- Solvent-Directed Epoxide Opening with Primary Amines for the Synthesis of β-Amino Alcohols
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An efficient synthesis of β-amino alcohols from a variety of epoxides and primary unbranched amines in the absence of any catalyst in high yields and regioselectivities is reported. A variety of polar mixed solvent systems allow for the selective formation of secondary amino alcohols over tertiary amino alcohols. The reaction scope extends to a wide variety of aromatic and aliphatic substituted epoxides and primary amines bearing complex functionality.
- Lizza, Joseph R.,Moura-Letts, Gustavo
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supporting information
p. 1231 - 1242
(2017/03/11)
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- Lipase-catalyzed green synthesis of enantiopure atenolol
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A new green route is proposed for the synthesis of enantiopure atenolol (a β1-blocker). An enzymatic kinetic resolution approach was used to synthesize the enantiopure intermediates (R)- and (S)-2-(4-(3-chloro-2-hydroxypropoxy)phenyl)acetamide from the corresponding racemic alcohol. Of the commercially available lipases screened, Candida antarctica lipase-A (CLEA) showed maximum enantioselectivity in the transesterification of the racemic alcohol using vinyl acetate as the acyl donor. The reactions afforded the (S)-alcohol along with the (R)-acetate, with 48.9% conversion (E = 210, eeP = 96.9% and eeS = 91.1%). Various reaction parameters were optimized in order to achieve maximum enantioselectivity. N-alkylation of the (S)-alcohol with isopropylamine afforded the (S)-atenolol, and the (R)-acetate was chemically hydrolyzed to the corresponding alcohol and further converted to the (R)-atenolol via N-alkylation of the (R)-alcohol with isopropylamine. The use of ionic liquids, to solve the solubility related problems of the drug intermediates, made this process greener and more efficient compared to the previously reported methods. This journal is
- Dwivedee, Bharat Prasad,Ghosh, Saptarshi,Bhaumik, Jayeeta,Banoth, Linga,Chand Banerjee, Uttam
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p. 15850 - 15860
(2015/03/04)
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- COMPOSITIONS AND METHODS FOR DIAGNOSING AND TREATING SALT SENSITIVITY OF BLOOD PRESSURE
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To characterize the urinary exosome miRNome, microarrays were used to identify the miRNA spectrum present within urinary exosomes from ten individuals that were previously classified for their salt sensitivity status. The present application discloses distinct patterns of selected exosomal miRNA expression that were different between salt-sensitive (SS), salt-resistant (SR), and inverse salt-sensitive (ISS) individuals. These miRNAs can be useful as biomarkers either individually or as panels comprising multiple miRNAs. The present invention provides compositions and methods for identifying, diagnosing, monitoring, and treating subjects with salt sensitivity of blood pressure. The applications discloses panels of miRNAs useful for comparing profiles, and in some cases one or more of the miRNAs in a panel can be used. The miRNAs useful for distinguishing SS and SR or ISS and SR subjects. One or more of the 45 miRNAs can be used. Some of the miRNAs have not been previously reported to be circulating. See those miRNAs with asterisks in FIG. 1 and below. The present invention encompasses the use of one or more of these markers for identifying and diagnosing SR, SS, and ISS subjects.
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- An efficient protocol for regioselective ring opening of epoxides using sulfated tungstate: Application in synthesis of active pharmaceutical ingredients atenolol, propranolol and ranolazine
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Sulfated tungstate was found to be a new and highly efficient catalyst for opening of epoxide rings by amines to give β-amino alcohols with high regioselectivity. Various advantages associated with this novel and environmental friendly protocol include solvent-free conditions, short reaction times, high product yields, simple workup procedure and easy recovery and reusability of the catalyst. This protocol has been applied for the synthesis of active pharmaceutical ingredients atenolol, propranolol and ranolazine.
- Pathare, Sagar P.,Akamanchi, Krishnacharya G.
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p. 6455 - 6459
(2013/11/19)
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- THERAPY FOR COMPLICATIONS OF DIABETES
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A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.
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- ANTIHYPERTENSIVE THERAPY
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A new use of darusentan is provided in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy with one or more drugs. The composition comprises darusentan in an amount providing a therapeutically effective daily dose; wherein (a) the composition is orally deliverable and/or (b) the daily dose of darusentan is effective to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures. Further provided is a new use of darusentan in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy, wherein the composition is administered adjunctively with at least one diuretic and at least one antihypertensive drug selected from ACE inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers and calcium channel blockers.
