- Synthesis and biological evaluation of novel azetidine derivatives as dopamine antagonist
-
In this study, azetidine derivatives were evaluated for their potency as dopaminergic antagonist. The study comprised derivatives substituted in 3-position with amide moiety. Further, the phenyl moiety of amide was modified at 2, 3, or 4-position. The substituted compounds were biologically evaluated for their affinity for D2 and D4 receptors. The most potent D2 and D4 antagonist among these compounds appeared to be the N-(1-benzhydryl-azetidin-3yl)-2-bromo-benzamide and N-(1-benzhydryl-azetidin-3yl)-4-bromo-benzamide, respectively. Various docking interactions of CPPMA with the D4 receptor and the same for compound 5 i.e., N-(1-benzhydryl-azetidin-3yl)-4-bromo-benzamide were found to have good correlation with observed biological activity.
- Metkar, Shashikant D.,Bhatia, Manish S.,Desai, Uday V.
-
p. 5982 - 5989
(2013/11/06)
-
- Process development of a novel azetidinyl ketolide antibiotic
-
Process development and the multikilogram synthesis of a novel azetidinyl ketolide antibiotic is described. Starting with clarithromycin, the eight-step synthesis features several telescoped operations and direct isolations, which results in a significant improvement in throughput and a major reduction in solvent usage and waste stream volume over the first scale-up campaign. Particular highlights of this effort include the development of an efficient synthesis of 3-hydroxy-1,5-naphthyridine-4-carbaldehyde via a Skraup process and engineering a robust final API synthesis. We also discovered a crystalline monotosylate salt that addressed significant formulation and degradation issues experienced when using the noncrystalline freebase.
- Li, Bryan,Magee, Thomas V.,Buzon, Richard A.,Widlicka, Daniel W.,Bill, Dave R.,Brandt, Thomas,Cao, Xiaoping,Coutant, Michael,Dou, Haijian,Granskog, Karl,Flanagan, Mark E.,Hayward, Cheryl M.,Li, Bin,Liu, Fengwei,Liu, Wei,Nguyen, Thuy-Trinh,Raggon, Jeffrey W.,Rose, Peter,Rainville, Joseph,Reilly, Usa Datta,Shen, Yue,Sun, Jianmin,Wilcox, Glenn E.
-
body text
p. 788 - 797
(2012/08/27)
-
- MACROLIDES
-
The invention relates to compounds of Formula (I): wherein R1, R2 and X are as defined herein. The invention also relates to pharmaceutical compositions and methods of treating bacterial infections using compounds of Formula (I).
- -
-
-
- Arylalkane, arylalkene and aryl azaalkane, medicaments containing said compounds and method for the production thereof
-
The present invention relates to compounds of general formula [in-line-formulae]R—Z1—Z2—Z3—R1, ??(I)[/in-line-formulae] wherein R, R1 and Z1 to Z3 are defined as in claim 1, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable pharmacological properties, particularly CGRP-antagonistic properties, pharmaceutical compositions containing these compounds, their use and processes for preparing them.
- -
-
Page/Page column 88
(2010/11/27)
-
- DIRECT AMINOLYSIS
-
In some aspects, the present invention provides a method of preparing a compound of the formula (I) comprising reacting a mesylate compound of the formula (II) by direct aminolysis with a reagent comprising ammonia. The reaction is preferably carried out
- -
-
Page/Page column 4
(2008/06/13)
-
- An efficient two-step synthesis of 3-amino-1-benzhydrylazetidine
-
A streamlined process for the synthesis of 3-amino-1-benzhydrylazetidine is described. Commercially available 1-benzhydrylazetidin-3-ol was reacted with methanesulfonyl chloride in the presence of triethylamine in acetonitrile, upon quench with water, the
- Li, Bryan,Witt, Michael F.,Brandt, Thomas A.,Whritenour, David
-
p. 478 - 480
(2007/10/03)
-
- Aqueous phosphoric acid as a mild reagent for deprotection of tert-butyl carbamates, esters, and ethers
-
(Chemical Equation Presented) Aqueous phosphoric acid (85 wt %) is an effective, environmentally benign reagent for the deprotection of tert-butyl carbamates, tert-butyl esters, and tert-butyl ethers. The reaction conditions are mild and offer good selectivity in the presence of other acid-sensitive groups, including CBZ carbamates, azetidine, benzyl and methyl esters, TBDMS, and methyl phenyl ethers. The mildness of the reaction is further demonstrated in the synthesis of clarithromycin derivative 4, in which a tert-butyl ester is removed in the presence of cyclic carbamate, lactone, ketal, acetate ester, and epimerizable methyl ketone functionalities. The reaction preserves the stereochemical integrity of the substrates. The reactions are high yielding, and the workup is convenient.
