Jeffrey A. Schultz

Identification of biaryl sulfone derivatives as antagonists of the histamine H3 receptor: Discovery of (R)-1-(2-(4′-(3-methoxypropylsulfonyl)biphenyl-4-yl)ethyl)-2-methylpyrrolidine (APD916)

The design of a new clinical candidate histamine-H(3) receptor antagonist for the potential treatment of excessive daytime sleepiness (EDS) is described. Phenethyl-R-2-methylpyrrolidine containing biphenylsulfonamide compounds were modified by replacement of the sulfonamide linkage with a sulfone. One compound from this series, 2j (APD916) increased wakefulness in rodents as measured by polysomnography with a duration of effect consistent with its pharmacokinetic properties. The identification of a suitable salt form of 2j allowed it to be selected for further development.

Design and evaluation of novel biphenyl sulfonamide derivatives with potent histamine H(3) receptor inverse agonist activity.

Antagonism of the histamine-H(3) receptor is one tactic being explored to increase wakefulness for the treatment of disorders such as excessive daytime sleepiness (EDS) as well as other sleep or cognitive disorders. Phenethyl-R-2-methylpyrrolidine containing biphenylsulfonamide compounds were shown to be potent and selective antagonists of the H(3) receptor. Several of these compounds demonstrated in vivo activity in a rat model of (R)-alpha-methyl histamine (RAMH) induced dipsogenia, and one compound (4e) provided an increase in wakefulness in rats as measured by polysomnographic methods. However, more detailed analysis of the PK/PD relationship suggested the presence of a common active metabolite which may preclude this series of compounds from further development.

Charging magnet for the floating coil of LDX

The charging coil (C-coil) for the joint Columbia University/MIT Levitated Dipole Experiment (LDX) is under development jointly by MIT and the Efremov Institute. The NbTi superconducting C-coil serves to charge/discharge inductively the floating superconducting magnet to/from 2277 A when it is resting in the charging port at the bottom of the LDX vacuum vessel. The C-coil is designed for 3200 charge-discharge cycles. The solenoid magnet is installed in a low heat leak liquid helium cryostat with a warm bore of more than 1 m. The magnet protection system has an external dump resistor, which dissipates most of the 12 MJ stored during a quench.

Design and fabrication of the cryostat for the floating coil of the Levitated Dipole Experiment (LDX)

The Levitated Dipole Experiment (LDX) is a new, innovative magnetic confinement fusion experiment being designed and installed in collaboration with Columbia University at the Massachusetts Institute of Technology (MIT). The primary objective of the experiment is to investigate the possibility of steady-state, high-beta plasma confinement with near classical transport. The main component of the experiment is a levitated cryostat with a 5.7 T Nb/sub 3/Sn superconducting magnet, housed in an Inconel high pressure helium vessel. The pressure vessel is surrounded by a large thermal mass radiation shield and an outer vacuum shell, all of which are magnetically levitated inside a much larger vacuum chamber. The cryostat, now under construction is described in this paper. The cryostat keeps the magnet temperature between 5 and 10 K during 8 hours of levitated operation.

Superconducting focusing quadrupoles for heavy ion fusion experiments

The Heavy Ion Fusion (HIF) Program is developing superconducting focusing magnets for both near-term experiments and future driver accelerators. In particular, single bore quadrupoles have been fabricated and tested for use in the High Current Experiment (HCX) at Lawrence Berkeley National Laboratory (LBNL). The next steps involve the development of magnets for the planned Integrated Beam Experiment (IBX) and the fabrication of the first prototype multi-beam focusing arrays for fusion driver accelerators. The status of the magnet R&D program is reported, including experimental requirements, design issues and test results.

Status of the floating coil of the Levitated Dipole Experiment

The Levitated Dipole Experiment (LDX) is a novel concept that examines plasma compressibility as a method for stable magnetic confinement of fusion grade plasmas. The experiment uses a 0.8 m diameter ring-type dipole coil that is levitated at the center of a 5 m diameter /spl times/ 3 m tall vacuum chamber to confine the plasma. This persistent mode, floating coil is wound from a prereacted Nb/sub 3/Sn conductor and encased in a toroidally shaped, constant volume helium cryostat to eliminate external connections to the coil during levitated operation. Although the peak field on the inductively charged floating coil is only 5.3 T, a Nb/sub 3/Sn conductor was selected because of its higher temperature capability. The cryostat, with on-board helium supply, is designed for 6-8 hours of levitated operation as the heat leak gradually warms the coil from 5 to 10 K. The cryostat consists of three concentric shells: a sealed, high pressure Inconel helium vessel that contains the floating coil and heat exchangers that are used to recool the coil before operation, a high heat capacity fiberglass-lead radiation shield, and an outer vacuum shell. The shells are kept separated by a support system designed to withstand impact forces up to 10 g in the case of a levitation failure. The paper summarizes the manufacture and initial driven-mode test of the floating coil, and describes the design, manufacture and test of the cryostat.

Multi-cylinder quadrupoles with square cross section

Compact superconducting quadrupole magnets with a total length of 150 mm, an integrated gradient of about 13 T, and good field quality are needed for the High Current Transport Experiment (HCX) at Lawrence Berkeley National Laboratory. The Advanced Magnet Lab, Inc. has developed a novel concept, called multi-cylinder coils, which is ideally suited for this application. In this concept a round mini-cable is placed in grooves, which are precisely machined in flat support plates. The plates are stacked on top of each other to build up multilayer coils. The grooves guarantee precise placement of the conductor with high design flexibility, giving unique control over random and systematic field errors and management of mechanical stress. The designed quadrupole consists of four subcoils, which form the four sides of a square cross section box. Each subcoil is built up from 6 plates, accommodating 6 layers of conductor. The complete quadrupole is wound from a continuous conductor with no internal splices. Test results from the first prototype magnet are presented.