On May 17, 2018, Zhao, Guohua; Devasthale, Pratik; Ye, Xiang-Yang; Selvakumar, Kumaravel; Dhanusu, Suresh; Balasubramanian, Palanikumar; Guernon, Leatte R.; Civiello, Rita; Han, Xiaojun; Parker, Michael F.; Jacutin-Porte, Swanee E. published a patent.Synthetic Route of 445490-78-8 The title of the patent was 3-Substituted propanoic acids as alpha V integrin inhibitors and their preparation. And the patent contained the following:
The invention provides compounds of formula I or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αV-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αV-containing integrins, such as pathol. fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions Compounds of formula I wherein A, E and G are independently N, O, S, NH and derivatives, CHR6b and CR6b; M and L are N and C, with the proviso that M and L are not both N; Z is (un)substituted C1-6 alkylene; Z is a bond, O, S, NH, (un)substituted O-C1-3 alkylene, etc.; R1 is guanidino, (un)substituted imidazolylamino, (un)substituted pyridinylamino, (un)substituted benzimidazolyl, etc.; R2 is H and C1-6 alkyl; R3 is H, C1-6 alkyl, C3-10 carbocyclyl, C6-10 aryl, etc.; R2R3 an be taken together to form and (un)substituted carbocyclyl and heterocyclyl; R4 is H, C1-10 alkyl, C3-10 carbocyclyl, 3- to 10-membered heterocyclyl, R5 is H, (un)substituted C1-6 alkyl, (un)substituted Ph, (un)substituted benzyl, etc.; R6b is H, halo, CN, NO2, OH, etc.; and pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by a multistep procedure (procedure given). The invention compounds were evaluated for their αV integrin inhibitory activity. From the assay, it was determined that compound II exhibited IC50 value of 50 nM, 2.4 nM, 1.5 nM and 262 nM towards αVβ6, αVβ3, αVβ5 and αVβ8, resp. 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).Synthetic Route of 445490-78-8
The Article related to substituted propanoic acid preparation alpha v integrin inhibitor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazoles and other aspects.Synthetic Route of 445490-78-8
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem