Synthesis of several 4-hydroxy-3,5-dimethoxybenzamides, their O-substituted derivatives and some related compounds as potential neurotropic agents

1985 ◽  
Vol 50 (2) ◽  
pp. 510-518 ◽  
Author(s):  
Vladimír Valenta ◽  
Miroslav Protiva
Keyword(s):  
Blood Pressure ◽  
Catalytic Hydrogenation ◽  
Anticonvulsant Activity ◽  
Sodium Hydride ◽  
Antiemetic Agent ◽  
Related Compounds ◽  
Neurotropic Agents ◽  
Amino Ether

Reactions of 4-benzyloxy-3,5-dimethoxybenzoyl chloride with pyrrolidine, piperidine, morpholine and 1-methylpiperazine gave the amides IIIa-IIId which were debenzylated by catalytic hydrogenation on palladium. The 4-hydroxy-3,5-dimethoxybenzamides IVa-IVc were then treated with sodium hydride and 2-dimethylaminoethyl chloride to give the O-(2-dimethylaminoethyl)amides Va-Vc. The 3,4,5-trimethoxybenzamide IX was prepared as a homologue of the antiemetic agent "trimethobenzamide" (II) and reduced to the benzylaniline derivative X. The substituted nicotinamide XI was obtained from nicotinoyl chloride and 4-(2-diethylaminoethoxy)aniline. Out of the compounds prepared the amides IIId and Vc had some anticonvulsant activity, the piperazide IVd revealed a significant α-adrenolytic effect and the amino ether X reduced the blood pressure of normotensive rats.

Synthesis and Ring Cyclization - Expansion - Contraction Reactions of Some New 2,2-Disubstituted Indan-1,3-diones and Related Compounds

2006 ◽  
Vol 59 (1) ◽  
pp. 59 ◽  
Author(s):  
Craig J. Roxburgh ◽  
Lee Banting
Keyword(s):  
Catalytic Hydrogenation ◽  
Pyridine Ring ◽  
Functional Group ◽  
Chemical Properties ◽  
Ring Expansion ◽  
Ring Structure ◽  
Side Reactions ◽  
The Third ◽  
Ring Expansion Reaction ◽  
Related Compounds

We have found that the hydrochloride of 2-phenyl-2-[2-(2-piperidyl)ethyl]-4,5,6,7-tetrahydroindan-1,3-dione 1 possesses marked analgesic activity (100% inhibition referenced to codeine) and report, as part of an extensive synthetic program, the synthesis of 38 new and structurally related compounds. Selective catalytic hydrogenation of the pyridine ring of 2-phenyl-2-[2-(2-pyridyl)ethyl]-indan-1,3-dione 2 yields the nine-membered nitrogen-containing heterocycle 6 by a novel ring cyclization–expansion reaction. The structural and functional group parameters required for this novel ring-expansion reaction have been extensively and thoroughly investigated through the synthesis of a series of structurally related compounds; principally by modification, substitution, and replacement of the various functionality contained within 2. In addition, we report the synthesis of a series of new 2-methyl-2-(ω-N-phthalimidoalkyl)-indan-1,3-diones 41, 45, and 53, two of which, like the parent 2-phenyl substituted indan-1,3-dione 2, also undergo a novel ring cyclization–expansion reaction to yield eight- and nine-membered nitrogen-containing rings. However, in these cases, further transannular reactions occur to produce the new 5,5- and 5,6-ring-fused nitrogen-containing heterocycles 44, 48 and 51, 52. Hydrazinolysis of the third, 2-methyl-2-(4-N-phthalimidobutyl)-indan-1,3-dione yields the new azepine-containing ring structure 56 by direct cyclization. Furthermore, some interesting and unexpected chemical properties of the final compounds, which include selective and non-selective pyridine-ring hydrogenations and a few unexpected side reactions, are described.

Blood pressure lowering action of adenosine diphosphate and related compounds

1961 ◽  
Vol 201 (6) ◽  
pp. 1123-1125 ◽  
Author(s):  
David B. Gordon ◽  
Donald H. Hesse
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Intravenous Injection ◽  
Low Dose ◽  
Adenosine Diphosphate ◽  
Blood Pressure Lowering ◽  
Arterial Blood ◽  
Pressure Lowering ◽  
Dose Levels ◽  
Related Compounds

It was found upon intravenous injection of adenosine and its mono-, di-, and triphosphate in the rat that ADP produced the greatest fall in arterial blood pressure. At low dose levels ADP was about 147 times as potent as adenosine and about 45 times as potent as AMP or ATP on an equimolar basis. The rat is more sensitive to the blood pressure lowering action of the adenosine compounds than other species thus far tested.

ChemInform Abstract: Synthesis and Anticonvulsant Activity of Some Benzopyranone Imino Derivatives (I) of GABA and Related Compounds.

