64714-79-0

Upstream product

• 3587-60-8 Benzyloxymethyl chloride 
• 141-97-9 ethyl acetoacetate 
• 623-73-4 diazoacetic acid ethyl ester 
• 19790-60-4 3-Benzyloxypropanal 
• 4799-68-2 3-benzyloxypropan-1-ol 

Downstream Products

• 95112-81-5 (S)-ethyl 5-benzyloxy-3-hydroxypentanoate 
• 113335-04-9 (R)-5-Benzyloxy-3-hydroxy-pentanoic acid ethyl ester 
• 309755-11-1 (R)-5-Benzyloxy-3-trimethylsilanyloxy-pentanoic acid ethyl ester 
• 365404-53-1 (2R,3S,6S)-2-Allyl-6-(2-benzyloxy-ethyl)-3-methyl-tetrahydro-pyran 
• 365404-52-0 Acetic acid (3S,6S)-6-(2-benzyloxy-ethyl)-3-methyl-tetrahydro-pyran-2-yl ester 
• 365404-50-8 (2S,5S)-7-Benzyloxy-5-(tert-butyl-dimethyl-silanyloxy)-2-methyl-heptanoic acid ((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-amide 
• 365404-31-5 (3S,6S)-6-(2-Benzyloxy-ethyl)-3-methyl-tetrahydro-pyran-2-one 
• 365404-32-6 [(2R,3S,6S)-6-(2-Benzyloxy-ethyl)-3-methyl-tetrahydro-pyran-2-yl]-acetaldehyde 
• 365404-49-5 (S)-5-(benzyloxy)-3-(tert-butyldimethylsilyloxy)pentan-1-ol 
• 365404-30-4 [3-benzyloxy-1-(2-iodo-ethyl)-propoxy]-tert-butyl-dimethyl-silane 
• 365404-48-4 5-benzyloxy-3-(tert-butyl-dimethyl-silanyloxy)-pentanoic acid ethyl ester 
• 365404-37-1 (S)-1-[(2R,3S,6S)-6-(2-Benzyloxy-ethyl)-3-methyl-tetrahydro-pyran-2-yl]-3-[(2S,6R)-4-methylene-6-(2-triisopropylsilanyloxy-ethyl)-tetrahydro-pyran-2-yl]-propan-2-ol 
• 727384-62-5 5-benzyloxy-2-dimethylaminomethylene-3-oxo-pentanoic acid ethyl ester 
• 1315318-98-9 tert-butyl(2-((2R,6S)-4-methylene-6-vinyltetrahydro-2H-pyran-2-yl)ethoxy)diphenylsilane 

Relevant academic research and scientific papers

Optimization of P2Y12 Antagonist Ethyl 6-(4-((Benzylsulfonyl)carbamoyl)piperidin-1-yl)-5-cyano-2-methylnicotinate (AZD1283) Led to the Discovery of an Oral Antiplatelet Agent with Improved Druglike Properties

P2Y12 antagonists are widely used as antiplatelet agents for the prevention and treatment of arterial thrombosis. Based on the scaffold of a known P2Y12 antagonist AZD1283, a series of novel bicyclic pyridine derivatives were designed and synthesized. The cyclization of the ester substituent on the pyridine ring to the ortho-methyl group led to lactone analogues of AZD1283 that showed significantly enhanced metabolic stability in subsequent structure-pharmacokinetic relationship studies. The metabolic stability was further enhanced by adding a 4-methyl substituent to the piperidinyl moiety. Compound 58l displayed potent inhibition of platelet aggregation in vitro as well as antithrombotic efficacy in a rat ferric chloride model. Moreover, 58l showed a safety profile that was superior to what was observed for clopidogrel in a rat tail-bleeding model. These results support the further evaluation of compound 58l as a promising drug candidate.

HYDROXYL PURINE COMPOUNDS AND USE THEREOF

Disclosed are a series of hydroxyl purine compounds and the use thereof as PDE2 or TNFα inhibitors, in particular, the compounds as shown in formula (I), or tautomers thereof or pharmaceutically acceptable salts thereof.

PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATMENT, AMELIORATION OR PREVENTION OF INFLUENZA

Provided herein is a compound of formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, prodrug, codrug, cocrystal, tautomer, racemate, enantiomer,or diastereomer or mixture thereof, which is useful in treating, ameliorating or preventing influenza.

Synthesis of β-keto esters in-flow and rapid access to substituted pyrimidines

We have developed an in-flow process for the synthesis of β-keto esters via the BF3·OEt2-catalyzed formal C-H insertion of ethyl diazoacetate into aldehydes. The β-keto esters were then condensed with a range of amidines to give a variety of 2,6-substituted pyrimidin-4-ols.

Non-charged thiamine analogs as inhibitors of enzyme transketolase

Inhibition of the thiamine-utilizing enzyme transketolase (TK) has been linked with diminished tumor cell proliferation. Most thiamine antagonists have a permanent positive charge on the B-ring, and it has been suggested that this charge is required for diphosphorylation by thiamine pyrophosphokinase (TPPK) and binding to TK. We sought to make neutral thiazolium replacements that would be substrates for TPPK, while not necessarily needing thiamine transporters (ThTr1 and ThTr2) for cell penetration. The synthesis, SAR, and structure-based rationale for highly potent non-thiazolium TK antagonists are presented.

Synthesis of the C1-C28 Portion of Spongistatin 1 (Altohyrtin A)

A synthetic approach was developed to the C1-C28 subunit of spongistatin 1 (altohyrtin A, 65). The key step was the coupling of the AB and CD spiroketal moieties via an anti-aldol reaction of aldehyde 62 and ethyl ketone 57. The development of a method for the construction of the AB spiroketal fragment is described and included the desymmetrization of C2-symmetric diketone 10 and the differentiation of the two primary alcohols of 16. Further elaboration of this advanced intermediate to the desired aldehyde 62 included an Evans' syn-aldol reaction and Tebbe olefination. The synthesis of the CD spiroketal fragment 56 involved the ketalization of a triol-dione, generated in situ by deprotection of 45, to provide a favorable ratio (6-7:1) of spiroketal isomers 46 and 47, respectively. The overall protecting group strategy, involving many selective manipulations of silyl protecting groups, was successfully developed to provide the desired C1-C28 subunit of spongistatin 1 (altohyrtin A) (65).