15128-52-6Relevant articles and documents
Synthesis of β3 adrenergic receptor agonist LY377604 and its metabolite 4-hydroxycarbazole, labeled with carbon-14 and deuterium
Czeskis, Boris A.,Wheeler, William J.
, p. 407 - 419 (2005)
Synthesis of 14C-radiolabeled 4-hydroxycarbazole was accomplished starting from aniline-[U-14C], based on zinc chloride initiated Fischer cyclization of the phenylhydrazone prepared from phenylhydrazine-[U-14C] and cyclohexane-1,3-dione. The resulting tetrahydrooxocarbazole was subjected to dehydrogenation-aromatization using palladium on carbon. The aromatized 4-hydroxycarbazole-[4b,5,6,7,8,8a- 14C] was then used for the synthesis of 14C-labeled β3 adrenergic receptor agonist LY377604. The introduction of four deuteria in the carbazole fragment of LY377604 accomplished by its initial bromination and subsequent catalytic deuteration of the resulting tetrabromide. A similar approach was used for the conversion of 4-hydroxycarbazole into its tetradeutero-isotopomer. Copyright
A catalyst free synthesis of 8, 9, 11-trihalo-5H-benzofuro[3,2-c]carbazol-10-ols
Ravi Shankar,Vijayakumar,Sivaramakrishnan,Nagarajan
, p. 3979 - 3983 (2017)
8, 9, 11-Trichloro-5H-benzofuro[3,2-c]carbazol-10-ol analogues have been synthesized by treating 2,3-dihydro-1H-carbazol-4(9H)-one with chloranil/fluoranil without any catalyst and is found to be applicable across a range of carbazolone substrates. A possible mechanism has been proposed.
Investigating 1,2,3,4,5,6-hexahydroazepino[4,3-b]indole as scaffold of butyrylcholinesterase-selective inhibitors with additional neuroprotective activities for Alzheimer's disease
Purgatorio, Rosa,de Candia, Modesto,Catto, Marco,Carrieri, Antonio,Pisani, Leonardo,De Palma, Annalisa,Toma, Maddalena,Ivanova, Olga A.,Voskressensky, Leonid G.,Altomare, Cosimo D.
, p. 414 - 424 (2019)
Due to the role of butyrylcholinesterase (BChE)in acetylcholine hydrolysis in the late stages of the Alzheimer's disease (AD), inhibitors of butyrylcholinesterase (BChE)have been recently envisaged, besides acetylcholinesterase (AChE)inhibitors, as candidates for treating mild-to-moderate AD. Herein, synthesis and AChE/BChE inhibition activity of some twenty derivatives of 1,2,3,4,5,6-hexahydroazepino[4,3-b]indole (HHAI)is reported. Most of the newly synthesized HHAI derivatives achieved the inhibition of both ChE isoforms with IC50s in the micromolar range, with a structure-dependent selectivity toward BChE. Apparently, molecular volume and lipophilicity do increase selectivity toward BChE, and indeed the N2-(4-phenylbutyl)HHAI derivative 15d, which behaves as a mixed-type inhibitor, resulted the most potent (IC50 0.17 μM)and selective (>100-fold)inhibitor toward either horse serum and human BChE. Moreover, 15d inhibited in vitro self-induced aggregation of neurotoxic amyloid-β (Aβ)peptide and displayed neuroprotective effects in neuroblastoma SH-SY5Y cell line, significantly recovering (P 1-42 and hydrogen peroxide insults. Overall, this study highlighted HHAI as useful and versatile scaffold for developing new small molecules targeting some enzymes and biochemical pathways involved in the pathogenesis of AD.
Divergent Coupling of 2-Carbonyl-anilines and Diazo-cyclopentanones: Asymmetric Total Synthesis of (+)-Leucomidine A
Yao, Xiaotong,Shan, Xiaosong,Zu, Liansuo
, p. 6498 - 6501 (2018)
The direct coupling of 2-carbonyl-anilines and diazo-cyclopentanones, promoted by a rhodium catalyst and diphenyl phosphate, is reported for the divergent generation of both carbazolones and indolones. The strategy allows for the successful transfer of the substituents/functionality and the chirality of the coupling partners into the functionalized heterocyclic products, thus serving as the strategic basis for natural product synthesis as demonstrated by the concise asymmetric total synthesis of (+)-leucomidine A.
A mild and effective method to synthesize carbazolones by CuI/L-proline-catalyzed intramolecular arylation
Yan, Shaoyu,Wu, Haihong,Wu, Nan,Jiang, Yongwen
, p. 2699 - 2702 (2007)
Substituted carbazol-4-ones and 3,4-dihydrocyclo-pental indole-1-ones could be prepared in good yields via the intramolecular coupling reaction of N-2-iodoaryl enaminones in the presence of Cul/L-proline under mild reaction conditions. Georg Thieme Verlag Stuttgart.
