Reference

An improved synthesis of 2-methyl-4-(2'-carboxyethyl)pyrrole

An improved synthesis of 2-methyl-4-(2'-carboxyethyl)pyrrole. Potential inhibitors of porphobilinogen deaminase. Wilen, Samuel H.; Shen, DeKang; Licata, Joseph M.; Baldwin, Enoch; Russell, Charlotte S. (City Coll., City Univ. New York, New York, NY 10031, USA). Heterocycles, 22(8), 1747-57 (English) 1984. CODEN: HTCYAM. 14794-31-1 is just another one chemical used in this study. ISSN: 0385-5414. DOCUMENT TYPE: Journal CA Section: 27 (Heterocyclic Compounds (One Hetero Atom)) Section cross-reference(s): 7 Hydrogenolysis of pyrrole I (R = CO2CH2Ph, R1 = R2 = Et) (II) gave the acids I (R = CO2H, R1 = H, Et; R2 = Et), which were decarboxylated using Cu(OAc)2-quinoline to give I (R = R2 = H, R1 = H, Et). The Et ester was hydrolyzed to form I (R-R2 = H), which was decarboxylated on melting or heating in boiling H2O to give the title pyrrole III in 49% overall yield from II. Condensation of 3-furan- and 3-thiophenecarboxaldehydes with (HO2C)2CH2 gave heterocycles IV (X = O, S; R = CH:CHCO2H), which gave IV (X = O, S; R = CH2CH2CO2H) on redn. At 50 mM, IV (X = O, S; R = CH:CHCO2H, CH2CH2CO2H) inhibited ~0 to 44% of the activity of 164 mM porphobilinogen deaminase (V), whereas III inhibited 57% of the activity of 69 mM V at 56 mM. Other carboxylic acids were generally less effective. .

Design, Synthesis, and Biological Evaluation of Novel Potent and Selective avb3/avb5 Integrin Dual Inhibitors with Improved Bioavailability

Design, Synthesis, and Biological Evaluation of Novel Potent and Selective avb3/avb5 Integrin Dual Inhibitors with Improved Bioavailability. Selection of the Molecular Core. Marugan, Juan Jose; Manthey, Carl; Anaclerio, Beth; Lafrance, Lou; Lu, Tianbao; Markotan, Tom; Leonard, Kristi A.; Crysler, Carl; Eisennagel, Stephen; Dasgupta, Malini; Tomczuk, Bruce (Johnson and Johnson Pharmaceutical Research & Development, L.L.C., Exton, IA 19341, USA). Journal of Medicinal Chemistry, 48(4), 926-934 (English) 2005 American Chemical Society. CODEN: JMCMAR. ISSN: 0022-2623. DOCUMENT TYPE: Journal CA Section: 27 (Heterocyclic Compounds (One Hetero Atom)) Section cross-reference(s): 1 A novel series of potent and selective avb3/avb5 dual inhibitors was designed, synthesized, and evaluated against several integrins. These compds. were synthesized through a Mitsunobu reaction between the guanidinium mimetics and the corresponding central templates. Guanidinium mimetics with enhanced rigidity [i.e., [(2-pyridinyl)amino]propoxy vs. the 2-(6-methylamino-2-pyridinyl)ethoxy] led to improved activity toward avb3. 14794-31-1 is also in the experiment. Exemplary oral bioavailability in mice was achieved using the indole central scaffold. Although, oral bioavailability was maintained when the indole mol. core was replaced with the bioisosteric benzofuran or benzothiophene ring systems, it was found to not significantly impact the integrin activity or selectivity. However, the indole series displayed the best in vivo pharmacokinetic properties. Thus, the indole series was selected for further structure-activity relationships to obtain more potent avb3/avb5 dual antagonist with improved oral bioavailability. The compds. thus prepd. and studied included 5-[3-(2-pyridinylamino)propoxy]-1H-indole-1-propanoic acid (I), 5-[2-[6-(methylamino)-2-pyridinyl]ethoxy]-1H-indole-1-propanoic acid, 6-[2-[6-(methylamino)-2-pyridinyl]ethoxy]benzo[b]thiophene-3-propanoic acid (II), and 6-[2-[6-(methylamino)-2-pyridinyl]ethoxy]-3-benzofuranpropanoic acid (III). .