104629-86-9Relevant articles and documents
4H- [1, 2, 4] TRIAZOLO [5, 1 -B] PYRIMIDIN-7 -ONE DERIVATIVES AS CCR2B RECEPTOR ANTAGONISTS
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Page/Page column 93, (2011/10/10)
The present invention relates to novel compounds for use in the compositions, to processes for their preparation, to intermediates useful in their preparation and to their use as therapeutic agents. The present invention also relates to pharmaceutical com
Novel isoxazole carboxamides as growth hormone secretagogue receptor (GHS-R) antagonists
Liu, Bo,Liu, Gang,Xin, Zhili,Serby, Micheal D.,Zhao, Hongyu,Schaefer, Verlyn G.,Falls, H. Douglas,Kaszubska, Wiweka,Collins, Christine A.,Sham, Hing L.
, p. 5223 - 5226 (2007/10/03)
Novel isoxazole carboxamides have been identified as growth hormone secretagogue receptor (GHS-R) antagonists. Substituent modification off the 5-position of the isoxazole ring led to analogues with potent binding affinity and functional antagonism of GHS-R. A potent analogue (32) with high aqueous solubility and good GPCR selectivity was also identified as a potential pharmacological tool for in vivo studies.
Discovery of a series of pyrrolidine-based endothelin receptor antagonists with enhanced ET(A) receptor selectivity
Boyd, Steven A.,Mantei, Robert A.,Tasker, Andrew S.,Liu, Gang,Sorensen, Bryan K.,Henry Jr., Kenneth J.,Von Geldern, Thomas W.,Winn, Martin,Wu-Wong, Jinshyun R.,Chiou, William J.,Dixon, Douglas B.,Hutchins, Charles W.,Marsh, Kennan C.,Nguyen, Bach,Opgenorth, Terry J.
, p. 991 - 1002 (2007/10/03)
Endothelins, ET-1, ET-2, and ET-3 are potent vasoconstricting and mitogenic 21-amino acid bicyclic peptides, which exert their effects upon binding to the ET(A) and ET(B) receptors. The ET(A) receptor mediates vasoconstriction and smooth muscle cell proliferation, and the ET(B) receptor mediates different effects in different tissues, including nitric oxide release from endothelial cells, and vasoconstriction in certain vascular cell types. Selective antagonists of endothelin receptor subtypes may prove useful in determining the role of endothelin in various tissue types and disease states, and hence as therapeutic agents for such diseases. The pyrrolidine carboxylic acid A-127722 has been disclosed as a potent and ET(A)-selective antagonist, and is currently undergoing clinical trials. In our efforts to find antagonists with altered selectivity (ET(A)-selective, ET(B)-selective, or nonselective), we investigated the SAR of the 2-substituent on the pyrrolidine. Compounds with alkyl groups at the 2-position possessed ET(A) selectivity improved over A-127722 (1400-fold selective), with the best of these compounds showing nearly 19,000-fold selectivity. Copyright (C) 1999 Elsevier Science Ltd.
Photodynamic antitumor agents: β-Methoxyethyl groups give access to functionalized porphycenes and enhance cellular uptake and activity
Richert,Wessels,Muller,Kisters,Benninghaus,Goetz
, p. 2797 - 2807 (2007/10/02)
Porphycene photosensitizers bearing two or four methoxyethyl side chains were synthesized in nine steps from commercially available starting materials. Ether cleavage led to (hydroxy-ethyl)- and (bromoethyl)porphycenes that were converted to vinyl and benzo derivatives. Five of the side chain- functionalized porphycenes were biologically studied in comparison with two tetra-n-propylporphycenes. Porphycenes were incorporated in small unilamellar liposomes and incubated with cultivated SSK2 murine fibrosarcoma cells. Cellular uptake and phototoxicity 24 h after 5 J/cm2 laser light treatment were determined. The porphycenes tested were between 17 and 220 times more photodynamically active than the currently clinically used sensitizer Photofrin, although extinction coefficients of the porphycenes' irradiated bands are only approximately 10-fold higher. The LD50 concentration for SSK2 cells in the incubation medium was as low as (8.5 ± 2.8) x 10-9 M for tetrakis(methoxyethyl)porphycene. Two methoxy or hydroxy groups enhanced cellular uptake, three or four methoxy groups both enhanced and accelerated cellular uptake of tetraalkylporphycenes. Half-life times of the uptake processes varied between (0.14 ± 0.04) and (14 ± 4) h and cellular saturation levels between (1.2 ± 0.2) and (26 ± 3) pmol/105 cells. When individual uptake rates were accounted for, all porphycenes had a similar 'cellular' phototoxicity, pointing toward a common mechanism of action. Evidence is presented for the assumption that cell membranes are the primary targets of the tested porphycenes and that membrane solubility may play a critical role in their photodynamic efficiency. The results show that nonionic polar side chain functionalities can strongly enhance cellular uptake and antitumor activity of lipophilic porphyrinoids and thus that the known lipophilicity/activity relationship can be reversed for very hydrophobic sensitizers.
Porphycene compounds for photodynamic therapy
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, (2008/06/13)
A porphycene having the structure STR1 wherein each R1 is, independently, (a) --(CH2)n --X, where n=1-4, X is OR2 and R2 is C1-6 alkyl, aralkyl or aryl; CN; OH; OSO2 R2 ; NH2 ; NHR2 ; NR22 ; SH; SR2 ; S(O)1-2 R2 ; COOH; CO2 R2 ; C(O)NH2 ; C(O)NHR2 ; C(O)NR22 ; halogen; or CHO; (b) --(CH2)m CH=CH2 where m is 0-2; or (c) --(CH2)n --O--G where G is a mono- or oligosaccharide; (d) --(CH2)2n --X, where X is an amino acid, oligopeptide covalently bonded by an ether-, ester- or amine-bond or --Y--(CH2)n -porphycene2 (porphycene2 being a compound of the same structure and Y is a direct bond; --O--; or --CH=CH2); or (e) where one, two or three of the substituents R1 are C1-6 alkyl or aryl and the remaining substituents are as above under (a)-(d), and salts and metal complexes thereof. The porphycene compounds and pharmaceutical compositions containing the compounds are useful in photodynamic therapy treatment of tumors and psoriasis.
