- Self-assembled mononuclear palladium(II) based molecular loops
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The meta-pyridine appended bidentate ligands L1, L2 and L3, crafted with flexible polyether spacer, are prepared by condensation of nicotinoyl chloride hydrochloride with di, tri-, and tetra-ethylene glycol, respectively. Self-assembled palladium(II) based mononuclear molecular loops of general formula cis-[Pd(N-N)(L)](NO 3)2 are obtained exclusively by combining 1 equiv. of a ligand L with 1 equiv. of a cis-protected palladium(II) component, cis-[Pd(N-N)(NO3)2]. Complexation of 2 equiv. of L with 1 equiv. of palladium(II) nitrate also resulted mononuclear complexes, i.e. [Pd(L)2](NO3)2. The ligands used in the complexation reactions are L1, L2 and L3 where as the cis-protecting units N-N employed are ethylenediamine (en), 2,2′-bipyridine (bpy), and 1,10-phenanthroline (phen). Thus 12 number of mononuclear complexes are prepared using all possible combination of above mentioned three number of ligands and four variety of palladium(II) components. Large chelate rings are realized irrespective of the spacer length or type of palladium(II) component used. All the resulted compounds are characterized by NMR and ESI-MS techniques and the structure of cis-[Pd(en)(L1)] (NO3)2, cis-[Pd(bpy)(L1)](NO3) 2 and [Pd(L3)2](NO3)2 are confirmed by single crystal X-ray diffraction. The binding abilities of cis-[Pd(phen)(L1)](NO3)2, cis-[Pd(phen)(L 2)](NO3)2 and cis-[Pd(phen)(L 3)](NO3)2 with DNA has been investigated by ethidium bromide displacement assay and gel electrophoresis.
- Sahoo, Himansu Sekhar,Tripathy, Debakanta,Chakrabortty, Sabyasachi,Bhat, Satish,Kumbhar, Avinash,Chand, Dillip Kumar
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- Asymmetric synthesis of tetracyclic substructures of Strychnos indole alkaloids
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The addition of the enolate of methyl 1-methyl-2-indoleacetate 1 and lithium 2-(lithiomethyl)indole-1-carboxylate 5 to pyridines and N-alkylpyridinium salts bearing a chiral auxiliary at the 3-position (tolylsulfinyl, acyl iron complexes, bornane-10,2-sultam), with subsequent acid cyclization of the resulting dihydropyridines, is investigated.
- Amat, Mercedes,Coll, M.-Dolors,Llor, Nuria,Escolano, Carmen,Molins, Elies,Miravitlles, Carles,Bosch, Joan
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- Synthesis and pharmacological evaluation of novel selective MOR agonist 6β-pyridinyl amidomorphines exhibiting long-lasting antinociception
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It was previously reported that 6β-aminomorphinan derivatives show high affinity for opiate receptors. Novel 6β-heteroarylamidomorphinanes were designed based on the MOR selective antagonist NAP. The 6β-aminomorphinanes were prepared by stereoselective Mitsunobu reaction and subsequently acylated with nicotinic acid and isonicotinic acid chloride hydrochlorides. The receptor binding and efficacy were determined in vitro and the analgesic activity was studied in vivo. The in vitro studies revealed moderate selectivity for the MOR. At least two compounds in this series exhibited a long-lasting analgesic response when administered subcutaneously and intracerebroventricularly. When the substances were given intracerebroventricularly to mice, they showed analgesic potency comparable to morphine.
- Urai, ákos,Váradi, András,Sz?cs, Levente,Komjáti, Balázs,Le Rouzic, Valerie,Hunkele, Amanda,Pasternak, Gavril W.,Majumdar, Susruta,Hosztafi, Sándor
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- Homochiral crystallization of helical coordination chains bridged by achiral ligands: Can it be controlled by the ligand structure?
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Homochiral/heterochiral crystallizations of helical chiral polymer chains bridged by achiral poly-pyridyl ligands dependent on the structures of the bridging ligands and independent on the solvent are described, implying a possible strategy to design achiral crystals of helical chains using chiral bridging ligands.
