Ghanta Mahesh Reddy

Alternative Total Synthesis of (−)-Galanthamine Hydrobromide

Abstract An alternative total synthesis of (−)-galanthamine (1) hydrobromide, employing ecofriendly amidation, oxidative coupling, and classical resolution strategies is accomplished.

Identification, characterization and synthesis of impurities of zafirlukast.

Zafirlukast is a drug in the treatment of pulmonary disorders such as asthma. During the process development of zafirlukast, five unknown impurities were detected at levels of below 0.10% (ranging from 0.05 to 0.15%) in reverse phase gradient high performance liquid chromatography (HPLC) method. The molecular weights were determined by LC-MS analysis. These impurities were isolated from crude samples of zafirlukast using gradient reverse phase preparative HPLC and were subsequently synthesized. Based on the spectral data, the structures of these impurities were characterized as 3-methoxy-4-(5-methoxycarbonylamino-1-methyl-1H-indol-3-ylmethyl)-benzoic acid (Impurity 1), {3-[2-methoxy-4-(toluene-2-sulfonylaminocarbonyl)-benzyl]-1-methyl-1H-indol-5-yl}-carbamic acid methyl ester (Impurity 2), {3-[2-methoxy-4-(toluene-3-sulfonylaminocarbonyl)-benzyl]-1-methyl-1H-indol-5-yl}-acetic acid cyclopentyl ester (Impurity 3), {3-[2-methoxy-4-(toluene-4-sulfonylaminocarbonyl)-benzyl]-1-methyl-1H-indol-5-yl}-acetic acid cyclopentyl ester (Impurity 4), and 4-(5-cyclopentyloxy carbonylamino-1-methyl-1H-indol-3-yl methyl)-3-methoxy-benzoic acid methyl ester (Impurity 5). The separation of the impurities by reverse phase HPLC, the confirmation of their structures by IR, MS and NMR spectral data, the mechanism of their formation and their syntheses are discussed in detail.

Improved Synthesis of Irbesartan, an Antihypertensive Active Pharmaceutical Ingredient

Abstract An improved synthesis of the antihypertensive drug irbesartan, based on the Suzuki reaction, has been described.

Synthesis and Spectral Characterization of Related Substances of Vardenafil, an Erectile Dysfunction Drug

Abstract Vardenafil hydrochloride trihydrate (Levitra) is used to treat erectile dysfunction (ED) and is an inhibitor of phosphodiesterase type 5 (PDE-5) enzyme. It maintains higher levels of cyclic guanosine monophosphate (cGMP), relaxes smooth muscles, promotes penile blood flow, and enhances erectile function. During the bulk drug synthesis of vardenafil hydrochloride trihydrate, six related substances (impurities), vardenafil dimer, vardenafil N-oxide, vardenafil glycene, vardenafil oxopiperazine, vardenafil oxoacetic acid, and phenyl vardenafil were identified, and these are reported herein for the first time. The present work describes the synthesis and characterization of these impurities. GRAPHICAL ABSTRACT

Improved One-Pot Synthesis of Telmisartan

Cost-effective and improved one-pot synthesis for telmisartan (1) is described that minimizes the reaction time and gives high-purity material.

Concise and Alternative Synthesis of Zafirlukast, an Anti-Asthma Drug

Abstract Concise and alternative synthesis of zafirlukast (1) is described. The synthesis features fewer steps, convergent synthesis, and novel intermediates. GRAPHICAL ABSTRACT

Synthesis and Characterization of Some New Benzimidazole Derivatives

Synthesis of nine new benzimidazole derivatives was reported. The products were identified by 1H NMR, mass spectroscopy, and infrared spectroscopy.

AN IMPROVED ONE-POT SYNTHESIS OF N-(2,3-DIH YDROBENZO[1,4]DIOXIN-2-CARBONYL)PIPERAZINE - USEFUL INTERMEDIATE FOR ANTI-HYPERTENSIVE DRUG - DOXAZOSIN

An improved process for the preparation of 7V-(2,3-dihydrobenzo[l,4]dioxin-2carbonyl)piperazine 2 and its hydrochloride from ethyl-2,3-dihydro-l,4-benzodioxin-2-carboxylate 3 and piperazine in a single step has been described. The compound 2 is an important intermediate in the preparation of anti-hypertensive agent, Doxazosin. 7V-Acylalkylenediamines are used to react with 4-amino-2-chloro-6,7-dimethoxy quinazolines 4 to give a variety of anti-hypertensive agents. For example Doxazosin mesylate 1 is an anti-hypertensive drug contains N-acylalkylenediamine moiety. Doxazosin mesylate 1 is indicated for the treatment of the urinary outflow obstruction and obstructive and irrigative symptoms associated with benign prostate hyperplasia (BPH), obstructive symptoms (hesitation, intermittency, dribbling, weak urinary stream, incomplete emptying of the bladder) and irritative symptoms (nocturia, daytime frequency, urgency, burning). Doxazosin mesylate 1 is also indicated for the treatment of hypertension. It shows a great structural similarity to the older representatives of this class, Prazosin hydrochloride and Terazosin hydrochloride, whereas the two latter active substances are used primarily in the treatment of high blood pressure. In the case of compound 1, there is an additional indication, namely, the treatment of BPH. Unlike Prazosin and Terazosin, 1 is used therapeutically not as hydrochloride but as the mesylate, that is, as a salt of methane sulfonic acid. The synthesis leads to an improved process for the preparation of 7V-(2,3-dihydro-l,4-benzodioxin-2-ylcarbonyl)piperazine 2 and its hydrochloride from ethyl-2,3-dihydro-l,4-benzodioxin-2-carboxylate 3 in a single step. The yields are comparatively higher and consistent. The compound N-(2,3-dihydro-1.4benzodioxin-2-yl carbonyl) piperazine 2 is an important intermediate in the preparation of antihypertensive agent, Doxazosin. Introduction