817562-87-1

Upstream product

• 54848-33-8 (S)-tetrahydro-5-oxo-2-furancarbonyl chloride 
• 100-39-0 benzyl bromide 
• 134000-24-1 2-(S)-5-oxotetrahydrofuran-2-carboxylic acid, tert-butyl ester 
• 124-63-0 methanesulfonyl chloride 
• 21461-84-7 (2S)-tetrahydro-5-oxofuran-2-carboxylic acid 
• 56-86-0 L-glutamic acid 
• 817562-86-0 2-(S)-2-hydroxypentanedioic acid, 1-tert-butyl-5-benzyl ester 

Downstream Products

• 817562-89-3 2-(R)-2-(4,7,10-tris-tert-butoxycarbonylmethyl-1,4,7,10-tetraazacyclododec-1-yl)-pentanedioic acid, 1-tert-butyl-5-benzyl ester 
• 873200-95-4 (2S,2'S,2''S)-5-tribenzyl-1-tri-tert-butyl-2,2',2''-(1,4,7,10-tetraazacyclododecane-1,4,7-triyl) tripentanedioate 
• 817562-88-2 2-(R)-2-(1,4,7,10-tetraazacyclododec-1-yl)pentanedioic acid, 1-tert-butyl-5-benzyl ester 

Relevant academic research and scientific papers

Enantiopure chelating agents for chelator coupled pharmaceuticals, corresponding preparation method thereof and chelator coupled pharmaceuticals

According to the present invention an enantiopure chelating compound of general Formula 10A or 10B is provided: wherein each of R1 through R3 is independently selected hydrogen, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C2-C20 alkenyl, substituted or unsubstituted C2-C20 alkynyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C6-C60 aryl, or -Si(R4)(R5)(R6), and each of R4 through R6 is independently selected a substituted or unsubstituted group consisting of C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 alkoxy, C3-C10 cycloalkyl, C6-C60 aryl, and C6-C60 aryloxy. The present invention further refers to a corresponding preparation method of the chelating compound and chelator coupled pharmaceuticals including the same.

Trivalent Gd-DOTA reagents for modification of proteins

The development of novel protein-targeted MRI contrast agents crucially depends on the ability to derivatise suitable targeting moieties with a high payload of relaxation enhancer (e.g., gadolinium(III) complexes such as Gd-DOTA), without losing affinity

Enantiopure bifunctional chelators for copper radiopharmaceuticals - Does chirality matter in radiotracer design?

It is well recognized that carbon chirality plays a critical role in the design of drug molecules. However, very little information is available regarding the effect of stereoisomerism of macrocyclic bifunctional chelators (BFC) on biological behaviors of

Serum albumin targeted, pH-Dependent Magnetic Resonance Relaxation Agents

The objective of this work was the synthesis of serum albumin targeted, GdIII-based magnetic resonance imaging (MRI) contrast agents exhibiting a strong pH-dependent relaxivity. Two new complexes (Gd-glu and Gd-bbu) were synthesized based on the DO3A macrocycle modified with three carboxyalkyl substituents α to the three ring nitrogen atoms, and a biphenylsulfonamide arm. The sulfonamide nitrogen coordinates the Gd in a pH-dependent fashion, resulting in a decrease in the hydration state, q, as pH is increased and a resultant decrease in relaxivity (r1). In the absence of human serum albumin (HSA), r1 increases from 2.0 to 6.0 mM-1 s-1 for Gd-glu and from 2.4 to 9.0 mM-1 s-1 for Gd-bbu from pH 5 to 8.5 at 37 °C, 0.47 T, respectively. These complexes (0.2 mM) are bound (>98.9 %) to HSA (0.69 mM) over the pH range 5-8.5. Binding to albumin increases the rotational correlation time and results in higher relaxivity. The r1 increased 120 % (pH 5) and 550 % (pH 8.5) for Gd-glu and 42 % (pH 5) and 260 % (pH 8.5) for Gd-bbu. The increases in r1 at pH 5 were unexpectedly low for a putative slow tumbling q=2 complex. The Gd-bbu system was investigated further. At pH 5, it binds in a stepwise fashion to HSA with dissociation constants K d1=0.65, Kd2=18, Kd3=1360 μM. The relaxivity at each binding site was constant. Luminescence lifetime titration experiments with the EuIII analogue revealed that the inner-sphere water ligands are displaced when the complex binds to HSA resulting in lower than expected r1 at pH 5. Variable pH and temperature nuclear magnetic relaxation dispersion (NMRD) studies showed that the increased r1 of the albumin-bound q=0 complexes is due to the presence of a nearby water molecule with a long residency time (1-2 ns). The distance between this water molecule and the Gd ion changes with pH resulting in albumin-bound pH-dependent relaxivity. Copyright

Development of a multigram asymmetric synthesis of 2-(R)-2-(4,7,10-tris tert-butylcarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)-pentanedioic acid, 1-tert-butyl ester, (R)-tert-Bu4-DOTAGA1

A process for the multigram asymmetric synthesis of the chiral tetraazamacrocycle 2-(R)-2-(4,7,10-tris tert-butylcarboxymethyl- 1,4,7,10-tetraazacyclododec-1-yl)-pentanedioic acid, 1-tert-butyl ester ((R)-tert-Bu4-DOTAGA, 4) has been devised and demonstrated. The nine-step synthesis features an improved synthesis of 2-(S)-5- oxotetrahydrofuran- 2-carboxylic acid, tert-butyl ester 8, the precursor to the novel alkylating agent (S)-5-benzyl 1-tert-butyl 2-(methylsulfonyloxy) pentanedioate 12, which was used to introduce an orthogonally protected chiral glutarate arm to the 1,4,7,10-tetraazacyclododecane (cyclen) nucleus in high optical purity. Cyclen derivative (R)-t-Bu4-DOTAGA, 4, a key intermediate for the manufacture of a magnetic resonance imaging (MRI) candidate, was produced with high chemical (≥95%) and optical (ee ≥ 97%) purity. The process developed was successfully applied to the kilogram-scale cGMP synthesis of (R)-t-Bu4-DOTAGA.

Optically pure and enriched isomers of chelating ligands and contrast agents

Organic chelating ligands, organic chelating ligand precursors, and metal chelates are disclosed. Methods for synthesizing the same are also described, including methods for preparing optically-enriched or optically-pure compositions of the same.