2465-97-6

Usage

InChI:InChI=1/C9H23N7/c10-8(11)15-6-2-1-4-14-5-3-7-16-9(12)13/h14H,1-7H2,(H4,10,11,15)(H4,12,13,16)

Upstream product

• 158474-89-6 N-[4-(trifluoroacetamido)butyl]-N-[3-(trifluoroacetamido)propyl]amine 
• 158474-92-1 N⁴-(4-Azidobenzyloxycarbonyl)-N¹,N⁸-bis(nitroguanidino)spermidine 
• 158474-90-9 [4-(2,2,2-Trifluoro-acetylamino)-butyl]-[3-(2,2,2-trifluoro-acetylamino)-propyl]-carbamic acid 4-azido-benzyl ester 
• 158474-91-0 (4-Amino-butyl)-(3-amino-propyl)-carbamic acid 4-azido-benzyl ester 
• 124-20-9 N-(3-aminopropyl)-1,4-diaminobutane 
• 334-50-9 spermidine trihydrochloride 
• 158474-93-2 N¹,N⁸-Bis(nitroguanidino)spermidine 

Relevant academic research and scientific papers

METHODS AND COMPOSITIONS COMPRISING GUANIDINES FOR TREATING BIOFILMS

Methods of treating or reducing biofilms, treating a biofilm-related disorder, triggering biofilm disassembly, and preventing biofilm formation using guanidines is described.

Synthesis and activity of biomimetic biofilm disruptors

Biofilms are often associated with human bacterial infections, and the natural tolerance of biofilms to antibiotics challenges treatment. Compounds with antibiofilm activity could become useful adjuncts to antibiotic therapy. We used norspermidine, a natural trigger for biofilm disassembly in the developmental cycle of Bacillus subtilis, to develop guanidine and biguanide compounds with up to 20-fold increased potency in preventing biofilm formation and breaking down existing biofilms. These compounds also were active against pathogenic Staphylococcus aureus. An integrated approach involving structure-activity relationships, protonation constants, and crystal structure data on a focused synthetic library revealed that precise spacing of positively charged groups and the total charge at physiological pH distinguish potent biofilm inhibitors.

Protecting-group strategies for the synthesis of N4-substituted, and N1,N8-disubstituted spermidines, exemplified by hirudonine

Methods are described for the preparation of derivatives of the polyamines 1,4-diaminobutane (putrescine), and N′-(3-amihopropyl)-l,4-diaminobutane (spermidine) in which a particular amino group is modified with, e.g., a guanidino function. Specific amino groups in these polyamines were protected as ;V-trifluoroacetyl, and yV-4-azidobenzyloxycarbonyl derivatives, which were unmasked chemoselectively using methanolic ammonia, and dithiothreitol-triethylamine, respectively. Guanidino functions were introduced by an improved procedure in which an amino group was treated with 3,5-dimethyl-Ar-nitro-!//-pyrazole-l-carboximidamide in methanol to give a nitroguanidine derivative, from which the nitro group was removed by catalytic transfer hydrogenation. The methodology is exemplified by the development of efficient preparative routes to agmatine, and hirudonine. The integrity of the sequence of protection/deprotection leading to hirudonine was confirmed by a crystal-structure analysis of its sulfate. The effect of selected compounds on the uptake of putrescine into rat lung cells was determined, and showed that N4-(4-azidobenzyloxycarbonyl)spermidine was the best inhibitor (Ki = 3.4 μM).

Stabilization of DNA structures through nucleobase modifications and bisguanidium polyamines

Spermine conjugation at N4 of 5-Me-dC in oligonucleotides (sp- ODNs) reduces the net negative charge and these as HG strands form trplexes with foremost stability at neutral pH (7.3), in contrast to unmodified ODNs which form stable triplexes at pH 5.5. The stability of sp-ODN triplexes is shown to arise from improved association with duplex caused by electrostatic interaction of polycationic spermine sidechain with anionic phosphate backbone of DNA and N3 protonation is not a prerequirement for triplexes constituted from sp-ODNs. The amplification of electrostatic component of interaction can be achieved by transformation of primary amino group of polyamines to corresponding guanidinium functions leading to improved binding and stabilization of DNA triplexes even at pH 7.0. 5- Amino-dU ODNs are shown to be compatible as a central strand in formation of triplexes in which pyrimidine would be in the middle position of a triad.

Discrimination of Spermidine Amino Functions by a New Protecting Group Strategy; Application to the Synthesis of Guanidinylated Polyamines, Including Hirudonine

Agmatine and hirudonine, guanidine derivatives of putrescine and spermidine, respectively, are synthesised by the application of a new protecting group strategy for polyamines, which uses N-nitroguanidinyl as a precursor of guanidine functions and selectively blocks spermidine at N-1 and N-8 with trifluoroacetyl and at N-4 by 4-azidobenzyloxycarbonyl.