90562-10-0Relevant articles and documents
Boron tribromide as a reagent for anti-Markovnikov addition of HBr to cyclopropanes
Chen, Shuming,Gieuw, Matthew H.,Houk, K. N.,Ke, Zhihai,Yeung, Ying-Yeung
, p. 9426 - 9433 (2020/10/02)
Although radical formation from a trialkylborane is well documented, the analogous reaction mode is unknown for trihaloboranes. We have discovered the generation of bromine radicals from boron tribromide and simple proton sources, such as water ortert-butanol, under open-flask conditions. Cyclopropanes bearing a variety of substituents were hydro- and deuterio-brominated to furnish anti-Markovnikov products in a highly regioselective fashion. NMR mechanistic studies and DFT calculations point to a radical pathway instead of the conventional ionic mechanism expected for BBr3
Mo-Based Oxidizers as Powerful Tools for the Synthesis of Thia- and Selenaheterocycles
Franzmann, Peter,Beil, Sebastian B.,Schollmeyer, Dieter,Waldvogel, Siegfried R.
supporting information, p. 1936 - 1940 (2019/01/14)
A highly efficient synthetic protocol for the synthesis of thia- and selenaheterocycles has been developed. By employing a MoCl5-mediated intramolecular dehydrogenative coupling reaction, a broad variety of structural motifs was isolated in yields up to 94 %. The electrophilic key transformation is tolerated by several labile moieties like halides and tertiary alkyl groups. Due to the use of disulfide or diselenide precursors, a high atom efficiency was achieved.
Syntheses and evaluation of a homologous series of aza-vesamicol as improved radioiodine-labeled probes for sigma-1 receptor imaging
Ogawa, Kazuma,Masuda, Ryohei,Mishiro, Kenji,Wang, Mengfei,Kozaka, Takashi,Shiba, Kazuhiro,Kinuya, Seigo,Odani, Akira
, p. 1990 - 1996 (2019/04/08)
Sigma-1 receptor imaging probes for determining the expression levels are desirable for diagnoses of various diseases and companion diagnoses of therapeutic agents targeting the sigma-1 receptor. In this study, we aimed to develop probes with higher affin
Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate, a muscarinic receptor antagonist with anti-inflammatory activity
Yamashita, Yasunobu,Tanaka, Ken-ichiro,Yamakawa,Asano,Kanda, Yuki,Takafuji,Kawahara, Masahiro,Takenaga, Mitsuko,Fukunishi, Yoshifumi,Mizushima
supporting information, p. 3339 - 3346 (2019/06/18)
The treatment for patients with chronic obstructive pulmonary disease (COPD) usually involves a combination of anti-inflammatory and bronchodilatory drugs. We recently found that mepenzolate bromide (1) and its derivative, 3-(2-hydroxy-2, 2-diphenylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (5), have both anti-inflammatory and bronchodilatory activities. We chemically modified 5 with a view to obtain derivatives with both anti-inflammatory and longer-lasting bronchodilatory activities. Among the synthesized compounds, (R)-(–)-12 ((R)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octane bromide) showed the highest affinity in vitro for the human muscarinic M3 receptor (hM3R). Compared to 1 and 5, (R)-(–)-12 exhibited longer-lasting bronchodilatory activity and equivalent anti-inflammatory effect in mice. The long-term intratracheal administration of (R)-(–)-12 suppressed porcine pancreatic elastase-induced pulmonary emphysema in mice, whereas the same procedure with a long-acting muscarinic antagonist used clinically (tiotropium bromide) did not. These results suggest that (R)-(–)-12 might be therapeutically beneficial for use with COPD patients given the improved effects seen against both inflammatory pulmonary emphysema and airflow limitation in this animal model.
RAB GERANYLGERANYL TRANSFERASE INHIBITORS
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Page/Page column 27; 28; 29, (2015/12/17)
The present invention relates to novel Rab geranylgeranyl transferase inhibitors of general formula (I) and stereoisomeric forms, hydrates, solvates and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions containing at least
4-alkyloxyimino derivatives of uridine-5′-triphosphate: Distal modification of potent agonists as a strategy for molecular probes of P2Y 2, P2Y4, and P2Y6 receptors
Jayasekara, P. Suresh,Barrett, Matthew O.,Ball, Christopher B.,Brown, Kyle A.,Hammes, Eva,Balasubramanian, Ramachandran,Harden, T. Kendall,Jacobson, Kenneth A.
