125356-51-6Relevant articles and documents
Matrix metalloproteinase inhibitors based on the 3-mercaptopyrrolidine core
Jin, Yonghao,Roycik, Mark D.,Bosco, Dale B.,Cao, Qiang,Constantino, Manuel H.,Schwartz, Martin A.,Sang, Qing-Xiang Amy
, p. 4357 - 4373 (2013/07/19)
New series of pyrrolidine mercaptosulfide, 2-mercaptocyclopentane arylsulfonamide, and 3-mercapto-4-arylsulfonamidopyrrolidine matrix metalloproteinase inhibitors (MMPIs) were designed, synthesized, and evaluated. Exhibiting unique properties over other MMPIs (e.g., hydroxamates), these newly reported compounds are capable of modulating activities of several MMPs in the low nanomolar range, including MMP-2 (～2 to 50 nM), MMP-13 (～2 to 50 nM), and MMP-14 (～4 to 60 nM). Additionally these compounds are selective to intermediate- and deep-pocket MMPs but not shallow-pocketed MMPs (e.g., MMP-1, ～850 to >50 000 nM; MMP-7, ～4000 to >25 000 nM). Our previous work with the mercaptosulfide functionality attached to both cyclopentane and pyrrolidine frameworks demonstrated that the cis-(3S,4R)-stereochemistry was optimal for all of the MMPs tested. However, in our newest compounds an interesting shift of preference to the trans form of the mercaptosulfonamides was observed with increased oxidative stability and biological compatibility. We also report several kinetic and biological characteristics showing that these compounds may be used to probe the mechanistic activities of MMPs in disease.
(1S,2R/1R,2S)-cis-cyclopentyl PNAs (cpPNAs) as constrained PNA analogues: Synthesis and evaluation of aeg-cpPNA chimera and stereopreferences in hybridization with DNA/RNA
Govindaraju,Kumar, Vaijayanti A.,Ganesh, Krishna N.
, p. 5725 - 5734 (2007/10/03)
Conformationally constrained chiral PNA analogues were designed on the basis of stereospecific imposition of a 1,2-cis-cyclopentyl moiety on an aminoethyl segment of aegPNA. It is known that the cyclopentane ring is a relatively flexible system in which the characteristic puckering dictates the pseudoaxial/pseudoequatorial dispositions of substituents. Hence, favorable torsional adjustments are possible to attain the necessary hybridization- competent conformations when the moiety is imposed on the conventional PNA backbone. The synthesis of the enantiomerically pure 1,2-cis-cyclopentyl PNA monomers (10a and 10b) was achieved by stereoselective enzymatic hydrolysis of a key intermediate ester 2. The chiral (1S,2R/1R,2S)-aminocyclopentylglycyl thymine monomers were incorporated into PNA oligomers at defined positions and through the entire sequence. Hybridization studies with complementary DNA and RNA sequences using UV-Tm measurements indicate that aeg-cpPNA. chimera form thermally more stable complexes than aegPNA with stereochemistry-dependent selective binding of cDNA/RNA. Differential gel shift retardation was observed on hybridization of aeg-cpPNAs with complementary DNA.
Synthesis and evaluation of new 1,7-dioxaspiro[5.5]undecane ligands: Implications for the use of diols in the desymmetrization of meso epoxides
Patra, Debasis,Yang, Lihua,Totah, Nancy I.
, p. 507 - 513 (2007/10/03)
The synthesis and preliminary evaluation of two new chiral 1,7- dioxaspiro[5.5]undecane ligands is described. The compounds of interest are readily available in enantiomerically pure form. Chiral organotitanium complexes prepared from these ligands cataly
