Apicore US LLC

Amersham Biosciences Corp

Nycomed Amersham Plc

Apicore, LLC

Other

Amersham Pharmacia Biotech UK Limited

Ge Healthcare Bio-sciences Corp.

Satyam Nampalli

Ravishanker Kovi

Peter Xavier Tharial

Shiv R Kumar

Mark McDougall

David Loakes

Clifford Leslie Smith

Alan L Hamilton

Adrian Christopher Simmonds

Daniel M Brown

Fergal Hill

Carl Williams Fuller

Weihong Zhang

William Jonathan Cummins

Sudhakar Rao

David Williams

Brijesh Patel

Constantin Neagu

Patrick Finn

Mahesh Khot

Shiy Kumar

Bernard F McArdle

Dan Brown

Isosulfan blue and processes for the preparation thereof are provided. A process is also provided for preparation of the intermediate, 2-chlorobenzaldehyde-5-sulfonic acid, sodium salt of formula (2), used in the preparation thereof and a procedure for the isolation of benzaldehyde-2, 5-disulfonic acid, di-sodium salt of the formula (3). Also provided is a process for the preparation of an isoleuco acid of formula (4), which upon oxidation gives rise to isosulfan blue of pharmaceutical grade which can be used for preparation of pharmaceutical formulations. The isolation and purification procedures provided in the process provide substantially pure isosulfan blue with HPLC purity 99.5% or greater.

Process for preparation of isosulfan blue

Isosulfan blue and processes for the preparation thereof are provided. A process is also provided for preparation of the intermediate, 2-chlorobenzaldehyde-5-sulfonic acid, sodium salt of formula (2), used in the preparation thereof and a procedure for the isolation of benzaldehyde-2,5-disulfonic acid, di-sodium salt of the formula (3). Also provided is a process for the preparation of an isoleuco acid of formula (4), which upon oxidation gives rise to isosulfan blue of pharmaceutical grade which can be used for preparation of pharmaceutical formulations. The isolation and purification procedures provided in the process provide substantially pure isosulfan blue with HPLC purity 99.5% or greater.

Process for the preparation of isosulfan blue

A process for the preparation of isosulfan blue (Active Pharmaceutical Ingredient) is provided. A process is also provided for preparation of the intermediate, 2-chlorobenzaldehyde-5-sulfonic acid, sodium salt of formula (2), used in the preparation thereof and a procedure for the isolation of benzaldehyde-2,5-disulfonic acid, di-sodium salt of the formula (3). Also provided is a process for the preparation of an isoleuco acid of formula (4), which upon mild oxidation gives rise to isosulfan blue of pharmaceutical grade which can be used for preparation of pharmaceutical formulations. The isolation and purification procedures provided in the process provide substantially pure isosulfan blue with HPLC purity 99.5% or greater.

A process for preparation of protriptyline hydrochloride from 5-dihydrobenzocycloheptatriene of formula (1) by coupling with chloropropyl alcohol in the presence of excess n-butyl Lithium in tetrahydrofuran under inert atmosphere, followed by preparation of mesylate derivative of formula (3) and finally the nucleophilic displacement of the mesylate group by reacting methylamine solution in methanol to give protriptyline free base of the formula (4). Also the present process reveals the hydrochloride salt formation and purification of the same to give pure pharmaceutical grade protriptyline hydrochloride with impurities less than 0.1% w/w.

Process for preparation of 5H-dibenzo[a,d] cycloheptene derivatives

Energy transfer dyes, their preparation, and their use as labels in biological systems is disclosed. The dyes are preferably in the form of cassettes which enable their attachment to a variety of biological materials. The dyes and the reagents that can be made from them offer a wide variety of fluorescent labels with large Stokes' shifts enabling their use in a variety of fluorescence applications over a wide range of the visible spectrum.

Energy transfer dyes

A kit for DNA sequencing comprising a first, second, third and fourth dye terminator molecules, each of the dye terminator molecules comprising a dye molecule, a linker of at least 10 atoms in length and either ddATP, ddCTP, ddGTP or ddTTP as a mono or tri-phosphate and a thermostable DNA polymerase.

Dideoxy dye terminators

Exploitation of suitably functionalized heterocyclic molecules, in the design and synthesis of Fluorescence Resonance Energy Transfer (FRET) cassettes and their corresponding dideoxynucleotide terminators culminated into efficient reagents for DNA sequencing. Additionally, these FRET cassettes/terminators, of the present invention, derived from different classes of heterocyclic systems have high potential to be used for general labelling of biological molecules to generate highly sensitized signals. Their preparation, energy transfer efficiency, and use as labels, specifically, in DNA sequencing reactions is disclosed.

Heterocyclic FRETdye cassettes for labeling biological molecules and their use in DNA sequencing

Base analogues

Nucleoside analogues or base analogues having structure (I), where X&equals;O or NH or S, Y&equals;N or CHR or CR , W&equals;N or NR or CHR or CR or S, n&equals;1 or 2; each R is independently H or O or alkyl or alkenyl or alkoxy or aryl or a reporter moiety; where necessary (i.e. when Y and/or W is N or CR where R is not O) a double bond is present between Y and W or W and W, and Q is H or a sugar or a sugar analogue or a nucleic acid backbone or backbone analogue.

Nucleoside analogues have structure (2) wherein Q is H or a sugar moiety or sugar analogue or a modified sugar or a nucleic backbone or backbone analogue, W is an alkylene or alkenylene chain of 0-5 carbon atoms, any of which may carry a substituent R , X is O or N or NR or CR , X&prime; is O or S or N, provided that when X&prime; is O or S, then X is C, Y is CH or N, R is NH or SMe or SO Me or NHNH , each of R and R is independently H or F or alkyl or alkenyl or aryl or acyl or a reporter moiety, R is independently H or alkyl or alkenyl or aryl or acyl or a reporter moiety, and R is H or &boxH;O or F or alkyl or aryl or a reporter moiety.

Tricyclic base analogues

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Hunt Valley, MD, United States of America

Satyam Nampalli