29636-87-1Relevant articles and documents
Homo- and Heterodinuclear Ir and Rh Imine-functionalized Protic NHC Complexes: Synthetic, Structural Studies, and Tautomerization/Metallotropism Insights
He, Fan,Wesolek, Marcel,Danopoulos, Andreas A.,Braunstein, Pierre
, p. 2658 - 2671 (2016)
The influence of the potentially chelating imino group of imine-functionalized Ir and Rh imidazole complexes on the formation of functionalized protic N-heterocyclic carbene (pNHC) complexes by tautomerization/metallotropism sequences was investigated. Chloride abstraction in [Ir(cod)Cl{C3H3N2(DippN=CMe)-κN3}] (1 a) (cod=1,5-cyclooctadiene, Dipp=2,6-diisopropylphenyl) with TlPF6 gave [Ir(cod){C3H3N2(DippN=CMe)-κ2(C2,Nimine)}]+[PF6]- (3 a+[PF6]-). Plausible mechanisms for the tautomerization of complex 1 a to 3 a+[PF6]- involving C2-H bond activation either in 1 a or in [Ir(cod){C3H3N2(DippN=CMe)-κN3}2]+[PF6]- (6 a+[PF6]-) were postulated. Addition of PR3 to complex 3 a+[PF6]- afforded the eighteen-valence-electron complexes [Ir(cod)(PR3){C3H3N2(DippN=CMe)-κ2(C2,Nimine)}]+[PF6]- (7 a+[PF6]- (R=Ph) and 7 b+[PF6]- (R=Me)). In contrast to Ir, chloride abstraction from [Rh(cod)Cl{C3H3N2(DippN=CMe)-κN3}] (1 b) at room temperature afforded [Rh(cod){C3H3N2(DippN=CMe)-κN3}2]+[PF6]- (6 b+[PF6]-) and [Rh(cod){C3H3N2(DippN=CMe)-κ2(C2,Nimine)}]+[PF6]- (3 b+[PF6]-) (minor); the reaction yielded exclusively the latter product in toluene at 110 C. Double metallation of the azole ring (at both the C2 and the N3 atom) was also achieved: [Ir2(cod)2Cl{μ-C3H2N2(DippN=CMe)-κ2(C2,Nimine),κN3}] (10) and the heterodinuclear complex [IrRh(cod)2Cl{μ-C3H2N2(DippN=CMe)-κ2(C2,Nimine),κN3}] (12) were fully characterized. The structures of complexes 1 b, 3 b+[PF6]-, 6 a+[PF6]-, 7 a+[PF6]-, [Ir(cod){C3HN2(DippN=CMe)(DippN=CH)(Me)-κ2(N3,Nimine)}]+[PF6]- (9+[PF6]-), 10 Et2O'toluene, [Ir2(CO)4Cl{μ-C3H2N2(DippN=CMe)-κ2(C2,Nimine),κN3}] (11), and 12-2 THF were determined by X-ray diffraction.
Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa)
Widler, Leo,Jaeggi, Knut A.,Glatt, Markus,Müller, Klaus,Bachmann, Rolf,Bisping, Michael,Born, Anne-Ruth,Cortesi, Reto,Guiglia, Gabriela,Jeker, Heidi,Klein, Rémy,Ramseier, Ueli,Schmid, Johann,Schreiber, Gerard,Seltenmeyer, Yves,Green, Jonathan R.
, p. 3721 - 3738 (2007/10/03)
Bisphosphonates (BPs) are pyrophosphate analogues in which the oxygen in P-O-P has been replaced by a carbon, resulting in a metabolically stable P-C-P structure. Pamidronate (1b, Novartis), a second-generation BP, was the starting point for extensive SAR studies. Small changes of the structure of pamidronate lead to marked improvements of the inhibition of osteoclastic resorption potency. Alendronate (1c, MSD), with an extra methylene group in the N-alkyl chain, and olpadronate (1h, Gador), the N,N-dimethyl analogue, are about 10 times more potent than pamidronate. Extending one of the N-methyl groups of olpadronate to a pentyl substituent leads to ibandronate (1k, Roche, Boehringer-Mannheim), which is the most potent close analogue of pamidronate. Even slightly better antiresorptive potency is achieved with derivatives having a phenyl group linked via a short aliphatic tether of three to four atoms to nitrogen, the second substituent being preferentially a methyl group (e.g., 4g, 4j, 5d, or 5r). The most potent BPs are found in the series containing a heteroaromatic moiety (with at least one nitrogen atom), which is linked via a single methylene group to the geminal bisphosphonate unit. Zoledronic acid (6i), the most potent derivative, has an ED50 of 0.07 mg/kg in the TPTX in vivo assay after sc administration. It not only shows by far the highest therapeutic ratio when comparing resorption inhibition with undesired inhibition of bone mineralization but also exhibits superior renal tolerability. Zoledronic acid (6i) has thus been selected for clinical development under the registered trade name Zometa. The results of the clinical trials indicate that low doses are both efficacious and safe for the treatment of tumor-induced hypercalcemia, Paget's disease of bone, osteolytic metastases, and postmenopausal osteoporosis.
Substituted 1H-imidazoles
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, (2008/06/13)
New substituted 1H-imidazoles and their salts, processes for the preparation thereof and pharmaceutical compositions. These compounds have the formula STR1 wherein R1, R2, R3 and R5 =hydrogen or C1 -C4 -alkyl; R4 =hydrogen, C1 -C4 -alkyl or C1 -C4 -alkoxy; Y1 =hydrogen and Y2 =OZ2 or the reverse; Z1 =Z2 =hydrogen or C1 -C4 -alkyl or Z1 and Z2 =--CH2 -- or --C(CH3)2 --. These compounds are prepared either by reducing a corresponding imidazole compound having a hydroxyl or alkoxy group on the methyl bridge between the imidazole and phenyl rings, or by hydrolyzing a 4-[[2,2-dimethyl-4H-1,3-benzodioxin-6(or 8)-yl]methyl]-1H-imidazole, or yet by reducing an alkyl 3-[(1H-imidazol-4-yl)methyl]-2-hydroxybenzoate. These compounds have cardiac, cerebral and tissular anti-ischemic activities.