Molecular structure and reactivity of the 1,2-dihydrocarbazol-4(3H)-one: X-ray crystal structure of N-methyl and N-(p-methylbenzenesulfonyl) derivatives
Rodriguez, Jose Gonzalo,Valle, Celestina del,Esteban-Calderon, Carmen,Martinez-Ripoll, Martin
, p. 249 - 258 (1995)
Synthesis and reactivity analysis of the 1,2-dihydrocarbazol-4(3H)-one, and the N-methyl, N-tosyl and 2,2-dimethyl derivatives have been carried out.Molecular structures of the N-methyl and N-tosyl derivatives have been analyzed by X-ray diffraction.Crystals of the N-methyl derivative are monoclinic, space group P21/c, a=8.868(1), b=16.652(1), c=7.5440(4) Angstroem, β=113.657(3).Crystals of the N-tosyl derivative are monoclinic, P21/c, a=12.0016(3), b=8.9178(2), c=16.0485(4) Angstroem, β=104.372(2).An extended conjugation from the carbonyl group to the nitrogen atom and an envelope conformation for the common cyclohexenone fragment are evident in both cases.Oximation and Beckmann rearrangement, and etherification of the carbonyl group is reported.KEY WORDS: Synthesis, reactivity, tetrahydrocarbazol-4-one.
Synthesis and in vitro and in vivo characteristics of an iodinated analogue of the β-adrenoceptor antagonist carazolol
Dubois, Eric A.,Van Den Bos, Jan C.,Doornbos, Tamme,Van Doremalen, Peter A. P. M.,Somsen, G. Aernout,Vekemans, Jozef A. J. M.,Janssen, Anton G. M.,Batink, Harry D.,Boer, Gerard J.,Pfaffendorf, Martin,Van Royen, Eric A.,Van Zwieten, Pieter A.
, p. 3256 - 3262 (1996)
A new (radio)iodinated, β-adrenoceptor ligand, (S)-(-)-4-[3-[(1,1- dimethyl-3-iodo-(2E)-propenyl)-amino]-2-hydroxypropoxy]carbazole (CYBL8E, 1), was prepared. 1 is an iodinated analogue of the high-affinity β- adrenoceptor antagonist carazolol (2). The asymmetric synthesis was achieved in four steps starting from 4-hydroxycarbazole. The iodine-123-labeled form was obtained by an iododestannylation reaction with [123I]NaI in the presence of H2O2. Using classical in vitro displacement experiments with membrane fractions of cardiac left ventricular muscle, 1 proved to have a high affinity for the receptor (K(i) = 0.31 ± 0.03). Biodistribution studies performed in New Zealand white rabbits demonstrated the specificity of the binding in vivo to the receptor. Uptake of [123I]1 was reduced significantly in both atrial muscle, left ventricular muscle, frontal cortex, cerebellum, and striatum, by the pretreatment of the animals with different β-adrenoceptor antagonists. In conclusion, 1 is a potent nonselective β-adrenoceptor antagonist, which binds specifically to the β- adrenoceptor in vivo, and is therefore a promising radioligand for the imaging of β-adrenoceptors using single photon emission computerized tomography.
A synthesis of calothrixin B
Sissouma, Drissa,Collet, Sylvain C.,Guingant, André Y.
, p. 2612 - 2614 (2004)
A new short and efficient synthesis of calothrixin B is reported. The key reaction is a hetero-Diels-Alder reaction between 3-bromo-9H-carbazole-1,4-dione and a 'push-pull' 2-aza-1,3-diene.
Hypervalent Iodine(III)-Mediated Counteranion Controlled Intramolecular Annulation of Exocyclic β-Enaminone to Carbazolone and Imidazo[1,2-a]pyridine Synthesis
Bhattacherjee, Dhananjay,Ram, Shankar,Chauhan, Arvind Singh,Yamini,Sheetal,Das, Pralay
supporting information, p. 5934 - 5939 (2019/04/08)
A highly efficient and flexible protocol for intramolecular annulation of exocyclic β-enaminones has been disclosed for the synthesis of carbazolones and imidazo[1,2-a]pyridines through a counter-anion-controlled free-radical mechanism promoted by hypervalent iodine(III). The cooperative behavior of HTIB and AgSbF6 plays a crucial role in the intramolecular annulation process through C?C and C?N bond formation to give the desired products. The mechanistic insights suggest that the two competitive reactions involved in the system are guided by the nature of the counteranion, which determines the formation of the final products. A wide variety of carbazolones and imidazo[1,2-a]pyridine molecules have been prepared and isolated in good to excellent yields.
Enantioselective Synthesis of 1- and 4-Hydroxytetrahydrocarbazoles through Asymmetric Transfer Hydrogenation
Dilek, ?mer,Patir, Süleyman,Ertürk, Erkan
supporting information, p. 69 - 72 (2019/01/04)
Several 1- and 4-hydroxytetrahydrocarbazoles were prepared in high yields (up to 99%) and excellent enantiomeric excesses (up to >99% ee) from the corresponding 1- and 4-oxotetrahydrocarbazoles through asymmetric transfer hydrogenation by using the commercially available Noyori-Ikariya ruthenium catalyst. The immediate use of the freshly prepared catalyst and the use of a HCO 2 H-DABCO (11:6) mixture as the hydrogen source are crucial for achieving high activity and enantioselectivity. In this way, a tetrahydrocarbazole heterocycle fused to a lactone moiety was synthesized in 45% yield and 97% ee.
