- Synthesis of Indole-Dihydroisoquinoline Sulfonyl Ureas via Three-Component Reactions
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Isoquinolines activated with sulfamoyl chlorides were reacted with indoles in a 3-component reaction to generate a library of dihydroisoquinoline derivatives. Using a differential protecting group strategy, products could be further derivatised. Synthesis of isoquinoline starting materials using several different methods is also described.
- Pearson, Stuart E.,Fillery, Shaun M.,Goldberg, Kristin,Demeritt, Julie E.,Eden, Jonathan,Finlayson, Jonathan,Patel, Anil
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p. 4963 - 4981
(2018/12/13)
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- Highly potent and selective zwitterionic agonists of the δ-opioid receptor. Part 1
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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,
- Middleton, Donald S.,Maw, Graham N.,Challenger, Clare,Jessiman, Alan,Johnson, Patrick S.,Million, William A.,Nichols, Carly L.,Price, Jenny A.,Trevethick, Michael
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p. 905 - 910
(2008/12/20)
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- Discovery of novel tetrahydroisoquinoline derivatives as potent and selective factor Xa inhibitors
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A series of novel 2,7-disubstituted tetrahydroisoquinoline derivatives were designed and synthesized. Among these derivatives, compounds 1 and 2 (JTV-803) exhibited potent inhibitory activity against FXa and good selectivity with respect to other serine proteases (thrombin, plasmin, and trypsin). In addition, compound 2 exhibited potent anti-FXa activity after intravenous and oral administration to cynomolgus monkey, and showed a dose-dependent antithrombotic effect in a rat model of venous thrombosis.
- Ueno, Hiroshi,Yokota, Katsuyuki,Hoshi, Jun-Ichi,Yasue, Katsutaka,Hayashi, Mikio,Uchida, Itsuo,Aisaka, Kazuo,Hase, Yasunori,Katoh, Susumu,Cho, Hidetsura
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p. 185 - 189
(2007/10/03)
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- AMINOISOQUINOLINE DERIVATIVES
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Aminoisoquinoline derivatives represented by formulae (I and II), analogs thereof or pharmaceutically acceptable salts of the same. Because of having excellent inhibitory effects on activated blood coagulation factor X, these compounds are useful as active ingredients in anticoagulants or preventives/remedies for thrombosis or embolism.
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- Compounds as delta opioid agonists
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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.
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- Heterocyclic derivatives and their use as antithrombotic agents
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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.
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- Improved procedures for large preperation of 6- and 7-oxy-substituted isoquinolines and a convenient work-up protocol for titanium supported reactions
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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.
- Kucznierz, Ralf,Dickhaut, Joachim,Leinert, Herbert,Von Der Saal, Wolfgang
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p. 1617 - 1625
(2007/10/03)
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- Thio-substituted cyclic phosphonate compounds, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism
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The present invention relates to thio-substituted cyclic phosphonate compounds including bisphosphonates and phosphonoalkylphosphinates, and the pharmaceutically-acceptable salts and esters thereof. The present invention further relates to pharmaceutical compositions containing a safe and effective amount of a compound of the present invention, and pharmaceutically-acceptable excipients. Finally, the present invention relates to methods for treating or preventing pathological conditions characterized by abnormal calcium and phosphate metabolism in humans or other mammals including treating or preventing osteoporosis and arthritis, especially rheumatoid arthritis and osteoarthritis. The compounds may be monocyclic or bicyclic and have the following general structure: STR1 wherein (a) X and Y are independently selected from nil, O, S, and N; (b) R is PO3 H2 or P(O)(OH)R4, wherein R4 is substituted or unsubstituted C1 -C8 alkyl; (c) m and n are integers from 0 to 5, and m+n equals 0 to 5; (d) p and q are integers from 0 to 3, and p+q equals 0 to 3; (e) s is an integer from 0 to 2 and when X is nil and m+n=0, s=2; and (f) R1 and R2 are selected from various substituents; provided that at least one thio substituent is present.
