77292-91-2Relevant articles and documents
Structure-activity relationship studies of 5-benzylaminoimidazo[1,2-c]pyrimidine-8-carboxamide derivatives as potent, highly selective ZAP-70 kinase inhibitors
Hirabayashi, Akihito,Mukaiyama, Harunobu,Kobayashi, Hiroaki,Shiohara, Hiroaki,Nakayama, Satoko,Ozawa, Motoyasu,Miyazawa, Keiji,Misawa, Keiko,Ohnota, Hideki,Isaji, Masayuki
experimental part, p. 284 - 294 (2011/02/28)
Zeta-associated protein, 70 kDa (ZAP-70), a spleen tyrosine kinase (Syk) family kinase, is normally expressed on T cells and natural killer cells and plays a crucial role in activation of the T cell immunoresponse. Thus, selective ZAP-70 inhibitors might
Small peptides containing phosphotyrosine and adjacent αMe- phosphotyrosine or its mimetics as highly potent inhibitors of Grb2 SH2 domain
Liu, Wang-Qing,Vidal, Michel,Gresh, Nohad,Roques, Bernard P.,Garbay, Christiane
, p. 3737 - 3741 (2007/10/03)
A series of small peptides with the sequence mAZ-pTyr-Xaa-Asn-NH2, where Xaa denotes α-methylphosphotyrosine or its carboxylic mimetics, were synthesized as inhibitors of the Grb2 SH2 domain. Peptide 3 with (α-Me)pTyr as Xaa has the highest aff
Carboxylic Acids and Tetrazoles as Isosteric Replacements for Sulfate in Cholecystokinin Analogues
Tilley, Jefferson W.,Danho, Waleed,Lovey, Kathleen,Wagner, Rolf,Swistok, Joseph,et al.
, p. 1125 - 1136 (2007/10/02)
A series of analogues of the satiely-inducing peptide cholecystokinin (CCK-8) was prepared in which the sulfated tyrosine required for activation of peripheral receptors was replaced with a carboxy(alkyl)- or tetrazolyl(alkyl)-phenylalanine to investigate whether an organic acid could serve the role of the sulfate group at the receptor.The necessary intermediates were prepared by previously reported procedures or by alkylation of carboxy(alkyl)- or tetrazolyl(alkyl)phenylmethyl bromides with a glycine-derived anion followed by protecting-group manipulations, and these were incorporated into derivatives of acetyl-CCK-7 using solid-phase synthesis.Peptide analogues were evaluated in a CCK-binding assay for affinity for either peripheral (CCK-B) receptors using homogenated rat pancreatic membranes as the receptor source or for central (CCK-B) receptors using bovine striatum as the receptor source.They were further evaluated for effects on food intake in rats after intraperitoneal (ip) injection.A number of the compounds reported are active in the CCK-A receptor binding assay although less potent than acetyl-CCK-7 and decrease food intake with comparable potency to acetyl-CCK-7.In a meal feeding model designed to assess appetite suppressant activity, acetyl-CCK-7 has an ED50 of 7 nmol/kg ip, while the ED50s of Ac-Phe(4-CH2CO2H)-Met-Gly-Trp-Met-Asp-Phe-NH2 (28) and Ac-Phe-Met-Gly-Trp-Met-Asp-Phe-NH2 (34) were 9 and 11 nmol/kg ip, respectively.An analogue of 28 lacking the N-terminal acetamido group, 3-propanoyl-Met-Gly-Trp-Met-Asp-Phe-NH2 (50), was also active in the meal feeding assay with an ED50 of 3 nmol/kg ip.Its anorexic effect was blocked by simultaneous administration of the CCK-A receptor antagonist MK 329, indicating that the observed anorexic activity is mediated by CCK-A receptors.We conclude from this work that the requirement for a negative charge at the CCK-A receptor provided in the natural substrate by a sulfate group can be satisfied by organic acids.
