220652-02-8

Upstream product

• 322474-21-5 N,N'-bis-Boc-S-methyl-isothiourea 
• 100-51-6 benzyl alcohol 
• 100-39-0 benzyl bromide 
• 107819-90-9 1,3-bis(tert-butoxycarbonyl)-2-methyl-2-thiopseudourea 
• 24424-99-5 di-tert-butyl dicarbonate 

Downstream Products

• 641611-38-3 17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-5'-bis-tert-butoxycarbonyl-(N'-benzyl)guanidinyl-3,14-dihydroxyindolo[2',3':6,7]morphinan 
• 641611-17-8 17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-5'-bis-tert-butoxycarbonyl-(N'-benzyl)guanidinylethyl-3,14-dihydroxyindolo[2',3':6,7]morphinan 
• 1176238-50-8 2,6-[(di-tert-butoxycarbonyl)diimido]-3-benzyl-5-tert-butoxycarbonyl-1,3,5,7,16-pentaazacyclotetracosan-4-one 
• 1176817-96-1 1-amino-17-(N₁,N₂-bis(tert-butoxycarbonyl)-N₁-(benzyl)guanidine)-9-azaheptadecane 
• 1334182-28-3 C₆₆H₇₉N₁₁O₁₀ 

Relevant academic research and scientific papers

A convenient synthesis of disubstituted guanidines via the Mitsunobu protocol

An efficient synthetic method for the preparation of disubstituted guanidines is described. Primary and secondary alcohols were treated with guanylating agents under Mitsunobu conditions and their subsequent reactions with amines provided disubstituted guanidines.

Synthesis, biological evaluation and mode of action studies of novel amidinourea inhibitors of hepatitis C virus (HCV)

Novel amidinourea derivatives have been synthesised and evaluated for their antiviral activity against Hepatitis C Virus (HCV). A compound with an amidinourea-spermine chemical structure, different from that of standard anti-HCV drugs, showed micromolar activity against HCV and excellent viability. Studies on the mode of action revealed that the new compound may act against HCV through the inhibition of IRES-mediated translation.

Design, synthesis, and: In vitro and in vivo characterization of 1-{4-[4-(substituted)piperazin-1-yl]butyl}guanidines and their piperidine analogues as histamine H3 receptor antagonists

Previously, we have shown that 1-substituted-[4-(7-phenoxyheptylpiperazin-1-yl)butyl]guanidine with electron withdrawing substituents at position 4 in the benzyl moiety exhibits high in vitro affinities toward the guinea pig jejunal histamine H3/sub

Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane

The design, synthesis and evaluation of a small series of potent amphiphilic norbornane antibacterial agents has been performed (compound 10 MIC = 0.25 μg/mL against MRSA). Molecular modelling indicates rapid aggregation of this class of antibacterial agent prior to membrane association and insertion. Two fluorescent analogues (compound 29 with 4-amino-naphthalimide and 34 with 4-nitrobenz-2-oxa-1,3-diazole fluorophores) with good activity (MIC = 0.5 μg/mL against MRSA) were also constructed and confocal microscopy studies indicate that the primary site of interaction for this family of compounds is the bacterial membrane.

Development of a peptidomimetic antagonist of neuropeptide FF receptors for the prevention of opioid-induced hyperalgesia

Through the development of a new class of unnatural ornithine derivatives as bioisosteres of arginine, we have designed an orally active peptidomimetic antagonist of neuropeptide FF receptors (NPFFR). Systemic low-dose administration of this compound to rats blocked opioid-induced hyperalgesia, without any apparent side-effects. Interestingly, we also observed that this compound potentiated opioid-induced analgesia. This unnatural ornithine derivative provides a novel therapeutic approach for both improving analgesia and reducing hyperalgesia induced by opioids in patients being treated for chronic pain.

Application of the guanidine-acylguanidine bioisosteric approach to argininamide-type NPY Y2 receptor antagonists

Strongly basic groups such as guanidine moieties are crucial structural elements, but they compromise the drug-likeness of numerous biologically active compounds, including ligands of G-protein-coupled receptors (GPCRs). As part of a project focused on the search for guanidine bioisosteres, argininamide-type neuropeptideY (NPY) Y2 receptor (Y2R) antagonists related to BIIE0246 were synthesized. Starting from ornithine derivatives, NG-acylated argininamides were obtained by guanidinylation with tailor-made mono-Boc-protected N-acyl-S-methylisothioureas. The compounds were investigated for Y2R antagonism (calcium assays), Y2R affinity, and NPY receptor subtype selectivity (flow cytometric binding assays). Most of the NG-substituted (S)-argininamides showed Y2R antagonistic activities and binding affinities similar to those of the parent compound, whereas NG-acylated or -carbamoylated analogues with a terminal amine were superior (Y2R: Ki and KB values in the low nanomolar range). This demonstrates that the basicity of the compounds, although 4-5 orders of magnitude lower than that of guanidines, is sufficient to form key interactions with acidic amino acids of the Y2R. The acylguanidines bind with high affinity and selectivity to Y2R over the Y1, Y4, and Y5 receptors. As derivatization of the amino group is tolerated, these compounds can be considered building blocks for the preparation of versatile fluorescent and radiolabeled pharmacological tools for invitro studies of the Y2R. The results support the concept of bioisosteric guanidine-acylguanidine exchange as a broadly applicable approach to retain pharmacological activity despite decreased basicity.

Synthesis and biological evaluation of guanidino compounds endowed with subnanomolar affinity as competitive inhibitors of maize polyamine oxidase

Previous studies on agmatine and its derivatives suggested that the presence of hydrophobic groups on the guanidine moiety was a crucial key for inhibitory activity of maize polyamine oxidase. Accordingly, new lipophilic agmatine and iminoctadine derivatives were synthesized and tested for their ability to inhibit this enzyme. Several compounds showed an affinity in the nanomolar range, while a cyclopropylmethyl derivative of iminoctadine was found to be the most potent inhibitor of maize polyamine oxidase reported so far (Ki = 0.08 nM).

Synthesis of new linear guanidines and macrocyclic amidinourea derivatives endowed with high antifungal activity against Candida spp. and Aspergillus spp.

New linear and cyclic guanidines were synthesized and tested in vitro for their antifungal activity toward clinically relevant strains of Candida species, in comparison to fluconazole. Macrocyclic compounds showed a minimum inhibitory concentration in the micromolar range and a biological activity profile in some cases better than that of fluconazole. One macrocyclic derivative was also tested against Aspergillus species and showed high antifungal activity comparable to that of amphotericin B and itraconazole.

Guanidino N-Substituted and N,N-Disubstituted Derivatives of the κ-Opioid Antagonist GNTI

Derivatives of the highly selective κ-opioid receptor antagonist GNTI (2a) have been prepared. Binding and functional studies conducted on cloned human opioid receptors expressed in Chinese hamster ovarian (CHO) cells suggested that adding a benzyl or a substituted benzyl group to the guanidino moiety led, in general, to a retention of high κ-affinity and antagonist potency. Disubstitution of the guanidino moiety led to reduced κ-selectivity.

A convenient and versatile method for the synthesis of protected guanidines

Aromatic, aliphatic and sterically hindered amines react smoothly with commercially available N, N'-bis-BOC-S-methylisothiourea 2 in the presence of mercury chloride to give the protected guanidine in good yield. It is particularly noteworthy that 2 can a