1.2.3.4- Tetrahydro-9//-pyrido indole

Tetrahydro-isochinoline1-7 — l,2,3,4-Tetrahydr-9H-(pyrido-indole) (1,2,3,4-Tetrahydro-/ -carboline)5,8... 

Many patents have been issued on the use of pyrogaUol derivatives as pharmaceuticals. PyrogaUol has been used extemaUy in the form of an ointment or a solution in the treatment of skin diseases, eg, psoriasis, ringworm, and lupus erythematosus. GaUamine triethiodide (16) is an important muscle relaxant in surgery it also is used in convulsive-shock therapy. Trimethoprim (2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine) is an antimicrobial and is a component of Bactrin and Septra. Trimetazidine (l(2,3,4-trimethoxybenzyl)piperazine (Vastarel, Yosimilon) is used as a coronary vasodilator. l,2,3,4-Tetrahydro-6-methoxy-l-(3,4,5-trimethoxyphenyl)-9JT-pyrido[3,4- ]indole hydrochloride is useful as a tranquilizer (52) (see Hypnotics, sedatives, ANTICONVULSANTS, AND ANXIOLYTICS). Substituted indanones made from pyrogaUol trimethyl ether depress the central nervous system (CNS) (53). Tyrosine-and glycine(2,3,4-trihydroxybenzyl)hydrazides are characterized by antidepressant and anti-Parkinson activity (54). 

Fischer indolization of 9-arylhydrazono-6,7,8,9-tetrahydro-4//-pyrido-[l,2-u]pyrimidin-4-ones 289 by heating in 85% phosphoric acid, or in PPA yielded 7,12-dihydropyrimido[l, 2 l,2]pyrido[3,4-Z)]indol-4(6//)-ones 290 (96JHC799, 99MI12, 00MI22). From the 3-ester and 3-carboxylic acid derivatives 289 (R = COOEt, COOH) and decarboxylated products 290 (R = H) were obtained. 

The formation of tetrahydro-jS-carbolines (l,2,3,4-tetrahydro-9//-pyrido[3,4-h]indoles) is well known (510R151), and many examples have been described. We have therefore chosen this plethora some recent transformations of Trp that allow some general conclusions about the stereochemistry of this transformation. 

The double bond of the 1,2,5,6-tetrahydropyridine may be part of an indole moiety, as in 2,3,4,9-tetrahydro-l-(chiral-substituted iminomethyl)-l//-pyrido[3,4,-/>]indole 3. Asymmetric alkylation of the A-protected derivative using the same procedure with iodomethane leads to the 1-methyl derivative in good yield and excellent enantioselectivity45. 

A 7-substituted 3,4,6,7-tetrahydro-2//-pyrido[2,l-h][l,3]oxazine was formed as by-product the alkylation of methyl 2-(benzyloxycarbonyl-6-oxo-l-phenylsulfonyl)indol-2-yl)-2-azabicyclo[2,2,2]octane-6-enrfo-car-boxylate with 3-iodopropanol from a 3-substituted l-(3-hydroxypropyl)-2,3-dihydropyridinium intermediate (90JOC6028). 

Chemical Name lH-Pyrido[4,3-b]indol-l-one, 2,3,4,5-tetrahydro-5-methyl-2-[(5-methyl-lH-imidazol-4-yl)methyl]-, monohydrochloride... 

The (i-carbolinc skeleton with its 9H-pyrido[ 3,4-fr ]indole (29) is frequently encountered in pharmacology due to its activity in the central nervous system at serotonin receptors. It also shows prominent biological properties at the benzodiazepine receptor (BzR) [45]. ZK 93423 (30) remarkably amplifies the agonist activity of such compounds towards BzR. 1,2,3>9-Telrahydro-(>-carbolines are common precursors of (i-carbolines [46]. 1,3.4,9-Tetrahydro-... 

The extension of the above regioselective 6-endo cyclization to appropriately substituted substrates provided a novel synthetic entry to the pyrido[4,3-b]carbazole skeleton of the indole alkaloid olivacine, which resulted in a concise total synthesis of its tetrahydro derivative ( )-guatambuine <6 IT 160 67CJC89>. 

Methyl-l-[(3,4-dimethoxyphenyl)methyl]-l,2,3,4-tetrahydro-9H-pyrido[3,4-b] indole... 

H- 6-Methyl-1,2,3,4-tetrahydro-l-oxo- E6b/1, 749 (2-Oxo-3-arylydrazono-piperidin/R — COOH)... 

Of much interest is the recent discovery of substances closely related to the harmala alkaloids in animals. One of these is adrenoglomerulotropine, a hormone of the pineal body, the chemical identity of which has been indicated as 2,3,4,9-tetrahydro-6-methoxy-i-methyl-iH-pyrido (3,4,6) indole. This substance is identical to 6-methoxyletrahydroharman which has been shown to be formed in vivo from 5-methoxy tryptamine and acetaldehyde. 6-methoxytetrahydroharman is an isomer of tetrahydro-harmine, one of the alkaloids in Banisteriopsis, and in the African Leptactinia densillora. One more substance, 6-methoxyharmalan, has been shown to derive, at least in vitro, from melatonin, which results from the methylation of acetylserotonin. The enzyme which makes this possible, hydroxyindole O-methyl transferase, has only been found in the pineal body. (Naranjo, in Efron et al. 

Pyrido[3,2-c] indoles, tetrahydro-, (tetrahydro-y-carbolines), general review 73KGS291. 

Pyrido[2,3-h]indoles (a-carbolines), synthesis and reactivity of 84KGS435. Pyrido[2,3-c]indoles (/S-carbolines), biochemistry of 83MIIO. Pyrido[3,2-c]indoles, tetrahydro- (tetrahydro-y-carbolines) 73KGS291. 3//-Pyrrolo[2,3-c]quinolines 78H(9) 1617. 

S)-(+)-/Vb-Methyltryptophan, (S)-(+)-/Vb-methyltryptophan methyl ester, (S)-(+)-/Vt/Vb-dimethyltryptophan, (,S)-(+)-N fl y dimethyltryptophan methyl ester, methyl (5)-2-methyl-2,3-4,9-tetrahydro-lW -pyrido- 3,4b indole-3-carboxylate... 

H-Pyrido[3,4-b]indole-3-carboxylic acid, 2,3,4,9-tetrahydro-, (S)- 2447a ... 

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