- Wang, Yong-Tao,Tong, Ming-Liang,Fan, Hai-Hua,Wang, He-Zhou,Chen, Xiao-Ming
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- Synthesis of Conjugates of hyaluronic and nicotinic acids
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Conjugates with nicotinic acid of hyaluronic acid carboxylic and hydroxyl groups were synthesized and exhibited polyampholyte properties.
- Ponedel'kina,Sal'nikova,Lukina,Tyumkina,Odinokov
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Read Online
- Unusual adsorption behaviours and responsive structural dynamics: Via selective gate effects of an hourglass porous metal-organic framework
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An hourglass porous metal-organic framework, LIFM-12, constructed on a T-shaped flexible ligand with Cu2+ paddle-wheel clusters, shows temperature and gas adsorption responsive structural dynamics upon reversible molecular guest binding. Temperature-dependent single crystal and powder X-ray diffraction experiments show that the open gate status of the framework with adaptive behaviours facilitates kinetic diffusion of gas molecules resulting in the sequential filling of pores of different sizes, thus creating a breathing behaviour reminiscent of the observation of several steps in adsorption isotherms. In addition, adsorption studies revealed that LIFM-12 performs exceptional adsorption selectivity of 10-25 for CO2versus light gases N2, CH4, and CO and up to 200 for C3H6versus CH4.
- Xiong, Ying,Fan, Yan-Zhong,Xiong, Ying,Wei, Zhang-Wen,Chen, Cheng-Xia,Chen, Sha,Wang, Dawei,Barboiu, Mihail,Jiang, Ji-Jun,Barboiu, Mihail,Su, Cheng-Yong,Su, Cheng-Yong
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Read Online
- N-Alkenylation of hydroxamic acid derivatives with ethynyl benziodoxolone to synthesizecis-enamides through vinyl benziodoxolones
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The stereoselective synthesis ofcis-β-N-alkoxyamidevinyl benziodoxolones (cis-β-N-RO-amide-VBXs) fromO-alkyl hydroxamic acids in the presence of an ethynyl benziodoxolone-acetonitrile complex (EBX-MeCN) is reported herein. The reaction was performed under mild conditions including an aqueous solvent, a mild base, and room temperature. The reaction tolerated variousO-alkyl hydroxamic acids derived from carboxylic acids, such as amino acids, pharmaceuticals, and natural products. Vinyl dideuteratedcis-β-N-MeO-amide-VBXs were also synthesized using deuterium oxide as the deuterium source. Valine-derivedcis-β-N-MeO-amide-VBX was stereospecifically derivatized to hydroxamic acid-derivedcis-enamides without the loss of stereoselectivity or reduction in the deuterium/hydrogen ratio.
- Shimbo, Daisuke,Maruyama, Toshifumi,Tada, Norihiro,Itoh, Akichika
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supporting information
p. 2442 - 2447
(2021/04/02)
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- ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP-1) INHIBITORS AND USES THEREOF
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Disclosed herein are methods and compounds of augmenting and enhancing the production of type I IFNs in vivo. In some embodiments, the compounds disclosed herein are ENPP-1 inhibitors, pharmaceutical compositions, and methods for the treatment of cancer or a viral infection.
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Paragraph 0449
(2019/03/17)
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- Catalytic hydrogenation of: N -4-nitrophenyl nicotinamide in a micro-packed bed reactor
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Recent advancements in micro-flow technologies and a drive toward more efficient, greener and safer processes have led to a renaissance in flow-chemistry for pharmaceutical production. In this work, we demonstrate the use of a stabilized Pd nanoparticle-organic-silica catalyst to selectively catalyze the hydrogenation of N-4-nitrophenyl nicotinamide, a functionalized active pharmaceutical ingredient (API) surrogate. Extensive catalyst and reactor characterization is provided to establish an in-depth understanding of the unique multiphase dynamics within the micro-packed bed reactor, including the identification of a large liquid holdup (74-84%), rapid multiphase mass transfer (kma > 1 s-1), and liquid residence time distributions. A kinetic analysis has revealed that the surface catalyzed hydrogenation progresses through a condensation mechanism whereby an azo dimer intermediate is formed and rapidly consumed. Finally, a parametric study was performed at various pressures, temperatures, residence times and flow regimes to achieve quantitative chemoselective conversion of the nitroarene to the corresponding primary amine.