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- FLUORESCENCE BASED DETECTION OF SUBSTANCES
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A method for the fluorescent detection of a substance, the method comprising providing particles comprising a metal or a metal oxide core, wherein one or more optionally fluorescently tagged antibodies or human specific peptide nucleic acid (PNA) oligomers for binding to a substance is/are bound, directly or indirectly, to the surface of the metal or metal oxide; contacting a substrate, which may or may not have the substance on its surface, with the particles for a time sufficient to allow the antibody/PNA oligomer to bind with the substance; removing those particles which have not bound to the substrate; if the antibodies or PNA oligomers are not fluorescently tagged, contacting the substrate with one or more fluorophores that selectively bind with the antibody and/or substance, then optionally washing the substrate to remove unbound fluorophores; and illuminating the substrate with appropriate radiation to show the fluorophores on the substrate.
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- One pot synthesis of (±)/(S)-atenolol and (±)/(S)-propranolol by employing polymer supported reagent
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(±)/(S)-Atenolol and (±)/(S)-propranolol were synthesized by using reaction of (±)/(S)-epichlorohydrin with polymer supported phenoxide anion followed by reaction with isopropylamine.
- Damle, Subhash V.,Patil, Prashant N.,Salunkhe, Manikrao M.
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p. 1639 - 1644
(2007/10/03)
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- A synthesis of atenolol using a nitrile hydration catalyst
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The synthesis of atenolol is described using a platinum containing homogeneous catalyst for the conversion of a nitrile to an amide. The catalytic reaction may be employed as the final step in the synthesis or in the preparation of the intermediate 4-hydroxyphenylacetamide. The structure of the nitrile intermediate, 1-(4′-cyanomethylphenoxy)-2-hydroxy-3-isopropylaminopropane, has been determined by X-ray crystallography.
- Akisanya, Joseph,Parkins, Adrian W.,Steed, Jonathan W.
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p. 274 - 276
(2013/09/08)
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- Phase transfer catalytic process for preparing intermediates of atenolol, propranolol, and their derivatives
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A phase transfer catalytic process for the preparation of epoxide and halohydrin intermediates, which can be subsequently and directly reacted with isopropylamine to produce beta-adrenergic antagonists such as atenolol, propanolol and their derivatives. In the process disclosed in the present invention, quaternary ammonium salts of high alkyl groups or tertiary ammonium salts of lower alkyl groups are used as catalyst in the phase transfer catalytic oxygenated-alkylation reaction between an aromatic alcohol such as p-hydroxyphenyl acetamide (for the production of atenolol) or α-naphthol (for the production of propranolol) and epichlorohydrin to yield epoxide and halohydrin intermediates. The quaternary ammonium salts of high alkyl groups are represented by the following formula: STR1 wherein R1, R2, R3, and R4 are C1 to C20 alkyl groups and at least one of the R1, R2, R3, or R4 is a C9 to C20 alkyl group, and X is a halide group. And the tertiary ammonium salts of lower alkyl groups are presented by the following formula: STR2 wherein R5 is a C1 to C20 alkyl group, H is hydrogen, and X is a halide group.
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- Process for producing optically active atenolol and intermediate thereof
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Improved process for producing an optically active atenolol useful as a β-adrenergic blocker for the treatment of angina pectoris, arrhythmia and hypertension, which comprising reacting a phenol compound with an optically active epihalohydrin to give an intermediate, optically active glycidyl ether compound, followed by reacting the intermediate with isopropylamine, and purification method of the optically active atenolol in high yield by means of forming a salt of atenolol with a Bronsted's acid whereby the salt of optically active atenolol having high optical purity can be separated from the salt of racemic atenolol by solid-liquid separation method.
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- Enteric coated mixture of 4-(2-hydroxy-3-isopropylamino-propoxy) indole and sodium lauryl sulphate
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The present invention provides a pharmaceutical composition for controlled release of 4-(2-hydroxy-3-isopropylamino-propoxy) indole in the intestinal tract, admixed with sodium lauryl sulphate, and enteric coated.
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- ALKANOLAMINE DERIVATIVES FOR TREATING HYPERTENSION
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1-(ELECTRONEGATIVELY-SUBSTITUTED-ALKYL-OR ALKENYLPHENOXY)-3-ALKYLAMINO-2-PROPANOL DERIVATIVES, FOR EXAMPLE 1-P-CARBAMOYLMETHYLPHENOXY-3-ISOPROPYLAMINO-2-PROPANOL, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM POSSESS β-ADRENERGIC BLOCKING ACTIVITY AND ARE USEFUL IN THE TREATMENT OF HEART DISEASES AND OTHER COMPLAINTS IN MAN.
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