- Oxidative degradation of the antihypertensive drug losartan by alkaline copper(III) periodate complex in the presence and absence of ruthenium(III) catalyst: a kinetic and mechanistic study of losartan metabolite
-
Spectrophotometric kinetic technique has been used to study the oxidation of losartan by diperiodatocuprate(III) (DPC) in the presence and absence of ruthenium(III) catalyst in aqueous alkaline medium at constant ionic strength of 0.90 mol dm-3
- Bolattin, Mallavva B.,Meti, Manjunath D.,Nandibewoor, Sharanappa T.,Chimatadar, Shivamurti A.
-
-
Read Online
- Synthesis and evaluation of new designed multiple ligands directed towards both peroxisome proliferator-activated receptor-γ and angiotensin II type 1 receptor
-
Because of the complex biological networks, many pathologic disorders fail to be treated with a molecule directed towards a single target. Thus, combination therapies are often necessary, but they have many drawbacks. An alternative consists in building molecules intended to interact with multiple targets, called designed multiple ligands. We followed such a strategy in order to treat metabolic syndrome, by setting up molecules directed towards both type 1 angiotensin II (AT1) receptor and peroxisome proliferator-activated receptor-γ (PPAR-γ). For this purpose, many molecules were prepared by merging both pharmacophores following three different strategies. Their ability to activate PPAR-γ and to block AT1 receptors were evaluated in vitro. This strategy led to the preparation of many new PPAR-γ activating and AT1 blocking molecules. Among them, some exhibited both activities, highlighting the convenience of this approach.
- Meyer, Maxime,Foulquier, Sébastien,Dupuis, Fran?ois,Flament, Stéphane,Grimaud, Linda,Henrion, Daniel,Lartaud, Isabelle,Monard, Gérald,Grillier-Vuissoz, Isabelle,Boisbrun, Michel
-
-
Read Online
- A convenient synthesis by microwave irradiation of an active metabolite (EXP-3174) of losartan
-
A novel and convenient microwave-assisted synthesis of an active metabolite (EXP-3174) of losartan is described. Room temperature and microwave irradiation of the reactions are compared. Synthesis by microwave irradiation gave the desired compound in higher yields and in shorter reaction times than those obtained at room temperature.
- Santagada, Vincenzo,Fiorino, Ferdinando,Perissutti, Elisa,Severino, Beatrice,Terracciano, Sara,Teixeira, Cleber Evandro,Caliendo, Giuseppe
-
-
Read Online
- SYNTHESIS OF DEUTERATED ALDEHYDES
-
Described are methods for preparing a deuterated aldehyde using N-heterocyclic carbene catalysts in a solvent comprising D2O. The methods may be used to convert a wide variety of aldehydes (e.g., aryl, alkyl, or alkenyl aldehydes) to C-1 deuterated aldehydes under mild reaction conditions without functionality manipulation.
- -
-
Paragraph 00192
(2021/03/13)
-
- Preparing method for EXP-3174
-
The invention discloses a preparing method for EXP-3174. The preparing method is characterized in that losartan is used as a starting raw material and is prepared into EXP-3174 through two-step oxidation. The preparing method has the greatest advantages that a reaction is moderate, the number of side reactions is small, aftertreatment is simple, and EXP-3174 with the purity of 99.9% can be obtained without column chromatography isolation.
- -
-
Paragraph 0015
(2016/10/09)
-
- DRUG DERIVATIVES
-
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.
- -
-
Paragraph 0186; 0190
(2013/09/12)
-
- New losartan-hydrocaffeic acid hybrids as antihypertensive-antioxidant dual drugs: Ester, amide and amine linkers
-
We report new examples of a series of losartan-hydrocaffeic hybrids that bear novel ester, amide and amine linkers. These compounds were made by linking hydrocaffeic acid to the side chain of losartan at the C-5 position of the imidazole ring through different strategies. Experiments performed in cultured cells demonstrate that these new hybrids retain the ability to block the angiotensin II effect and have increased antioxidant ability. Most of them reduced arterial pressure in rats better or as much as losartan.
- García, Gonzalo,Serrano, Isabel,Sánchez-Alonso, Patricia,Rodríguez-Puyol, Manuel,Alajarín, Ramón,Griera, Mercedes,Vaquero, Juan J.,Rodríguez-Puyol, Diego,álvarez-Builla, Julio,Díez-Marqués, María L.
-
experimental part
p. 90 - 101
(2012/07/13)
-
- DRUG DERIVATIVES
-
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.
- -
-
Page/Page column 69
(2012/05/31)
-
- PROCESS FOR PRODUCTION OF BIPHENYL DERIVATIVE
-
The invention provides a production method of a biaryltetrazole derivative useful as an intermediate for an angiotensin II receptor antagonist. The method comprises reacting an aryltetrazole derivative with a benzene derivative, deprotecting or reducing the resulting compound, and halogenating the deprotected or reduced compound
- -
-
Page/Page column 32-33
(2012/09/22)
-
- Synthesis of angiotensin II receptor blockers by means of a catalytic system for C-H Activation
-
A highly efficient catalytic system for C-H activation has been worked out that involves inexpensive RuCl3·xH2O and a specific amount of PPh3. This procedure has been successfully applied to a practical synthesis of angiotensin II receptor blockers (ARBs). The residual ruthenium that existed in the reaction mixture was thoroughly removed by treatment with properly selected metal scavengers. The new process permits ready access to the important class of drugs in a highly atom-economical and sustainable manner (Figure presented).
