Pyrimidines pyrrolo

Wilson MB, Schreiner SJ, Choi HJ et al. Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for SRC family kinases in BCR-ABL signal transduction and oncogenesis. Oncogene 2002 21 8075-8088. 

In a detailed study of a pyrrolo-pyrimidine, BW 58-271 (VI), Norton and Jewett found that the compound was a potent hypnotic agent (three times as active as hexobarbital). It also had local anesthetic and hypotensive activity. Its most unusual effect was sudden suppression of the EEC in conscious cats lasting for several minutes after intravenous injection. 

Interesting constructs of molecules such as pyrrolo-pyridines, pyrrolo-quinolines, pyrrolo-pyrazines, pyrrolo-quinoxalines and pyrrolo-pyrimidines could be constructed by intramolecular Chichibain-type reaction. Davis and co-workers were the first to show the first of these examples, where p-methylazines react with nitriles to give the corresponding fused bicycle in the presence of excess base (2.5 equiv). For example, P-picoline reacts with benzonitrile in the presence of LDA to give the pyrrolo-pyridine adduct 61 in a 90% yield and traces of 62a. Under similar conditions and if... 

Ibbercidin Streptomyces tubercidicus 4-Amino-7-pyrrolo- pyrimidine Ribose Adenosine... 

Lauria A, Diana P, Barraja P, Montalbano A, Dattolo G, Cirrincione G (2004) Docking of indolo- and pyrrolo-pyrimidines to DNA. New DNA-interactive polycycles from amino-indoles/pyrroles and BMMA. ARKIVOC 5(2) 263-271... 

An interesting case study by Pfizer on pyrrolo-pyrimidine-based HSP-90 inhibitors illustrates the need for careful selection of the position on a ligand and the functional group deployed to displace conserved water molecules eloquently (Figures 13.13 and 13.14). 

Davies, L.P., Jamieson, D.D., Baird-Lambert, J.A., and Kazlauskas, R. (1984) Halogenated pyrrolo-pyrimidine analogues of adenosine from marine organisms, pharmacological activities and potent inhibition of adenosine kinase. Biochem. Pharmacol, 33, 347-355. 

Most recendy the stmcture of pyrrolosine has been shown to be an isomeric C-nucleoside analogue of 9-dea2ainosine, which is 7-(P-D-ribofuranosyl)-4-oxo-3Ff,5E -pyrrolo[3-2-i/ pyrimidine (29). Pyrrolosine inhibits development of starfish embryos. 

Pyrrolo[2,3-d]pyrimidine, 5-cyano-bromination, 4, 506 Pyrrolo[2,3-d]pyrimidine, 5-nitroso-nucleophilic reactions, 4, 507 Pyrrolo[l, 2- c]pyrimidine-3-carboxylic acids methyl ester synthesis, 4, 293 Pyrrolopyrimidine-2,4-diones Mannich reaction, 4, 504 Vilsmeier reaction, 4, 505 Pyrrolopyrimidines synthesis, 4, 514, 517, 524, 527 Pyrrolopyrimidines, chloro-nucleophilic attack, S, 312 Pyrrolo[2,3-d]pyrimidines NMR, 4, 500... 

H-Pyrrolo[3,2-d]pyrimidines synthesis, 3, 345 Pyrrolo[3,4-d]pyrimidines synthesis, 4, 524 Pyrrolopyrimidinones synthesis, 4, 518... 

In addition, Namazi and coworkers expanded the DHPM core by constructing pyrrolo[3,4-rf pyrimidines via the classical approach. First, DHPM 59 was delivered in 60% yield using the standard Biginelli conditions. 59 was then brominated in high yield to afford 60. Substitution of bromide 60 with methylamine followed by cyclization of the intermediate amino ester furnished pyrrolo[3,4-rf pyrimidine 61 in 53% yield. 

Intramolecular cycloadditions of 4/f-pyrido[l,2-n]pyrimidin-4-ones 235 (R = H, Me Ph) and MeNHOH HCl gave tetracyclic isoxazolo derivatives 237. In the case of 235 (R = Me) a minor epimer 238 was also isolated (00JCR(S)414). Similar reaction of 235 (R = H, Me, Ph) and sarcosine ethyl ester HCl afforded an isomeric mixture of epimeric tetracyclic pyrrolo derivatives 239 and 240. In the reaction of 235 (R = H) and PhCHjNHCHjCOOEt only one product 241 was obtained. 

The structures of pyrrolo[l,2-c]pyrimidine 139 and its N-protonated form 140 were obtained from MP2/6-31G calculations (Scheme 92) [99JOC7788]. Proton affinities computed at the same level reveal that N-protonation is slightly preferred over protonation at the C7 position. The most stable tautomers of 2-substituted 5-methyl-7-hydroxy-l,2,4-tiiazolo[l,5-a]pyrimidine 141 were... 

It was known that the K+ -competitive imidazopyridine compound, SCH28080, inhibits acid secretion. Then, many reversible inhibitors were developed. These contain protonatable nitrogens but have a variety of core structures such as imidazopyiidines, piperidinopyr-idines, substituted 4-phenylaminoquinolines, pyrrolo [3,2-c]quinolines, guanidinothiazoles, and 2,4-diamino-pyrimidine derivatives. Several reversible inhibitors have been in clinical trials. 

Besides furo[2,3-d]pyrimidines, 6-substituted 5H-pyrrolo[2,3-h]pyrazines have also been obtained in a microwave-promoted one-pot process starting from N-mesyl protected 2-amino-3-chloropyrazine (Scheme 60) [74]. The... 

The hydrazine 70 reacts with triethyl orthoformate, sodium nitrite in acetic acid, or pyruvic acid, to yield l,2,4-triazolo[4,3-c]-, tetrazolo[l,5-c]- and l,2,4-triazino[5,6-c]pyrano [4 ,3 4,5]pyrrolo[3,2-e]pyrimidine derivatives 71(X= CH), 71(X= N) and 72 respectively <95KGS700 96CA(124)176023>. 

---