10335-69-0

Usage

Biological Activity

mmp-2 inhibitor i, a hydroxamate-based, long-chain fatty acid, is a reversible inhibitor of matrix metalloproteinase (mmp)-2.matrix metalloproteinases (mmps) have been involved in the degradation of extracellular matrix. mmps contribute to long-term remodeling processes such as embryogenesis, tumor invasion, inflammation, angiogenesis, and wound healing. mmp-2, also known as gelatinase a or type iv collagenase, has been involved in regulating diverse cellular functions independent of its action on the extracellular matrix, including vascular tone, platelet aggregation, and mediation of the acute mechanical dysfunction of the heart immediately after ischemia and reperfusion [2]. up-regulation of mmp-2 has been associated with tumor invasion and metastasis [3].mmp-2 inhibitor i inhibited the activity of matrix metalloproteinase (mmp)-2 with the ki value of 1.6 μm [1]. mmp-2 inhibitor i attenuated cancer cell migration [3]. mmp-2 inhibitor i had also been used to preserve blood-brain barrier function in a wistar rat model of pneumococcal meningitis [4].

references

[1] berton a, rigot v, huet e, et al. involvement of fibronectin type ii repeats in the efficient inhibition of gelatinases a and b by long-chain unsaturated fatty acids[j]. journal of biological chemistry, 2001, 276(23): 20458-20465.[2] wang w, schulze c j, suarez-pinzon w l, et al. intracellular action of matrix metalloproteinase-2 accounts for acute myocardial ischemia and reperfusion injury[j]. circulation, 2002, 106(12): 1543-1549.[3] emmert-buck m r, roth m j, zhuang z, et al. increased gelatinase a (mmp-2) and cathepsin b activity in invasive tumor regions of human colon cancer samples[j]. the american journal of pathology, 1994, 145(6): 1285.[4] barichello t, generoso j s, michelon c m, et al. inhibition of matrix metalloproteinases-2 and-9 prevents cognitive impairment induced by pneumococcal meningitis in wistar rats[j]. experimental biology and medicine, 2014, 239(2): 225-231.

InChI:InChI=1/C18H35NO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(20)19-21/h9-10,21H,2-8,11-17H2,1H3,(H,19,20)/b10-9-

Upstream product

• 111-62-6 oleic acid ethyl ester 
• 112-77-6 (Z)-9-octadecenoyl chloride 
• 112-80-1 cis-Octadecenoic acid 
• 79-37-8 oxalyl dichloride 
• 112-62-9 Methyl oleate 
• 6114-18-7 elaidic acid ethyl ester 
• 64833-92-7 oleoylimidazole 
• 122-32-7 trioleoylglycerol 

Downstream Products

• 112-79-8 Elaidic acid 
• 1610968-09-6 benzyl N-[(8Z)-heptadec-8-en-1-yl]carbamate 

Relevant academic research and scientific papers

Design, synthesis and CoMFA studies of OEA derivatives as FAAH inhibitors

A total of 26 novel oleoylethanolamide derivatives were designed, synthesized, and characterized. All synthesized targets compounds were screened for their inhibitory activities against fatty acid amide hydrolase. Among of them, 13 compounds inhibit fatty acid amide hydrolase by 50% at the concentration of 100 μM. Of these compounds, the most active one is compound 9, which inhibit fatty acid amide hydrolase activity 98.35% at the concentration of 100 μM. Comparative molecular field analysis analyzes were performed based on obtained biological activities data and resulted in a statistically reliable comparative molecular field analysis model with high predictive abilities (r2 = 0.978, q2 = 0.613).

P(III)-Assisted Electrochemical Access to Ureas via in situ Generation of Isocyanates from Hydroxamic Acids

An external oxidant-free protocol for the generation of isocyanates from hydroxamic acids assisted by trivalent phosphine under mild electrochemical conditions was reported. The process started with the anodic oxidation of hydroxamic acids, followed by reacting with phosphine to form corresponding alkoxyphosphoniums and subsequent rearrangement with the release of tri-substituted phosphine oxide as the driving force to give isocyanates, which were trapped by N-based nucleophiles to produce various ureas. This method provides a broadly applicable procedure to access isocyanate intermediates under mild electrochemical conditions.

An Environmentally Sustainable Mechanochemical Route to Hydroxamic Acid Derivatives

An operationally simple, and cost efficient conversion of carboxylic acids into hydroxamic acid derivatives via a high-energy mechanochemical activation is presented. This ball milling methodology was applied to a wide variety of carboxylic acids dramatically improving purification issues associated with this class of molecules, which still remain one of the main bottlenecks of classical methodologies. (Figure presented.).