- Seki, Masahiko,Nagahama, Masaki
-
p. 10198 - 10206
(2012/02/03)
-
- Process for the preparation of losartan
-
The invention relates to a improved process for the preparation of Losartan and its potassium salt, which comprises: (i) reacting bromo OTBN with BCFI in the presence of a base and a phase transfer catalyst to produce a cyano aldehyde; reacting the formed cyano aldehyde with sodium azide in the presence of tributyl tin chloride to produce aldehyde tetrazole; reducing the formed aldehyde tetrazole with sodium borohydride to produce Losartan; and, if desired, converting the formed Losartan to its potassium salt by known method.
- -
-
Page/Page column 8
(2010/09/07)
-
- PROCESS FOR THE PREPARATION OF LOSARTAN
-
The invention relates to a improved process for the preparation of Losartan and its potassium salt, which comprises (i) reacting bromo OTBN with BCFI in the presence of a base and a phase transfer catalyst to get cyano aldehyde, reacting the cyano aldehyde sodium azide in the presence of tributyl tin chloride to form aldehyde tetrazole , reducing the aldehyde tetrazole with sodium borohydride to give Losartan and , if desired , converting it to its potassium salt by known method .
- -
-
Page/Page column 16-17; 19-20
(2008/06/13)
-
- New NO-releasing pharmacodynamic hybrids of losartan and its active metabolite: Design, synthesis, and biopharmacological properties
-
In a preliminary work, we reported two NO-sartans, possessing the characteristics of an AT1 antagonist and a "slow NO donor", obtained by adding NO-donor side chains to losartan 1. The NO release from an NO-sartan should be modulated in order to strengthen the antihypertensive activity of the native drug and to ensure additional effects, such as the antiplatelet and anti-ischemic ones. To obtain a collection of proto-typical NO-sartans, showing different rates of NO release, new NO-donor moieties have been linked to 1 or its active metabolite 2 (EXP 3174). Almost all the synthesized compounds exhibited both AT1-antagonist and NO-mediated vasorelaxing properties, with a wide range of NO-releasing rates. Further pharmacological investigation on compound 4a showed that it possessed antihypertensive and cardiac antihypertrophic effects similar to those of the reference AT1-blocking or ACE-inhibiting drugs. Furthermore, the additional anti-ischemic cardio-protective properties and antiplatelet effects of 4a have been preliminarily investigated.
- Breschi, Maria C.,Calderone, Vincenzo,Digiacomo, Maria,Macchia, Marco,Martelli, Alma,Martinotti, Enrica,Minutolo, Filippo,Rapposelli, Simona,Rossello, Armando,Testai, Lara,Balsamo, Aldo
-
p. 2628 - 2639
(2007/10/03)
-
- Use of an angiotensin II receptor antagonist for the preparation of drugs to increase the survival rate of renal transplant patients
-
The present invention relates to the use, for the preparation of drugs to increase the survival rate of transplant patients, including renal and heart transplant patients, of a therapeutically effective amount of an angiotension II receptor antagonist compound, such as the class of substituted imidazoles represented by formula (I) and in particular by losartan potassium, 2-butyl-4-chloro-[(2′-tetrazol-5-yl)biphenyl-4-il]methyl]-5-(hydroxymethyl)imidazole potassium salt.
- -
-
-
- Tri-higher alkyl tin azide and its use
-
Disclosed are a compound of the formula (R)3 SnN3, wherein R is a C7-18 alkyl, and a process for producing a tetrazolylbenzene compound which comprises reacting a cyanobenzene compound with a (R)3 SnN3. This process is useful for a safe and commercially profitable production of the tetrazolylbenzene compound which is employed for producing a tetrazole derivative having a hypotensive action based on angiotensin II-antagonizing activity or a production intermediate thereof.
- -
-
-
- ANGIOTENSIN II RECEPTOR BLOCKING IMIDAZOLES
-
Substituted imidazoles such as STR1 are useful as angiotensin II blockers. These compounds have activity in treating hypertension and congestive heart failure.
- -
-
-
- Treatment of congestive heart failure with angiotensin 11 receptor blocking imidazoles
-
Substituted imidazoles such as STR1 are useful as angiotensin II blockers. These compounds have activity in treating hypertension and congestive heart failure.
- -
-
-
- Nonpeptide Angiotensin II Receptor Antagonists: The Discovery of a Series of N-(Biphenylylmethyl)imidazoles as Potent, Orally Active Antihypertensives
-
A new series of nonpeptide angiotensin II (AII) receptor antagonists has been prepared.These N-(biphenylylmethyl)imidazoles, e.g. 2-butyl-1--4-chloro-5-(hydroxymethyl)imidazole, differ from the previously reported N-(benzamidobenzyl)imidazoles and related compounds in that they produce a potent antihypertensive effect upon oral administration; the earlier series generally were active only when administered intravenously.It has been found that the acidic group at the 2'-position of the biphenyl is essential.Only ortho-substituted acids possess both high affinity for the AII receptor and good oral antihypertensive potency.The carboxylic acid group has been replaced with a variety of acidic isosteres, and the tetrazole ring has been found to be the most effective.The tetrazole derivative, DuP 753, is currently in development for the treatment of hypertension.
- Carini, David J.,Duncia, John V.,Aldrich, Paul E.,Chiu, Andrew T.,Johnson, Alexander L.,et al.
-
p. 2525 - 2547
(2007/10/02)
-
