. Independent claims are included for new diastereomerically enriched salts of (I) having formula (I).HRx> (I') and new enantiomerically enriched salts of (I) having formula (I).HX' (I''). Rx>anion of an enantiomerically enriched organic acid, and X' : halide.
- -
-
Page/Page column 8
(2010/02/10)
-
- METHOD FOR PRODUCING 1-(NITROARYL)ALKYLAMINE
-
PROBLEM TO BE SOLVED: To provide a method for recovering a 1-(nitroaryl)alkylamine by simply reducing an oxime derivative of a nitroaryl alkyl ketone. SOLUTION: The method for producing the 1-(nitroaryl)alkylamine represented by formula (1) (wherein, Rsu
- -
-
Page/Page column 11-12; 14
(2008/06/13)
-
- Src kinase inhibitor compounds
-
Pyrimidine compounds (Formula I), or their pharmaceutically acceptable salts, hydrates, solvates, crystal forms and individual diastereomers, and pharmaceutical compositions including the same, which are inhibitors of tyrosine kinase enzymes, and as such are useful in the prophylaxis and treatment of protein tyrosine kinase-associated disorders, such as immune diseases, hyperproliferative disorders and other diseases in which inappropriate protein kinase action is believed to play a role, such as cancer, angiogensis, atheroscelerosis, graft rejection, rheumatoid arthritis and psoriasis.
- -
-
-
- Methods for inhibiting mrp1
-
The present invention relates to a compound of formula (I), which is useful for inhibiting resistant neoplasms where the resistance is conferred in part or in total by MRP1.
- -
-
-
- Benzodiazepine Receptor Binding Activity of 9-(1-Phenylethyl)purines
-
Several α-methyl analogues of the 9-benzylpurines that bind to the benzodiazepine receptor (BZR) were synthesized and tested for BZR-binding activity.Although introduction of a m-amino group and an 8-bromo substituent gave an additive increase in BZR affinity with 9-(3-aminobenzyl)-8-bromo-6-(dimethylamino)-9H-purine (4), addition of an α-methyl group to 4 resulted in loss in BZR affinity.This loss in affinity is apparently due to repulsive, steric interactions between the 8-bromo and 9-(1-phenylethyl) substituents, which results in a conformation that is not optimal for interaction with the BZR.Several compounds were tested on a modified Geller-Seifter conflict schedule, but none exhibited significant anxiolytic activity.
- Kelley, James L.,McLean, Ed W.,Ferris, Robert M.,Howard, James L.
-
p. 1910 - 1914
(2007/10/02)
-