ChemInform ◽  
2010 ◽  
Vol 23 (20) ◽  
pp. no-no
Author(s):  
A. ARNOLDI ◽  
L. MERLINI ◽  
M. L. QUADRI ◽  
A. BONSIGNORI ◽  
P. MELLONI ◽  
...  
Keyword(s):  
Anticonvulsant Activity ◽  
Related Compounds

Synthesis of 3-amino- and 3-azidoanalogs of 9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA)

1989 ◽  
Vol 54 (2) ◽  
pp. 446-454 ◽  
Author(s):  
Antonín Holý
Keyword(s):  
Acid Hydrolysis ◽  
Sodium Salt ◽  
Catalytic Hydrogenation ◽  
Alkaline Hydrolysis ◽  
Benzoyl Chloride ◽  
Sodium Hydride ◽  
Acid Catalyzed ◽  
Excess Sodium ◽  
Chloride Treatment

1-Azidopropane-2,3-diol (IIb) reacts with p-toluenesulfonyl chloride to give the tosyl derivative IIIa which, on acid catalyzed condensation with 2,3-dihydropyran, afforded 1-azido-2-(tetrahydropyran-2-yloxy-3-(p-toluenesulfonyloxy)propane (IIIb). Treatment of adenine sodium salt with IIIb resulted in the intermediate IV which was transformed by acid hydrolysis to 9-(RS)-(3-azido-2-hydroxypropyl)adenine (V). Catalytic hydrogenation of V led to 9-(RS)-(3-amino-2-hydroxypropyl)adenine (VI). 9-(RS)-(3-Azido-2-hydroxypropyl)-N6-benzoyladenine (VII) was obtained from V by chlorotrimethylsilane/benzoyl chloride treatment. Reaction of the compound VII with dimethyl p-toluenesulfonyloxymethanephosphonate (VIII) in the presence of excess sodium hydride, followed by alkaline hydrolysis, afforded methyl 9-(3-azido-2-phosphonylmethoxypropyl)adenine (IXa) which was transformed to the parent acid IXb by bromotrimethylsilane treatment. Hydrogenolysis of IXb yielded 9-(RS)-(3-amino-2-phosphonylmethoxypropyl)adenine (X).

Synthesis of Some 2'-C-Alkyl Derivatives of 9-(2-Phosphonomethoxyethyl)adenine and Related Compounds

1994 ◽  
Vol 59 (9) ◽  
pp. 2069-2094 ◽  
Author(s):  
Hana Dvořáková ◽  
Antonín Holý ◽  
Ivan Rosenberg
Keyword(s):  
Reaction Pathway ◽  
Sodium Hydride ◽  
Amino Group ◽  
Trimethylsilyl Derivative ◽  
Phosphonic Acids ◽  
Alkyl Derivatives ◽  
Hydrolysis Of ◽  
Trifluoromethyl Derivative ◽  
Derivatives Of ◽  
Related Compounds

To study the effect of β-substitution in 2'-alkyl derivatives of 9-(2-phosphonomethoxyethyl)adenine (Ia) on the antiviral activity or group specificity, these derivatives were synthesized. 9-(2-Hydroxyalkyl)adenines VIII were prepared by alkylation of adenine with suitably substituted oxiranes XIII or 2-hydroxyalkyl p-toluenesulfonates IV and VI. After protection of the adenine amino group by benzoylation (compounds IX) or amidine formation (compounds X), the intermediates were alkylated with diisopropyl p-toluenesulfonyloxymethanephosphonate (XI) in the presence of sodium hydride. After deprotection, the obtained phosphonate diesters XII were converted into phosphonic acids I by transsilylation and hydrolysis. This synthetic scheme was used for the preparation of ethyl (Ie), propyl (If), 2-propyl (Ig), 2-methylpropyl (Ih), cyclopropyl (Ii), cyclohexyl (Ij), benzyl (Ik) and phenyl (Il) derivatives. The 2'-trifluoromethyl derivative XXIIa was prepared analogously from 9-(2-hydroxy-3,3,3-trifluoropropyl)adenine (XXa), obtained by alkylation of adenine sodium salt with 2-hydroxy-3,3,3-trifluoropropyl bromide. 2'-Trimethylsilyl derivative XIXa was obtained by alkylation of adenine with 2-diisopropylphosphonomethoxy-3-(4-toluenesulfonyloxy)propyltrimethylsilane (XVII) followed by transsilylation and hydrolysis of diester XVIIIa. 2,6-Diaminopurine derivatives XVIIId and XXIIb were obtained analogously. 9-(3-Phosphonomethoxybutyl)adenine (XXVIII) and 9-(2-methyl-2-phosphonomethoxypropyl)adenine (XXXV) were prepared from the corresponding hydroxy derivatives XXVIb and XXXII, respectively, by the same reaction pathway as derivatives I.

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