Palladium(0)‐catalyzed phenylation of imidazo[4,5‐<i>b</i>]pyridines

Grivas, Spiros; Lindström, Stefan B.

doi:10.1002/jhet.5570320214

Cited by 22 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Briefly, 5-bromo 2,3-diaminopyridine 2 was treated with benzyl chloroformate to give benzyl carbamate 3 . 29 The urethane was reduced to a methyl group with lithium aluminum hydride and the diamine was cyclized to the urea 5 , utilizing triphosgene. 30 Palladium mediated coupling reactions of 5 were accomplished efficiently when the acidic urea NH was protected with a trityl group as in 6 .…”

Section: Resultsmentioning

confidence: 99%

Structure Guided Development of Novel Thymidine Mimetics Targeting Pseudomonas aeruginosa Thymidylate Kinase: From Hit to Lead Generation

Choi

Plummer²,

Starr³

et al. 2012

J. Med. Chem.

View full text Add to dashboard Cite

Thymidylate kinase (TMK) is a potential chemotherapeutic target because it is directly involved in the synthesis of an essential component, thymidine triphosphate, in DNA replication. All reported TMK inhibitors are thymidine analogs, which might retard their development as potent therapeutics due to cell permeability and off-target activity against human TMK. A small molecule hit (1, IC50 = 58 μM), which has reasonable inhibition potency against Pseudomonas aeruginosa TMK (PaTMK), was identified by the analysis of the binding mode of thymidine or TP5A in a PaTMK homology model. This hit (1) was co-crystallized with PaTMK, and several potent PaTMK inhibitors (leads, 46, 47, 48, and 56, IC50 = 100–200 nM) were synthesized using computer aided design approaches including virtual synthesis/screening, which was used to guide the design of inhibitors. The binding mode of the optimized leads in PaTMK overlaps with that of other bacterial TMKs, but not with human TMK which shares few common features with the bacterial enzymes. Therefore, the optimized TMK inhibitors described here should be useful for the development of antibacterial agents targeting TMK without undesired off-target effects. In addition, an inhibition mechanism associated with the LID loop, which mimics the process of phosphate transfer from ATP to dTMP, was proposed based on X-ray co-crystal structures, homology models, and SAR results.

show abstract

Section: Resultsmentioning

confidence: 99%

Structure Guided Development of Novel Thymidine Mimetics Targeting Pseudomonas aeruginosa Thymidylate Kinase: From Hit to Lead Generation

Choi

Plummer²,

Starr³

et al. 2012

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…By contrast, the spectra of 2 H 5 -phenyl congener 25 displayed doublets, J = 8. whereas the spectrum of 2-amino-1-methyl-6-bromoimidazo[4,5-b]pyridine, showed doublets at 7.89 (d, J = 1.9 Hz, H-5) and 7.56 (d, J = 1.9 Hz, H-7) [13]. III.…”

Section: % 45%mentioning

confidence: 95%

“…d, J = 6.8 Hz, 2H), 7.66 (dd, J = 7.9, 1.5 Hz, 1H), 7.32 (app. d, J = 7.9 Hz, 2H), 7.19 (dd, J = 7.8, 5.1 Hz, 1H), 3.41 (s, N-CH 3 ), 2.33 (s, CH 3 ); 13 …”

Section: -Amino-5-phenylpyridine (8)mentioning

confidence: 99%

Synthesis and mutagenic potency of structural isomers of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine

Chrisman

Tanga

Knize

2008

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

1-Me-5-Ph-IP97 ± 7.30 TA 98 revertant counts/μg CH 3 N N N NH 2 CH 3Synthesis of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), three structural isomers, and two desphenyl PhIP congeners has been carried out. Mutagenic potency was evaluated using S. typhimurium strain TA98 in the Ames test. Mutagenic potency increased in relation to structural features in these heterocyclic amines that allow extended resonance between the phenyl and imidazo [4,5-b]pyridine N 2 -amino substituents. By contrast, PhIP isomers, whose substitution disallows involvement of the phenyl group in their aminoimidazo resonance hybrids, and desphenyl congeners were from 86-to 234-fold less mutagenic than PhIP.

show abstract

“…After introduction of ZnCl 2 , cross-coupling with 4-iodotoluene was optimized. [27] Scheme 5. Successful C-Cbond formation was highly dependent on substituents on the applied halide (R = 2-NO 2 , 2-OCOCH 3 In a study on the preparation of 4-arylated phenylalanines, chlorine in the 2-position of 13 was found to be a suitable leaving group, and good yields were obtained for this transformation under microwave irradiation (Scheme 5).…”

Section: Negishi Reactionmentioning

confidence: 99%

Cross‐Coupling Reactions on Azoles with Two and More Heteroatoms

et al. 2006

View full text Add to dashboard Cite

Recent progress in the field of transition‐metal‐catalyzed cross‐coupling reactions on various azole systems is summarized. Most important C–C‐ and C–X‐bond formation methodologies (Negishi, Suzuki–Miyaura, Stille, Kumada–Corriu–Tamao, Hiyama, Sonogashira, Heck, C–H activation) are reviewed and discussed for the imidazole, oxazole, thiazole, pyrazole, isoxazole, and isothiazole system, as well as for azoles with more than two heteroatoms. This review covers the literature that appeared in the past ten years up to the end of 2005 with corresponding azoles used either as metal organyl or halide (including triflates and some other less frequently applied leaving groups); literature describing azole structures only as ligands was not included.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

show abstract

Palladium(0)‐catalyzed phenylation of imidazo[4,5‐b]pyridines

Cited by 22 publications

References 31 publications

Structure Guided Development of Novel Thymidine Mimetics Targeting Pseudomonas aeruginosa Thymidylate Kinase: From Hit to Lead Generation

Structure Guided Development of Novel Thymidine Mimetics Targeting Pseudomonas aeruginosa Thymidylate Kinase: From Hit to Lead Generation

Synthesis and mutagenic potency of structural isomers of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine

Cross‐Coupling Reactions on Azoles with Two and More Heteroatoms

Contact Info

Product

Resources

About