33451-85-3Relevant articles and documents
Neutral and Anionic Monomeric Zirconium Imides Prepared via Selective C=N Bond Cleavage of a Multidentate and Sterically Demanding β-Diketiminato Ligand
Kurogi, Takashi,Chu, Jiaxiang,Chen, Yaofeng,Mindiola, Daniel J.
, p. 2629 - 2638 (2019)
A sterically encumbering multidentate β-diketiminato ligand, tBuL2 (tBuL2=[ArNC(tBu)CHC(tBu)NCH2CH2N(Me)CH2CH2NMe2]?, Ar=2,6-iPr2C6H3), is reported in this study along with its coordination chemistry to zirconium(IV). Using the lithio salt of this ligand, Li(tBuL2) (4), the zirconium(IV) precursor (tBuL2)ZrCl3 (6) could be readily prepared in 85 % yield and structurally characterized. Reduction of 6 with 2 equiv of KC8 resulted in formation of the terminal and mononuclear zirconium imide-chloride [C(tBu)CHC(tBu)NCH2CH2N(Me)CH2CH2NMe2]Zr(=NAr)(Cl) (7) as the result of reductive C=N cleavage of the imino fragment in the multidentate ligand tBuL2 by an elusive ZrII species (tBuL2)ZrCl (A). The azabutadienyl ligand in 7 can be further reduced by 2 e? with KC8 to afford the anionic imide [K(THF)2]{[CH(tBu)CHC(tBu)NCH2CH2N(Me)CH2CH2N(Me)CH2]Zr=NAr} (8-2THF) in 42 % isolated yield. Complex 8-2THF results from the oxidative addition of an amine C?H bond followed by migration to the vinylic group of the formal [C(tBu)CHC(tBu)NCH2CH2N(Me)CH2CH2NMe2]? ligand in 7. All halides in 6 can be replaced with azides to afford (tBuL2)Zr(N3)3 (9) which was structurally characterized, and reduction with two equiv of KC8 also results in C=N bond cleavage of tBuL2 to form [C(tBu)CHC(tBu)NCH2CH2N(Me)CH2CH2NMe2]Zr(=NAr)(N3) (10), instead of the expected azide disproportionation to N3? and N2. Solid-state single crystal structural studies confirm the formation of mononuclear and terminal zirconium imido groups in 7, 8-Et2O, and 10 with Zr=NAr distances being 1.8776(10), 1.9505(15), and 1.881(3) ?, respectively.
Nonpeptide bradykinin B2 receptor antagonists: Conversion of rodent-selective bradyzide analogues into potent, orally-active human bradykinin B2 receptor antagonists
Dziadulewicz, Edward K.,Ritchie, Timothy J.,Hallett, Allan,Snell, Christopher R.,Davies, John W.,Wrigglesworth, Roger,Dunstan, Andrew R.,Bloomfield, Graham C.,Drake, Gillian S.,McIntyre, Peter,Brown, Michael C.,Burgess, Gillian M.,Lee, Wai,Davis, Clare,Yaqoob, Mohammed,Phagoo, Steve B.,Phillips, Elsa,Perkins, Martin N.,Campbell, Elizabeth A.,Davis, Andrew J.,Rang, Humphrey P.
, p. 2160 - 2172 (2007/10/03)
The 1-(2-nitrophenyl)thiosemicarbazide (TSC) derivative, (S)-l-[4-(4-benzhydrylthiosemicarbazido)-3-nitrobenzenesulfonyl] pyrrolidine-2-carboxylic acid {2-[(2-dimethylaminoethyl)methylamino]ethyl} amide (bradyzide; (S)-4), was recently disclosed as a novel, potent, orally active nonpeptide bradykinin (BK) B2 receptor antagonist. The compound inhibited the specific binding of [3H]BK to NG108-15 cell membrane preparations (rodent neuroblastoma-glioma) expressing B2 receptors with a Ki of 0.5 ± 0.2 nM. Compound (S)-4 also demonstrated oral efficacy against Freund's complete adjuvant (FCA)-induced mechanical hyperalgesia in rats with an ED50 value of 0.84 μmol/kg. After we optimized the terminal binding determinants projecting from the TSC framework, we found that it was possible to replace the potentially toxicophoric nitro and divalent sulfur moieties with only a 15-fold loss in binding affinity ((S)-14a). However, bradyzide and its congeners were found to have much lower affinities for cloned human B2 receptors, expressed in Cos-7 cells. The hitherto synthesized TSC series was screened against the human B2 receptor, and the dibenzosuberane (DBS) pharmacophore emerged as the key structural requirement for potency. Incorporation of this group resulted in a series of derivatives ((S)-14d,e and 19b-d) with Ki ranges of 10.7-176 nM in NG108-15 cells (expressing the rodent B2 receptor) and 0.79-253 nM in Cos-7 cells (expressing the human B2 receptor). There was no evidence of agonist activity with any of the nonpeptides in any of the cell lines tested. In vivo, oral administration of compound 19c reversed FCA-induced and turpentine-induced mechanical hyperalgesia in rodents with ED50 values of 0.027 and 0.32 μmol/kg, respectively. The selectivity profiles of compounds (S)-14f and (S)-14g were also assessed to determine the conformational and/or steric preferences of the double-ring arrangement. The affinity of (S)-14g for the human B2 receptor suggested that it may be a hydrophobic interaction with the ethane bridge of the DBS moiety that accounts for the increased potency of compounds (S)-14d,e and 19b,c at this receptor, by favoring a binding mode inaccessible to the unsubstituted diphenylmethyl derivative, (S)-4.
Sequence-Specific Osmium Reagents for Polynucleotides. 2. A Method for Thymine-Cytosine Pairs
Ford, H.,Chang, C.-H.,Behrman, E.J.
, p. 7773 - 7779 (2007/10/02)
We have modified the dinucleoside monophosphate, deoxythymidylyldeoxycytidine (d-TpC), by replacement of the exocyclic amino group of cytosine with a series of ligands, H2N(CH2)nN(CH3)CH2CH2N(CH3)2, where n = 2, 4, and 6.The kinetics of the reactions of these modified dinucleoside monophosphates with osmium tetroxide were measured.The modified nucleotides react with osmium tetroxide 4200, 7900, and 1200 times faster than the unmodified species for n = 6, 4, and 2, respectively.The products of the reactions are macrocyclic oxoosmium (VI) esters for which 360-MHz proton NMR spectra are reported.
