The EDISFAR Programs. Rational Drug Series Design

Abstract

The computer package EDISFAR is described. The programs can manage physico‐chemical information from a database (MONOBASE) of the fragment parameters classically used in drug design, providing assistance in the use of the techniques related with the Hansch‐Fujita analysis. The user can make design of exploring series of bioactive compounds, using a great variety of techniques, and once a QSAR model has been obtained, can calculate optimum derivatives using the parameters of the MONOBASE. The program has been designed emphasizing its flexibility, accessibility by the practical chemist, and compatibility with other statistics programs or computers.

Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 5. Study of the Physicochemical Influence of the Pharmacophore on 5-HT1A/α1-Adrenergic Receptor Affinity: Synthesis of a New Derivative with Mixed 5-HT1A/D2 Antagonist Properties

“…The meaning of the parameters I A , I B and I n is illustrated in Table . The aromatic substituent R was selected using the database (387 substituents) of the EDISFAR program . This method considers three levels (+, 0, −) to each parameter, the marker points (Table ).…”

“…The aromatic substituent R was selected using the database (387 substituents) of the EDISFAR program. 12 This method considers three levels (+, 0, -) to each parameter, the marker points (Table 2). The program calculated the values of the marker points of each parameter using eqs 1-3:…”

“…The amide moiety is a bicyclohydantoin or a diketopiperazine (X ) -(CH 2 ) 3 -, -(CH 2 ) 4 -; m ) 0, 1), the spacer length is 3 or 4 methylene units, which are the optimum values for both receptors, and the aromatic substituent R occupies the ortho-or meta-position and has been selected from a database of 387 substituents using the EDISFAR program. 12 In the present paper we report the design, synthesis and binding profile on 5-HT 1A and R 1 -adrenergic receptors of compounds VI. This data set will be used to derive classical QSAR and neural networks models for both receptors (following paper), which will be useful in the design of the new ligand EF-7412 (46) (5-HT 1A : K i ) 27 nM; R 1 : K i > 1000 nM).…”

“…To gain insight into the physicochemical influence of 5-HT 1A and α 1 pharmacophores, we have designed a training set of 32 compounds of general structure VI . The amide moiety is a bicyclohydantoin or a diketopiperazine (X = −(CH 2 ) 3 −, −(CH 2 ) 4 −; m = 0, 1), the spacer length is 3 or 4 methylene units, which are the optimum values for both receptors, and the aromatic substituent R occupies the ortho - or meta -position and has been selected from a database of 387 substituents using the EDISFAR program . In the present paper we report the design, synthesis and binding profile on 5-HT 1A and α 1 -adrenergic receptors of compounds VI .…”

New Developments of EDISFAR Programs. Experimental Design in QSAR Practice

“…-[log Act] = 0.52(±0.06) , 2 + 0.03(±0.09)MR, -0.008(±0.002)MR,2-1.53(±0.96)ffm2 + 10.28 (9) n = 9 r2 = 0.997 F= 333.62 However, the series is not suitable for testing parabolic effects, and it must be completed with some other compounds.…”