109384-19-2Relevant articles and documents
Synthesis of C-substituted cyclic amines using azacycloalkyl organozinc reagents
Billotte
, p. 379 - 380 (1998)
Azetidine and piperidine derived organozinc species have been prepared from the corresponding azacycloalkyl iodides by direct Zn insertion. They have been shown to readily undergo Pd(0) mediated cross-coupling reactions and to transmetallate with CuCN.2LiCl.
One-pot synthesis of novel tert-butyl-4-substituted phenyl-1H-1,2,3-triazolo piperazine/piperidine carboxylates, potential GPR119 agonists
Bashetti, Nagaraju,Shanmukha Kumar,Seelam, Naresh Varma,Prasanna,Mintz, Akiva,Damuka, Naresh,Devanathan, Sriram,Solingapuram Sai, Kiran Kumar
, (2019)
We have synthesized a new series of 1,2,3-triazolo piperazine and piperidine carboxylate derivatives using a simple and one-pot click chemistry with significantly reduced reaction times (~5 min) and enhanced reaction yields (~95–98%). The fourteen novel compounds thus synthesized were tested for ability to target GPR119, a G-protein coupled target receptor that plays critical role in regulation of type-2 diabetes mellitus. Four analogs (3e, 3g, 5e and 5g) demonstrated similar or better EC50 values over previously reported AR231453 activity towards GPR119.
Design, synthesis, and biological evaluation of radioiodinated benzo[d]imidazole-quinoline derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging
Effendi, Nurmaya,Mishiro, Kenji,Takarada, Takeshi,Yamada, Daisuke,Nishii, Ryuichi,Shiba, Kazuhiro,Kinuya, Seigo,Odani, Akira,Ogawa, Kazuma
, p. 383 - 393 (2019)
Several malignant tumors and fibrotic diseases are associated with PDGFRβ overexpression and excessive signaling, making this receptor attractive for molecular targeting and imaging approaches. A series of benzo[d]imidazole-quinoline derivatives were designed and synthesized to develop radioiodinated compounds as PDGFRβ-specific imaging probes. The structure activity relationship (SAR) evaluation of the designed compounds was performed. Among them, 2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]-8-(piperazin-1-yl)quinoline (5a) and 4-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}morpholine (5d) exhibited a relatively high PDGFRβ-TK inhibitory potency, whereas iodinated 5a derivative 5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]-8-(piperazin-1-yl)quinoline (8) exhibited a superior inhibitory potency as PDGFRβ inhibitor than iodinated 5d derivative 4-{5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}morpholine (11). Furthermore, [125I]8 and [125I]11 were synthesized and evaluated for PDGFRβ radioligand ability, both in vitro and in vivo. Cellular uptake experiments showed that [125I]8 had a higher uptake in BxPC3-luc cells as PDGFRβ-positive cells than [125I]11. Incubation of [125I]8 after pretreatment of PDGFRβ ligands significantly reduced the uptake of [125I]8. In biodistribution experiments using tumor-bearing mice, [125I]8 accumulation in the tumor 1 h postinjection was higher than that of the benzo[d]imidazol-quinoline derivative [125I]IIQP, used in our previous research. These results indicate that [125I]8 could be a promising PDGFRβ imaging agent. Although its clinical application requires further structural modifications, the results obtained in this research may be useful for the development of PDGFRβ-specific radioligands.
Regioselective samarium diiodide induced couplings of carbonyl compounds with 1,3-diphenylallene and alkoxyallenes: A new route to 4-hydroxy-1-enol ethers
Hoelemann, Alexandra,Reissig, Hans-Ulrich
, p. 5493 - 5506 (2004)
Since its introduction into synthetic organic chemistry, samarium diiodide has found broad application in a variety of synthetically important transformations. Herein, we describe the first successful intermolecular additions of samarium ketyls to typical allenes such as 1,3-diphenylallene (7), methoxyallene (12) and benzyloxyallene (25). Reaction of different samarium ketyls with 1,3-diphenylallene (7) occurred exclusively at the central carbon atom of the allene to afford products 9 in moderate to good yields. In contrast, reductive coupling of cyclic ketones to methoxyallene (12) regioselectively provided 4-hydroxy-1-enol ethers 13, which derive from addition to the terminal allene carbon atom of 12, in moderate to good yields. Whereas the E/Z selectivity with respect to the enol ether double bond is low, excellent diastereoselectivity has been observed in certain cases with regard to the ring configuration (e.g. compound 13 b). Studies with deuterated tetrahydrofuran and alcohol were performed to gain information about the reaction mechanism of this coupling process, which involves alkenyl radicals. The couplings of samarium ketyls derived from acyclic ketones and aldehydes gave lower yields, and in several cases cyclopentanols 20 are formed as byproducts. Branched acyclic ketones and conformationally more flexible cyclic ketones such as cycloheptanone led to a relatively high amount of cyclopentanol derivatives 20, whose formation involves an intramolecular hydrogen atom transfer through a geometrically favoured six-membered transition state followed by a cyclization step. The samarium diiodide mediated addition of 8b to benzyloxyallene (25) afforded the expected enol ethers 26, albeit in only low yield. Additionally, spirocyclic compounds 27 and 28 were obtained, which are formed by a cascade reaction involving an addition/cyclization sequence. In the novel coupling process described here methoxyallene (12) serves as an equivalent of acrolein. The 1,4-dioxygenated products obtained contain a masked aldehyde functionality and are therefore valuable building blocks in organic synthesis.
Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis
Albrecht, Markus,Begall, Jenny,Craen, David Van,Gro?kurth, Johannes,Himmel, Leonard,Isaak, Elisabeth,Linnenberg, Oliver
, p. 2338 - 2345 (2020)
The stereoselectivity of a Diels–Alder reaction within the periphery of hierarchically assembled titanium(IV) helicates formed from mixtures of achiral, reactive and chiral, unreactive ligands was investigated in detail. Following the pathway of the chiral induction, the chiral ligands, solvents as well as substituents at the dienophile were carefully varied. Based on the results of the stoichiometric reaction, a secondary amine-catalyzed nitro-Michael reaction is performed as well which afforded reasonable diastereoselectivities.
A novel amalgamation of 1,2,3-triazoles, piperidines and thieno pyridine rings and evaluation of their antifungal activity
Darandale, Sunil N.,Mulla, Nayeem A.,Pansare, Dattatraya N.,Sangshetti, Jaiprakash N.,Shinde, Devanand B.
, p. 527 - 532 (2013)
It is the first report of the novel amalgamation of 1,2,3-triazoles, piperidines, thieno pyridine rings and evaluation of their antifungal activity. The synthesized compounds showed interesting moderate to good antifungal activity, wherein they were able to discriminate between the two species Aspergillus flavus and Aspergillus niger of the same genus. In addition, the main highlight of this series is the sensitivity of the fungal strain Cryptococcus neoformans to the compounds having p-chlorobenzoyl (9h), methane sulfonyl (9i) and p-methylbenzene sulfonyl (9j) attached to the piperazine nitrogen.
Selective reduction of ketones using water as a hydrogen source under high hydrostatic pressure
Tomin, Anna,Lazarev, Alexander,Bere, Matthew P.,Redjeb, Hana,T?r?k, Béla
, p. 7321 - 7326 (2012)
A selective reduction of a broad variety of ketones is described. The method is based on the combination of a Ni-Al alloy and high hydrostatic pressure (HHP, 2.8 kbar) in an aqueous medium. The reaction of the Ni-Al alloy with water provides in situ hydrogen generation and the high pressure ensures that the H2 formed remains in the solution, thus the CO reduction readily occurs. The application of the HHP resulted in selective formation of the desired products and the common problem of non-selective overhydrogenation could be avoided. In most cases the reductions resulted in high yields and excellent selectivities without the use of any base.
An Efficient approach to the securinega alkaloids empowered by cooperative n-heterocyclic carbene/lewis acid catalysis
Elsohly, Adel M.,Wespe, Daniel A.,Poore, Tyler J.,Snyder, Scott A.
, p. 5789 - 5794 (2013)
Folding it all together: Most of the syntheses developed for the securinega alkaloid class require lengthy sequences to create their bridging butenolide domains. A novel approach uses N-heterocyclic carbenes (NHCs) and Lewis acids to forge the entire domain in a single step from appropriate precursors, showing that ynal-derived homoenolates can participate as nucleophiles in intramolecular settings (see scheme). Copyright
Water-soluble pleuromutilin derivative with excellent in vitro and in vivo antibacterial activity against Gram-positive pathogens
Hirokawa, Yoshimi,Kinoshita, Hironori,Tanaka, Tomoyuki,Nakata, Katsuhisa,Kitadai, Noriyuki,Fujimoto, Koichi,Kashimoto, Shigeki,Kojima, Tsuyoshi,Kato, Shiro
, p. 1991 - 1994 (2008)
Although earlier pleuromutilin analogues showed potent in vitro antibacterial activity against some Gram-positive pathogens, their in vivo efficacy was low because of insufficient pharmacokinetic properties. We designed novel thioether pleuromutilin derivatives having a purine ring as a polar and water solubilizing group and identified a promising pleuromutilin analogue 6 with good solubility in water (～50 mg/mL). Compound 6 exhibited excellent in vitro and in vivo antibacterial activity against some Gram-positive strains, including drug-resistant pathogens.
An air and moisture tolerant iminotrihydroquinoline-ruthenium(ii) catalyst for the transfer hydrogenation of ketones
Li, Jiaoyan,Ma, Yingmiao,Wang, Zheng,Liu, Qingbin,Solan, Gregory A.,Ma, Yanping,Sun, Wen-Hua
, p. 8738 - 8745 (2018)
Reaction of 8-amino-5,6,7,8-tetrahydroquinoline with RuCl2(PPh3)3 at room temperature affords the ruthenium(ii) chelate (8-NH2-C9H10N)RuCl2(PPh3)2 (E), in which the two triphenylphosphine ligands are disposed mutually cis. By contrast, when the reaction is performed at reflux ligand oxidation/dehydrogenation occurs along with cis-trans reorganization of the triphenylphosphines to form the 8-imino-5,6,7-trihydroquinoline-ruthenium(ii) complex, (8-NH-C9H9N)RuCl2(PPh3)2 (F). Complex F can also be obtained in higher yield by heating a solution of E alone to reflux. Comparison of their molecular structures highlights the superior binding properties of the bidentate imine ligand in F over its amine-containing counterpart in E. Both complexes are highly effective in the transfer hydrogenation of a wide range of alkyl-, aryl- and cycloalkyl-containing ketones affording their corresponding secondary alcohols with loadings of as low as 0.1 mol%. Significantly, F can deliver excellent conversions even in bench quality 2-propanol in reaction vessels open to the air, whereas the catalytic efficiency of E is diminished by the presence of air but only operates efficiently under inert conditions.
