16101-08-9

Usage

Synthesis Reference(s)

Journal of Medicinal Chemistry, 28, p. 708, 1985 DOI: 10.1021/jm00383a004

InChI:InChI=1/C18H16N2O/c1-10-13-6-7-19-11(2)14(13)9-16-15-8-12(21-3)4-5-17(15)20-18(10)16/h4-9,20H,1-3H3

Upstream product

• 1165923-81-8 2-(3-methoxy-2-methylphenyl)ethanamine 
• 56724-03-9 3-methoxy-2-methyl-benzaldehyde 
• 95835-23-7 methyl-1 β-nitroethyl-2 methoxy-6 carbazole 
• 95835-24-8 methyl-1 β-acetamido-ethyl-2 methoxy-6 carbazole 
• 79853-92-2 2-<2-(methylamino)ethyl>-6-methoxy-1-methyl-9H-carbazole 
• 94200-72-3 4,6-dihydro-9-methoxy-1,2,5-trimethyl-3H-pyrido[4,3-b]carbazolium chloride 
• 93841-60-2 2-<2-(acetylmethylamino)ethyl>-6-methoxy-1-methyl-9H-carbazole 
• 95835-26-0 dimethyl-1,5 dihydro-3,4 methoxy-9-6H-pyrido<4,3-b>carbazole 
• 95835-22-6 methyl-1 trans-β-nitrovinyl-2 methoxy-6 carbazole 
• 95835-25-9 2-(6-methoxy-1-methyl-9H-carbazol-2-yl)ethylamine 
• 72237-80-0 6-methoxy-1-methyl-carbazole-2-carbaldehyde 
• 95589-87-0 9-methoxyguatambuine 

Downstream Products

• 70173-18-1 9-hydroxyolivacine 

Relevant academic research and scientific papers

Synthesis and activity against mycobacterium tuberculosis of olivacine and oxygenated derivatives

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as a key step. In a test for the inhibition of the growth of Mycobacterium tuberculosis, 9-methoxyolivacine showed the most significant inhibitory activity against Mycobacterium tuberculosis, with an MIC90 value of 1.5 μM.

Synthesis and cytotoxic activity of hydroxylated derivatives of olivacine in relation with their biotransformation

The chemical synthesis of 9-hydroxyolivacine and 7-hydroxyolivacine based on a biomimetic approach is described. These two hydroxylated derivatives have been found as main in vitro metabolites of olivacine after incubation with rat hepatic microsomes. The pretreatment of animals with benzo[a]pyrene caused a large increase in both microsomal hydroxylations, whereas the pretreatment with phenobarbital caused a weak increase, with a preservation of 9-hydroxylation/7-hydroxylation ratio >1 in both cases. The two hydroxyolivacines have been also found as principal in vivo metabolites of olivacine in rat bile as glucuronide and sulfate conjugates. The pretreatment of animals with benzo[a]pyrene reverses the 9-hydroxyolivacine/7-hydroxyolivacine ratio excretion in bile to a value that is 1H NMR spectra. Hydroxylation at position 9 increases the in vitro cytotoxicity against leukemia L1210 cells (ID50 = 0.06 μM compared to 2.03 μM for olivacine) and an opposite effect is observed for hydroxylation at position 7 (ID50 = 12.8 μM). On the other hand, hydroxylation at position 9 has no effect on the in vivo antitumor activity against L1210. This might be related to the oxidative and conjugative metabolic pathways that play an important role in antitumor activity and deactivation of olivacine and its hydroxy metabolites.

Synthesis and biological activity of N-(N,N-dialkylaminoalkyl)-1-aminomethyl-5-methyl-9-methoxy (6H) pyrido-[4,3-b] carbazoles (ellipticines)

9-methoxy olivacine, which was obtained by a 6-step synthesis starting from 1-methyl 2-formyl 6-methoxy carbazole, undergoes 1-methyl oxidation by selenic anhydride, giving 1-formyl 5-methyl 9-methoxy (6H0 pyrido [4,3-b] carbazole. Reductive amination by amine plus sodium borohydride then leads to 1-aminomethyl N(dialkylaminoalkyl) substituted 5-methyl 9-methoxy (6H) pyrido [4,3-b] carbazoles. These new aminomethyl substituted olivacine derivatives exhibit some cytotoxic properties but weak antitumoral activity.