64740-39-2Relevant articles and documents
Discovery of Second Generation RORγ Inhibitors Composed of an Azole Scaffold
Kotoku, Masayuki,Maeba, Takaki,Fujioka, Shingo,Yokota, Masahiro,Seki, Noriyoshi,Ito, Keisuke,Suwa, Yoshihiro,Ikenogami, Taku,Hirata, Kazuyuki,Hase, Yasunori,Katsuda, Yoshiaki,Miyagawa, Naoki,Arita, Kojo,Asahina, Kota,Noguchi, Masato,Nomura, Akihiro,Doi, Satoki,Adachi, Tsuyoshi,Crowe, Paul,Tao, Haiyan,Thacher, Scott,Hashimoto, Hiromasa,Suzuki, Takayoshi,Shiozaki, Makoto
supporting information, p. 2837 - 2842 (2019/03/11)
Starting from a previously reported RORγ inhibitor (1), successive efforts to improve in vivo potency were continued. Introduction of metabolically beneficial motifs in conjunction with scaffold hopping was examined, resulting in discovery of the second generation RORγ inhibitor composed of a 4-(isoxazol-3-yl)butanoic acid scaffold (24). Compound 24 achieved a 10-fold improvement in in vivo potency in a mouse CD3 challenge model along with significant anti-inflammatory effects in a mouse dermatitis model.
18F-Labeled Derivatives of Irbesartan for Angiotensin II Receptor PET Imaging
Hoffmann, Matthias,Chen, Xinyu,Hirano, Mitsuru,Arimitsu, Kenji,Kimura, Hiroyuki,Higuchi, Takahiro,Decker, Michael
, p. 2546 - 2557 (2018/11/23)
The renin angiotensin aldosterone system (RAAS) is a hormonal cascade involved in the regulation of blood pressure and electrolyte balance, and represents a common target for the treatment of various diseases including hypertension, heart failure, and diabetes. Herein we present a novel 18F-labeled derivative of the drug irbesartan, one of the most prescribed angiotensin II type 1 receptor (AT1R) antagonists, for in vivo positron emission tomography (PET). This allows the in vivo measurement of AT1R expression, and thus the evaluation of functional changes in its expression under pathophysiological conditions. We followed various synthetic approaches optimized for the introduction of fluorine into different positions of the aliphatic side chain of irbesartan. Radioligand binding studies revealed that fluorine atoms at specified positions (α-position (IC50=6.6 nm) and δ-position (IC50=8.5 nm) of the aliphatic side chain) do not alter the binding properties of irbesartan (IC50=1.6 nm). After successful radiolabeling with fluorine-18 in a radiochemical yield of 11 %, we observed high renal uptake in healthy rats and pigs, which could be decreased by pretreatment with the parent compound irbesartan.
Total synthesis of s (+)-curcuphenol, s (+)-curcuquinone and s (+)-curcuhydroquinone
Chinta, Ramakoteswara Rao,Harikrishna,Tulam, Vijaya Kumar,Bejjanki, Naveen Kumar,Mainkar, Prathama S.,Dubey
, p. 771 - 778 (2016/03/01)
A synthesis of (-)-curcuphenol, (-)-curcuquinone and (-)-curcuhydroquinone from o-valerolactone is described. The key steps include an Evans asymmetric methylation of 5-(benzyloxy)pentanoic acid (5), an oxidative aromatization of enone (11) and a regioselective oxidation of the phenol to o-quinone derivative with bis(trifluoro acetate)iodobenzene.
Stereoselective α-Hydroxylation of Amides Using Oppolzer's Sultam as Chiral Auxiliary
Zhang, Lumin,Zhu, Lili,Yang, Jun,Luo, Jisheng,Hong, Ran
, p. 3890 - 3900 (2016/05/24)
An Oppolzer's sultam-based highly stereoselective α-hydroxylation of amides was developed to deliver the desired products in good yield and excellent diastereoselectivity (>20/1). The generally crystalline products and the recyclability of the chiral auxiliary illustrate the practicability and scalability of the current approach.
TRIAZOLE-ISOXAZOLE COMPOUND AND MEDICAL USE THEREOF
-
Paragraph 2913; 2914, (2016/06/06)
A compound represented by Formula [I]: or pharmaceutically acceptable salt thereof, wherein each symbol is as defined in the description.
A study of the reaction of n-BuLi with Ti(Oi-Pr)4 as a method to generate titanacyclopropane and titanacyclopropene species
Rassadin, Valentin A.,Six, Yvan
supporting information, p. 787 - 794 (2014/01/23)
The use of the combination of reagents Ti(Oi-Pr)4/n-BuLi, introduced by the group of J.J. Eisch in 2001, has only found a few applications so far, with sometimes conflicting observations. This article describes a study aimed at clarifying the nature, the stability and the reactivity of the active organometallic species involved. Reactions with CO2 and other trapping reagents reveal that it is generated within a few minutes at 0 C in THF, where it can be considered to be stable for 30 min. Most of our results are consistent with the expected titanacyclopropane nature of this reagent but some observations suggest that the chemistry at play may be more complicated.
Asymmetric radical addition of TEMPO to titanium enolates
Mabe, Phillip J.,Zakarian, Armen
supporting information, p. 516 - 519 (2014/04/03)
A mild method for a-hydroxylation of N-acyl oxazolidinones by asymmetric radical addition of the 2,2,6,6-tetramethylpiperidine N-oxy (TEMPO) radical to titanium enolates was developed. The high diastereoselectivity and broad scope of the reaction show synthetic utility for the a-hydroxylation of substrates that are not tolerant to strongly basic conditions.
Synthesis of the polyketide (E)-olefin of the jamaicamides
Watanabe, Satoshi,Watanabe, Sho,Aoki, Naoto,Usuki, Toyonobu
supporting information, p. 1397 - 1403 (2013/05/22)
The jamaicamides, isolated in Jamaica from the cyanobacterium Lyngbya majuscula, are new mixed polyketide-peptides that are known to be sodium channel blockers. The polyketide moiety contains an (E)-vinyl chloride, an undetermined methyl stereocenter (C9), and an (E)-olefin. Herein, we report the synthesis of the (E)-olefin moiety of the polyketide of the jamaicamides utilizing a Kocienski-Julia coupling. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
A simple method for asymmetric trifluoromethylation of N-acyl oxazolidinones via Ru-catalyzed radical addition to zirconium enolates
Herrmann, Aaron T.,Smith, Lindsay L.,Zakarian, Armen
supporting information; experimental part, p. 6976 - 6979 (2012/06/15)
A Ru-catalyzed direct thermal trifluoromethylation and perfluoroalkylation of N-acyloxazolidinones has been developed. The reaction is experimentally simple and requires inexpensive reagents while providing good yields of products with good levels of stereocontrol. Preliminary studies have shown notable compatibility with functional groups, aromatics, and certain heteroaromatic substituents. The described method provides a useful alternative for the synthesis of fluorinated materials in an experimentally convenient manner.
AMIDE COMPOUND AND MEDICINAL USE THEREOF
-
Page/Page column 72, (2013/02/27)
A compound of formula [I-W]: wherein each symbol is as defined in the description, or a pharmaceutically acceptable salt thereof.
