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Upstream product

• 3764-94-1 5-chlorotryptamine 
• 108-24-7 acetic anhydride 
• 142-26-7 2-acetylaminoethanol 
• 17422-32-1 5-chloro-1H-indole 
• 136788-90-4 Nb-acetyl-1-hydroxytryptamine 
• 98258-88-9 N(b)-acetyl-1-methoxytryptamine 
• 258267-49-1 Nb-acetyl-1-(2-methoxycarbonyl-1-methyl)ethoxytryptamine 
• 258267-48-0 Nb-acetyl-1-(2-methoxycarbonyl)ethoxytryptamine 

Relevant academic research and scientific papers

Mutasynthesis of Physostigmines in Myxococcus xanthus

The alkaloid physostigmine is an approved anticholinergic drug and an important lead structure for the development of novel therapeutics. Using a complementary approach that merged chemical synthesis with pathway refactoring, we produced a series of physostigmine analogues with altered specificity and toxicity profiles in the heterologous host Myxococcus xanthus. The compounds that were generated by applying a simple feeding strategy include the promising drug candidate phenserine, which was previously accessible only by total synthesis.

Iridium-catalyzed direct synthesis of tryptamine derivatives from indoles: Exploiting N-protected β-amino alcohols as alkylating agents

The selective C3-alkylation of indoles with N-protected ethanolamines involving the "borrowing hydrogen" strategy is described. This method provides convenient and sustainable access to several tryptamine derivatives.

CARBAZOLE, CARBOLINE, AND INDOLE DERIVATIVES USEFUL IN THE INHIBITION OF VEGF PRODUCTION

In accordance with the present invention, compounds that inhibit the expression of VEGF post-transcriptionally have been identified, and methods for their use provided. In one aspect of the invention, compounds and compositions useful in the inhibition of BEGF production, and/or in the inhibition of angiogenesis, and/or in the treatment of cancer, diabetic retinopathy or exudative macular degeneration are provided. In another aspect of the invention, methods are provided for the inhibition of VEGF production, the inhibition of angiogenesis, and/or the treatment of cancer, diabetic retinopathy or exudative macular degeneration using the compounds of the invention.

A novel methodology for preparing 5-chloro- and 5-bromotryptamines and tryptophans, and its application to the synthesis of (±)-bromochelonin B

A novel methodology for introducing chlorine or bromine into the 5- position of tryptamines was found through 1-hydroxytryptamines. The chemistry was applied to the syntheses of (±)-5-chloro-, -5-bromotryptophan derivatives, and (±)-bromochelonin B.

Melatonin receptor ligands: Synthesis of new melatonin derivatives and comprehensive comparative molecular field analysis (CoMFA) study

The CoMFA methodology was applied to melatonin receptor ligands in order to establish quantitative structure-affinity relationships. One hundred thirty-three compounds were considered: they were either collected from literature or newly synthesized in order to gain information about the less explored positions. To this end, various melatonin derivatives were prepared and their affinity for quail optic tecta melatonin receptor was tested. Compounds were aligned on the putative active conformation of melatonin proposed by our previously reported pharmacophore search, and their relative affinities were calculated from the displacement of 2-[125I]-iodomelatonin on different tissues expressing aMT receptors. Compounds were grouped into three sets according to their topology. Subset A: melatonin-like compounds; subset B: N-acyl-2-amino-8-methoxytetralins and related compounds; subset C: N-acyl-phenylalkylamines and related compounds. CoMFA models were derived for each set, using the steric, electrostatic, and lipophilic fields as structural descriptors; the PLS analyses were characterized by good statistical parameters, taking into account the heterogeneity of the binding data, obtained with different experimental protocols. From the CoMFA model for the melatonin-like compounds, besides the well-known positive effect of 2-substitution, a low steric tolerance for substituents in 1, 6, and 7, and a negative effect of electron-rich 4-substituents were observed; the information provided by the newly synthesized compounds was essential for these results. Moreover, a comprehensive model for the 133 compounds, accounting for a common alignment and a common mode of interaction at the melatonin receptor, was derived (Q2 = 0.769, R2 = 0.905). This model validates our previously reported pharmacophore search and offers a clear depiction of the structure-affinity relationships for the melatonin receptor ligands.

N-acyl-5- and -2,5-substituted tryptamines: Synthesis, activity and affinity for human mt1 and mt2 melatonin receptors

The synthesis and in vitro evaluation of a number of N-acyltryptamines are reported. Structural changes include the N-acyl group and the 5- (H,CH3,Halogen), and 2- (Br, Ph) substituents. 5Br (6d) and 2,5-diBr (6j) proved to be high affinity melatonin agonists, thus proving that Br can substitute for the 5-OMe group without loss of affinity to melatonin receptors (mt1, MT2). 6j is the first example of a melatonin agonist devoid of the 5-OMe group and endowed with better affinity for mt1 and MT2 receptors than that of melatonin itself. SAR for selectivity and intrinsic activity of the title compounds were also drawn.

Structure-activity relationships for substrates and inhibitors of pineal 5-hydroxytryptamine-N-acetyltransferase: Preliminary studies

Tryptamine, (1-naphthyl)ethylamine and phenethylamine derivatives were tested as substrates of ovine pineal serotonin-N-acetyl transferase (5-HT-NAT), a key enzyme involved in the synthesis of melatonin. Almost all of the indole derivatives possessed affinity similar to that of tryptamine (K(m) - 0.05 mM), while the substituted naphthalene and phenyl derivatives were less potent. However, the K, values seem be influenced by the steric hindrance and polar properties of the substituent. V(max) values for the naphthyl and phenyl derivatives were generally 10-20-fold higher than those of the indole derivatives and no clear structure-activity relationship was observed. Melatonin and several bioisoteric derivatives were shown to be inhibitors of 5-HT-N-acetyltransferase. Preliminary data suggested that over the 5-50-μM concentration range, melatonin was a competitive inhibitor (IC50 = 10 μM) with a concentration-dependent inhibitory effect on its own synthesis in the pineal gland. However, the bioisosteric naphthalene derivatives were characterized instead as mixed inhibitors. (1-Napthyl)ethylacetamido, a putative melatoninergic antagonist, was also shown to be an inhibitor of 5-HT-N-acetyltransferase (IC50 = 8 μM) and is a promising tool for the regulation of melatonin synthesis and the understanding of its role.