- Process for synthesis of hydrochloric acid ramiah of lercanidipine (by machine translation)
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The invention discloses a process for synthesizing hydrochloric acid ramiah of lercanidipine, its synthesis process comprises the following steps : (1) 3 -? Hydroxy-propionitrile (I) and (II) reaction of ketene dimer, to obtain compound (VI) ; (2) compound (III) with (VI) reaction between formaldehyde nitrobenzene, to obtain compound (VII) ; (3) compound (VII) with β-amino-crotonic acid ethyl ester (IV) reaction, to obtain compound (VIII) ; (4) by strong alkali hydrolysis of compound (VIII), to obtain compound (IX) ; (5) compound (IX) using chiral organic alkali splitting, to obtain compound (X) ;? (6) compound (X) with benzyl quick (V) reaction, to obtain compound (XI) ; (7) a solution of compound (XI) by adding hydrogen chloride, hydrochloric acid ramiah horizontal (XII) can be obtained. Synthetic process of this invention has the following several advantages : (1) mild reaction conditions, each step the product is easy to separate, purification, controllable quality ; (2) higher yield for each step, the used original helping material is easy to obtain, the total cost is low ; (3) do not need to be too column, is suitable for industrial production. (by machine translation)
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Paragraph 0010
(2016/12/01)
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- Synthesis and characterization of impurities of barnidipine hydrochloride, an antihypertensive drug substance
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Barnidipine hydrochloride is a long term dihydropyridine calcium channel blocker used for the treatment of hypertension. During the process development of barnidipine hydrochloride, four barnidipine impurities were detected by high-performance liquid chromatography (HPLC) with an ordinary column (Agilent ZORBAX Eclipse XDB-C18, 150 mm × 4.6 mm, 5 m). All these impurities were identified, synthesized, and subsequently characterized by their respective spectral data (MS, 1H-NMR, and 13C-NMR). The identification of these impurities should be useful for quality control in the manufacture of barnidipine.
- Cheng, Zhi-Gang,Dai, Xu-Yong,Li, Li-Wei,Wan, Qiong,Ma, Xiang,Xiang, Guang-Ya
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p. 1344 - 1352
(2014/02/14)
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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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- Stereoselectivity of a Potent Calcium Antagonist, 1-Benzyl-3-pyrrolidinyl Methyl 2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
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Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated.The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a*HBr as well as 3a*HCl.The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation.The potency order of the four enantiomers was (S,S)-3a > (S,R)-3b > (R,R)-3d > (R,S)-3c.Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a*HCl or 3a*HBr.On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5.The conformational restriction may be a factor causing stereoselectivity of antagonism.
- Tamazawa, Kazuharu,Arima, Hideki,Koijma, Tadao,Isomura, Yasuo,Okada, Minoru,et al.
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p. 2504 - 2511
(2007/10/02)
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