- Yang, Cuixian,Teixeira, Andrew R.,Shi, Yanxiang,Born, Stephen C.,Lin, Hongkun,Li Song, Yunfei,Martin, Benjamin,Schenkel, Berthold,Peer Lachegurabi, Maryam,Jensen, Klavs F.
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supporting information
p. 886 - 893
(2018/03/02)
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- Synthesis and Quantitative Structure-activity Relationships Study for Arylpropenamide Derivatives as Inhibitors of Hepatitis B Virus Replication
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A series of new arylpropenamide derivatives containing different aryl groups were synthesized, characterized, and evaluated for their anti-hepatitis B virus (HBV) activities. A new high accuracy QSAR model of arylpropenamide was constructed based on a more completely activities data and calculation parameter. The 2D-QSAR equations, by using DFT and multiple linear regression analysis methods, revealed that higher value of thermal energy (TE) and lower entropy (S?) increase the anti-HBV activities of the arylpropenamide molecules. Predictive 3D-QSAR models were established by SYBYL multifit molecular alignment rule. The optimum models were all statistically significant with cross-validated and conventional coefficients, indicating that they were reliable enough for activity prediction.
- Min, Ma,Xingjun, Jiang,Xueding, Wang,Hao, Zou,Weiqing, Yang,Yuanyuan, Zhang,Changrong, Peng,Zicheng, Li,Jing, Yang,Quan, Du,Menglin, Ma
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p. 451 - 459
(2016/10/19)
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- Binuclear dichlorido(η6-p-cymene)ruthenium(II) complexes with bis(nicotinate)- And bis (isonicotinate)-polyethylene glycol ester ligands
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Neutral binuclear ruthenium complexes 1-8 of the general formula [{RuCl2(η6-p-cym)}2 μ-(N∩N)] (N∩N=bis(nicotinate)- and bis (isonicotinate)-polyethylene glycol esters: (3-py)COO(CH2CH2O)nCO(3-py) and (4-py)COO(CH2CH2O)nCO(4-py), n =1-4), as well as mononuclear [RuCl2(η6-p-cym)((3-py)COO(CH2CH2OCH3)-κN)], complex 9, were synthesized and characterized using elemental analysis and electrospray ionization high-resolution mass spectrometry, infrared, 1H NMR and 13C NMR spectroscopies. Stability of the binuclear complexes in the presence of dimethylsulfoxide was studied. Furthermore, formation of a cationic complex containing bridging pyridine-based bidentate ligand was monitored using 1H NMR spectroscopy. Ligand precursors, polyethylene glycol esters of nicotinic (L1·2HCl-L4·2HCl and L9·HCl) and isonicotinic acid dihydrochlorides (L5·2HCl-L8·2HCl), binuclear ruthenium(II) complexes 1-8 and mononuclear complex 9 were tested for in vitro cytotoxicity against 518A2 (melanoma), 8505C (anaplastic thyroid cancer), A253 (head and neck tumour), MCF-7 (breast tumour) and SW480 (colon carcinoma) cell lines.
- Eichhorn, Thomas,Hey-Hawkins, Evamarie,Maksimovi-Ivani, Danijela,Moji, Marija,Schmidt, Jürgen,Mijatovi, Sanja,Schmidt, Harry,Kaluderovi, Goran N.
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- Synthesis and anti-hypertensive effects of the twin drug of Nicotinic Acid and Quercetin Tetramethyl Ether
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A novel twin drug consisting of nicotinic acid (VB3) and quercetin tetramethyl ether (QTME) has been synthesized as an antihypertensive in a total yield of 79.2% through methylation, hydrolysis, acylation and esterification starting from rutin. The structures of synthesized compounds were elucidated by 1H-NMR, 13C-NMR and elemental analysis. The anti-hypertensive effects of an oral daily dose (15 mg/kg) of the synthesized compounds in spontaneously hypertensive (SHR) rats and normotensive Wistar Kyoto (WKY) rats were analysed. The data demonstrate that the twin drug VB3-QTME both reduces the elevated blood pressure and prolongs the action time in SHR rats without effect on WKY rats. However, definitive evidence of a precise mechanism of action by which VB3-QTME might decrease blood pressure remains elusive. Based on the results, the therapeutic potential of this twin drug is discussed.
- Wang, Zhonglei,Yang, Liyan,Cui, Shuai,Liang, Yingxi,Zhang, Xiaohua
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p. 4791 - 4801
(2014/05/20)
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- NOVEL BIS-INDOLIC DERIVATIVES, A PROCESS FOR PREPARING THE SAME AND THEIR USES AS A DRUG
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The present invention relates to novel bis-indolic derivatives, processes for their preparation, and their potential use as new antibacterial drugs.
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Paragraph 0360
(2013/03/26)
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- BIS-INDOLIC DERIVATIVES, THEIR USES IN PARTICULAR AS ANTIBACTERIALS
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The present invention relates to novel bis-indolic derivatives, processes for their preparation, and their potential use as new antibacterial drugs.
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Page/Page column 48; 49
(2013/03/26)
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- BIS-INDOLIC DERIVATIVES, A PROCESS FOR PREPARING THE SAME AND THEIR USES AS A DRUG
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The present invention relates to novel bis-indolic derivatives, processes for their preparation, and their potential use as new antibacterial drugs.
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Page/Page column 75
(2013/03/26)
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- Consequence of presence and absence of π-clouds at strategic locations of designed binuclear Pd(II) complexes on packing: Self-assembly of self-assembly by intermolecular locking and packing
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Self-assembled binuclear coordination cages of general formula [Pd 2(N-N)2(L)2](X)4, 1a/b-4a/b are prepared by the combination of N,N′-bis(m-pyridyl)urea, L, with a variety of cis-protected palladium(II) components, Pd(N-N)(X)2. The cis-protecting units "N-N" employed for the synthesis of 1-4 are ethylenediamine (en), tetramethylethylenediamine (tmeda), 2,2′-bipyridine (bpy), and 1,10-phenanthroline (phen), respectively. The term "X" stands for nitrate and perchlorate for a and b, respectively. The assemblies are characterized by NMR and electrospray ionization mass spectrometry (ESI-MS) techniques, and in some cases (i.e., 1a, 2b, 3b, 4a, and 4b) the structures are confirmed by single crystal X-ray diffraction. The conformations of bound L in the crystal structures of all the Pd(II) complexes are found to be syn-syn. The influence of the presence and absence of π cloud at the cis-protecting units on the crystal packing has been studied in detail. In the packing of [Pd 2(phen)2L2](NO3)4, 4a, one unit of [Pd2(phen)2L2]4+ is associated with two other units by π-π stacking interactions thus giving a one-dimensional growth as envisioned on the basis of a design principle. In the case of [Pd2(en)2(L)2](NO3) 4, 1a, and [Pd2(tmeda)2(L)2] (ClO4)4, 2b, such packing is not observed due to the absence of π-cloud at the strategic locations, instead notable H-bonding interactions are seen. However, [Pd2(bpy)2(L) 2](ClO4)4, 3b, displays a π-π interactions using only two units of [Pd2(bpy)2(L) 2]4+(ClO4)-.
- Naranthatta, Mili C.,Das, Deepika,Tripathy, Debakanta,Sahoo, Himansu S.,Ramkumar, Venkatachalam,Chand, Dillip K.
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p. 6012 - 6022
(2013/03/13)
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- Phase transfer-catalyzed, one-pot synthesis of some novel N-pyrimidinyl-N'-nicotinyl thiourea derivatives
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A new series of acyl thiourea derivatives were synthesized in one-pot using PEG-600 as the phase transfer catalyst (PTC). The structures of title compounds were characterized by 1H NMR, IR, MS, and elemental analysis. In addition, the fungicidal activity of the acyl thiourea derivatives were tested, which showed that most of them exhibit moderate activity. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
- Liu, Xing-Hai,Tan, Cheng-Xia,Weng, Jian-Quan
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experimental part
p. 552 - 557
(2011/05/07)
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- Synthesis, crystal structure, DNA-binding and cytotoxicity in vitro of novel cis-Pt(II) and trans-Pd(II) pyridine carboxamide complexes
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In an attempt to establish fundamental structure-activity relationships (SAR) of Pt/Pd-based anti-tumour compounds, we have recently designed monodentate pyridyl amide ligand containing central amide units which possess external metal co-ordinating pyridyl group and internal amide functionality. It was prepared in one step from commercially available compounds in moderate to good yield. Surprisingly, treatment of K2[MCl4] [M = Pt(II), Pd(II)] with ligand N-(4-chlorophenyl)-3-pyridinecarboxamide (L) in the same reaction condition affords two different hydrogen-bonded polymers: cis-[PtL2Cl2]·CH3OH·DMF (1) and trans-[PdL2Cl2]·2DMF (2). Fluorescence analysis indicates that the two complexes can bind to fish sperm DNA (FS-DNA) and gel electrophoresis assay demonstrates the ability of the complexes to cleave the pBR322 plasmid DNA. The two complexes exhibit cytotoxic specificity and significant cancer cell inhibitory rate. Furthermore, cytotoxicity values are higher in the case of cis-Pt(II) complex than trans-Pd(II) complex in four different cancer cell lines.
- Shi, Chun-Yue,Gao, En-Jun,Ma, Shuang,Wang, Mei-Lin,Liu, Qi-Tao
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scheme or table
p. 7250 - 7254
(2011/01/12)
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- Mechanistic insights on the magnesium(II) ion-activated reduction of methyl benzoylformate with chelated NADH peptide β-lactam models
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(Chemical Equation Presented) Mechanistic details of the Mg2+ ion-activated enantioselective reduction of methyl benzoylformate have been investigated at a B3LYP/6-31G* theory level, using peptide NADH models 1 rigidified with a β-lactam ring. Computation of the reaction pathway revealed important structural differences between the intermediate NADH/Mg 2+/ArCOCO2R ternary complexes 3 and the corresponding transition states leading to enantiomeric methyl mandelates. Thus, ternary complexes showed the dihydronicotinamide moiety placed quasiequatorial to a seven-membered chelation pseudoplane including the two amide carbonyls and the Mg2+ cation, whereas productive transition states were strongly deformed with the dihydronicotinamide group oriented quasiaxial to the chelation pseudoplane. This chelation model was further applied to acyclic nonrigidified NADH models and, based on the fluxional mobility of the peptide chain bonds, experimental enantioselectivities were correctly predicted. Parallel experiments were also conducted in deuterated acetonitrile, using NMR techniques, to study the structure of the binary complexes 2 (NADH/Mg2+) and ternary complexes 3 (NADH/Mg2+/PhCOCO2Me). Finally, owing to the incorporation of two diastereotopic trimethylsilyl NMR-tags in the β-lactam-NADH peptidomimetics, a nonproductive ternary complex predicted by calculations could be observed and its structure characterized on the basis of ROESY experiments and molecular modeling.
- Aizpurua, Jesus M.,Palomo, Claudio,Fratila, Raluca M.,Ferron, Pablo,Benito, Ana,Gomez-Bengoa, Enrique,Miranda, Jose I.,Santos, Jose I.
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supporting information; experimental part
p. 6691 - 6702
(2009/12/30)
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- Biodegradable pyridinium ionic liquids: Design, synthesis and evaluation
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A range of ionic liquids (ILs) with a pyridinium cation were synthesised and their biodegradability was evaluated using the CO2 Headspace test (ISO 14593). ILs bearing an ester side chain moiety were prepared from either pyridine or nicotinic acid and showed high levels of biodegradation under aerobic conditions and can be classified as 'readily biodegradable'. In contrast, pyridinium ILs with alkyl side chains showed significantly lower levels of biodegradability in the same test. The utility of the biodegradable IL 6c as a reaction solvent for the Diels-Alder reaction was also investigated.
- Harjani, Jitendra R.,Singer, Robert D.,Garcia, M. Teresa,Scammells, Peter J.
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experimental part
p. 83 - 90
(2010/04/22)
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- Design and synthesis of eugenol derivatives, as potent 15-lipoxygenase inhibitors
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A group of 4-allyl-2-methoxyphenol (eugenol) esters were designed, synthesized, and evaluated as potential inhibitors of soybean 15-lipoxygenase (SLO). Compounds 4c, 4d 4f, 4p, and 4q showed the best IC50 in SLO inhibition (IC50 = 1.7, 2.3, 2.1, 2.2, and 0.017 μM, respectively). All compounds were docked into SLO active site and showed that allyl group of compounds is oriented toward the iron atom in the active site of SLO. It is assumed that lipophilic interaction of ligand-enzyme would be in charge of inhibiting the enzyme activity. The selectivity of eugenol derivatives in inhibiting 15-HLOb was also compared with 15-HLOa by molecular modeling and multiple alignment techniques.
- Sadeghian, Hamid,Seyedi, Seyed Mohammad,Saberi, Mohammad Reza,Arghiani, Zahra,Riazi, Mehdi
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p. 890 - 901
(2008/09/17)
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- PHARMACEUTICAL COMPOSITIONS FOR THE PREVENTION AND TREATMENT OF COMPLEX DISEASES AND THEIR DELIVERY BY INSERTABLE MEDICAL DEVICES
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The present invention relates to polyphenol-like compounds that are useful for inhibiting VCAM-1 expression, MCP-1 expression and/or SMC proliferation in a mammal. The disclosed compounds are useful for regulating markers of inflammatory conditions, including vascular inflammation, and for treatment and prevention of inflammatory and cardiovascular diseases and related disease states.
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Page/Page column 73
(2008/06/13)
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- Long chain aliphatic alcohol derivatives and methods of making and using same
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This application pertains to compounds comprising unbranched long chain aliphatic alcohols linked to a heterocyclic carboxylic acid moiety by means of an ester or ether linkage. The aliphatic alcohols may include aliphatic alcohols present in polycosanol, such as octacosanol. The heterocyclic carboxylic acid moieties include a 5-membered ring, a 6-membered ring, or a bicyclic ring. In one embodiment, the compounds of the invention include 1-octacosanyl nicotinate and salts thereof. The invention includes prodrugs, pharmaceutically acceptable salts, and pharmaceutical compositions of the compounds, and methods of making and using the compounds.
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Page/Page column 7; 8-9
(2008/06/13)
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- PYRAZOLOPYRIDINE DERIVATES
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New compounds of formula (I) and the salts, solvates and prodrugs thereof, wherein the meanings for the various substituents are as disclosed in the description. These compounds are useful as p38 kinase inhibitors.
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- 4-thia-1-aza-bicyclo[4,2,0]oct-2-ene derivatives
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A compound selected from the group consisting of a compound of the formula STR1 wherein R is selected from the group consisting of STR2 and Rb --NH--, Ra is an organic radical, Ri and Rj are individually selected from the group consisting of hydrogen, aliphatic hydrocarbon, aromatic hydrocarbon and heterocycle or taken together with the nitrogen atom to which they are attached form an optionally substituted ring, Rb is selected from the group consisting of carbocyclic aryl and heterocyclic aryl, both optionally substituted, R1A is selected from the group consisting of STR3 RA ' and RB ' are individually selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, ZA is selected from the group consisting of a simple bond, --O-- and optionally oxidize sulfur, R3A is selected from the group consisting of optionally substituted carbocyclic aryl and heterocyclic aryl, optionally substitute quaternary ammonium, acetyl, carbamoyl, alkoxycarbonyl, alkyl and haloalkyl of 1 to 4 carbon atoms, --CN and azido, R4 is selected from the group consisting of hydrogen and methoxy, A is selected from the group consisting of hydrogen, alkali metal, alkaline earth metal, magnesium, --NH4, an organic amine and esterified carboxy or --COOA is --COO?, n2 is an integer from 0 to 2 and their non-toxic, pharmaceutical acceptable acid addition salts having excellent antibiotic activity.
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- Brain-specific drug delivery
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The subject compounds, which are adapted for the site-specific/sustained delivery of centrally acting drug species to the brain, are: (a) compounds of the formula wherein [D] is a centrally acting drug species, and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine pyridinium salt redox carrier, with the proviso that when [DHC] is STR1 wherein R is lower alkyl or benzyl and [D] is a drug species containing a single NH2 or OH functional group, the single OH group when present being a primary or secondary OH group, said drug species being linked directly through said NH2 or OH function group to the carbonyl function of [DHC], then [D] must be other than a sympathetic stimulant, steroid sex hormone or long chain alkanol; and (b) non-toxic pharmaceutically acceptable salts of compounds of formula (I) wherein [D] is a centrally acting drug species and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine pyridinium salt redox carrier. The corresponding ionic pyridinium salt type drug/carrier entitles [D--QC]+ X- are also disclosed.
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- Method for treating male sexual dysfunction
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The invention provides a method for treating sexual dysfunction in male mammals using a compound of the formula[E--DHC] (I)or a non-toxic pharmaceutically acceptable salt thereof, wherein [E] is an estrogen and [DHC] is the reduced, biooxidizable, blood-brain barrier-penetrating, lipoidal form of a dihydropridine pyridinium salt redox carrier. Compositions for use in the subject method are also disclosed. A preferred compound for use in the method and compositions is an estradiol derivative, namely, 17β-[(1-methyl-1,4-dihydro-3-pyridinyl)carbonyloxy]estra-1,3,5(10)-trien-3-ol.
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- Method and compositions for weight control
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The invention provides a method for controlling mammalian body weight using a compound of the formula or a non-toxic pharmaceutically acceptable salt thereof, wherein [E] is an estrogen and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating, lipoidal form of a dihydropyridine pyridinium salt redox carrier. Novel compositions for weight control comprising a compound of formula (I) or its salt are also disclosed. A preferred compound for use in the subject method and compositions is an estradiol derivative, namely, 17 β-[(1-methyl-1,4-dihydro-3-pyridinyl)carbonyloxy]estra-1,3,5(10)-trien-3-ol.
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- Spectral, Electrochemical and Base-Binding Studies of Heterodinuclear Ruthenium-Cobalt Complexes of meso-α,α,α,α-Tetra(nicotinamidophenyl)porphine
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The spectral, electrochemical, and ligand addition properties of metal complexes of the modified porphyrin (nic)4H2TPP have been examined.The porphyrin has the feature that two metal ions may be coordinated and held in close proxomity to each other, one ion in the porphyrin ring and the other coordinated to the pyridine-like nitrogens of the nicotinamide pickets.The results for the RuCl2(nic)4CoTPP complex studied indicate that the "neutral" fixed axial ligand Ru(II)Cl2 has very little effect on the electrochemistry and spectroscopy of the cobalt porphyrin when compared with simple CoTPP.However, oxidation of Ru(II) to Ru(III) greatly increases the Lewis acid strength of Co(II) relative to the strength of that center in CoTPP.The binding constant for the Ru(III)-Co(II) species with pyridine is found to be three orders of magnitude larger than that for Ru(II)-Co(II); the binding constant for Ru(III)-Co(III) with pyridine is seven orders of magnitude greater than that for Ru(III)-Co(II).In the presence of high concentrations of N-methylimidazole, the Ru(III)-Co(III) appears to form a bis-adduct, presumably by allowing partial entry of a 1-MeIm molecule into the porphyrin pocket.
- Elliott, C. Michael,Arnette, J. Kenneth,Krebs, R. R.
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p. 4904 - 4911
(2007/10/02)
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- Brain-specific drug delivery
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The subject compounds, which are adapted for the site-specific/sustained delivery of centrally acting drug species to the brain, are: (a) compounds of the formula wherein [D] is a centrally acting drug species, and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine pyridinium salt redox carrier, with the proviso that when [DHC] is STR1 wherein R is lower alkyl or benzyl and [D] is a drug species containing a single NH2 or OH functional group, the single OH group when present being a primary or secondary OH group, said drug species being linked directly through said NH2 or OH functional group to the carbonyl function of [DHC], then [D] must be other than a sympathetic stimulant, steroid sex hormone or long chain alkanol; and (b) non-toxic pharmaceutically acceptable salts of compounds of formula (I) wherein [D] is a centrally acting drug species and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine pyridinium salt redox carrier. The corresponding ionic pyridinium salt type drug/carrier entities [D-QC]+ Y- are also disclosed.