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- Quaternary nitrogen-containing phosphonate compounds, pharmaceutical compositions, and methods of treating abnormal calcium and phosphate metabolism and methods of treating and preventing dental calculus and plaque
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The present invention relates to quaternary nitrogen-containing phosphonate compounds, and the pharmaceutically-acceptable salts and esters thereof and having the general structure: STR1 wherein R1, R2, R5 and R8 are defined in claim 1, m and n are integers from 0 to 10; m+n is from 0 to 10; Z is a saturated, unsaturated, or aromatic, monocyclic or polycyclic carbocycle or monocyclic or polycyclic heterocycle containing one or more heteroatoms selected from O, S, or N, wherein at least one heteroatom is a quaternary nitrogen atom; R is COOH; PO3 H2 ; SO3 H; or P(O)(OH)R4, wherein R4 is substituted or unsubstituted alkyl of 1-8 carbon atoms; The present invention further relates to pharmaceutical compositions containing a safe and effective amount of a compound of the present invention, and pharmaceutically-acceptable excipients. Finally, the present invention relates to methods for treating or preventing pathological conditions characterized by abnormal calcium and phosphate metabolism such as osteoporosis, rheumatoid arthritis, and osteoarthritis in humans or other mammals and to methods for treating or preventing dental calculus, plaque and gingivitis.
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- Cyclopalladiated Aromatic Imines in Organic Synthesis: The Preparation of Cinnamonitriles, Cinnamates, Unsymmetrical Stilbenes, Isoquinolones, and Isoquinolines
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The preparation and characterisation of some new ortho-palladiated benzaldimine complexes and their reaction with olefins are described.The reaction of di-μ-1-chloro-bis(2-alkyl-2,1-benzazapalladole) complexes (1) with styrene in trifluoroacetic acid-acetic acid mixtures yielded stilbene-2-carbaldehydes (10).These were converted into 2-methyl-3-phenyl-1(2H)-isoquinolones (12) via a mercury(II) mediated cyclisation of the N-methylimine derivatives of the stylbenes.Reaction of the complexes (1) with methyl acrylate produced methyl 2-(N-t-butyliminomethyl)cinnamates (7; Y=CO2Me) and with acrylonitril, the 2-(N-t-butyliminomethyl)cinnamonitriles (7; Y=CN), which upon in situ thermolysis gave the corresponding isoquinolines (8).
- Girling, Ian R.,Widdowson, David A.
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p. 1317 - 1324
(2007/10/02)
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- CYCLOPALLADATED IMINES IN SYNTHESIS 2: A NEW SYNTHESIS OF ISOQUINOLINES
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Reaction of cyclopalladated arylimines with acrylonitrile, followed by thermolysis gives isoquinolines by an electrocyclic ring forming process and a subsequent eliminative aromatisation step.
- Girling, I. R.,Widdowson, D. A.
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p. 4281 - 4284
(2007/10/02)
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- A ONE-POT ISOQUINOLINE SYNTHESIS BY CYCLODEHYDROGENATION OF BENZYLAMINOACETALS WITH CHLOROSULFONIC ACID
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A direct preparation of the fully aromatized isoquinolines (3a-l) by the cyclodehydrogenation of benzylamnoacetals (2a-l) with chlorosulfonic acid is described.Comparing the behavior of chlorosulfonic acid with that of sulfuric acid toward 1,2-dihydroisoquinoline, it is able to be suggested that benzylaminoacetals were cyclized first to 1,2-dihydroisoquinolines, subsequently, dehydrogenated to the fully aromatized isoquinolines by the hydride abstraction with ClSO3H.Subtitution by a larger R3 group than isopropyl in the acetal ArCH(R3)NHCH2CH(OEt)2, interfered this second step, so the corresponding isoquinolines could not be obtained.
- Kido, Kazuko,Watanabe, Yasuo
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p. 1151 - 1154
(2007/10/02)
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