19230-57-0Relevant articles and documents
A Journey through Hemetsberger–Knittel, Leimgruber–Batcho and Bartoli Reactions: Access to Several Hydroxy 5- and 6-Azaindoles
Radix, Sylvie,Hallé, Fran?ois,Mahiout, Zahia,Teissonnière, Amélie,Bouchez, Grégoire,Auberger, Ludovic,Barret, Roland,Lomberget, Thierry
, (2022/02/22)
The preparation of various 5- and 6-azaindoles, heterocyclic structures that are frequently part of molecules in clinical development, and their monohydroxy analogues were described. Different strategies, relying on the de novo pyrrole ring formation, were investigated and, thanks to Hemetsberger–Knittel, Bartoli and Leimgruber–Batcho approaches, 4- and 7-monohydroxy 5- and 6-azaindoles were obtained. The crucial introduction of the oxygen atom was carried out from halogen derivatives, using nucleophilic substitution reactions under basic conditions with or without a copper catalyst. Some preliminary oxidation reactions have shown that it was yet not possible to synthesize the azaquinone indole structure from monohydroxy azaindole, using molecular oxygen in the presence of salcomine as a catalyst.
Substituted-3H-imidazo[4,5-c]pyridine and 1H-pyrrolo[2,3-c]pyridine series of novel Ectonucleotide Pyrophosphatase/Phosphodiesterase-1 (ENPP1) and Stimulator for Interferon Genes (STING) modulators as cancer immunotherapeutics
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Paragraph 0290-0291, (2020/02/19)
Substituted -3H-imidazo[4,5-c]pyridine and 1H-pyrrolo[2,3-c]pyridine series of novel Ectonucleotide Pyrophosphatase/Phosphodiesterase-1 (ENPP1) and related compounds, which are useful as inhibitors of ENPP1; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the ENPP1.
Technological method for preparing 2- amino -6-5-methyl-substituted-pyridine (by machine translation)
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Paragraph 0055-0057, (2020/01/12)
The reaction solvent of 2 - the method is reacted in a reaction solvent under the action, of 2 - an, acid anhydride and an acid,binding, agent and an amination reagent under the action. of an acid anhydride and 2 - an acid-binding agent and, an amination reagent, 2 -4 - 93/7, 99.8%, 70%. (by machine translation)
Towards Identification of Essential Structural Elements of Organoruthenium(II)-Pyrithionato Complexes for Anticancer Activity
Kladnik, Jerneja,Kljun, Jakob,Burmeister, Hilke,Ott, Ingo,Romero-Canelón, Isolda,Turel, Iztok
supporting information, p. 14169 - 14182 (2019/11/13)
An organoruthenium(II) complex with pyrithione (2-mercaptopyridine N-oxide) 1 a has previously been identified by our group as a compound with promising anticancer potential without cytotoxicity towards non-cancerous cells. To expand the rather limited research on compounds of this type, an array of novel chlorido and 1,3,5-triaza-7-phosphaadamantane (pta) organoruthenium(II) complexes with methyl-substituted pyrithiones has been prepared. After thorough investigation of the aqueous stability of these complexes, their modes of action have been elucidated at the cellular level. Minor structural alterations in the ruthenium-pyrithionato compounds resulted in fine-tuning of their cytotoxicities. The best performing compounds, 1 b and 2 b, with a chlorido or pta ligand bound to ruthenium, respectively, and a methyl group at the 3-position of the pyrithione scaffold, have been further investigated. Both compounds trigger early apoptosis, induce the generation of reactive oxygen species and G1 arrest in A549 cancer cells, and show no strong interaction with DNA. However, only 1 b also inhibits thioredoxin reductase. Wound healing assays and mitochondrial function evaluation have revealed differences between these two compounds at the cellular level.
