33229-08-2Relevant academic research and scientific papers
Discovery of Novel 1-Cyclopentenyl-3-phenylureas as Selective, Brain Penetrant, and Orally Bioavailable CXCR2 Antagonists
Lu, Hongfu,Yang, Ting,Xu, Zhongmiao,Lin, Xichen,Ding, Qian,Zhang, Yueting,Cai, Xin,Dong, Kelly,Gong, Sophie,Zhang, Wei,Patel, Metul,Copley, Royston C. B.,Xiang, Jianing,Guan, Xiaoming,Wren, Paul,Ren, Feng
supporting information, p. 2518 - 2532 (2018/03/26)
CXCR2 has emerged as a therapeutic target for not only peripheral inflammatory diseases but also neurological abnormalities in the central nervous system (CNS). Herein, we describe the discovery of a novel 1-cyclopentenyl-3-phenylurea series as potent and CNS penetrant CXCR2 antagonists. Extensive SAR studies, wherein molecules' property forecast index (PFI) was carefully optimized for overall balanced developability profiles, led to the discovery of the advanced lead compound 68 with a desirable PFI. Compound 68 demonstrated good in vitro pharmacology with excellent selectivity over CXCR1 and other chemokine receptors. Rat and dog pharmacokinetics (PK) revealed good oral bioavailability, high oral exposure, and desirable elimination half-life of the compound in both species. In addition, the compound demonstrated dose-dependent efficacy in the in vivo pharmacology neutrophil infiltration "air pouch" model in rodents after oral administration. Further, compound 68 is a CNS penetrant molecule with high unbound fraction in brain tissue.
Synthesis of enantiopure (R,R)- and (S,S)-cis-2,3-propanoprolines
Kopylova, Natalia A.,Grygorenko, Oleksandr O.,Komarov, Igor V.,Groth, Ulrich
scheme or table, p. 2868 - 2871 (2011/03/19)
A novel approach to the synthesis of an enantiopure bicyclic proline analogue, hexahydrocyclopenta[b]pyrrole-6a(1H)-carboxylic acid ('2,3-propanoproline'), has been developed. The method relied on tandem Strecker-nucleophilic cyclization reaction of 2-(2-
Cathodic cyclisation of N-(oxoalkyl)pyridinium salts - Formation of tricyclic indolizidine and quinolizidine derivatives in aqueous medium
Heimann, Jens,Schaefer, Hans J.,Froehlich, Roland,Wibbeling, Birgit
, p. 2919 - 2932 (2007/10/03)
The cathodic cyclisation of N-(oxoalkyl)pyridinium salts, derived from 4-methylpyridine and cyclic ketones, afforded functionalised tricyclic indolizidine and quinolizidine derivatives in high yields. Through systematic variation of the ring size of the k
SYNTHESIS OF (+/-)-11-DEOXYPROSTAGLANDIN-E1
Dombrovskii, V. A.,Fonskii, D. Yu.,Filippova, T. M.,Mironov, V. A.
, p. 1471 - 1480 (2007/10/02)
A new method was developed for the alkylation of 2-methoxycarbonylcyclopentanone and 2,3-diethoxycarbonylcyclopentanone with α,ω-dibromoalkanes, which led to 2-(ω-bromoalkyl)-2-ethoxycarbonylcyclopentanones and 2-(ω-bromoalkyl)-2,3-diethoxycarbonylcyclopentanones, i.e., key synthons for the production of 11-deoxyprostaglandins.A new scheme for the synthesis of (+/-)-11-deoxyprostaglandin-E1 from 2-(6-bromohexyl)-2,3-diethoxycarbonylcyclopentanone in seven stages was realized.
Synthons for Syntheses of Spiroheptane Analogues of Prostaglandins
Jarowicki, Krzysztof,Jaworski, Tadeusz
, p. 605 - 612 (2007/10/02)
Methods for the preparation of synthons for syntheses of spiroheptane analogues of prostaglandins are described.Two of them (1a and 1b) enable the syntheses of 11-deoxy-type compounds and were prepared from spiroheptan-4-one (3) which after transformation into the 5-phenylthio-α, β-unsaturated ketone 5 was subjected to conjugate addition of organocuprate reagent 6.The third synthon (2) - a potential intermediate in syntheses of complete spiroheptane analogues of prostaglandins-was prepared from the bicyclic ketone 10 by Baeyer-Villiger oxidation follo wed by epoxidation. - Keywords: Prostaglandin analogues; Spiroheptan-4-ones; 2H-Cyclopentafuran-2-ones; Desulfurization; Conjugate addition of cuprate
