876-05-1Relevant articles and documents
Synthesis, antiproliferative activity in cancer cells and DNA interaction studies of [Pt(cis-1,3-diaminocycloalkane)Cl2] analogs
Hoeschele, James D.,Kasparkova, Jana,Kostrhunova, Hana,Novakova, Olga,Pracharova, Jitka,Pineau, Paul,Brabec, Viktor
, p. 913 - 924 (2020/09/01)
Abstract: The search for more effective platinum anticancer drugs has led to the design, synthesis, and preclinical testing of hundreds of new platinum complexes. This search resulted in the recognition and subsequent FDA approval of the third-generation Pt(II) anticancer drug, [Pt(1,2-diaminocyclohexane)(oxalate)], oxaliplatin, as an effective agent in treating colorectal and gastrointestinal cancers. Another promising example of the class of anticancer platinum(II) complexes incorporating the Pt(1,n-diaminocycloalkane) moiety is kiteplatin ([Pt(cis-1,4-DACH)Cl2], DACH = diaminocyclohexane). We report here our progress in evaluating the role of the cycloalkyl moiety in these complexes focusing on the synthesis, characterization, evaluation of the antiproliferative activity in tumor cells and studies of the mechanism of action of new [Pt(cis-1,3-diaminocycloalkane)Cl2] complexes wherein the cis-1,3-diaminocycloalkane group contains the cyclobutyl, cyclopentyl, and cyclohexyl moieties. We demonstrate that [Pt(cis-1,3-DACH)Cl2] destroys cancer cells with greater efficacy than the other two investigated 1,3-diamminocycloalkane derivatives, or cisplatin. Moreover, the investigated [Pt(cis-1,3-diaminocycloalkane)Cl2] complexes show selectivity toward tumor cells relative to non-tumorigenic normal cells. We also performed several mechanistic studies in cell-free media focused on understanding some early steps in the mechanism of antitumor activity of bifunctional platinum(II) complexes. Our data indicate that reactivities of the investigated [Pt(cis-1,3-diaminocycloalkane)Cl2] complexes and cisplatin with glutathione and DNA binding do not correlate with antiproliferative activity of these platinum(II) complexes in cancer cells. In contrast, we show that the higher antiproliferative activity in cancer cells of [Pt(cis-1,3-DACH)Cl2] originates from its highest hydrophobicity and most efficient cellular uptake. Graphic abstract: [Figure not available: see fulltext.]
TREK Channel Family Activator with a Well-Defined Structure-Activation Relationship for Pain and Neurogenic Inflammation
Qiu, Yunguang,Huang, Lu,Fu, Jie,Han, Chenxia,Fang, Jing,Liao, Ping,Chen, Zhuo,Mo, Yiqing,Sun, Peihua,Liao, Daqing,Yang, Linghui,Wang, Jing,Zhang, Qiansen,Liu, Jin,Liu, Feng,Liu, Tingting,Huang, Wei,Yang, Huaiyu,Jiang, Ruotian
, p. 3665 - 3677 (2020/04/30)
TWIK-related K+ (TREK) channels are potential analgesic targets. However, selective activators for TREK with both defined action mechanism and analgesic ability for chronic pain have been lacking. Here, we report (1S,3R)-3-((4-(6-methylbenzo[d]
Conformational Restriction and Enantioseparation Increase Potency and Selectivity of Cyanoguanidine-Type Histamine H4 Receptor Agonists
Geyer, Roland,Nordemann, Uwe,Strasser, Andrea,Wittmann, Hans-Joachim,Buschauer, Armin
supporting information, p. 3452 - 3470 (2016/05/19)
2-Cyano-1-[4-(1H-imidazol-4-yl)butyl]-3-[2-(phenylsulfanyl)ethyl]guanidine (UR-PI376, 1) is a potent and selective agonist of the human histamine H4 receptor (hH4R). To gain information on the active conformation, we synthesized analogues of 1 with a cyclopentane-1,3-diyl linker. Affinities and functional activities were determined at recombinant hHxR (x: 1-4) subtypes on Sf9 cell membranes (radioligand binding, [35S]GTPγS, or GTPase assays) and in part in luciferase assays on human or mouse H4R (HEK-293 cells). The most potent H4R agonists among 14 racemates were separated by chiral HPLC, yielding eight enantiomerically pure compounds. Configurations were assigned based on X-ray structures of intermediates and a stereocontrolled synthetic pathway. (+)-2-Cyano-1-{[trans-(1S,3S)-3-(1H-imidazol-4-yl)cyclopentyl]methyl}-3-[2-(phenylsulfanyl)ethyl]guanidine ((1S,3S)-UR-RG98, 39a) was the most potent H4R agonist in this series (EC50 11 nM; H4R vs H3R, >100-fold selectivity; H1R, H2R, negligible activities), whereas the optical antipode proved to be an H4R antagonist ([35S]GTPγS assay). MD simulations confirmed differential stabilization of the active and inactive H4R state by the enantiomers.