Olefin cross-metathesis as a valuable tool for the preparation of renewable polyesters and polyamides from unsaturated fatty acid esters and carbamates

Olefin cross-metathesis of unsaturated fatty acid methyl ester (FAME) derived benzyl carbamates with methyl acrylate is described. The obtained by-product, an α,β-unsaturated ester, was further modified via thia-Michael addition reactions in order to synthesize branched AA-type or AB-type monomers for the preparation of polyesters, which are tuneable by oxidation. Cross-metathesis of fatty acid derived carbamates was used as a novel approach to prepare linear AB-type monomers, which can be used for the preparation of renewable polyamides PA11, PA12 and PA15. The necessary fatty acid carbamates were prepared by applying a catalytic Lossen rearrangement procedure. The presented synthesis strategy has potential for the bio-sourced preparation of monomers for the production of polyamides. All prepared polymers were fully characterized by NMR, SEC, and DSC analyses. Additionally, the Young's modulus of the prepared long-chain polyamide PA15 was determined. This journal is the Partner Organisations 2014.

Introducing catalytic lossen rearrangements: Sustainable access to carbamates and amines

A new, highly efficient and environmentally benign catalytic variant of the Lossen rearrangement is described. Dimethyl carbonate (DMC) as green activation reagent of hydroxamic acids in presence of catalytic amounts of tertiary amine bases {1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), 1,8-biazabicyclo 5.4.0 undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), and triethylamine} and small quantities of methanol initiate the rearrangement. Methyl carbamates were obtained in good to moderate yields when aliphatic hydroxamic acids were employed in this catalytic Lossen rearrangement; under the same conditions aromatic hydroxamic acids yielded anilines. Notably, the mixture of DMC/methanol was recycled several times without observing decreased yields, thus minimizing the produced waste. Moreover, several other organic carbonates were successfully employed in the introduced catalytic Lossen rearrangement procedure. Copyright

An expeditious hydroxyamidation of carboxylic acids

Capitalizing on in situ activation with the cyclic phosphonic anhydride PPAA (1), the conversion of carboxylic acids into hydroxamic acids has been reduced to an experimentally simple one-pot operation that addresses the issue of polyacylation without resorting to a large excess of hydroxylamine or to protection. Scope and selectivity were satisfactory with a wide range of substrates, including α,β-unsaturated acids and hydroxyacids.

Inhibitors of oleamide hydrolase

Inhibitors of oleamide hydrolase, responsible for the hydrolysis of an endogenous sleep-inducing lipid (1, cis-9-octadecenamide) were designed and synthesized. The most potent inhibitors possess an electrophilic carbonyl group capable of reversibly forming a (thio) hemiacetal or (thio) hemiketal to mimic the transition state of a serine or cysteine protease catalyzed reaction. In particular, the tight binding alpha -keto ethyl ester 8 (1.4 nM) and the trifluoromethyl ketone inhibitor 12 (1.2 nM) were found to have exceptional inhibitory activity. In addition to the inhibitory activity, some of the inhibitors displayed agonist activity which resulted in the induction of sleep in laboratory animals.

INHIBITORS OF OLEAMIDE HYDROLASE

Inhibitors of oleamide hydrolase, responsible for the hydrolysis of an endogenous sleep-inducing lipid (1, cis-9-octadecenamide) were designed and synthesized. The most potent inhibitors possess an electrophilic carbonyl group capable of reversibly forming a (thio) hemiacetal or (thio) hemiketal to mimic the transition state of a serine or cysteine protease catalyzed reaction. In particular, the tight binding alpha-keto ethyl ester 8 (1.4 nM) and the trifluoromethyl ketone inhibitor 12 (1.2 nM) were found to have exceptional inhibitory activity. In addition to the inhibitory activity, some of the inhibitors displayed agonist activity which resulted in the induction of sleep in laboratory animals.

Inhibition of oleamide hydrolase catalyzed hydrolysis of the endogenous sleep-inducing lipid cis-9-octadecenamide

Oleamide (1, cis-9-octadecenamide) is a naturally occurring brain constituent that has been shown to accumulate and disappear under conditions of sleep deprivation and sleep recovery, respectively. Synthetic 1 has been found to induce sleep in a structurally specific manner at nanomolar quantities. Hydrolysis of 1 by an enzyme (oleamide hydrolase) present in the cell membrane rapidly degrades oleamide to oleic acid (cis-9-octadecenoic acid). Such observations suggest 1 may constitute a prototypical member of a class of fatty acid primary amide biological signaling molecules in which the diversity and selectivity of function are derived from the length of the alkane chain as well as the position, stereochemistry, and degree of unsaturation. A series of inhibitors of oleamide hydrolase were designed and prepared which were expected to derive their properties through interactions with the putative active site cysteine residue within oleamide hydrolase. This approach yielded a series of rapid, selective, and highly potent inhibitors (K(i) = 13 μM to 1 nM) which in addition to their potential therapeutic value may serve as useful tools to define the biological role of oleamide.