- MODULATORS OF HSD17B13 AND METHODS OF USE THEREOF
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The disclosure relates to compounds and pharmaceutical compositions capable of modulating the hydroxysteroid 17-beta dehydrogenase (HSD17B) family member proteins including inhibiting the HSD17B member proteins, e.g. HSD17B13. The disclosure further relates to methods of treating liver diseases, disorders, or conditions with the compounds and pharmaceutical compositions disclosed herein, in which the HSD17B family member protein plays a role.
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Paragraph 0491
(2021/01/23)
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- Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters
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Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.
- Shi, Yongjie,Tan, Xuefeng,Gao, Shuang,Zhang, Yao,Wang, Jingxin,Zhang, Xumu,Yin, Qin
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supporting information
p. 2707 - 2713
(2020/03/30)
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- TMSCl-Catalyzed Electrophilic Thiocyano Oxyfunctionalization of Alkenes Using N-Thiocyano-dibenzenesulfonimide
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Numerous electrophilic thiocyano oxyfunctionalization reactions of alkenes have been achieved using N-thiocyano-dibenzenesulfonimide, which is a new electrophilic thiocyanation reagent and could be easily prepared in two steps from dibenzenesulfonimide. T
- Ye, Ai-Hui,Zhang, Ye,Xie, Yu-Yang,Luo, Hui-Yun,Dong, Jia-Wei,Liu, Xiao-Dong,Song, Xu-Feng,Ding, Tongmei,Chen, Zhi-Min
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supporting information
p. 5106 - 5110
(2019/09/03)
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- Highly enantioselective [3+2] coupling of cyclic enamides with quinone monoimines promoted by a chiral phosphoric acid
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Enantioselective [3+2] coupling of cyclic enamides with quinone monoimines was realised using a chiral phosphoric acid as a catalyst. This transformation allowed for the synthesis of highly enantioenriched polycyclic 2,3-dihydrobenzofurans (up to 99.9% ee). The absolute configuration of one product was determined by an X-ray crystal structural analysis. We also found a possible mechanism for this reaction.
- Zhang, Minmin,Yu, Shuowen,Hu, Fangzhi,Liao, Yijun,Liao, Lihua,Xu, Xiaoying,Yuan, Weicheng,Zhang, Xiaomei
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supporting information
p. 8757 - 8760
(2016/07/15)
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- One-pot synthesis of tetralin derivatives from 3-benzoylpropionic acids: Indium-catalyzed hydrosilylation of ketones and carboxylic acids and intramolecular cyclization
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This reducing system was composed of a small amount (1 mol%) of In(OAc)3, Me2PhSiH, and I2 that effectively catalyzed the hydrosilylation of two different carbonyl groups, a ketone and a carboxylic acid found in 3-benzoylpropionic acids, followed by a subsequent intramolecular cyclization that led to the one-pot preparation of tetralin derivatives.
- Sakai, Norio,Kobayashi, Taichi,Ogiwara, Yohei
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supporting information
p. 1503 - 1505
(2015/11/24)
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- Design, synthesis and antihypertensive screening of novel pyridazine substituted s-triazin-2-imine/one/thione derivatives
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Some new 7-substituted-phenyl-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3, 5]triazin-2-imine/one/thione derivatives were synthesized by a sequence of reactions starting from appropriate aryl hydrocarbons. The final compounds were screened for antihypertensive activities by non-invasive method using Tail Cuff method. All the test compounds showed significant antihypertensive activity; 7-(biphenyl-4-yl)-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine (4p) exhibited antihypertensive activity more than the reference standard drugs.
- Mishra, Ravinesh,Siddiqui, Anees A.,Husain, Asif,Rashid, Mohd.,Goda, Chirag
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supporting information
p. 552 - 559
(2013/05/08)
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- A practical procedure for the synthesis of esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid, an antirheumatic agent (part 1).
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An efficient and practical procedure for the synthesis of esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (1), a new antirheumatic drug, has been developed. The intermediate, 2-methylene-4-(4-methylphenyl)-4-oxobutanoic acid (2), was prepared by Friedel-Crafts acylation of toluene with itaconic anhydride (3) in the presence of aluminum trichloride and nitrobenzene in 63% yield without silica gel column purification. Compound 1 was prepared by Michael addition of 2 with thioacetic acid (4) in 74% yield. Overall, 1 was obtained in 47% yield from 3. The structures and synthetic mechanisms of by-products (five compounds) of 2 were also clarified.
- Noguchi, Toshiya,Onodera, Akira,Tomisawa, Kazuyuki,Yokomori, Sadakazu
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p. 1407 - 1412
(2007/10/03)
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- Ion triggered alkylation of biological targets by silyloxy aromatic agents
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A silyloxy aromatic derivative capable of alkylating a target biological molecule when activated by ionic strength. A sequence directed reagent may be constructed by conjugating a methyl silyloxy aromatic derivative to a hexamethylamino linker attached to either the 5' or 3' terminus of an oligonucleotide. Annealing this modified fragment of DNA to its complementary sequence allows for target modification subsequent to ionic activation. The product of this reaction is a covalent crosslink between the reagent and target strands resulting from an alkylation of DNA by the activated silyloxy aromatic derivative. In a preferred embodiment, a nitrophenyl or bromo group is attached to a methyl group of the silyloxy aromatic derivative. This reagent may be similarly linked to an oligonucleotide probe. Activation of the alkylating agent by an ionic signal (X) which may naturally occur, or may be introduced into the media containing the target molecule, such as by the introduction of a salt (MX).
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- Biogenetic-type Synthesis of Sesquichamaenol
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A hypothetical biosynthetic pathway for the conversion of farnesylpyrophosphate into seaquichamaenol 1, a modified sesquiterpenoid isolated from Chaemaecyparis formosensis Matsum is proposed. The synthesis of 1 which lends experimental support to the prop
- Paknikar, Shashikumar K.,Naik,Ramanamma
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p. 729 - 733
(2007/10/03)
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- Ion triggered alkylation of biological targets by silyloxy aromatic agents
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A silyloxy aromatic derivative capable of alkylating a target biological molecule when activated by ionic strength. A sequence directed reagent may be constructed by conjugating a methyl silyloxy aromatic derivative to a hexamethyiamino linker attached to either the 5' or 3' terminus of an oligonucleotide. Annealing this modified fragment of DNA to its complementary sequence allows for target modification subsequent to ionic activation. The product of this reaction is a covalent crosslink between the reagent and target strands resulting from an alkylation of DNA by the activated silyloxy aromatic derivative. In a preferred embodiment, a nitrophenyl or bromo group is attached to a methyl group of the silyloxy aromatic derivative. This reagent may be similarly linked to an oligonucleotide probe. Activation of the alkylating agent by an ionic signal (X) which may naturally occur, or may be introduced into the media containing the target molecule, such as by the introduction of a salt (MX).
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- New Syntheses of 4-Isopropyl-4-m-tolyl-γ-butyrolactone and 2-Methyl-3-p-tolylcyclopent-2-enone
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New routes for the synthesis of 4-isopropyl-4-m-tolyl-γ-butyrolactone (7) and 2-methyl-3-p-tolylcyclopent-2-enone (13) are reported.The compounds (7) and (13) are key intermediates in the synthesis of several aromatic sesquiterpenoids.
- Ramanama, C. V.,Naik, C. G.,Paknikar, S. K.
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p. 761 - 762
(2007/10/02)
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