195053-89-5Relevant articles and documents
3,4,5-TRISUBSTITUTED-1,2,4-TRIAZOLES AND 3,4,5-TRISUBSTITUTED-3-THIO-1,2,4-TRIAZOLES AND USES THEREOF
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, (2018/12/02)
The present disclosure describes novel compounds that are somatostatin receptor type 4 agonists.
DOUBLE-ACYLATED GLP-1 DERIVATIVES
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, (2016/07/27)
The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 37 of GLP-1 (7-37) (SEQ ID NO: 1), a second K residue at a position corresponding to position 26 of GLP-1 (7-37), and a maximum of ten amino acid modifications as compared to GLP-1 (7-37), wherein the first K residue is designated K37, and the second K residue is designated K26, which derivative comprises two albumin binding moieties attached to K26 and K37, respectively, wherein the albumin binding moiety comprises a protracting moiety selected from: ????????Chem. 1:?????HOOC-(CH2)x-CO-* ????????Chem. 2:?????HOOC-C6H4-O-(CH2)y-CO-* ????????Chem. 3:?????R1-C6H4-(CH2)z-CO-* ????????Chem. 4:?????HOOC-C4SH2-(CH2)w-CO-* in which x is an integer in the range of 6-18, y is an integer in the range of 3-17, z is an integer in the range of 1-5, R1 is a group having a molar mass not higher than 150 Da, and w is an integer in the range of 6-18; with the proviso that when the protracting moiety is Chem. 1, the albumin binding moiety further comprises a linker of formula Chem. 5: *-NH-(CH2)2-(O-(CH2)2)k-O-(CH2)n-CO-*, wherein k is an integer in the range of 1-5, and n is an integer in the range of 1-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptides and side chain intermediates. The derivatives are suitable for oral administration.
Synthesis and structure-activity relationships of cyanoguanidine-type and structurally related histamine H4 receptor agonists
Igel, Patrick,Geyer, Roland,Strasser, Andrea,Dove, Stefan,Seifert, Roland,Buschauer, Armin
supporting information; experimental part, p. 6297 - 6313 (2010/03/24)
Recently, we identified high-affinity human histamine H3 (hH3R) and H4 receptor (hH4R) ligands among a series of NG-acylated imidazolylpropylguanidines, which were originally designed as histamine H2 receptor (H2R) agonists. Aiming at selectivity for hH4R, the acylguanidine group was replaced with related moieties. Within a series of cyanoguanidines, 2-cyano-1-[4-(1H-imidazol-4-yl)butyl]-3-[(2-phenylthio)ethyl]guanidine (UR-PI376, 67) was identified as the most potent hH4R agonist (pEC50=7.47, α=0.93) showing negligible hH1R and hH2R activities and significant selectivity over the hH3R (pKB=6.00, α=-0.28), as determined in steady-state GTPase assays using membrane preparations of hHxR-expressing Sf9 cells. In contrast to previously described selective H4R agonists, this compound and other 3-substituted derivatives are devoid of agonistic activity at the other HR subtypes. Modeling of the binding mode of 67 suggests that the cyanoguanidine moiety forms chargeassisted hydrogen bonds not only with the conserved Asp-94 but also with the hH4R-specific Arg-341 residue. 2-Carbamoyl-1-[2-(1H-imidazol-4-yl)ethyl]-3-(3-phenylpropyl)guanidine (UR-PI97, 88) was unexpectedly identified as a highly potent and selective hH3R inverse agonist (pKB=8.42, >300-fold selectivity over the other HR subtypes). 2009 American Chemical Society.
