- ALLOSTERIC CHROMENONE INHIBITORS OF PHOSPHOINOSITIDE 3-KINASE (PI3K) FOR THE TREATMENT OF DISEASES ASSOCIATED WITH P13K MODULATION
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The disclosure relates to compounds of Formula (I) as allosteric chromenone inhibitors of phosphoinositide 3-kinase (PI3K) useful in the treatment of diseases or disorders associated with PI3K modulation, Formula (I), or a prodrug, solvate, enantiomer, st
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Paragraph 1258
(2021/10/11)
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- Construction of CF3-containing tetrahydropyrano[3,2- b]indoles through DMAP-catalyzed [4+1]/[3+3] domino sequential annulation
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A [4+1]/[3+3] domino sequential annulation reaction of o-aminotrifluoroacetophenone derivatives and β′-acetoxy allenoates enabled by DMAP has been reported. A variety of CF3-containing tetrahydropyrano[3,2-b]indoles were obtained as a single diastereomer in high yields (≤98%) under mild conditions. The reaction can build one C-N bond, one C-C bond, and one C-O bond sequentially in a single step. The synthetic utility was demonstrated with gram-scale reactions and various transformations of the products.
- Zhu, Yannan,Huang, You
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p. 6750 - 6755
(2020/09/15)
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- ERBB/BTK INHIBITORS
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Disclosed are compounds inhibiting ErbBs (e. g., EGFR or Her 2), especially mutant forms of ErbBs, and BTK, pharmaceutically acceptable salts, hydrates, solvates or stereoisomers thereof and pharmaceutical compositions comprising the compounds. The compou
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- The Reaction of o-Aminoacetophenone N-Tosylhydrazone and CO2 toward 1,4-Dihydro-2H-3,1-benzoxazin-2-ones
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A transition-metal-free reaction of o-aminoacetophenone N-tosylhydrazone and CO2 has been developed, leading to a series of 1,4-dihydro-2H-3,1-benzoxazin-2-ones in moderate to good yields. This procedure proceeds with the sequential fixation of CO2 by amino leading to carbamic acid and the intra- molecular insertion of hydroxyl to carbene. (Figure presented.).
- Xiong, Hao,Wu, Xiaopeng,Wang, Hepan,Sun, Song,Yu, Jin-Tao,Cheng, Jiang
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supporting information
p. 3538 - 3542
(2019/07/10)
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- Phosphine-Catalyzed Intermolecular Annulations of Fluorinated ortho-Aminophenones with Alkynones – The Switchable [4+2] or [4+2]/[3+2] Cycloaddition
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A phosphine-catalyzed intermolecular annulation reaction of functionalized ortho-aminoacetophenones with alkynones has been disclosed in this paper. A variety of 2-alkynylquinolines and benzo-fused indolizine were selectively afforded in moderate to good yields at different reaction temperatures and with different phosphine catalysts via the in situ generated zwitterionic intermediate derived from alkynone and phosphine. (Figure presented.).
- Zhang, Yanshun,Sun, Yaoliang,Wei, Yin,Shi, Min
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p. 2129 - 2135
(2019/03/13)
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- NHC-Cu(I)-Catalyzed Friedl?nder-Type Annulation of Fluorinated o-Aminophenones with Alkynes on Water: Competitive Base-Catalyzed Dibenzo[b,f][1,5]diazocine Formation
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An efficient, easily scalable synthesis of 4-trifluoromethylquinolines and naphthydrines (as well as their difluoro- and perfluoro-analogues) as a result of tandem direct catalytic alkynylation/dehydrative condensation of o-aminofluoromethylketones (o-FMKs), for the first time catalyzed by NHC-copper(I) complexes on water, is reported. A wide range of terminal alkynes is tolerated under the reaction conditions, including β-lactam-, steroid-, and sugar-derived ones, leading to desired quinolines and naphthydrines with good yields. Further investigations proved that o-FMKs could be efficiently transformed into a rare class of heterocyclic compounds - dibenzo[b,f][1,5]diazocines - by a base-catalyzed condensation, also on water. The developed method was applied for gram-scale synthesis of a fluorinated analogue of G protein-coupled receptor antagonist (GPR91).
- Czerwiński, Pawe?,Michalak, Micha?
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p. 7980 - 7997
(2017/08/14)
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- Synthesis of 3-fluoromethyl-2,1-benzisoxazoles
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A convenient synthetic method to access hitherto unknown 3-(trifluoromethyl)- and 3-(difluoromethyl)-2,1-benzisoxazoles by the reaction of sodium azide with 1-(2-halophenyl)-2,2,2-trifluoroethanones or 1-(2-halophenyl)-2,2-difluoroethanones was developed. 3-Fluoromethyl-2,1-benzisoxazoles are versatile precursors for o-fluoroacetylanilines.
