102852-52-8Relevant academic research and scientific papers
Studies on Ca2+ channel antagonists. 5-[(3,4-dimethoxyphenethyl)methylamino]-2-)3,4- dimethoxyphenyl)-2-isopropylpentyl isothiocyanate, a chemoaffinity ligand derived from verapamil
Theodore,Nelson,Zobrist,et al.
, p. 1789 - 1792 (1986)
Reduction of 1 (verapamil) afforded amine, which was converted with thiophosgene to isothiocyanate 3, a chemoaffinity ligand for Ca2+ channels. Compound 3 showed concentration-dependent negative inotropic effects in rat right myocardial ventric
Unveiling RNA-Binding Properties of Verapamil and Preparation of New Derivatives as Inhibitors of HIV-1 Tat-TAR Interaction
Martin, Céline,De Piccoli, Serena,Gaysinski, Marc,Becquart, Cécile,Azoulay, Stéphane,Di Giorgio, Audrey,Duca, Maria
, p. 207 - 216 (2020)
Targeting RNA using small molecules is now established as a very promising strategy for many therapeutic applications since coding and non-coding RNAs bear a pivotal role both in viral and bacterial infections as well as in diseases such as cancer. Here, we focused on HIV-1 TAR RNA as a promising target for the development of new anti-HIV therapies but also as an ideal model to validate the discovery of original RNA ligands. First, we performed an initial screening of a library of compounds against TAR that led to the discovery of verapamil, a marketed calcium-channel blocker, as a promising chemical structure for the development of new RNA ligands. The synthesis of a series of analogs of verapamil led to promising structure activity relationships and to the discovery of a conjugate between verapamil and an indole fragment, as an efficient and selective TAR binder able to inhibit Tat/TAR interaction with an IC50 of 18.8 μM. This work supports the potential of library screening for the discovery of original and selective RNA ligands and illustrates how existing drugs directed against protein targets still need to be studied for RNA binding as a promising strategy in the field of RNA targeting by small molecules.
DRUG DERIVATIVES
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Paragraph 0449; 0450, (2013/09/12)
The present invention relates to derivatives of known active pharmaceutical compounds. These derivatives are differentiated from the parent active compound by virtue of being redox derivatives of the active compound. This means that one or more of the functional groups in the active compound has been converted to another group in one or more reactions which may be considered to represent a change of oxidation state. We refer to these compounds generally as redox derivatives. The derivatives of the invention may be related to the original parent active pharmaceutical compound by only a single step transformation, or may be related via several synthetic steps including one or more changes of oxidation state. In certain cases, the functional group obtained after two or more transformations may be in the same oxidation state as the parent active compound (and we include these compounds in our definition of redox derivatives). In other cases, the oxidation state of the derivative of the invention may be regarded as being different from that of the parent compound. In many cases, the compounds of the invention have inherent therapeutic activity on their own account. In some cases, this activity relative to the same target or targets of the parent compound is as good as or better than the activity which the parent compound has against the target or targets.
DRUG DERIVATIVES
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Page/Page column 119, (2012/05/31)
The present invention relates to derivatives of known active pharmaceutical compounds. These derivatives are differentiated from the parent active compound by virtue of being redox derivatives of the active compound. This means that one or more of the functional groups in the active compound has been converted to another group in one or more reactions which may be considered to represent a change of oxidation state. We refer to these compounds generally as redox derivatives. The derivatives of the invention may be related to the original parent active pharmaceutical compound by only a single step transformation, or may be related via several synthetic steps including one or more changes of oxidation state. In certain cases, the functional group obtained after two or more transformations may be in the same oxidation state as the parent active compound (and we include these compounds in our definition of redox derivatives). In other cases, the oxidation state of the derivative of the invention may be regarded as being different from that of the parent compound. In many cases, the compounds of the invention have inherent therapeutic activity on their own account. In some cases, this activity relative to the same target or targets of the parent compound is as good as or better than the activity which the parent compound has against the target or targets.
Synthesis and study of new paramagnetic and diamagnetic verapamil derivatives
Bognár, Balázs,Ahmed, Shabnam,Lakshmi Kuppusamy,Selvendiran, Karuppaiyah,Khan, Mahmood,Jeko, József,Hankovszky, Olga H.,Kálai, Tamás,Kuppusamy, Periannan,Hideg, Kálmán
experimental part, p. 2954 - 2963 (2010/07/06)
New derivatives of verapamil (1) modified with nitroxides and their precursors were synthesized and screened for reactive oxygen species (ROS)-scavenging activities. The basic structure was modified by changing the nitrile group to an amide or the methyl substituent on tertiary nitrogen with nitroxides and their reduced forms (hydroxylamine and secondary amines). Among the new verapamil derivatives compound 16B [Mohan, I. K.; Kahn, M.; Wisel, S.; Selvendiran, K.; Sridhar, A.; Carnes, C.A.; Bognár, B.; Kálai, T.; Hideg, K.; Kuppusamy, P. Am. J. Physiol. Heart Circ. Physiol. 2009, 296, 140], modified with hydroxylamine salt of 2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridine-1-yloxyl proved to be the best ROS scavenger in vitro and protected HSMC and CHO cells against H2O2 induced damage.
