260065-79-0Relevant 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.
Lipase-catalyzed Kinetic Resolution of (+/-)-trans- and cis-2-Azidocycloalkanols
Ami, Ei'ichi,Ohrui, Hiroshi
, p. 2150 - 2156 (2007/10/03)
The lipase-catalyzed kinetic resolution of trans- and cis-2-azidocycloalkanols and the preparation of enantiomerically pure trans- and cis-2-aminocycloalkanols are described. Four kinds of lipases were screened for the acetylation of trans- and cis-2-azidocycloalkanols. Among them, Pseudomonas sp. lipases (lipase PS and lipase AK, Amamo Pharmaceutical Co.) showed the highest enantioselectivity. These products were converted to the corresponding 2-aminocycloalkanols to determine their enantiomeric excess (ee) and absolute configurations by HPLC and CD analyses, using (S)-TBMB carboxylic acid [(S)-2-tert-butyl-2-methyl-1,3-benzodioxole-4-carboxylic acid] as the chiral conversion reagent. The results of the CD analysis proved N,O-bis-(S)-TBMB carboxylated cis-2-aminocycloalkanols to adopt a predominantly N-equatorial conformation. The partially resolved trans- and cis-2-aminocycloalkanols, except for trans-2-aminocyclopentanol, were recrystallized from ethyl acetate to give enantiomerically pure forms.
