29636-87-1Relevant academic research and scientific papers
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Bisphosphonates (BPs) are pyrophosphate analogues in which the oxygen in P-O-P has been replaced by a carbon, resulting in a metabolically stable P-C-P structure.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.
Imidazole-containing inhibitors of farnesyl protein transferase
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, (2008/06/13)
Inhibition of farnesyl transferase, which is an enzyme involved in ras oncogene expression, is effected by compounds of the formula their enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs, and solvates, wherein:, G is G1 is G2 is or -NR10-CH(Q1)-;, J, K and L are each, independently, N, NR9, O, S or CR10 with the provisos that only one of the groups J, K and L can be O or S, and at least one of the groups J or L must be N, NR9, O or S to form a fused five-membered heteroring; the bond between J and K or K and L may also form one side of a phenyl ring fused to the fused five-membered heteroring;, Q is aryl;, Q1, A1 and A2 are each, independently, H, alkyl, substituted alkyl, phenyl or substituted phenyl;, G3 is R11, -C(O)OR11, -C(O)NR11R12, 5-tetrazolyl, -C(O)N(R13)OR11, -C(O)NHSO2R14 or -CH2OR11;, G4 is attached at the 1, 2, 4 or 5 position and optionally substituted, at any of the available position or positions on the ring, with halo, alkyl or substituted alkyl having 1 to 20 carbon atoms, alkoxy, aryl, aralkyl, hydroxy, alkanoyl, alkanoyloxy, amino, alkylamino, dialkylamino, alkanoylamino, thiol, alkylthio, alkylthiono, alkylsulfonyl, sulfonamido, nitro, cyano, carboxy, carbamyl, N-hydroxycarbamyl, N-alkylcarbamyl, N-dialkylcarbamyl, alkoxycarbonyl, phenyl, substituted phenyl, or a combinaton of these groups;, Y and Z are each, independently, -CH2- or -C(O)-;, R1 - R14 are each, independently, H or alkyl having 1 to 20 carbon atoms;, R7, R8 and R14 may also be aryl or aralkyl, and R3, R9, R11, R12 and R13 may also be aralkyl;, m, n and p are each, independently, 0 or an integer from 1 to 2;, q is 0 or an integer from 1 to 4; and, the dotted line represents an optional double bond.
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.
ELECTROCHEMICAL REDUCTIONS IN LIQUID AMMONIA: ELECTROLYTIC BIRCH REACTIONS AND CHEMICAL BOND FISSIONS
Chaussard, J.,Combellas, C.,Thiebault, A.
, p. 1173 - 1174 (2007/10/02)
A procedure of electrochemical reduction in liquid ammonia using a single-compartment cell equiped with a soluble anode is described and illustrated in the case of aromatic compounds and esters.
Synthesis of 4(5)-Hydroxymethylimidazoles by Hydroxymethylation and Decarboxylation of Imidazole-4(5)-carboxylic Acids
Kim, Choong S.,Lee, Kee J.,Kim, Hong S.,Chae, Yung B.
, p. 1417 - 1418 (2007/10/02)
4(5)-Hydroxymethylimidazoles were prepared by hydroxymethylation and decarboxylation of imidazole-4(5)-carboxylic acid esters.The reaction was simply carried out with aqueous formaldehyde solution in the presence of base.
ANTISECRETORY IMIDAZOLE AMIDINE COMPOUNDS, COMPOSITION AND METHOD OF USE
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, (2008/06/13)
Novel heterocyclic compounds shown by the formula STR1 wherein Het represents a 5-membered or 6-membered heterocyclic group which may have substituent(s); Z represents a sulfur atom or oxygen atom; X represents an oxygen atom or the unsubstituted or substituted imino group shown by N--R 1 (wherein R 1 is a hydrogen atom, a lower alkyl group, a cyano group, an unsubstituted or alkyl substituted carbamoyl group, an unsubstituted or lower alkyl substituted thiocarbamoyl group, or a lower alkanoylamino group); Y represents a hydrogen atom, a lower alkyl group which may have substituent(s), a cycloalkyl group of 3-6 carbon atoms, a lower alkenyl group, a lower alkynyl group, an aryl group which may have substituent(s), an aralkyl group which may have substituent(s), a hydroxyl group, a cyano group, a carbamoyl group, an amidino group, an alkanoyl group which may have been substituted by halogen atom(s), an alkanoylamino group, an arylcarbonylamino group, an alkylamino group, an arylamino group, an arylsulfamoyl group, a lower alkoxycarbamoyl group, or an oxamoylamino group; and m and n represent an integer of 1-3; when X is N--R 1, said X and Y may combine with each other to form a 5-membered or 6-membered heterocyclic ring containing 2-3 nitrogen atoms which may have substituent(s), and the pharmacologically acceptable acid addition salts thereof.The compounds of this invention are useful as gastric acid secretion inhibitors.
Process for the production of hydroxymethylimidazoles
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, (2008/06/13)
This invention discloses a process for the production of hydroxymethylimidazoles which comprises reacting imidazolecarboxylic acids, their esters or inorganic salts with a formaldehyde agent in the presence of an alkali in an aqueous medium.
ANTISECRETORY HETEROCYCLIC AMIDINE COMPOUNDS
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, (2008/06/13)
Novel heterocyclic compounds shown by the formula STR1 wherein Het represents a 5-membered or 6-membered heterocyclic group which may have substituent(s); Z represents a sulfur atom or oxygen atom; X represents an oxygen atom or the unsubstituted or substituted imino group shown by N--R 1 (wherein R 1 is a hydrogen atom, a lower alkyl group, a cyano group, an unsubstituted or alkyl substituted carbamoyl group, an unsubstituted or lower alkyl substituted thiocarbamoyl group, or a lower alkanoylamino group); Y represents a hydrogen atom, a lower alkyl group which may have substituent(s), a cycloalkyl group of 3-6 carbon atoms, a lower alkenyl group, a lower alkynyl group, an aryl group which may have substituent(s), an aralkyl group which may have substituent(s), a hydroxyl group, a cyano group, a carbamoyl group, an amidino group, an alkanoyl group which may have been substituted by halogen atom(s),an alkanoylamino group, an arylcarbonylamino group, an alkylamino group, an arylamino group, an arylsulfamoyl group, a lower alkoxycarbamoyl group, or an oxamoylamino group; and m and n represent an integer of 1-3; when X is N-R 1, said X and Y may combine with each other to form a 5-membered or 6-membered heterocyclic ring containing 2-3 nitrogen atoms which may have substituent(s), and the pharmaceutically acceptable acid addition salts thereof.The compounds of this invention are useful as gastric acid secretion inhibitors.
