16909-09-4Relevant articles and documents
2-Hydroxy-4-methoxy-trans-cinnamic Acid as a Precursor of Herniarin in Artemisia dracunculus
Hofer, Otmar,Szabo, Geza,Greger, Harald
, p. 1219 - 1222 (1986)
The isolation of (E)-2-hydroxy-4-methoxycinnamic acid (1) from Artemisia dracunculus L. supports strongly the assumption that this compound is an intermediate in the biosynthesis of 7-methoxycoumarin (herniarin, 3).The structure of the UV-unstable compound 1 was derived from 1H-NMR data and by comparison of the stable dimethylated derivative with synthetic (E)-2,4-dimethoxycinnamic acid methyl ester (2). - Keywords: Coumarins; Biosynthesis; Herniarin; Artemisia dracunculus; Compositae
A Concise Enantiodivergent Synthesis of Equol
Uemura, Takahito,Saito, Yusuke,Sonoda, Motohiro,Tanimori, Shinji
supporting information, p. 693 - 696 (2020/12/23)
Equol, a nonsteroidal estrogen produced from the metabolism of the isoflavonoid phytoestrogen daidzein, has been synthesized as both enantioenriched forms based on MacMillan's α-Arylation of carbonyl compound mediated by amino acid derived indazolidinones and copper precatalysts. The natural form of (S)-equol and its enantiomer (R)-equol have been synthesized in 8 steps from 2,4-dimethoxybenzaldehyde with good enantiomeric purity (90% ee and 90% ee, respectively).
Design, synthesis and biological evaluation of (E)-5-styryl-1,2,4-oxadiazoles as anti-tubercular agents
Atmaram Upare, Abhay,Gadekar, Pradip K.,Sivaramakrishnan,Naik, Nishigandha,Khedkar, Vijay M.,Sarkar, Dhiman,Choudhari, Amit,Mohana Roopan
supporting information, p. 507 - 512 (2019/02/19)
Cinnamic acid and its derivatives are known for anti-tubercular activity. The present study reports the synthesis of cinnamic acid derivatives via bioisosteric replacement of terminal carboxylic acid with “oxadiazole”. A series of cinnamic acid derivatives (styryl oxadiazoles) were designed and synthesized in good yields by reaction of substituted cinnamic acids (2, 15a-15s) with amidoximes. The synthesized styryl oxadiazoles were evaluated in vitro for anti-tubercular activity against Mycobacterium tuberculosis (Mtb) H37Ra strain. The structure-activity relationship (SAR) study has identified several compounds with mixed anti-tubercular profiles. The compound 32 displayed potent anti-tubercular activity (IC50 = 0.045 μg/mL). Molecular docking studies on mycobacterial enoyl-ACP reductase enzyme corroborated well with the experimental findings providing a platform for structure based hit-to-lead development.
Substituted cinnamic anhydrides act as selective inhibitors of acetylcholinesterase
Gie?el, Josephine M.,Serbian, Immo,Loesche, Anne,Csuk, René
, (2019/06/19)
Cinnamic anhydrides have been shown to be more than reactive reagents, but they also act as inhibitors of the enzyme acetylcholinesterease (AChE). Thus, out of a set of 33 synthesised derivatives, several of them were mixed type inhibitors for AChE (from electric eel). Thus, (E)-3-(2,4-dimethoxyphenyl)acrylic anhydride (2c) showed Ki = 8.30 ± 0.94 μM and Ki′ = 9.54 ± 0.38 μM, and for (E)-3-(3-chlorophenyl)acrylic anhydride (2u) Ki = 8.23 ± 0.93 μM and Ki′ = 13.07 ± 0.46 μM were measured. While being not cytotoxic to many human cell lines, these compounds showed an unprecedented and noteworthy inhibitory effect for AChE but not for butyrylcholinesterase (BChE).
Development of sulfonamides incorporating phenylacrylamido functionalities as carbonic anhydrase isoforms I, II, IX and XII inhibitors
Angapelly, Srinivas,Ramya, P.V. Sri,Angeli, Andrea,Del Prete, Sonia,Capasso, Clemente,Arifuddin, Mohammed,Supuran, Claudiu T.
, p. 5726 - 5732 (2017/10/09)
A series of novel sulfonamides incorporating phenylacrylamido functionalities were synthesized and investigated for the inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The physiologically and pharmacologically relevant human (h) isoforms hCA I and II (cytosolic isozymes), as well as the transmembrane tumor-associated hCA IX and XII were included in the study. These compounds showed low nanomolar or sub-nanomolar inhibition constants against hCA II (KIs in the range of 0.50–50.5 nM), hCA IX (KIs of 1.8–228.5 nM), and hCA XII (KIs of 3.5–96.2 nM) being less effective as inhibitors of the off target isoform hCA I. A detailed structure–activity relationship study demonstrates that the nature and position of substituents present on the aromatic part of the scaffold strongly influence the inhibition of CA isoforms. As hCA II, IX and XII are involved in pathologies such as glaucoma and hypoxic, and metastatic tumors, compounds of the type reported in this work may be useful preclinical candidates.
ANTI-HIV COMPOUNDS
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Paragraph 0370, (2016/07/05)
This invention provides, among other things, tetrahydroisoquinolines useful for treating viral infections, pharmaceutical formulations containing such compounds, as well as methods of inhibiting the replication of a virus, such as HIV, or treating a disease, such as AIDS.
