256386-82-0Relevant articles and documents
INHIBITOR CONTAINING TRICYCLIC DERIVATIVE, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
-
Paragraph 0113; 0437-0440, (2021/04/16)
An inhibitor containing a tricyclic derivative, a preparation method therefor and a pharmaceutical composition comprising the inhibitor, as well as a use thereof as a phosphoinositide 3 kinase (PI3K) inhibitor in the treatment of cancer and diseases or conditions mediated by or dependent on PI3K imbalance.
Crystal form containing triple-fused-ring derivative free alkali and pharmaceutical composition thereof
-
Paragraph 0415-0421, (2021/05/26)
The invention relates to a crystal form containing triple-fused-ring derivative free alkali and a pharmaceutical composition thereof. The invention specifically relates to a crystal form of a compound free alkali with a general formula (I), a preparation method, a pharmaceutical composition containing a therapeutically effective amount of the crystal form, and an application of the crystal form in preparation of drugs for treating PI3K-mediated related diseases.
Visible-Light-Mediated Liberation and In Situ Conversion of Fluorophosgene
Petzold, Daniel,Nitschke, Philipp,Brandl, Fabian,Scheidler, Veronica,Dick, Bernhard,Gschwind, Ruth M.,K?nig, Burkhard
supporting information, p. 361 - 366 (2018/11/23)
The first example for the photocatalytic generation of a highly electrophilic intermediate that is not based on radical reactivity is reported. The single-electron reduction of bench-stable and commercially available 4-(trifluoromethoxy)benzonitrile by an organic photosensitizer leads to its fragmentation into fluorophosgene and benzonitrile. The in situ generated fluorophosgene was used for the preparation of carbonates, carbamates, and urea derivatives in moderate to excellent yields via an intramolecular cyclization reaction. Transient spectroscopic investigations suggest the formation of a catalyst charge-transfer complex-dimer as the catalytic active species. Fluorophosgene as a highly reactive intermediate, was indirectly detected via its next downstream carbonyl fluoride intermediate by NMR. Furthermore, detailed NMR analyses provided a comprehensive reaction mechanism including a water dependent off-cycle equilibrium.
Synthesis and evaluation of a potent, well-balanced EP2/EP3 dual agonist
Kinoshita, Akihiro,Higashino, Masato,Yoshida, Koji,Aratani, Yoshiyuki,Kakuuchi, Akito,Hanada, Keisuke,Takeda, Hiroyuki,Naganawa, Atsushi,Matsuya, Hidekazu,Ohmoto, Kazuyuki
, p. 200 - 214 (2017/12/06)
A highly potent and well-balanced dual agonist for the EP2 and EP3 receptors is described. Optimization of the lead compound was accomplished in consideration of the relative agonist activity against each EP subtype receptor and the pharmacokinetic profile. As the result, 2-[(2-{(1R,2R)-2-[(1E,4S)-5-cyclopentyl-4-hydroxy-4-methyl-1-penten-1-yl]-5-oxocyclopentyl}eth-yl)thio]-1,3-thiazole-4-carboxylic acid (10) showed excellent potency (human EC50 EP2 = 1.1 nM, EP3 = 1.0 nM) with acceptable selectivity over the EP1 and EP4 subtypes (>2000-fold). Further fine-tuning of compound 10 led to identification of ONO-8055 as a clinical candidate. ONO-8055 was effective at an extremely low dose (0.01 mg/kg, po, bid) in rats, and dose-dependently improved voiding dysfunction in a monkey model of underactive bladder (UAB). ONO-8055 is expected to be a novel and highly promising drug for UAB.
DIFLUOROMETHYL-AMINOPYRIDINES AND DIFLUOROMETHYL-AMINOPYRIMIDINES
-
Page/Page column 142, (2016/06/13)
The invention relates to novel phosphoinositide 3-kinase (PI3K),mammalian target of rapamycin (mTOR)and PI3K-related kinase(PIKKs)inhibitor compounds of formula (I), wherein X1, X2 and X3 are N or CH, with the proviso that
PYRAZOLYL DERIVATIVES AS SYK INHIBITORS
-
Page/Page column 142-143, (2014/01/09)
The present invention provides novel pyrazole derivatives of formula I which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD, rheumatoid arthritis, and cancer.
Pd-catalyzed carboamination of oxazolidin-2-ones: A stereoselective route to trans -2,5-disubstituted pyrrolidines
Lemen, Georgia S.,Wolfe, John P.
supporting information; experimental part, p. 2322 - 2325 (2010/07/14)
Palladium-catalyzed carboamination reactions between aryl bromides and 4-(but-3-enyl)-substituted oxazolidin-2-ones are described. These transformations afford bicyclic oxazolidin-2-one derivatives that can be converted to trans-2,5-disubstituted pyrrolid
Mild and catalytic transesterification reaction using K2HPO 4 for the synthesis of methyl esters
Shinada, Tetsuro,Hamada, Makoto,Miyoshi, Kota,Higashino, Masato,Umezawa, Taiki,Ohfune, Yasufumi
experimental part, p. 2141 - 2145 (2010/11/02)
K2HPO4 is an efficient catalyst for the transesterification reaction to produce methyl esters. Various functional groups are compatible under the mild reaction conditions. Georg Thieme Verlag Stuttgart New York.
Stereoselective syntheses of (E)-α,β-didehydroamino acid and peptide containing its residue utilizing oxazolidinone derivative
Kometani, Miki,Ihara, Kohki,Kimura, Rumi,Kinoshita, Hideki
experimental part, p. 364 - 380 (2009/06/28)
Reaction of methyl N-Boc-N-phenoxycarbonylglycinate with various aldehydes afforded the corresponding cis-4,5-oxazolidinone derivatives, which were effectively converted to (E)-α,β-didehydroamino acids by means of a base. Furthermore, N-deprotection of the oxazolidinone derivatives and subsequent coupling reaction with Boc-amino acid furnished the corresponding dipeptides, which were transformed to dipeptide containing α,α- didehydroamino acid with high E selectivity.
