Halide salts of antimigraine agents eletriptan and naratriptan.
Molecules of eletriptan hydrobromide monohydrate (systematic name: (1S,2R)-1-methyl-2-{5-[2-(phenylsulfonyl)ethyl]-1H-indol-3-ylmethyl}pyrrolidinium bromide monohydrate), C(22)H(27)N(2)O(2)S(+) x Br(-) x H(2)O, (I), and naratriptan hydrochloride (systematic name: 1-methyl-4-{5-[2-(methylsulfamoyl)ethyl]-1H-indol-3-yl}piperidinium chloride), C(17)H(26)N(3)O(2)S(+) x Cl(-), (II), adopt conformations similar to other triptans. The C-2 and C-5 substituents of the indole ring, both of which are in a region of conformational flexibility, are found to be oriented on either side of the indole ring plane in (I), whilst they are on the same side in (II). The N atom in the C-2 side chain is protonated in both structures and is involved in the hydrogen-bonding networks. In (I), the water molecules create helical hydrogen-bonded chains along the c axis. In (II), the hydrogen bonding of the chloride ions results in macrocyclic R(4)(2)(20) and R(4)(2)(24) ring motifs that form sheets in the bc plane. This structural analysis provides an insight into the molecular structure-activity relationships within this class of compound, which is of use for drug development.
Ravikumar
K
K
Laboratory of X-ray Crystallography, Indian Institute of Chemical Technology, Hyderabad, India. sshiya@yahoo.com
Sridhar
B
B
Krishnan
Harihara
H
Singh
A N
AN
D000700:Analgesics / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006219:Halogens / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008881:Migraine Disorders / Q000188:drug therapy; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry* / Q000627:therapeutic use; D011759:Pyrrolidines / Q000737:chemistry* / Q000627:therapeutic use; D012492:Salts / Q000737:chemistry* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000737:chemistry* / Q000627:therapeutic use
D000700:Analgesics; D006219:Halogens; D010880:Piperidines; D011759:Pyrrolidines; D012492:Salts; D014363:Tryptamines; C115647:eletriptan; C106783:naratriptan