Methyl 3,5-diiodo-4-(3-isopropyl-4-methoxybenzoyl)benzoate

Abstract

C19 H181204, orthorhombic, Iba2, a = 20.998 (3), b = 24.002 (4), c = 8.032 (1) A, z = 8, M r = 564.2, D c = 1.85 Mg m-3; for 2281 observed data R = 6.6%. The conformation of the diphenyl ketone bridge is skewed and the 3'-isopropyl group distally oriented, as is observed for many thyroid hormone analogue structures. There is a short I...O inter- molecular contact between I(5) and the carbonyl oxygen (3.17 (10) A). Introduction. Structural studies show that the thyroid hormones (Fig. la) are characterized by an oxygen bridging angle of 120 ° and diphenyl ether conforma- tion that is either skewed (i.e. the phenyl ring planes are mutually perpendicular and bisecting) or twist-skewed (Cody, 1980). Either conformation minimizes the steric interactions between the bulky 3,5 inner-ring iodines and the ortho hydrogens of the outer phenyl ring. The observed biological activity and protein-binding affinity of non-oxygen-bridged (S,CH 2) hormone analogues suggests that the requirement for oxygen is not absolute (Jorgensen, 1978). As part of a program to study the effects of oxygen-bridge substitution, as well as to design hormone analogues that could be used as photo affinity probes of hormone-protein binding, a number of carbonyl-bridged thyroid hormone analogues were synthesized and their nuclear receptor protein-binding affinities measured. Here is reported the crystal structure of a ketone-bridged analogue (Fig. l b), which is shown to possess significant nuclear binding affinity (Cheung, unpublished results). Crystals were grown by slow evaporation at room temperature from an ethanol solution. Crystallo- graphic data were measured from a 0.07 × 0.4 × 0.9 mm crystal on a Nicolet P3 automated diffractometer using Nb-filtered Mo Kc~ radiation. Cell dimensions were obtained by a least-squares refinement based on