- Li, Bryan,Berliner, Martin,Buzon, Richard,Chiu, Charles K.-F.,Colgan, Stephen T.,Kaneko, Takushi,Keene, Nandell,Kissel, William,Le, Tung,Leeman, Kyle R.,Marquez, Brian,Morris, Ronald,Newell, Lisa,Wunderwald, Silke,Witt, Michael,Weaver, John,Zhang, Zhijun,Zhang, Zhongli
-
p. 9045 - 9050
(2007/10/03)
-
- N-HETEROCYCLYL-SUBSTITUTED AMINO-THIAZOLE DERIVATIVES AS PROTEIN KINASE INHIBITORS
-
Aminothiazole compounds with N-containing cycloalkyl at the 2-amino position which are represented by the Formula (I), or a pharmaceutically acceptable prodrug of said compound, or pharmaceutically acceptable salt of said compound, modulate and/or inhibit the cell proliferation and activity of protein kinases.
- -
-
-
- Thiophene derivatives useful as anticancer agents
-
The invention relates to compounds of the formula 1 or a pharmaceutically acceptable salt and to pharmaceutically acceptable salts and hydrates thereof, wherein X, Y, R1, R2 and R11 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula 1 and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula 1.
- -
-
-
- Bis-piperidinyl-pyrimidin-2-ones as alpha 1a adrenergic receptor antagonists
-
Pyrimidinone, oxazolidinone, and (alkyl)aryl derivatives, their synthesis, and their use as alpha 1a adrenergic receptor antagonists are disclosed. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are
- -
-
-
- Compounds enhancing antitumor activity of other cytotoxic agents
-
This invention relates to certain heterocyclic compounds and their pharmaceutically acceptable salts, which are useful for sensitizing multidrug-resistant tumor cells to anticancer agents and multidrug resistant forms of malaria, tuberculosis, leishmania and amoebic dysentery to chemotherapeutants. The compounds and their pharmaceutically acceptable salts are also inhibitors of the active drug transport capability of P-glycoprotein which is encoded by the human MDR1 gene, as well as of certain other related ATP-binding-cassette transporters from eukaryotic and prokaryotic organisms (e.g., pfmdr from Plasmodium falciprum, and murine mdr1 and mdr3 gene products).
- -
-
-
- Alpha 1a adrenergic receptor antagonists
-
This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as alpha 1a adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.
- -
-
-
- Quantitative structure-activity relationships of antibacterial agents, 7-heterocyclic amine substituted 1-cyclopropyl-6,8-difluoro-4-oxoquinoline-3-carboxylic acids
-
Quantitative structure-activity relationships (QSAR) of various 7-(3-substituted-azetidin-1-yl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro -4-oxoquinoline-3-carboxylic acids, 14-25, were studied to clarify the structural requirements for 3-substituted azetidi
- Okada,Ezumi,Yamakawa,Sato,Tsuji,Tsushima,Motokawa,Komatsu
-
p. 126 - 131
(2007/10/02)
-
- 3-aminoazetidine, its salts and intermediates of synthesis
-
The 3-aminoazetidine, its salts, new intermediates of formula STR1 wherein X' represents hydrogen or a protecting group and both X" represent hydrogen or, together with the nitrogen atom, a phthalimido group, X' not and both X" being hydrogen at the same
- -
-
-