, p. 3874 - 3883 (2014/05/20)
Extended N4-(3-arylpropyl)oxy derivatives of uridine-5′-triphosphate were synthesized and potently stimulated phospholipase C stimulation in astrocytoma cells expressing G protein-coupled human (h) P2Y receptors (P2YRs) activated by UTP (P2Y2/4R) or UDP (P2Y6R). The potent P2Y4R-selective N4-(3- phenylpropyl)oxy agonist was phenyl ring-substituted or replaced with terminal heterocyclic or naphthyl rings with retention of P2YR potency. This broad tolerance for steric bulk in a distal region was not observed for dinucleoside tetraphosphate agonists with both nucleobases substituted. The potent N 4-(3-(4-methoxyphenyl)-propyl)oxy analogue 19 (EC50: P2Y2R, 47 nM; P2Y4R, 23 nM) was functionalized for chain extension using click tethering of fluorophores as prosthetic groups. The BODIPY 630/650 conjugate 28 (MRS4162) exhibited EC50 values of 70, 66, and 23 nM at the hP2Y2/4/6Rs, respectively, and specifically labeled cells expressing the P2Y6R. Thus, an extended N4-(3- arylpropyl)oxy group accessed a structurally permissive region on three G q-coupled P2YRs, and potency and selectivity were modulated by distal structural changes. This freedom of substitution was utilized to design of a pan-agonist fluorescent probe of a subset of uracil nucleotide-activated hP2YRs.
Nickel-catalyzed cross-coupling of potassium aryl- and heteroaryltrifluoroborates with unactivated alkyl halides
Molander, Gary A.,Argintaru, O. Andreea,Aron, Ioana,Dreher, Spencer D.
supporting information; experimental part, p. 5783 - 5785 (2011/03/18)
A method for the cross-coupling of alkyl electrophiles with various potassium aryl- and heteroaryltrifluoroborates has been developed. Nearly stoichiometric amounts of organoboron species could be employed to cross-couple a large variety of challenging heteroaryl nucleophiles. Several functional groups were tolerated on both the electrophilic and the nucleophilic partners. Chemoselective reactivity of C(sp3) - Br bonds in the presence of C(sp2) - Br bonds was achieved.
AMINE COMPOUND AND PHARMACEUTICAL USE THEREOF
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Page/Page column 94, (2010/04/25)
Provided is a novel amine compound represented by the following formula (I) having a superior peripheral blood lymphocyte decreasing action and superior in the immunosuppressive action, rejection suppressive action and the like, which shows decreased side effects of, for example, bradycardia and the like, or a pharmaceutically acceptable acid addition salt thereof, or a hydrate thereof, or a solvate thereof. wherein each symbol is as defined in the specification.
Development of prodrug 4-chloro-3-(5-methyl-3-{[4-(2-pyrrolidin-1-ylethoxy) phenyl]amino}-1,2,4-benzotriazin-7-yl)phenyl benzoate (TG100801): A topically administered therapeutic candidate in clinical trials for the treatment of age-related macular degene
Palanki, Moorthy S. S.,Akiyama, Hideo,Campochiaro, Peter,Cao, Jianguo,Chow, Chun P.,Dellamary, Luis,Doukas, John,Fine, Richard,Gritzen, Colleen,Hood, John D.,Hu, Steven,Kachi, Shu,Kang, Xinshan,Klebansky, Boris,Kousba, Ahmed,Lohse, Dan,Chi, Ching Mak,Martin, Michael,McPherson, Andrew,Pathak, Ved P.,Renick, Joel,Soll, Richard,Umeda, Naoyasu,Yee, Shiyin,Yokoi, Katsutoshi,Zeng, Binqi,Zhu, Hong,Noronha, Glenn
, p. 1546 - 1559 (2008/12/21)
Age-related macular degeneration (AMD) is one of the leading causes of loss of vision in the industrialized world. Attenuating the VEGF signal in the eye to treat AMD has been validated clinically. A large body of evidence suggests that inhibitors targeti
2-AMINO-5-SUBSTITUTED PYRIMIDINE INHIBITORS
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Page/Page column 110, (2010/11/29)
Compounds having the general structure (A) are provided. The compounds of the invention are capable of inhibiting kinases, such as members of the Src kinase family, Vegfr and various other specific receptor and non-receptor kinases. Formula (I):
