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The structure-activity relationships of two series of novel retinoids (2-pyrazinylcarboxamidobenzoates and beta-ionylideneacetamidobenzoates) have been investigated by evaluating their ability to induce differentiation in both human promyelocytic leukemia (HL60) cells and mouse embryonal carcinoma (P19) cells. The most active compound (ED50 = 8.3 x 10(-9) M) of the 2-pyrazinylcarboxamidobenzoates is 4-[2-(5,6,7,8-tetrahydro-5,5,8, 8-tetramethylquinoxalyl)carboxamido]benzoic acid (9u), while the most active analogue of the beta-ionylideneacetamidobenzoates is 4-[3-methyl-5-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-(2E, 4E)-pentadienamido]benzoic acid (10a, ED50 = 3.2 x 10(-8) M). Our studies identify an absolute requirement for the carboxylic acid moiety on the aromatic ring to be para relative to the amide linkage for activity. Benzoate substitutions in the ortho position relative to the terminal carboxylate (9d,k,r) are well-tolerated; however, a methoxy substituent meta relative to the terminal carboxylate gives rise to only weakly active analogues (9x). Conformational studies (NMR, X-ray crystallography) of the 2-pyrazinylcarboxamidobenzoates indicate that the preferred conformation exhibits a trans-amide bond and an internal hydrogen bond between the quinoxaline N1 and HN amide which locks the torsional angle between C2 and CO in the s-trans conformation. N-Methylation (9y) results in loss of activity. Studies indicate that there is now a cis-amide bond present which redirects the carboxylate toward the pharmacophoric gem-dimethyl groups. The distance between the gem-dimethyl group and the terminal carboxylate appears to be too short to activate the retinoid receptor. N-Methylation in the beta-ionylideneacetamidobenzoate series (10c) also results in the formation of a cis-amide bond and loss of activity.

Magnetic interactions in a-VO(HP04).2H20 are reported. The antiferromagnetic interaction between V4+ centers occurs by spin transfer through the phosphate bridges. Despite the layer structure built from connecting V06 chains, the compound behaves magnetically as isolated dimers. Emphasis is made on the role of the local probe (31P solid-state NMR) to elucidate the exchange mechanism and eliminate the possible ambiguities derived from observation of the structure only.In recent years there has been significant interest by solid-state chemists in the V-P-O system, given ita catalytic relevance,'$ in particular, oxovanadium(V) (w-VOPO, and related intercalated phases have been widely studied.3-7 On the other hand, oxovanadium(IV) phosphates offer a large variety of crystal structures yielding different types of low-dimensional magnetic interactions? Hence, the magnetic behavior ranges from isolated vanadyl dimers in VO(HP04)J/2H20,9 to regular vanadyl chains in VO-(P03)2 and VO(H2P04)28J0 and to double chains in (V-O)2P207 and VO(HPO4)-4H20."J2Recently, other members of the family of hydrogen phosphate hydrates have been isolated, namely, VO-(HP04)*nH20 with n = 1 , 2 (a and B), and 3;13 the crystal structures of the two forms of the dihydrate have been determined.l4*ls Although all of these structures are based on linking of V06 octahedra and PO, tetrahedra, they are actually very different. The magnetic properties differ not only on the type of interactions (dimers, single or double chains) but also on their strength. The observed exchange constants 14, vary from 2K for VO(H2P04)2 to 43K forconnections has been proposed which is able to offer a consistent qualitative magnetustructural correlation for the known oxovanadium(IV) phosphate^.'^ This classification is based on the fact that the exchange pathways seem to involve to some extent the [PO,] tetrahedra. If this is the case, one should expect some difference in the 31P NMR spectra, due to the shift created by the presence of a finite spin density at the phosphorus nuclei. In fact, some correlation exists between the shift of the NMR line and the exchange ~0 n s t a n t . l~~In this article we present the magnetic properties of the dihydrate a-VO(HP04).2H20 and their interpretation on the basis of an isotropic Heisenberg model. Experimental evidence of the role of [PO,] groups in the exchange mechanism is also given: the shift observed in the 31P N M R line and ita thermal variation c o n f i i the presence of a fiiite spin density at the phosphorus nuclei. The crystal structure of a-VO(HP04).2H20 has been recently e~tablished.'~ The unit cell is monoclinic, space group R 1 / c with a = 7.621 A, b = 7.439 A, c = 9.493 A and B = 95.44O. The structure consists of infinite chains of comer sharing [vo6] octahedra running along the b axis.These chains are linked together by HPO, groups which share two oxygen atoms with two adjacent [VO,] octahedra from the same chain and a third one with an octahedron belonging to an adjacent chain (Figure 1). Vanadyl hydrogen phosp...