1354039-86-3 Usage
Description
(R)-2-[(S)-(1-3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl]-N-isopropyl-2-phenylacetamide, also known as ACT 335827, is a compound with a complex chemical structure. It is an orally available, brain penetrant orexin receptor type 1 selective antagonist. (R)-2-[(S)-(1-3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl]-N-isopropyl-2-phenylacetamide has been found to elicit anxiolytic-like effects without promoting sleep, making it a promising candidate for the treatment of anxiety disorders.
Uses
Used in Pharmaceutical Industry:
ACT 335827 is used as a therapeutic agent for the treatment of anxiety disorders. The compound acts as a selective antagonist of the orexin receptor type 1, which is involved in the regulation of wakefulness and arousal. By blocking this receptor, ACT 335827 is able to reduce anxiety levels without causing drowsiness or sedation, which is a common side effect of many traditional anxiolytic medications.
Used in Research Applications:
In addition to its potential therapeutic use, ACT 335827 can also be utilized in research settings to better understand the role of orexin receptors in anxiety and other related disorders. By studying the effects of this compound on orexin receptor activity, researchers can gain valuable insights into the underlying mechanisms of anxiety and potentially identify new targets for the development of novel anxiolytic drugs.
Used in Drug Delivery Systems:
While the provided materials do not specifically mention the use of ACT 335827 in drug delivery systems, it is worth noting that the development of novel drug delivery systems is a common strategy to improve the efficacy and bioavailability of various pharmaceutical compounds. In the case of ACT 335827, researchers may explore the use of nanoparticles, liposomes, or other advanced drug delivery technologies to enhance its delivery to the brain and improve its therapeutic potential for the treatment of anxiety disorders.
Biological Activity
act 335827 is a potent and selective antagonist of oxr-1 with ic50 values of 120 and 2300 nm for oxr-1 and oxr-2, respectively [1].orexin receptor 1 (oxr-1) is a g-protein coupled receptor for neuropeptide orexin-a and regulates feeding behaviour. oxr-1 is expressed in the hypothalamus.act 335827 is a potent and selective oxr-1 antagonist with kb values of 41 and 560 nm for oxr-1 and oxr-2, respectively [1].in the fear-potentiated startle rats, act-335827 (300 mg/kg) inhibited fear-induced startle reactions. also, act-335827 (300 mg/kg) significantly reduced stress-induced tachycardia and hyperthermia. in the rat polydipsia model, act-335827 (300 mg/kg) inhibited compulsive drinking behavior [1]. in rats exposed to novelty stress, act-335827 (100 mg/kg) reduced the tachycardic and pressor by 48% and 32%, respectively [2]. in a diet-induced obesity(dio) rat model, act-335827 increased the level of high-density lipoprotein and water intake. also, it slightly increased body weight, which suggested that inhibition of oxr-1 had minimal impact in this model [3].
Enzyme inhibitor
This brain-penetrant and orally available orexin receptor antagonist (FW = 518.64 g/mol; CAS 1354039-86-3; Soluble to 100 mM in DMSO, also known as (aR,1S)-1-[(3,4-Dimethoxyphenyl)methyl]-3,4-dihydro-6,7dimethoxy-N-(1-methylethyl)-a-phenyl-2(1H)-isoquinoline acetamide, elicits its anxiolytic effects in vivo by targeting OX1 (Ki = 41 nM) and OX2 (Ki = 560 nM) receptors. ACT-335827 decreases fear, compulsive behaviors, and autonomic stress reactions in rats.
references
[1]. steiner ma, gatfield j, brisbare-roch c, et al. discovery and characterization of act-335827, an orally available, brain penetrant orexin receptor type 1 selective antagonist. chemmedchem, 2013, 8(6): 898-903. [2]. beig mi, dampney bw, carrive p. both ox1r and ox2r orexin receptors contribute to the cardiovascular and locomotor components of the novelty stress response in the rat. neuropharmacology, 2015, 89: 146-156.[3]. steiner ma, sciarretta c, pasquali a, et al. the selective orexin receptor 1 antagonist act-335827 in a rat model of diet-induced obesity associated with metabolic syndrome. front pharmacol, 2013, 4: 165.
Check Digit Verification of cas no
The CAS Registry Mumber 1354039-86-3 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,3,5,4,0,3 and 9 respectively; the second part has 2 digits, 8 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 1354039-86:
(9*1)+(8*3)+(7*5)+(6*4)+(5*0)+(4*3)+(3*9)+(2*8)+(1*6)=153
153 % 10 = 3
So 1354039-86-3 is a valid CAS Registry Number.
1354039-86-3Relevant articles and documents
Discovery and Characterization of ACT-335827, an Orally Available, Brain Penetrant Orexin Receptor Type1 Selective Antagonist
Steiner, Michel A.,Gatfield, John,Brisbare-Roch, Catherine,Dietrich, Hendrik,Treiber, Alexander,Jenck, Francois,Boss, Christoph
supporting information, p. 898 - 903 (2013/07/27)
Stress relief: Orexin neuropeptides regulate arousal and stress processing through orexin receptor type1 (OXR-1) and 2 (OXR-2) signaling. A selective OXR-1 antagonist, represented by a phenylglycine-amide substituted tetrahydropapaverine derivative (ACT-335827), is described that is orally available, penetrates the brain, and decreases fear, compulsive behaviors and autonomic stress reactions in rats. Copyright
