Zolmitriptan oxalate and zolmitriptan camphorsulfonate: the first structural study of salt complexes of the antimigraine drug zolmitriptan.

Zolmitriptan hydrogen oxalate [(S)-dimethyl(2-{5-[(2-oxo-1,3-oxazolidin-4-yl)methyl]-1H-indol-3-yl}ethyl)azanium hydrogen oxalate], C16H22N3O2(+)·C2HO4(-), (I), and zolmitriptan camphorsulfonate [(S)-dimethyl(2-{5-[(2-oxo-1,3-oxazolidin-4-yl)methyl]-1H-indol-3-yl}ethyl)azanium (S,R)-{2-hydroxy-7,7-dimethylbicyclo[2.2.1]heptan-1-yl}methanesulfonate], C16H22N3O2(+)·C10H15O4S(-), (II), are the first reported salt complexes of the antimigraine drug zolmitriptan. Compound (I) crystallizes in the space group P2(1) with two molecules of protonated zolmitriptan and two oxalate monoanions in the asymmetric unit, while compound (II) crystallizes in the space group P2(1)2(1)2(1) with one protonated zolmitriptan molecule and one camphorsulfonate anion in the asymmetric unit. The orientations of the ethylamine side chain and the oxazolidinone ring with respect to the indole ring of the zolmitriptan cation are different for (I) and (II). In (I), they are oriented in opposite directions and the molecule adopts a step-like appearance, while in (II) the corresponding side chains are folded in the same direction, giving the molecule a cup-like appearance. The zolmitriptan molecules of (I) form an R2(2)(8) dimer, while in (II) they form a helical chain with a C(11) motif. The oxalate monoanions of (I) interact with the zolmitriptan cations and extend the dimer into a three-dimensional hydrogen-bonded network. In (II), the camphorsulfonate anion forms an R2(2)(15) ring motif with the zolmitriptan cation.

Frovatriptan salts of aliphatic carboxylic acids.

The interaction of the antimigraine pharmaceutical agent frovatriptan with acetic acid and succinic acid yields the salts (±)-6-carbamoyl-N-methyl-2,3,4,9-tetrahydro-1H-carbazol-3-aminium acetate, C14H18N3O(+)·C2H3O2(-), (I), (R)-(+)-6-carbamoyl-N-methyl-2,3,4,9-tetrahydro-1H-carbazol-3-aminium 3-carboxypropanoate monohydrate, C14H18N3O(+)·C4H5O4(-)·H2O, (II), and bis[(R)-(+)-6-carbamoyl-N-methyl-2,3,4,9-tetrahydro-1H-carbazol-3-aminium] succinate trihydrate, 2C14H18N3O(+)·C4H4O4(2-)·3H2O, (III). The methylazaniumyl substitutent is oriented differently in all three structures. Additionally, the amide group in (I) is in a different orientation. All the salts form three-dimensional hydrogen-bonded structures. In (I), the cations form head-to-head hydrogen-bonded amide-amide catemers through N-H···O interactions, while in (II) and (III) the cations form head-to-head amide-amide dimers. The cation catemers in (I) are extended into a three-dimensional network through further interactions with acetate anion acceptors. The presence of succinate anions and water molecules in (II) and (III) primarily governs the three-dimensional network through water-bridged cation-anion associations via O-H···O and N-H···O hydrogen bonds. The structures reported here shed some light on the possible mode of noncovalent interactions in the aggregation and interaction patterns of drug molecule adducts.

Three novel benzothiazine-fused triazoles as potential centrally acting muscle relaxants.

The structures of the novel triazolobenzothiazines 2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-1-one (IDPH-791), C(9)H(7)N(3)OS, (I), a potential muscle relaxant, its benzoyl derivative, 2-(2-oxo-2-phenylethyl)-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-1-one, C(20)H(17)N(3)O(4)S, (II), and the ß-keto ester derivative, ethyl 3-oxo-2-(1-oxo-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-2-yl)-3-phenylpropanoate, C(17)H(13)N(3)O(2)S, (III), are the first examples of benzothiazine-fused triazoles in the crystallographic literature. The heterocyclic thiazine rings in all three structures adopt a distorted half-chair conformation. Compound (III) exists in the trans-ß-diketo form. Other than N-H···O hydrogen bonds in (I) forming dimers, no formal intermolecular hydrogen bonds are involved in the crystal packing of any of the three structures, which is dominated by C-H···O/N and π-π stacking interactions.

Structures of benzoxazine-fused triazoles as potential diuretic agents.

6,8-Dinitro-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]oxazin-1-one, C(9)H(5)N(5)O(6), (I), a potential diuretic, and its acetylacetone derivative (E)-2-(2-hydroxy-4-oxopent-2-en-3-yl)-6,8-dinitro-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]oxazin-1-one, C(14)H(11)N(5)O(8), (II), both crystallize from methanol but in centrosymmetric and noncentrosymmetric space groups, respectively. To the best of our knowledge, this is the first report of crystal structures of benzoxazine-triazole fused systems. The acetylacetone group in (II) exists as the keto-enol tautomer and is oriented perpendicular to the triazol-3-one ring. Of the two nitro groups present, one is rotated significantly less than the other in both structures. The oxazine ring adopts a screw-boat conformation in (II), whereas it is almost planar in (I). N-H···N and N-H···O hydrogen bonds form centrosymmetric dimers in (I), while C-H···O interactions associate the molecules into helical columns in (II).