- A novel and efficient route to zafirlukast
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Zafirlukast, an important drug for allergic pulmonary disorders such as asthma, is synthesized by a five-step, high-yielding, and inexpensive process.
- Srinivas, Keesari,Srinivasan, Neti,Krishna, Muddasani Rama,Reddy, Chinta Raveendra,Arunagiri, Muthulingam,Lalitha, Routhu,Reddy, Kikkura Sri Rami,Reddy, Bijjula Sreenivasa,Reddy, Ghanta Mahesh,Reddy, Padi Pratap,Kumar, Muppa Kishore,Reddy, Manne Satyanaraya
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Read Online
- Investigation into the acidification process of zafirluskast nitroacid leads to a surprising improvement in product quality
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An investigation into the acidification step of the zafirlukast nitroacid process was conducted by varying a range of parameters, including acid molarity, addition time, final pH, and temperature. A significant and unexpected improvement in product quality was achieved by using dilute rather than concentrated acid, independent of the final pH, and without a reduction in yield. The change to the dilute-acid process could be accommodated within the constraints of the existing registered process.
- Ancell, Claire L.,Derrick, Ian,Moseley, Jonathan D.,Stott, Jeffery A.
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Read Online
- Benzylic C(sp3)-C(sp2) cross-coupling of indoles enabled by oxidative radical generation and nickel catalysis
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A mechanistically unique functionalization strategy for a benzylic C(sp3)-H bond has been developed based on the facile oxidation event of indole substrates. This novel pathway was initiated by efficient radical generation at the benzylic position of the substrate, with subsequent transition metal catalysis to complete the overall transformation. Ultimately, an aryl or an acyl group could be effectively delivered from an aryl (pseudo)halide or an acid anhydride coupling partner, respectively. The developed method utilizes mild conditions and exhibits a wide substrate scope for both substituted indoles and C(sp2)-based reaction counterparts. Mechanistic studies have shown that competitive hydrogen atom transfer (HAT) processes, which are frequently encountered in conventional methods, are not involved in the product formation process of the developed strategy.
- Kim, Weonjeong,Koo, Jangwoo,Lee, Hong Geun
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p. 4119 - 4125
(2021/04/06)
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- PROCESS FOR THE PREPARATION OF ZAFIRLUKAST AND ANALOGS THEREOF
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The present invention relates to a process for the preparation of (1-alkylindol-3-ylmethyl) benzoic acid derivatives, in particular Zafirlukast and analogs thereof. Further, this process is based on protection group free and C-H bond activation strategy involving all step catalytic transformation sequence and comprises the following steps: Sonogashira coupling, indole formation by Sp3 C-H activation, reductive hydrogenation and amidation.
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- Concise and alternative synthesis of zafirlukast, an anti-asthma drug
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Concise and alternative synthesis of zafirlukast (1) is described. The synthesis features fewer steps, convergent synthesis, and novel intermediates.
- Goverdhan, Gilla,Reddy, Anumula Raghupathi,Himabindu, Vurimidi,Reddy, Ghanta Mahesh
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p. 498 - 504
(2013/01/15)
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- An improved and scalable process for zafirlukast: An asthma drug
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An improved and scalable process for the large-scale production of zafirlukast (Accolate), an important drug for asthma, is discussed along with impurity and scale-up-related issues.
- Goverdhan, Gilla,Reddy, Anumula Raghupathi,Sampath, Aalla,Srinivas, Kurella,Himabindu, Vurimidi,Reddy, Ghanta Mahesh
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experimental part
p. 67 - 72
(2010/04/22)
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- SUBSTITUTED INDOLES
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Disclosed herein are substituted indole cysteinyl leukotriene receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 53
(2009/08/14)
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- PROCESSES FOR PREPARING ZAFIRLUKAST
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An improved process for the preparation of substantially pure zafirlukast and pharmaceutical compositions thereof.
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Page/Page column 9-10
(2009/06/27)
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- Evolution of a series of peptidoleukotriene antagonists: Synthesis and structure/activity relationships of 1,3,5-substituted indoles and indazoles
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1,3,5-Substituted indoles and indazoles have been studied as receptor antagonists of the peptidoleukotrienes. The best of these compounds generally had a methyl group at the N1 position, a [(cyclopentyloxy)carbonyl]amino or 2-cyclopentylacetamido or N'-cyclopentylureido group at the C-5 position, and an arysulfonyl amide group as part of the acidic chain at the C-3 position of the ring. Such compounds had in vitro dissociation constants K(B) in the range 10-9-10-11 M on guinea pig trachea against LTE4 as agonist and inhibition constants (K(i)) ≤ 10-9 M on guinea pig parenchymal membranes against [3H]LTD4. A number of compounds were orally effective at doses ≤1 mg/kg in blocking LTD4-induced 'dyspnea' in guinea pigs. Compound 45 [N-[4-[[5-[[cyclopentyloxy)carbonyl]amino]-1-methylindol-3-yl]methyl]- 3-methoxybenzoyl]-2-methyl]benzenesulfonamide, ICI 204,219; pK(B) = 9.67 ± 0.13, K(i) = 0.3 ± 0.03 nM, po ED50 = 0.3 mg/kg] is currently under clinical investigation for asthma. In the indole series, certain alkylsulfonyl amides possessing a 3-cyanobenzyl substituent at the N-1 position (60, 61) were produced that had K(B) ≤ 10-9 M on guinea pig trachea.
- Matassa,Maduskuie Jr.,Shapiro,Hesp,Snyder,Aharony,Krell,Keith
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p. 1781 - 1790
(2007/10/02)
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- Heterocyclic amide derivatives and pharmaceutical use
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The invention concerns novel, pharmaceutically useful, amide derivatives of certain benzoheterocyclylalkanoic acids (and related tetrazoles and acylsulphonamides) of the formula I and salts thereof, wherein the radicals R1, R2, L, X, Y, Z, A1, Q, A2 and M have the meanings set out in the specification. The invention also includes pharmaceutical compositions incorporating a formula I compound or a salt thereof, a process for the manufacture of the said compound, together with intermediates for use in the latter process. STR1
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