- Golubev,Shidlovskii,Peregudov,Kagramanov
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p. 2264 - 2270
(2015/06/22)
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- Trifluoromethyl-promoted homocamptothecins: Synthesis and biological activity
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The homocamptothecin (hCPT) represents a new class of topoisomerase inhibitor which combines enhanced plasma stability and strong antitumor activity. Fluorine imparts desirable characteristics to drugs by modulating both the pharmacokinetics and pharmacodynamic properties of a drug. Therefore, in an attempt to improve the antitumor activity of homocamptothecins, seven new 7-trifluoromethylated homocamptothecin derivatives were prepared by proline-catalyzed Friedlander annulation. The antitumor activity in vitro and in vivo on cancer cell lines, and inhibitory properties of topoisomerase I-mediated DNA cleavage of compounds 6c and 8b were evaluated. Several of these trifluoromethylated hCPT derivatives (such as 6a, 6b and 6c) possessed higher in vitro antitumor activity than topotecan (TPT). Especially, the compound 6c showed effective in vivo antitumor activity comparable to that of TPT.
- Zhu, Lingjian,Miao, Zhenyuan,Sheng, Chunquan,Guo, Wei,Yao, Jianzhong,Liu, Wenfeng,Che, Xiaoying,Wang, Wenya,Cheng, Pengfei,Zhang, Wannian
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experimental part
p. 2726 - 2732
(2010/08/07)
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- An alternative route for synthesis of o-trifluoroacetylanilines as useful fluorine-containing intermediates
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A series of o-trifluoroacetyl aniline derivatives were synthesized in three steps. In this method, we first utilized trifluoroacetic anhydride to introduce trifluoroacetyl group to the ortho position of aniline with higher yield than that of some previously reported methods. In addition, the procedure is shown to be highly regiospecific. This type of compounds can be used as the key intermediates in the preparation of a variety of inhibitors of HIV reverse transcriptase which is an important pharmacological target of many anti-AIDS agents.
- Zhu, Lingjian,Miao, Zhenyuan,Sheng, Chunquan,Yao, Jianzhong,Zhuang, Chunlin,Zhang, Wannian
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experimental part
p. 800 - 804
(2010/09/04)
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- Selective colorimetric sensing of anions in aqueous media through reversible covalent bonding
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(Chemical Equation Presented) Selective colorimetric sensing of anions in aqueous media has been studied, which involves reversible covalent bonding as key binding interactions. By introducing a simple nitro chromophore into an o-(carboxamido)trifluoroace
- Kim, Dae-Sik,Chung, Yun-Mi,Jun, Mieun,Ahn, Kyo Han
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supporting information; experimental part
p. 4849 - 4854
(2009/10/09)
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- 4,4-DISUBSTITUTED-1,4-DIHYDRO-2H-3,1-BENZOXAZIN-2-ONES USEFUL AS HIV REVERSE TRANSCRIPTASE INHIBITORS AND INTERMEDIATES AND PROCESSES FOR MAKING THE SAME
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The present invention relates to benzoxazinones of formula I, or stereoisomeric forms or mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, and to pharmaceutical compositions and diagnostic kits comprising the same, methods of using same for treating viral infection or as an assay standard or reagent, and intermediates and processes for making the same.
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- Synthesis and evaluation of analogs of Efavirenz (SUSTIVA(TM)) as HIV-1 reverse transcriptase inhibitors
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Efavirenz (SUSTIVA(TM)) is a potent non-nucleoside reverse transcriptase inhibitor. Due to the observation of breakthrough mutations of the reverse transcriptase enzyme during Efavirenz therapy, we sought to develop an optimized second generation series. To that end, SAR of the substituents on the aromatic ring was undertaken and the results are summarized here. The 5,6-difluoro (4f) and the 6-methoxy (4m) substituted benzoxazinones were determined to be equipotent, and as a result such substitution patterns will be incorporated in second generation scaffolds.
- Patel, Mona,Ko, Soo S.,McHugh Jr., Robert J.,Markwalder, Jay A.,Srivastava, Anurag S.,Cordova, Beverly C.,Klabe, Ronald M.,Erickson-Viitanen, Susan,Trainor, George L.,Seitz, Steven P.
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p. 2805 - 2810
(2007/10/03)
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- 4,4-disubstitued-1,4-dihydro-2H-3,1-benzoxazin-2-ones useful as HIV reverse transcriptase inhibitors and intermediates and processes for making the same
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The present invention relates to benzoxazinones of formula I: STR1 or stereoisomeric forms or mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, and to pharmaceutical compositions and diagnostic kits comprising the same, methods of using the same for treating viral infection or as an assay standard or reagent, and intermediates and processes for making the same.
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