170450-77-8Relevant academic research and scientific papers
HYDROXY FORMAMIDE DERIVATIVES AND THEIR USE
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Page/Page column 80, (2017/01/26)
Disclosed are compounds having the formula: (I) wherein R1, R2 and R3 are as defined herein, and methods of making and using the same, including use as inhibitors of BMP1, TLL1 and/or TLL2 and in treatment of diseases associated with BMP1, TLL1 and/or TLL2 activity.
HYDROXY FORMAMIDE DERIVATIVES AND THEIR USE
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Paragraph 0388; 0389, (2016/12/16)
Disclosed are compounds having the formula: wherein R1, R2 and R3 are as defined herein, and methods of making and using the same, including use as inhibitors of BMP1, TLL1 and/or TLL2 and in treatment of diseases associated with BMP1, TLL1 and/or TLL2 activity.
Condensation of Carboxylic Acids with Non-Nucleophilic N-Heterocycles and Anilides Using Boc2O
Umehara, Atsushi,Ueda, Hirofumi,Tokuyama, Hidetoshi
, p. 11444 - 11453 (2016/11/28)
A novel condensation reaction of carboxylic acids with various non-nucleophilic N-heterocycles and anilides was developed. The reaction proceeds in the presence of di-tert-butyl dicarbonate (Boc2O), catalytic 4-(dimethylamino)pyridine (DMAP), a
HYDROXY FORMAMIDE DERIVATIVES AND THEIR USE
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Page/Page column 72; 73, (2015/07/23)
Disclosed are compounds having the formula (I): wherein R1, R2 and R3 are as defined herein, and methods of making and using the same, including use as inhibitors of BMP1, TLL1 and/or TLL2 and in treatment of diseases associated with BMP1, TLL1 and/or TLL2 activity.
Synthesis and SAR of succinamide peptidomimetic inhibitors of cathepsin S
Chatterjee, Arnab K.,Liu, Hong,Tully, David C.,Guo, Jianhua,Epple, Robert,Russo, Ross,Williams, Jennifer,Roberts, Michael,Tuntland, Tove,Chang, Jonathan,Gordon, Perry,Hollenbeck, Thomas,Tumanut, Christine,Li, Jun,Harris, Jennifer L.
, p. 2899 - 2903 (2008/12/22)
Peptidic, non-covalent inhibitors of lysosomal cysteine protease cathepsin S (1 and 2) were investigated due to low oral bioavailability, leading to an improved series of peptidomimetic inhibitors. Utilizing phenyl succinamides as the P2 residue increased the oral exposure of this lead series of compounds, while retaining selective inhibition of the cathepsin S isoform. Concurrent investigation of the P1 and P2 subsites resulted in the discovery of several potent and selective inhibitors of cathepsin S with good pharmacokinetic properties due to the elimination of saturated aliphatic P2 residues.
Inhibition of membrane-type 1 matrix metalloproteinase by hydroxamate inhibitors: An examination of the subsite pocket
Yamamoto, Minoru,Tsujishita, Hideki,Hori, Noriyuki,Ohishi, Yuichi,Inoue, Shintaro,Ikeda, Shoji,Okada, Yasunori
, p. 1209 - 1217 (2007/10/03)
The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been reported to mediate the activation of pro-gelatinase A (proMMP-2), which is associated with tumor proliferation and metastasis. MT1-MMP can also digest extracellular matrix (ECM) such as interstitial collagens, gelatin, and proteoglycan and thus may play an important role in pathophysiological digestion of ECM. We studied the inhibitory effect of various hydroxamate MMP inhibitors, including known inhibitors such as BB-94, BB-2516, GM6001, and Ro31-9790, on a deletion mutant of MT1-MMP lacking the transmembrane domain (ΔMT1) to further characterize the enzyme and develop a selective inhibitor for MT1-MMP. The evaluation of the inhibitory activities of various hydroxamates reveals general structural profiles affecting selectivities toward MMPs. In particular, a longer side chain at the P1' position is preferable for the binding to MMP-2, -3, and -9 and MT1-MMP. For the P2' position, an α-branched alkyl group is critical for the binding toward ΔMT1, while the introduction of a bulky group at the α-position of hydroxamic acid seems to diminish the activity against ΔMT1. Summation of the data on the sensitivity of ΔMT1 to various hydroxamate inhibitors indicates that (1) the volume of the S1' subsite of ΔMT1 is similar to that of MMP-2, -3, and -9, which is bigger than that of MMP-1, and (2) the S1 and S2' subsites are narrower than those in other MMPs. On the basis of these results, the hydroxamates with a P1' phenylpropyl and P2' α-branched alkyl group were synthesized and evaluated for inhibitory activity. These inhibitors (1h,i) showed strong activity against ΔMT1 over MMP-1, but no selectivity between ΔMT1 and MMP-9. These results are explained using molecular modeling studies conducted on MT1-MMP.
Potent carboxylate inhibitors of stromelysin containing P2' piperazic acids and P1' biaryl moeities
Cherney, Robert J.,Decicco, Carl P.,Nelson, David J.,Wang, Li,Meyer, Dayton T.,Hardman, Karl D.,Copeland, Robert A.,Arner, Elizabeth C.
, p. 1757 - 1762 (2007/10/03)
Several carboxylate derivatives with variation at the P1' residue were synthesized and evaluated as stromelysin (MMP-3) inhibitors. Compounds containing a bipbenyl moiety at P1' were found to be potent inhibitors of MMP-3. An X-ray crystal structure of the most potent compound, carboxylate 19, revealed an important interaction between the inhibitor's biphenyl and histidine 224 in the S1' pocket of MMP-3.
Orally active inhibitors of stromelysin-1 (MMP-3)
Chapman, Kevin T.,Durette, Philippe L.,Caldwell, Charles G.,Sperow, Kelly M.,Niedzwiecki, Lisa M.,Harrison, Richard K.,Saphos, Cheryl,Christen, Amy J.,Olszewski, Julie M.,Moore, Vernon L.,MacCoss, Malcolm,Hagmann, William K.
, p. 803 - 806 (2007/10/03)
Further development of N-carboxyalkyl dipeptide inhibitors of stromelysin-1 (MMP-3) led to the discovery of C-carboxyalkyl dipeptide analogs with improved oral bioavailability. An in vivo assay of human MMP-3 mediated degradation of a macromolecular substrate in an extravascular space is described and inhibition studies are reported.
