- Multiple Halogenation of Aliphatic C?H Bonds within the Hofmann–L?ffler Manifold
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An innovative approach to position-selective polyhalogenation of aliphatic hydrocarbon bonds is presented. The reaction proceeded within the Hofmann-L?ffler manifold with amidyl radicals as the sole mediators to induce selective 1,5- and 1,6-hydrogen-atom transfer followed by halogenation. Multiple halogenation events of up to four innate C?H bond functionalizations were accomplished. The broad applicability of this new entry into polyhalogenation and the resulting synthetic possibilities were demonstrated for a total of 27 different examples including mixed halogenations.
- Del Castillo, Estefanía,Martínez, Mario D.,Bosnidou, Alexandra E.,Duhamel, Thomas,O'Broin, Calvin Q.,Zhang, Hongwei,Escudero-Adán, Eduardo C.,Martínez-Belmonte, Marta,Mu?iz, Kilian
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supporting information
p. 17225 - 17229
(2018/11/10)
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- Tricyclic [1,2,4]triazine 1,4-dioxides as hypoxia selective cytotoxins
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A series of novel tricyclic triazine-di-N-oxides (TTOs) related to tirapazamine have been designed and prepared. A wide range of structural arrangements with cycloalkyl, oxygen-, and nitrogen-containing saturated rings fused to the triazine core, coupled with various side chains linked to either hemisphere, resulted in TTO analogues that displayed hypoxia-selective cytotoxicity in vitro. Optimal rates of hypoxic metabolism and tissue diffusion coefficients were achieved with fused cycloalkyl rings in combination with both the 3-aminoalkyl or 3-alkyl substituents linked to weakly basic soluble amines. The selection was further refined using pharmacokinetic/pharmacodynamic model predictions of the in vivo hypoxic potency (AUCreq) and selectivity (HCD) with 12 TTO analogues predicted to be active in vivo, subject to the achievement of adequate plasma pharmacokinetics.
- Hay, Michael P.,Hicks, Kevin O.,Pchalek, Karin,Lee, Ho H.,Blaser, Adrian,Pruijn, Frederik B.,Anderson, Robert F.,Shinde, Sujata S.,Wilson, William R.,Denny, William A.
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supporting information; experimental part
p. 6853 - 6865
(2009/12/03)
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- TRICYCLIC 1,2,4-TRIAZINE OXIDES AND COMPOSITIONS THEREFROM FOR THERAPEUTIC USE IN CANCER TREATMENTS
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The invention relates to novel tricyclic 1,2,4-triazine-1-oxides and novel tricyclic 1,2,4-triazine-1,4-dioxides of formula: (I); and to related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.
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Page/Page column 120
(2008/06/13)
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- 4-SUBSTITUTED IMIDAZOLE-2-THIONES AND IMIDAZOL- 2-ONES AS AGONISTS OF THE ALPHA- 2B AND ALPHA-2C ADRENERGIC RECEPTORS
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Compounds of Formula (I): where X is S and the variables have the meaning defined in the specification are specific or selective to alpha2B and/or alpha2C adrenergic receptors in preference over alpha2A adrenergic receptors, and as such have no or only minimal cardivascular and/or sedatory activity. These compounds of Formula (I) are useful as medicaments in mammals, including humans, for treatment of diseases and or alleviations of conditions which are responsive to treatment by agonists of alpha2B adrenergic receptors. Compounds of Formula (I) where X is O also have the advantageous property that they have no or only minimal cardivascular and/or sedatory activity and are useful for treating pain and other conditions with no or only minimal cardivascular and/or sedatory activity.
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Page 107, 108
(2008/06/13)
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- Synthesis and thromboxane A2 antagonistic activity activity of indane derivatives.
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A new series of indane derivatives were prepared and evaluated for their thromboxane A2 (TXA2, 1) antagonistic activity. Among these compounds, 24a (Z-335) was found to be a potent TXA2 antagonist in oral administration.
- Shinozaki,Sato,Iwakuma,Sato,Kurimoto,Yoshida
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p. 401 - 406
(2007/10/03)
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- Remedy for hyperlipidemia
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The invention relates to a remedy for hyperlipidemia, which comprises, as an active ingredient, an indane derivative represented by the general formula (1): STR1 wherein R1 means an alkyl group having 1-12 carbon atoms, a benzyl group, a styryl
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- Indan derivative and thromboxane antagonist containing the same
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The present invention relates to indan derivatives represented by the formula (1) or pharmaceutically acceptable salts thereof: STR1 [wherein R1 represents C1 to C12 alkyl, benzyl, styryl, naphthyl, optionally substituted phenyl or optionally s
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- New potent prolyl endopeptidase inhibitors: Synthesis and structure- activity relationships of indan and tetralin derivatives and their analogues
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New compounds were synthesized by structural modification of 1-[1-(4- phenylbutanoyl)-L-prolyl]-pyrrolidine (SUAM-1221, 1) or 1-[1- (benzyloxycarbonyl)-L-prolyl]prolinal (Z-Pro-prolinal, 2) and were tested for in vitro inhibitory activities against purified prolyl endopeptidase (PEP) from canine brain. In a series of compounds which lack a formyl or a cyano group, 3-[3-[(S)-2-(1,2,3,4-tetrahydronaphthyl)acetyl]-L- thioprolyl]thiazolidine (13) exhibited an approximately 20-fold (IC50 = 2.3 nM) increase in potency compared with 1. Compounds having a formyl or a cyano group showed much more potent inhibitory activities than those which lack such a functional group. Among all compounds tested in vitro, 1-[1-(2- indanylacetyl)-L-prolyl]prolinal (27), 1-[1-[(S)-2-(1,2,3,4- tetrahydronaphthyl)acetyl]-L-prolyl]prolinal (29), 1-[3-[(S)-2-(1,2,3,4- tetrahydronaphthyl)-acetyl]-L-thioprolyl]prolinal (30), (S)-2-cyano-1-[2- [(S)-2-(1,2,3,4-tetrahydronaphthyl)acetyl]-L-prolyl]pyrrolidine (34), and (S)-2-cyano-1-[3-[(S)-2-(1,2,3,4-tetrahydronaphthyl)acetyl]-L- thioprolyl]pyrrolidine (35) showed an approximately 2-fold (IC50 ? 0.5 nM) increase in potency compared with 2. The structure-activity relationships of these compounds are discussed.
- Tanaka,Niwa,Nishioka,Yamanaka,Torizuka,Yoshinaga,Kobayashi,Ikeda,Arai
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p. 2071 - 2078
(2007/10/02)
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- Diene intermediates for indantetrol derivatives
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Compounds are provided having the structure SPC1 Wherein n is 1, 2 or 3, m and m' are 0, 1 or 2, R1, R2, R3 and R4 may be the same or different and can be hydrogen, lower alkyl, halolower alkyl, acyl, lower alkoxy-carbonyl EQU1 amido EQU2 or lower alkoxyalkylene, X is a straight or branched bivalent aliphatic radical and Y is EQU3 These compounds are useful in the treatment of hypertension.
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