477908-26-2

Upstream product

• 39684-28-1 O-(tert-butyl)hydroxylamine hydrochloride 
• 960113-56-8 (R)-2-(4-nitrophenylsulfonamido-N-(pyridin-3-ylmethyl))-3-methylbutanoic acid 
• 640-68-6 D-Val-OH 
• 7146-15-8 D-Valine methyl ester hydrochloride 
• 98-74-8 4-Nitrobenzenesulfonyl chloride 
• 477908-20-6 (2R)-3-methyl-2-[(4-nitrobenzenesulfonyl)amino]butanoic acid methyl ester 
• 477908-23-9 methyl 2(R)-[[(4-nitrophenyl)sulfonyl](3-picolyl)amino]-3-methylbutanoate 

Downstream Products

• 477908-29-5 N-hydroxy-2(R)-[[(4-nitrophenyl)sulfonyl](3-picolyl)amino]-3-methylbutanamide 

Relevant academic research and scientific papers

Novel fluorinated derivatives of the broad-spectrum MMP inhibitors N-hydroxy-2(R)-[[(4-methoxyphenyl)sulfonyl](benzyl)- and (3-picolyl)-amino]-3- methyl-butanamide as potential tools for the molecular imaging of activated MMPs with PET

An approach to the in vivo imaging of locally upregulated and activated matrix metalloproteinases (MMPs) found in many pathological processes is offered by positron emission tomography (PET). Hence, appropriate PET radioligands for MMP imaging are required. Here, we describe the syntheses of novel fluorinated MMP inhibitors (MMPIs) based on lead structures of the broad-spectrum inhibitors N-hydroxy-2(R)-[[(4-methoxyphenyl)sulfonyl](benzyl)-amino]-3-methyl-butanamide (CGS 25966) and N-hydroxy-2(R)-[[(4-methoxyphenyl)sulfonyl](3-picolyl)-amino]-3- methyl-butanamide (CGS 27023A). Additionally, tailor-made precursor compounds for radiolabeling with the positron-emitter 18F were synthesized. All prepared hydroxamate target compounds showed high in vitro MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13. As a consequence, the promising fluorinated hydroxamic acid derivative 1f was resynthesized in its 18F-labeled version via two different procedures yielding the potential PET radioligand [18F]If. As expected, the biodistribution behavior of this novel compound and that of the more hydrophilic variant [ 18F]1j, also developed by our group, indicates that there was no tissue specific accumulation in wild-type (WT) mice.

Synthesis of MMP inhibitor radiotracers [11C]methyl-CGS 27023A and its analogs, new potential PET breast cancer imaging agents

[11C]Methyl-CGS 27023A (1a) and its analogs [11C]methyl-2-picolyl-CGS 27023A (1b), [11C]methyl-benzyl-CGS 27023A (1c), [11C]methyl-2-nitro-CGS 27023A (1d), [11C]methyl-3-nitro-CGS 27023A (1e), and [11C]methyl-4-nitro-CGS 27023A (1f), novel radiolabeled matrix metalloproteinase (MMP) inhibitors, have been synthesized for evaluation as new potential positron emission tomography (PET) breast cancer imaging agents. The appropriate precursors for radiolabeling were obtained in four to five steps from starting material amino acid D-valine with moderate to excellent chemical yields. Precursors were labeled by [11C]methyl triflate through 11C-O-methylation method at the aminohydroxyl position under basic conditions and isolated by solid-phase extraction (SPE) purification to produce pure target compounds in 40-60% radiochemical yields (decay corrected to end of bombardment), in 20-25 min synthesis time. Copyright