The discovery of the potent and selective prostaglandin D2 (PGD2) receptor (DP) antagonist [(3R)-4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (13) is presented. Initial lead antagonists 6 and 7 were found to be potent and selective DP antagonists (DP Ki = 2.0 nM for each); however, they both suffered from poor pharmacokinetic profiles, short half-lives and high clearance rates in rats. Rat bile duct cannulation studies revealed that high concentrations of parent drug were present in the biliary fluid (Cmax = 1100 microM for 6 and 3900 microM for 7). This pharmacokinetic liability was circumvented by replacing the 7-methylsulfone substituent present in 6 and 7 with a fluorine atom resulting in antagonists with diminished propensity for biliary excretion and with superior pharmacokinetic profiles. Further optimization led to the discovery of the potent and selective DP antagonist 13.

Accurate navigation systems are required in the scope of Mars precision landing missions. This paper reviews some assumptions of the literature concerning the availability of the vehicle states for guidance during its atmospheric entry on Mars. It is demonstrated that currently used measurements are not sufficient to get complete observability of the entry dynamics. Therefore, four innovative measurement scenarios based on radio ranging are proposed to resolve the observability issue. The analyses and simulations show that the addition of the range measurements from known references helps to estimate accurately the position states along with some critical model parameters, contrary to inertial measurement unit navigation alone. Finally, the addition of the range measurement from a secondary free-falling dummy vehicle with known aerodynamics also ensures the observability of aerodynamic parameters of the lander vehicle. Nomenclature A, B, C, D = state-space matrices a B = acceleration components in the body frame, m=s 2 B = ballistic parameter, m 2 =kg C D = aerodynamic drag coefficient C L = aerodynamic lift coefficient D = aerodynamic drag force, N d = aerodynamic drag deceleration, m=s 2 g = gravitational acceleration, m=s 2 h = altitude, m h s = atmospheric scale height, m h 0 = reference altitude, m L = aerodynamic lift force, N L=D = lift-to-drag ratio m = vehicle mass, kg Q o = observability matrix q = dynamic pressure, kg=m s 2 R e = equatorial radius, m r = radial distance, m S = aerodynamic surface, m s = downrange, m t = time. s u = input vector v = inertial velocity, m=s 0= trim angle of attack, rad = flight-path angle, rad = latitude, rad = longitude, rad M = Mars gravitational constant, m 3 =s 2 = atmospheric density, kg=m 3 0 = atmospheric reference density, kg=m 3 = bank angle, rad = azimuth (clockwise from north), rad ! B = angular rate components in body frame

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