PROCESS FOR PREPARATION OF LUMACAFTOR
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Paragraph 0164, (2017/05/07)
The present invention relates to a process for the preparation of amorphous lumacaftor. The present invention relates to a process for the preparation of intermediate 6-amino-2- halo-3-methylpyridine compounds used in the preparation of lumacaftor. The present invention relates to lumacaftor hydrobromide, process for its preparation and conversion thereof to lumacaftor.
SOLID FORMS OF LUMACAFTOR, ITS SALTS AND PROCESSES THEREOF
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Page/Page column 49, (2017/11/04)
Aspects of the present application relate to solid forms of Lumacaftor, its salts and processes thereof. Specific aspects of the present application relate to alternate processes for the preparation of Lumacaftor and intermediates thereof. Present application further relates to the solid forms of Lumacaftor and its salts.
Exploring the influence of the protein environment on metal-binding pharmacophores
Martin, David P.,Blachly, Patrick G.,McCammon, J. Andrew,Cohen, Seth M.
supporting information, p. 7126 - 7135 (2014/11/07)
The binding of a series of metal-binding pharmacophores (MBPs) related to the ligand 1-hydroxypyridine-2-(1H)-thione (1,2-HOPTO) in the active site of human carbonic anhydrase II (hCAII) has been investigated. The presence and/or position of a single methyl substituent drastically alters inhibitor potency and can result in coordination modes not observed in small-molecule model complexes. It is shown that this unexpected binding mode is the result of a steric clash between the methyl group and a highly ordered water network in the active site that is further stabilized by the formation of a hydrogen bond and favorable hydrophobic contacts. The affinity of MBPs is dependent on a large number of factors including donor atom identity, orientation, electrostatics, and van der Waals interactions. These results suggest that metal coordination by metalloenzyme inhibitors is a malleable interaction and that it is thus more appropriate to consider the metal-binding motif of these inhibitors as a pharmacophore rather than a "chelator". The rational design of inhibitors targeting metalloenzymes will benefit greatly from a deeper understanding of the interplay between the variety of forces governing the binding of MBPs to active site metal ions.
Discovery of pyridone-containing imidazolines as potent and selective inhibitors of neuropeptide Y Y5 receptor
Ando, Makoto,Sato, Nagaaki,Nagase, Tsuyoshi,Nagai, Keita,Ishikawa, Shiho,Takahashi, Hirobumi,Ohtake, Norikazu,Ito, Junko,Hirayama, Mioko,Mitobe, Yuko,Iwaasa, Hisashi,Gomori, Akira,Matsushita, Hiroko,Tadano, Kiyoshi,Fujino, Naoko,Tanaka, Sachiko,Ohe, Tomoyuki,Ishihara, Akane,Kanatani, Akio,Fukami, Takehiro
experimental part, p. 6106 - 6122 (2009/12/24)
A series of 2-pyridone-containing imidazoline derivatives was synthesized and evaluated as neuropeptide Y Y5 receptor antagonists. Optimization of the 2-pyridone structure on the 2-position of the imidazoline ring led to identification of 1-(difluoromethy
Discovery of potent imidazole and cyanophenyl containing farnesyltransferase inhibitors with improved oral bioavailability
Tong, Yunsong,Lin, Nan-Horng,Wang, Le,Hasvold, Lisa,Wang, Weibo,Leonard, Nicholas,Li, Tongmei,Li, Qun,Cohen, Jerry,Gu, Wen-Zhen,Zhang, Haiying,Stoll, Vincent,Bauch, Joy,Marsh, Kennan,Rosenberg, Saul H.,Sham, Hing L.
, p. 1571 - 1574 (2007/10/03)
A pyridyl moiety was introduced into a previously developed series of farnesyltransferase inhibitors containing imidazole and cyanophenyl (such as 4), resulting in potent inhibitors with improved pharmacokinetics.
Farnesyltransferase inhibitors
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, (2008/06/13)
Substituted imidazoles and thiazoles having the formula are useful for inhibiting farnesyltransferase. Also disclosed are farnesyltransferase-inhibiting compositions and methods of inhibiting farnesyltransferase in a patient.