Complexation of tetrakis(acetato)chloridodiruthenium with naphthyridine-2,7-dicarboxylate - Characterization and catalytic activity
Lee, Chia-Han,Wu, Cai-Ling,Hua, Shao-An,Liu, Yi-Hung,Peng, Shie-Ming,Liu, Shiuh-Tzung
, p. 1417 - 1423 (2015/03/18)
The reaction of calcium naphthyridine-2,7-dicarboxylate (Cadcnp) with Ru2(OAc)4Cl in water resulted in the formation of Ca[Ru2(dcnp)(OAc)3]2 (3). X-ray crystal structural analysis of 3 confirmed its molecular structure and showed that the calcium ion binds to the lateral carboxylate groups of four neighboring anionic units of [Ru2(dcnp)(μ-OAc)3] and two acetone molecules to form a two-dimensional framework. The RuII-RuII valence state of the diruthenium core was supported by superconducting quantum interference device (SQUID) magnetometry [μeff (300 K) = 2.77 μB]. Complex 3 appears to be an efficient catalyst for the oxidative cleavage of olefins in aqueous media under mild conditions. Typically, the reaction of pulegone with NaIO4 in water catalyzed by 3 (1 mol-%) at 45 C afforded 3-methyladipic acid quantitatively. The reaction of calcium naphthyridine-2,7-dicarboxylate (Cadcnp) with Ru2(OAc)4Cl provides Ca[Ru2(dcnp)(OAc)3]2 as the exclusive product. The complex is catalytically active for the oxidative cleavage of olefins in aqueous media.
Tetrapropylammonium perruthenate catalyzed glycol cleavage to carboxylic (Di)acids
Schmidt, Andrea-Katharina C.,Stark, Christian B. W.
supporting information; experimental part, p. 5788 - 5791 (2011/12/05)
A new method to accomplish glycol cleavage to carboxylic (di)acids in one step using catalytic amounts of tetrapropylammonium perruthenate (TPAP) together with N-methylmorpholine N-Oxide (NMO) as the stoichiometric oxidant is presented. In addition to regenerating the active catalyst, the N-oxide stabilizes intermediary carbonyl hydrates and thereby shifts a crucial equilibrium. The mild oxidation protocol is applicable to a broad range of substrates providing the respective acids, diacids, or keto acids in high yields.
Aryl sulfones: A new class of γ-secretase inhibitors
Teall, Martin,Oakley, Paul,Harrison, Timothy,Shaw, Duncan,Kay, Euan,Elliott, Jason,Gerhard, Ute,Castro, Jose L.,Shearman, Mark,Ball, Richard G.,Tsou, Nancy N.
, p. 2685 - 2688 (2007/10/03)
The development of a novel series of 4-aryl, 4-phenylsulfonyl cyclohexananone-derived γ-secretase inhibitors for the potential treatment of Alzheimer's disease is described.
Synthesis and antiviral activities of some novel carbocyclic nucleosides
Carmen Balo,Fernandez, Franco,Lens, Evangelina,Lopez, Carmen,De Clercq, Erik,Andrei, Graciela,Snoeck, Robert,Baizarini, Jan
, p. 1335 - 1346 (2007/10/03)
cis-3-Aminomethylcyclopentylmethanol (4), prepared from norbornene (5) in four steps and 51% overall yield, was used as a precursor in the synthesis of carbocylic nucleosides 13 - 18 containing guanine and 8-azaguanine bases. None of these compounds had a
Unusual Stereochemical Results in the Reaction of Alpha-Lithio Derivatives of Bicyclic Sulfoxides
Ben, Robert N.,Breau, Livain,Bensimon, C.,Durst, T.
, p. 6061 - 6076 (2007/10/02)
The stereochemistry of the reaction of the lithio derivatives of two sets of isomeric 3-thiaoctane-3-oxides with electrophiles such as benzyl bromide, acetone and D2O has been studied.Introduction of deuterium always occurred cis to the S=O bond as expected on the basis of earlier results described by Marquet for the related thiane-S-oxides.In contrast, benzyl groups were introduced either cis or trans to the existing S=O bond.The results are most readily rationalized in terms of a planar configuration at the α-carbanion center. the unexpected cis benzylations are due to steric hindrance of the preferred approach anti to the S=O bond by either the ethano bridge or the 8-endo methyl group.
Preparation of Bicycloalkanes by Electrochemical Reduction of 1,3-Dibromocycloalkanes
Hoffmann, Joachim,Voss, Juergen
, p. 1415 - 1420 (2007/10/02)
Good yields of bicyclo pentane (17) and bicyclo-hexane(3) are obtained on electroreduction of the corresponding 1,3-dibromocycloalkanes.The results do not depend upon the stereochemistry of the starting material (14 vs. 15 or 11 vs. 12).Key Words: Electrochemical reduction / Bicycloalkanes / Cycloalkanes, 1,3-dibromo / Hunsdiecker reaction / 1,3-Cycloalkanedicarboxylic acids
Enantioselective synthesis of (+) and (-)-cis-3-aminocyclopentanecarboxylic acids by enzymatic asymmetrization
Chenevert,Martin
, p. 199 - 200 (2007/10/02)
Both enantiomers of cis-3-aminocyclopentanecarboxylic acid (GABA analogs, inhibitory neurotransmitter) have been prepared via enzymatic asymmetrization of cis -1,3-cyclopentanedicarboxylic acid.
