51043-75-5Relevant academic research and scientific papers
ARYL ANNULATED MACROCYCLIC INDOLE DERIVATIVES
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Page/Page column 168-169, (2019/06/05)
The present invention relates to aryl annulated macrocyclic indole derivatives of general formula (I): in which R1, R2, R3, R4, R5, R6, A and L are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.
Synthesis and structure-activity relationships of 5,6,7,8-tetrahydropyrido[3,4-b]pyrazine-based hydroxamic acids as HB-EGF shedding inhibitors
Yoshiizumi, Kazuya,Yamamoto, Minoru,Miyasaka, Tomohiro,Ito, Yasuko,Kumihara, Hiroshi,Sawa, Masaaki,Kiyoi, Takao,Yamamoto, Takeshi,Nakajima, Fumio,Hirayama, Ryoichi,Kondo, Hirosato,Ishibushi, Etsuko,Ohmoto, Hiroshi,Inoue, Yoshimasa,Yoshino, Kohichiro
, p. 433 - 450 (2007/10/03)
HB-EGF Shedding inhibitors have been expected to become effective medicines for skin diseases caused by the proliferation of keratinocytes. In order to discover novel HB-EGF shedding inhibitors and clarify their structure-activity relationships, 5,6,7,8-tetrahydronaphthylidine-based hydroxamic acid and 5,6,7,8-tetrahydropyrido[3,4-b]pyrazine-based hydroxamic acids have been synthesized. Among the synthesized compounds, the ethoxyethoxy derivative 3o and the methoxypropoxy derivative 3p exhibited much more potent HB-EGF shedding inhibitory activity than CGS 27023A. The structural modification of 5,6,7,8-tetrahydropyrido[3,4-b]pyrazine-based hydroxamic acids enabled us to establish the following structure-activity relationships; the existences of the hydroxamic acid, the sulfonamide, and the phenyl moieties are crucial for a potent HB-EGF shedding inhibitory activity, and the stereochemistry of the alpha carbon of hydroxamic acid is also important. In addition, from the comparison of their HB-EGF shedding inhibitory activities with their MMPs inhibitory activities, we found that the S1′ pocket of the responsible enzyme for HB-EGF shedding is deep unlike that of MMP-1.
Keratinocyte growth inhibitors and hydroxamic acid derivatives
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Page 20, (2010/02/06)
This invention relates to a keratinocyte-proliferation inhibitor comprising as active ingredient a compound having an activity of inhibiting the solubilization of heparin-binding EGF-like growth factor bound to cell membranes and a compound of the formula (I); or pharmaceutically acceptable salt thereof, wherein R1, R2, R3 are hydrogen atom or alkyl and X is substituted benzene or the like.
Design of low molecular weight hematoregulatory agents from the structure-activity relationship of a dimeric pentapeptide
Cuthbertson, Alan S.,Husbyn, Mette,Engebretsen, May,Hartmann, Michael,Lange, Meinolf,Sandosham, Jessie,Fischer, Peter M.,Fjerdingstad, Hege,L?vhaug, Dagfinn
, p. 2876 - 2882 (2007/10/03)
We report herein, a new class of simple hematoregulatory semipeptides, formally derived from the cystine-dimerized peptide pGlu-Glu-Asp-Cys-Lys-OH, where the disulfide bond has been replaced by an isosteric dicarba bridge. The structure-activity relationship (SAR) of a series of analogues incorporating replacements at positions 1 and 2 of peptide 1 led to the design of active conformationally constrained cyclic peptides (12, 13). Ring closure was achieved by cyclization of the N-terminal amino groups at position 2 of peptide 2 using pyrazine-2,3-dicarboxylic acid. Subsequent excision of the putative C-terminal scaffold domain from the active cyclic peptides resulted in the discovery of a new class of low molecular weight hematoregulatory agents exemplified by compound 16. This semipeptide analogue, comprising two D-Ser residues connected via amide bonds to the acid groups of pyrazine-2,3-dicarboxylic acid, had comparable biological activity to the lead peptide 1. The stereochemical requirements for the observed biological activity of these novel compounds were examined. Furthermore, the hematopoietic synergistic activity induced by compound 16 in stromal cell cultures was blocked by an antibody known to neutralize the hematoregulatory effect of 1, indicating a common mechanistic end point. Compounds of the class typified by 16 may form the basis for the development of novel therapeutic agents within the area of immunoregulation.
PHARMACOLOGICALLY ACTIVE GUANIDINE COMPOUNDS
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, (2008/06/13)
The compounds are substituted thioalkyl-, aminoalkyl-and oxyalkyl-guanidines which are inhibitors of histamine activity.
PHARMACOLOGICALLY ACTIVE THIOUREA AND UREA COMPOUNDS
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, (2008/06/13)
The compounds are substituted thioalkyl-, aminoalkyl-and oxyalkyl-thioureas and ureas which are inhibitors of histamine activity.
