General method for the synthesis of selectively N-alkylated polyamines

Nordlander, J. Eric; Payne, Matthew; BALK, M. A.; GRESS, J. L.; HARRIS, F. D.; LANE, J. S.; Lewe, R. F.; Marshall, Sue; Nagy, D.; Rachlin, D. J.

doi:10.1021/jo00175a028

Cited by 17 publications

(6 citation statements)

References 3 publications

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“…The replacement of the amidic functionality by a sul-famide group bioisostere (43) also results in an increase of affinity (logic Kh: -13.19). On the contrary, introduction of larger aromatic groups (23,25) or optionally substituted (24), phenylalkyl (26,28,29), diphenylalkyl (27), or tertiary aminoalkyl (30,31) groups strongly decreases affinity. These results clearly confirm the crucial role played by the N-acyl side chain on the binding affinity for the melatonin receptors.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis and Structure-Activity Relationships of Novel Naphthalenic and Bioisosteric Related Amidic Derivatives as Melatonin Receptor Ligands

Depreux¹,

Lesieur²,

Mansour³

et al. 1994

J. Med. Chem.

148

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A series of N-naphthylethyl amide derivatives were synthesized and evaluated as melatonin receptor ligands. The affinity of each compound for the melatonin receptor was determined by binding studies using [2-125I]iodomelatonin on ovine pars tuberalis membrane homogenates. Structure-activity relationships led to the conclusion that naphthalene is a bioisostere of the indole moiety of melatonin. Moreover it appears that the affinity is strongly affected by the size of the substituent of the nitrogen of the amidic function. Many of these ligands give biphasic dose-response curves which suggests that there may be two melatonin receptor subtypes within the ovine pars tuberalis cells. The replacement of naphthalene by benzofuran or benzothiophene did not strongly alter the affinity for the melatonin receptor. In contrast, the benzimidazole analogue was a poor ligand. Compound 7, the naphthalenic analogue of melatonin, a selective ligand of the melatonin receptor and an agonist derivative, has been selected for clinical development.

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Section: Resultsmentioning

confidence: 99%

“…General Procedure for the Synthesis of the 2-Tertiary [(Aminoacyl)amino]alkyl Derivatives (30,31). The method adopted for the synthesis of N-[2-(7-methoxy-l-naphthyl)ethyl]-2-morphohn-l'-ylacetamide (30) is described.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Structure-Activity Relationships of Novel Naphthalenic and Bioisosteric Related Amidic Derivatives as Melatonin Receptor Ligands

Depreux¹,

Lesieur²,

Mansour³

et al. 1994

J. Med. Chem.

148

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“…Flash column chromatography of the residue on silica allowed the purification of the expected secondary amine. 1) (previously described as the dihydrochloride salt) [40]. Colorless oil.…”

Section: General Procedures For the 1ox-mediated N-alkylation Of Primary Aliphatic Amines With Aminesmentioning

confidence: 99%

A one-pot chemoselective synthesis of secondary amines by using a biomimetic electrocatalytic system

Largeron¹

2009

Electrochimica Acta

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A one-pot electrochemically induced oxidation-imine formation-reduction route to secondary amines is described in detail. The key step of the process consists of the oiminoquinone-mediated chemoselective catalytic oxidation of a primary aliphatic amine substrate, in the presence of a second amine used as the alkylating agent. Through the examination of the scope of the reaction by systematically varying both amine substrate and amine alkylating agent, it can be shown that this reaction sequence, leaving ammonia as the sole by-product, allows the rapid synthesis of various secondary amines in moderate to good yields. This process, that highlights the pre-eminent green advantages of electrochemical synthesis, especially the utilization of electricity as energy instead of chemical reagents, high atom economy as well as ambient temperature and pressure, could be a mild alternative to already reported synthetic methods.

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“…In some cases, DIBAH, AlH 3 or Ra-Ni-mediated desulfurization of the corresponding thioamide has been used to obtain cleaner reductions. Thus, Nordlander et al [151] synthesized N-alkylated SPD analogues, such as 104 (Figure 18), using the amino acids βAla and γAba to provide the NϪC 3 ϪNϪC 4 skeleton, whereas Bergeron et al obtained the SPM analogue 105 with the acylation of Et 2 N(CH 2 ) 3 NH 2 with succinyl chloride as the key-reaction.…”

Section: Acylation Of Amines With Carboxylic Acid Derivatives Followementioning

confidence: 99%

“…[170] This group also reported an efficient synthesis of T(S) 2 using SPS techniques and the Dde or its analogue Nde group for primary amino group protection. [120] Thus, the N 1 ,N 8 -Dde 2 -SPD was attached to a NovaSyn ® TGA support, derivatized with the HMPA linker, to give the corresponding polymeric SPD derivative, which was then used to obtain the fully protected polymeric T(SH) 2 (151). From 151, T(S) 2 was readily obtained through sequential N-deprotection and simultaneous TFA-mediated removal of the side-chain protecting groups and detachment from the resin, followed by aerial oxidation.…”

Section: Selective Functionalization Of Amino Functions Of Polyaminesmentioning

confidence: 99%

Structure, Biological Activity and Synthesis of Polyamine Analogues and Conjugates

Karigiannis

Papaioannou²

2000

Eur. J. Org. Chem.

119

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The structure and the biological significance of naturally occurring and synthetic polyamine analogues and conjugates are presented and the available methodologies for their synthesis are described. These methodologies involve either the selective functionalization of the amino functions, using suitable protecting groups or acylating agents, or fragment synthesis protocols. The latter employ suitable amino components and simple reactions, like Michael addition to α,β‐unsaturated nitriles, alkylation of amines and sulfonamides, reductive alkylation and acylation followed by reduction of the thus‐obtained amides, as key‐reactions, or azides as key‐intermediates, for the assembly of the polyamine skeleton. Syntheses performed in solution as well as in the solid phase are discussed.

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General method for the synthesis of selectively N-alkylated polyamines

Cited by 17 publications

References 3 publications

Synthesis and Structure-Activity Relationships of Novel Naphthalenic and Bioisosteric Related Amidic Derivatives as Melatonin Receptor Ligands

Synthesis and Structure-Activity Relationships of Novel Naphthalenic and Bioisosteric Related Amidic Derivatives as Melatonin Receptor Ligands

A one-pot chemoselective synthesis of secondary amines by using a biomimetic electrocatalytic system

Structure, Biological Activity and Synthesis of Polyamine Analogues and Conjugates

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