On December 13, 2007, Arnould, Jean-Claude; Delouvrie, Benedicte; Ducray, Richard; Lambert-Van Der Brempt, Christine Marie Paul published a patent.COA of Formula: C15H22N2O3 The title of the patent was Preparation of tyrosine derivatives, especially N-(benzoyl)-O-[2-[(pyridin-2-yl)amino]ethyl]-L-tyrosines and related compounds, as α5β1 integrin antagonists for treating solid tumors. And the patent contained the following:
The invention is related to tyrosine derivatives I [Xa = O, S; R1 = Br, Cl, cyclopentylmethyl, C1-3 alkyl, etc.; R2, each R3 = independently H, halo, CN, OH, NH2, (un)substituted alk(en/yn)yl, alkanoylamino, N-alkylsulfamoyl, etc.; or R2R3 = C1-3 alkylenedioxy; m = 0-3; R4 = H, (un)substituted heterocyclyl, heteroaryl, etc.; A = Ph, pyridinyl, thiophenyl; n = 0-4; each R5 = independently halo, OH, SH, carbamoyl, sulfamoyl, alkylsulfonyl, alkynoylamino, etc.; or 2 R5’s optionally form a C1-3 alkylenedioxy; X = a bond, O, S, SO, SO2, CO, (un)substituted CH:CH, etc.; Y = (un)substituted alkylene, cycloalk(en)ylene, heterocyclyl; Z = a bond, O, S, (un)substituted alkylene, CC, etc.;] and their pharmaceutically acceptable salts and prodrugs, to processes for preparing them, and to pharmaceutical compositions containing them for use as α5β1 integrin antagonists in the treatment in warm-blooded animals such as humans of diseases that have a significant angiogenesis or vascular component such as for treatment of solid tumors. The invention is also related to α5β1 antagonists that also exhibit appropriate selectivity profile(s) against other integrins. Thus, etherification of tert-Bu 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate with Me N-(2,6-dichlorobenzoyl)-L-tyrosinate (preparation given), cleavage of the tert-butoxycarbonyl group and saponification of the Me ester gave tyrosine derivative II. The effects of compounds I as α5β1 integrin inhibitors were tested (e.g., the invention compound II had IC50 values of 0.0004 μM in a binding assay and 0.002 μM in an adhesion assay). The experimental process involved the reaction of tert-Butyl 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate(cas: 445490-78-8).COA of Formula: C15H22N2O3
The Article related to tyrosine preparation alpha5beta1 integrin antagonist solid tumor, antitumor benzoyl pyridinylaminoethyl tyrosine derivative preparation alpha5beta1 integrin antagonist, Amino Acids, Peptides, and Proteins: Amino Acids and other aspects.COA of Formula: C15H22N2O3
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem