7651-83-4Relevant articles and documents
A solution- and solid-state investigation of medium effects on charge separation in metastable photomerocyanines
Patel, Dinesh G.,Paquette, Michelle M.,Kopelman, Roni A.,Kaminsky, Werner,Ferguson, Michael J.,Frank, Natia L.
, p. 12568 - 12586 (2010)
The effects of solution-state dielectric and intermolecular interactions on the degree of charge separation in metastable spirooxazine photomerocyanines (PMCs) is investigated. We report the first X-ray diffraction (XRD) analyses of an open form, a metastable photomerocyanine, of the spirooxazine class of photochromic molecules in two derivatives: spiro[azahomoadamantane- isoquinolinoxazine] (1) and spiro[azahomoadamantane-phenanthrolinoxazine] (2). Using the results of XRD analysis of the open photomerocyanine forms, in conjunction with computation, solvatochromism, and solution NMR studies, we have investigated the effect of the medium on the ground-state structure of these photomerocyanines. Solvatochromism and NMR chemical shift studies of 1 and 2 support the assignment of a quinoidal structure in nonpolar solvents and a zwitterionic structure in high-polarity solvents. The effect of azahomoadamantyl substitution is explored by comparing 1 and 2 with the analogous indolyl derivatives, spiro[indoline-isoquinolinoxazine] (3) and spiro[indoline- phenanthrolinoxazine] (4) through XRD analysis of the closed spirooxazine (SO) forms, solution-state kinetic experiments, solvatochromism, and NMR studies. Longer Cspiro-O bond lengths in the SO form and slower rates of thermal PMC → SO isomerization for the azahomoadamantyl derivatives are associated with greater zwitterionic character in the PMC form, as found in the solvatochromism studies. XRD analysis of photomerocyanines 1 and 2 indicate a greater contribution from the canonical zwitterionic resonance form relative to the quinoidal form in the solid state. Structural differences observed in two pseudopolymorphs of 2-PMC suggest that the degree of charge-separated character is influenced by the crystal packing environment. These results provide direct structural evidence for the effects of the medium polarity on charge-separated states of photomerocyanines.
Photochromism of a spirooxazine in the single crystalline phase
Patel, Dinesh G.,Benedict, Jason B.,Kopelman, Roni A.,Frank, Natia L.
, p. 2208 - 2210 (2005)
The single crystals of a closed form spirooxazine spiro[azahomoadamantane- isoquinolinoxazine] were found for the first time to undergo photocoloration processes consistent with photochromism in the single crystalline phase. The Royal Society of Chemistry 2005.
Copper-catalyzed hydrolysis of bromoisoquinolines: Preparation of hydroxyisoquinolines
Xingjun, Jiang,Jianbo, He,Hongli, Chen,Weiqing, Yang,Yuanyuan, Zhang,Menglin, Ma
, p. 65 - 70 (2019/01/16)
A complex phenomenon was observed in the process of preparing hydroxyisoquinoline through copper-catalyzed hydrolysis of bromoisoquinoline. The copper (II) complexes of hydroxyisoquinoline (L2Cu.5H2O) were characterized by high resolution mass spectra, thermogravimetric analysis, IR, 1H nuclear magnetic resonance (NMR), and 2D-NMR. The Cu (II) complexes were mononuclear and coordinated with oxygen and nitrogen atom of two hydroxyisoquinoline and five water molecules in which a strong hydrogen bond was present. Two optimized methods had been studied to prevent the formation of copper (II) complexes. The isoquinoline with 4, 5, 6, 7, and 8 hydroxyl substitutions were successfully prepared by copper-catalyzed hydrolysis of corresponding bromoisoquinoline and then workup by sodium sulfide or adjusted pH by dry ice or carbon dioxide gas.
Total synthesis of (±)-cortistatin J from furan
Nilson, Mark G.,Funk, Raymond L.
supporting information; experimental part, p. 12451 - 12453 (2011/10/09)
A concise, diastereoselective total synthesis of (±)-cortistatin J has been completed in 20 steps from furan. Key steps include an intramolecular [4 + 3] cyclization of a disubstituted furan with a (Z)-2-(trialkylsilyloxy)-2- enal to construct the tetracyclic core and a (Z)-vinylsilane/iminium ion cyclization to form the A ring.
Farnesyl pyrophosphate synthase enantiospecificity with a chiral risedronate analog, [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501): Synthetic, structural, and modeling studies
Deprele, Sylvine,Kashemirov, Boris A.,Hogan, James M.,Ebetino, Frank H.,Barnett, Bobby L.,Evdokimov, Artem,McKenna, Charles E.