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- Substitutions on Pyridines Activated by Oxazolines via Nucleophilic Additions or Metalation-Alkylation
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Pyridyloxazolines, derived from nicotinic acid or isonicotinic acid, have been shown to metalate at the 4- and 3-positions, respectively.These react with a variety of electrophiles to provide 4- and 3-substituted pyridines in good yield.Alternatively, 3-pyridyloxazolines, when treated with organolithium or Grignard reagents, give addition to the 4-position and provide a series of 4-substituted 1,4-dihydropyridines.
- Meyers, A. I.,Gabel, Richard A.
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p. 2633 - 2637
(2007/10/02)
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- Palladium-Catalyzed Reaction of Tributyltin Hydride with Acyl Chlorides. A Mild, Selective, and General Route to Aldehydes
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Tetrakis(triphenylphosphine)palladium(0), various palladium(II) complexes, and even PdCl2 in the presence of triphenylphosphine catalyze the reaction of acyl chlorides with tri-n-butyltin hydride to specifically give aldehydes under very mild conditions and in very good yields.The reaction is quite general and tolerates the presence of many other reducible groups on the acyl chloride.Tetrakis(triphenylphosphine)palladium(0) also catalyzes the tributyltin hydride reduction of α,β-unsaturated carbonyl compounds to saturated carbonyl compounds; however, α,β-unsaturated acyl chlorides may be reduced to α,β-unsaturated aldehydes with a very good selectivity.The mechanism of the catalytic reductions is discussed.
- Four, P.,Guibe, F.
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p. 4439 - 4445
(2007/10/02)
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- THE MASS SPECTRAL FRAGMENTATION BEHAVIOR OF PYRIDINE CARBOXYLIC AND THIOCARBOXYLIC ACID ESTERS
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The mass spectral fragmentation behavior of pyridine carboxylic acid and thioacid methyl esters shows several peculiarities not observed with other aromatic esters, viz., i.a., (a) COOCH3 groups in α-position are involved in rearrangement processes under participation of N; (b) neighboring COOCH3 groups fragment by ortho-effects; (c) COSCH3, CSOCH3 and CSSCH3 groups suffer complex rearrangements leading to, e.g. loss of CO, CH2CO or S2 from M+, especially when located in α-position.
- Budzikiewicz, H.,Lange, E.,Ockels, W.
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- 8-Oxa-3-azabicyclo(3.2.1)octane analgesic compositions and method of alleviating pain in animals
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Disclosed are compounds, having the following general formula, which are useful as analgesics in living animals. SPC1 Wherein R is a radical selected from the group consisting of aralkyl, aryl, aminoalkyl, arylalkanoyl, heteroaroyl, alkoxy substituted aroyl, alkenyl (C2 to C4), halogen substituted aralkyl, guanadinoalkyl, halogen substituted aroyl, alkyl substituted aroyl, halogen substituted arylalkanoyl, hexahydrobenzoyl, arylalkenoyl, o- or p-alkyl substituted phenylalkanoyl, alkyl substituted naphthylalkanoyl, alkanoyl (C3 to C20), haloalkyl substituted aroyl, alkoxy substituted aralkyl, heteroaralkyl, anilinocarbonyl, adamantanecarbonyl, arylsulfonyl, carboxyl substituted aroyl, hydroxyl substituted aroyl, alkanoyloxy substituted aroyl, arylglyoxylyl, alicyclic, arylene dicarbonyl-8-oxa-3-azabicyclo(3.2.1)octane, alkylene-8-oxa-3-azabicyclo (3.2.1)octane, alkylene dicarbonyl-8-oxa-3-azabicyclo(3.2.1)octane, and the pharmacologically acceptable acid addition salts thereof.
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