Amino acids as selective sulfonamide acylating agents

Gomes, Paula; Gomes, J.R.; Rodrigues, Manuela; Moreira, Rui

doi:10.1016/s0040-4020(03)01206-7

Cited by 10 publications

(15 citation statements)

References 35 publications

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“…This is particularly true when the carriers contain a terminal nucleophilic amino group so that drug release would occur through aminomediated intramolecular cyclative cleavage of the drug-carrier bond, i.e., intramolecular aminolysis. Peptides have also been used/proposed as carriers to provide the basic amino group for such purpose [11,12,23,24].…”

Section: Cyclization-elimination Involving An Amino Groupmentioning

confidence: 99%

“…Therefore, adequate linear dipeptide derivatives could act as prodrugs for DKP-based drugs. However, the major role of DKP in prodrug design falls in the domain of approach (ii): by linking adequate dipeptide carriers to a drug, a prodrug can be created which undergoes a strictly chemical cyclization-elimination process by intramolecular aminolysis of the dipeptide moiety to a DKP, with simultaneous departure of the free parent drug (Scheme 10) [55,56]. In this connection, peptide derivatives of some drugs have been prepared and evaluated as prodrug candidates where prodrug activation processes involved DKP formation.…”

Section: Peptide Carriers A) Peptide Cyclization and Prodrug Designmentioning

confidence: 99%

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Cyclization-activated Prodrugs

2007

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Many drugs suffer from an extensive first-pass metabolism leading to drug inactivation and/or production of toxic metabolites, which makes them attractive targets for prodrug design. The classical prodrug approach, which involves enzyme-sensitive covalent linkage between the parent drug and a carrier moiety, is a well established strategy to overcome bioavailability/toxicity issues. However, the development of prodrugs that can regenerate the parent drug through non-enzymatic pathways has emerged as an alternative approach in which prodrug activation is not influenced by inter-and intraindividual variability that affects enzymatic activity. Cyclization-activated prodrugs have been capturing the attention of medicinal chemists since the middle-1980s, and reached maturity in prodrug design in the late 1990s. Many different strategies have been exploited in recent years concerning the development of intramoleculary-activated prodrugs spanning from analgesics to anti-HIV therapeutic agents. Intramolecular pathways have also a key role in two-step prodrug activation, where an initial enzymatic cleavage step is followed by a cyclization-elimination reaction that releases the active drug. This work is a brief overview of research on cyclization-activated prodrugs from the last two decades.

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Section: Cyclization-elimination Involving An Amino Groupmentioning

confidence: 99%

Section: Peptide Carriers A) Peptide Cyclization and Prodrug Designmentioning

confidence: 99%

Cyclization-activated Prodrugs

2007

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“…[10] This same process was applied for different compositions of 2-aminothiazole and p-acetamidobenzenesulfonyl chloride for different acid acceptors (3:1, 1:1, and 1:3). [11] The obtained 12 samples were investigated using melting point apparatus, and three best samples (one from each composition) were chosen and were further investigated using FT-IR spectrophotometer for which results were reported.…”

Section: Synthesismentioning

confidence: 99%

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Keerthi

2017

AJP

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Aim: The major scope of the work is to find best suitable conditions and process for the preparation of sulfa drug where the yield can be maximum with reduced periods. Materials and Methods: Sulfathiazole is prepared by chlorosulfonation of acetanilide (at 114°C) to obtain an intermediate which is reacted with 2-aminothiazole. The samples of intermediate and 2-aminothiazole with ratios (3:1, 1:1, and 1:3) and with different acid acceptors named pyridine, sodium bicarbonate, dimethylaniline, and ammonium hydroxide are studied. Results and Discussion: Chlorosulfonation at 114°C yielded good which further gave good results (91% yield) with 3:1 intermediate and 2-aminothiazole concentration and pyridine as an acid acceptor. The analysis was performed using infrared (IR) spectroscopy in Fourier transform IR spectroscopy which is found to be the best method for identification of samples. Conclusions: Among the reaction ratios studied for sulfathiazole, sample with 3:1 ratio of p-acetamidobenzenesulfonyl chloride to 2-aminothiazole with pyridine as an acid acceptor is proved to be the best reactant ratio with yield 91.34%. The process employed for experimentation proved to be an efficient and time-saving process.

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“…However, the complete absence of N-acylation at the 8-amino group was noteworthy and made us wonder if Boc-amino acids were acting as selective acylants, as previously observed in similar N 4 -acylations of sulfanilamides. 12,13 To further investigate whether the quinoline's 8-amino substituent was completely inert towards acylation, we worked on the acetylation of 2a by two different methods. Acetyl was chosen as acyl component to differ from the amino acid acylants and to rule out, or not, the putative influence of the latter on regioselectivity.…”

Section: Regioselectivitymentioning

confidence: 99%

“…Previous reports described N a -protected amino acids as selective sulfanilamide acylants, where only monoacylation at the sulfanilamide's N-4 occurred by employing classical carbodiimide-mediated coupling methods, leaving the sulfonamide's N 1 unreacted. 12,13 Thus, it was reasonable to assume that by equally resorting to a BocAAOH as acylating agent and to carbodiimide-mediated coupling, we would achieve our purpose, i.e., regioselective production of compounds 5. The regioselectivity and efficiency of the coupling reactions were tested using imidazolidin-4-ones 2a and 2b (2 in Scheme 1 with, respectively, R reaction conditions and solvents were assayed, so we now wish to herein report and discuss the results thus obtained.…”

Section: Introductionmentioning

confidence: 99%

Amino acids as selective acylating agents: regioselective N1-acylation of imidazolidin-4-one derivatives of the antimalarial drug primaquine

et al. 2008

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a b s t r a c tThe acylation of bioactive primaquine-based imidazolidin-4-ones was studied using N a -Boc-protected glycine as acylating agent. Two synthesis routes, eight different coupling methods and seven distinct solvents were compared. Mild carbodiimide-based couplings on high dielectric constant solvents such as DMF or MeCN increased acylation yields, whereas alcohols inhibited carbodiimide-mediated acylations to take place. Achievement of the synthetic goals was limited by the size of the imidazolidin-4-one ring substituents R 1 , R 2 and R 3 , but resort to MW-assisted synthesis allowed overcoming such obstacle, though with very modest reaction yields. All reactions involving a Boc-protected amino acid were regioselective, independent of reaction conditions employed. In contrast, regioselective acetylation of the imidazolidin-4-ones could only be achieved by resort to very mild coupling procedures.

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Amino acids as selective sulfonamide acylating agents

Cited by 10 publications

References 35 publications

Cyclization-activated Prodrugs

Cyclization-activated Prodrugs

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Amino acids as selective acylating agents: regioselective N1-acylation of imidazolidin-4-one derivatives of the antimalarial drug primaquine

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