Discovery of a New Inhibitor of Myeloid Differentiation 2 from Cinnamamide Derivatives with Anti-Inflammatory Activity in Sepsis and Acute Lung Injury
Chen, Gaozhi,Zhang, Yali,Liu, Xing,Fang, Qilu,Wang, Zhe,Fu, Lili,Liu, Zhiguo,Wang, Yi,Zhao, Yunjie,Li, Xiaokun,Liang, Guang
, p. 2436 - 2451 (2016/04/10)
Acute inflammatory diseases, including acute lung injury and sepsis, remain the most common life-threatening illness in intensive care units worldwide. Cinnamamide has been incorporated in several synthetic compounds with therapeutic potentials including anti-inflammatory properties. However, the possible mechanism and direct molecular target of cinnamamides for their anti-inflammatory effects were rarely investigated. In this study, we synthesized a series of cinnamamides and evaluated their anti-inflammatory activities. The most active compound, 2i, was found to block LPS-induced MD2/TLR4 pro-inflammatory signaling activation in vitro and to attenuate LPS-caused sepsis and acute lung injury in vivo. Mechanistically, we demonstrated that 2i exerts its anti-inflammatory effects by directly targeting and binding MD2 in Arg90 and Tyr102 residues and inhibiting MD2/TLR4 complex formation. Taken together, this work presents a novel MD2 inhibitor, 2i, which has the potential to be developed as a candidate for the treatment of sepsis, and provides a new lead structure for the development of anti-inflammatory agents targeting MD2.
Synthesis and leishmanicidal activity of cinnamic acid esters: Structure-activity relationship
Otero, Elver,Robledo, Sara M.,Diaz, Santiago,Carda, Miguel,Munoz, Diana,Panos, Julian,Velez, Ivan D.,Cardona, Wilson
, p. 1378 - 1386 (2014/03/21)
Several cinnamic acid esters were obtained via Fischer esterification of cinnamic acids derivatives with aliphatic alcohols. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes and cytotoxic activity was evaluated against mammalian U-937 cells. The compounds 11, 15-17, and 23, were active against Leishmania parasite and although toxic for mammalian cells, they still are potential candidates for antileishmanial drug development. A SAR analysis indicates that first, while smaller alkyl chains lead to higher selectivity indices (10, 11 vs. 12-17); second, the degree of oxygenation is essential for activity, primarily in positions 3 and 4 (17 vs. 18-20 and 22); and third, hydroxyl groups increase both activity and cytotoxicity (14 vs. 23). On the other hand, the presence of a double bond in the side chain is crucial for cytotoxicity and leishmanicidal activity (12 vs. 21). However, further studies are required to optimize the structure of the promising molecules and to validate the in vitro activity against Leishmania demonstrated here with in vivo studies.
Formal homo-nazarov and other cyclization reactions of activated cyclopropanes
De Simone, Filippo,Saget, Tanguy,Benfatti, Fides,Almeida, Sofia,Waser, Jerome
supporting information; experimental part, p. 14527 - 14538 (2012/02/04)
The Nazarov cyclization of divinyl ketones gives access to cyclopentenones. Replacing one of the vinyl groups by a cyclopropane leads to a formal homo-Nazarov process for the synthesis of cyclohexenones. In contrast to the Nazarov reaction, the cyclization of vinyl-cyclopropyl ketones is a stepwise process, often requiring harsh conditions. Herein, we describe two different approaches for further polarization of the three-membered ring of vinyl-cyclopropyl ketones to allow the formal homo-Nazarov reaction under mild catalytic conditions. In the first approach, the introduction of an ester group α to the carbonyl on the cyclopropane gave a more than tenfold increase in reaction rate, allowing us to extend the scope of the reaction to non-electron-rich aryl donor substituents in the β position to the carbonyl on the cyclopropane. In this case, a proof of principle for asymmetric induction could be achieved using chiral Lewis acid catalysts. In the second approach, heteroatoms, especially nitrogen, were introduced β to the carbonyl on the cyclopropane. In this case, the reaction was especially successful when the vinyl group was replaced by an indole heterocycle. With a free indole, the formal homo-Nazarov cyclization on the C3 position of indole was observed using a copper catalyst. In contrast, a new cyclization reaction on the N1 position was observed with BrAnsted acid catalysts. Both reactions were applied to the synthesis of natural alkaloids. Preliminary investigations on the rationalization of the observed regioselectivity are also reported.
FLAVAN-3-OL CONTAINING FOODSTUFFS
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, (2010/04/23)
The use of a compound for the reduction or elimination of bitterness caused by flavan-3-ols is provided. Compositions having greater than 0.01 wt % flavan-3-ols and that comprise an effective amount of the compound are also provided. The compound conforms to the general formula (I): wherein R1 represents C2-C3 saturated or unsaturated divalent hydrocarbon radical, n is an integer from 0 to 3, and each X is independently selected from C1-C3 alkyloxy and OH; and wherein if n is 0 then R1 is C3 saturated divalent hydrocarbon radical or C2-C3 unsaturated divalent hydrocarbon radical; and wherein if n is greater than 0 then the compound has formula (II)