, p. 2878 - 2882 (2008/12/23)
The complex formed from crystallization of human farnesyl pyrophosphate synthase (hFPPS) from a solution of racemic [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501, 8), a chiral analog of the anti-osteoporotic drug risedronate, contained the R enantiomer in the enzyme active site. This enantiospecificity was assessed by computer modeling of inhibitor-active site interactions using Autodock 3, which was also evaluated for predictive ability in calculations of the known configurations of risedronate, zoledronate, and minodronate complexed in the active site of hFPPS. In comparison with these structures, the 8 complex exhibited certain differences, including the presence of only one Mg2+, which could contribute to its 100-fold higher IC50. An improved synthesis of 8 is described, which decreases the number of steps from 12 to 8 and increases the overall yield by 17-fold.
Highly potent and selective zwitterionic agonists of the δ-opioid receptor. Part 1
Middleton, Donald S.,Maw, Graham N.,Challenger, Clare,Jessiman, Alan,Johnson, Patrick S.,Million, William A.,Nichols, Carly L.,Price, Jenny A.,Trevethick, Michael
, p. 905 - 910 (2008/12/20)
A series of zwitterionic δ-opioid agonists, with targeted physicochemistry, as a strategy to limit potential for CNS exposure, were prepared. These agents were found to possess exquisite potency and selectivity over mu and κ-opiate activity. Furthermore,
Compounds as delta opioid agonists
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, (2008/06/13)
Compounds of the formula (I)—shown below—are described. The compounds are useful in the manufacture of a pharmaceutical composition for preventing or treating inflammatory diseases such as arthritis, psoriasis, asthma, or inflammatory bowel disease, disorders of respiratory function, gastrointestinal disorders such as functional bowel disease, functional GI disorders such as irritable bowel syndrome, functional diarrhoea, functional distension, functional pain, non-ulcerogenic dyspepsia or others associated with disorders of motility or secretion, urogenital tract disorders such as incontinence, as analgesics for treating pain including non-somatic pain, or as immunosuppressants to prevent rejection in organ transplant and skin graft.
Heterocyclic derivatives and their use as antithrombotic agents
-
, (2008/06/13)
The present invention relates to antithrombotic compounds comprising the group Q, Q having formula (I), wherein the substructure (i) is a structure selected from (a, b and c), wherein X is O or S; X′ being independently CH or N; and m is 0, 1, 2 or 3; wherein the group Q is bound through an oxygen atom or an optionally substituted nitrogen or carbon atom, or a pharmaceutically acceptable salt thereof or a prodrug thereof. The compounds of the invention are therapeutically active and in particular are antithrombotic agents.
Improved procedures for large preperation of 6- and 7-oxy-substituted isoquinolines and a convenient work-up protocol for titanium supported reactions
Kucznierz, Ralf,Dickhaut, Joachim,Leinert, Herbert,Von Der Saal, Wolfgang
, p. 1617 - 1625 (2007/10/03)
Improved procedures for large scale preparation of oxy-substituted isoquinolines are reported. Moreover, a simple and convenient protocol for alkaline work-up of titanium containing reaction mixtures is given, which is expected to be of general interest even for reactions on a technical scale.
Tetrahydro-isoquinoline-based factor Xa inhibitors
Kucznierz, Ralf,Grams, Frank,Leinert, Herbert,Marzenell, Klaus,Engh, Richard A.,Von der Saal, Wolfgang
, p. 4983 - 4994 (2007/10/03)
Derivatives of (2-amidino-1,2,3,4-tetrahydro-isoquinolin-7- yloxy)phenylacetic acid (TIPAC) were developed as inhibitors of factor Xa (fXa). The compounds are prepared using 15 synthetic steps on average. The most potent compounds (14, 17, 22-26) display inhibition constants of K(i) = 21-55 nM but do not inhibit thrombin (K(i) = 5-> 100 μM) and only weakly inhibit trypsin (K(i) = 0.08-5 μM). They bear a second basic moiety, e.g., substituted 1-(iminomethyl)piperidines, which is linked to C-4 of the phenyl group of TIPAC via an oxygen atom. The inhibition constants of these compounds are almost independent of the size of the (iminomethyl)piperidine substituent. Due to the fact that fXa displays two cation binding sites, namely, the S1 and S4 sites, in principle two binding modes are conceivable for the novel dibasic fXa inhibitors. Molecular modeling experiments based on the X-ray structures of uninhibited fXa and the DX-9065a/fXa complex were carried out. The results taken together with the inhibition constants clearly favor one binding mode: the tetrahydro-isoquinoline fills the S1 pocket even better than the naphthalene moiety of DX-9065a, and the (iminomethyl)piperidine residues occupy the S4 site.
