Geometric and electronic factors in the structure–activity relationships of some 5-phenyl-1,4-benzodiazepines

Structures of lorazepam isopropyl alcohol solvate (I) and isoamyl alcohol solvate (II)

“…We also found some 5.60 8.75 differences around C(3): it appears that substitution of 3.76 C(3)-H by hydroxyl causes an increase in the 3.32 C(2)-C(3)-N(4) angle by some 2-3 ° 4.74 4.58 In common with other benzodiazepines, the seven- 5.04 are the same as those found in the ethanol solvate 6.64 (Bandoli & Clemente, 1976 title compounds and other benzodiazepines is in the orientation of the 5-phenyl ring to the benzene ring of the benzodiazepine. However, the values of 88.9 (5) ° in (II) and 88.4 (5) and 84.9 (5) ° in (I) (XANADU: Roberts & Sheldrick, 1975) agree well with the values given by Chananont et al (1981) for the benzodiazepine where the 5-phenyl ring also carries an o-chloro substituent. Intermolecular contact distances are listed in …”

“…By comparison with other analogous molecules, the ring angle at N(1) is in good agreement with that in N(1)-H benzodiazepines (Chananont et al, 1981 (2) 3612 (I) 2020 (2) 1939 (2) N(1) 508 (3) 1851 (4) 4073 (4) N(4) 1150 (3) 3430 (3) 336 (4) O (12) -303 (3) 664 (3) 2970 (3) O (13) -662 (3) 3051 (3) 520 (4) C (7) 1798 (3) 5359 (4) 4294 (5) C (8) 1232 (4) 4340 (4) 5796 (5) C (9) 804 (4) 3216 (5) 5675 (5) C (10) 939 (3) 3056 (4) 4090 (4) C (11) 1556 (3) 4050 (4) 2598 (4) C (6) 1971 (3) 5204 (4) 2731 (5) C (2) 58 (3) 1765 (4) 2893 (5) C (3) 38 (3) 3126 (4) 1438 (5) C (5) 1814 (3) 3870 (4) 897 (4) C (14) 2941 (3) 4239 (4) -258 (5) C (15) 3823 (4) 3468 (5) 97 (6) C (16) 4858 (4)...…”

“…They found a formulation in which one ethanol molecule is present for two lorazepam molecules. Several structural studies of benzodiazepines have been published since then (Gilli, Bertolasi, Sacerdoti & Borea, 1977, 1978aChananont, Hamor & Martin, 1980, 1981Butcher, * Lorazepam: 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-l,4-benzodiazepin-2-one.…”

Structures of 7-chloro-5-phenyl-1-[(S)-1-phenylethyl]-1,3-dihydro-2H-1,4-benzodiazepin-2-one and its 3-methyl derivative

“…748 (4) 1.377 (7) 1.404 (7) 1.382 (7) 1.404 (6) 1.527 (9) 1.516 (7) I. -C(18) 121.9 (6) 120.6 (3) C (5) The conformation of active and nonactive benzodiazepines has not revealed any significant difference; it has also been proved that no correlation exists between molecular geometry and activity (Bandoli & Clemente, 1976;Gilli, Bertolasi, Sacerdoti & Borea, 1977, 1978Chananont, Hamor & Martin, 1980;Chananont & Hamor, 1981).…”

Structure of 7,8,17,18-tetrahydro-10,20-diphenyl-5,9,15,19-tetraazadibenzo[ai]cyclohexadecene-6,16(5H,15H)-dione, C32H28N4O2

“…An interesting feature of this compound is the trans conformation of the amide fragment within the molecule. In 1,4-benzodiazepines studied earlier (Gilli, Bertolasi, Sacerdoti & Borea, 1978;Chananont, Hamor & Martin, 1981;Andronati, Dvorkin, Korotenko, Voronina, Simonov & Shibanova, 1982), the amide fragment has a cis conformation which results in the dimerization of the molecules by NH...O bonds. The inversion of the amide group from the cis to the trans configuration prevents the formation of intermolecular hydrogen bonds and results in the formation of two strong intramolecular hydrogen bonds N(1)H...N(2) [N(1)-H=1.06, N(2)...H=1.68A, angle N(1)--H--N(2) = 150 °] which apparently contributes to the flattening of the fragment C(10),N(1),-C(6),C(7),N(2),C(8) and to the stabilization of the observed molecular conformation.…”