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Professor
Graham Richards is Chairman of Chemistry at Oxford and one
of the world's leading figures in computational approaches to drug discovery.
He is the author of over 300 scientific papers and 15 books. He was the
scientific founder of Oxford Molecular Group Plc, now part of Pharmacopeia
Inc. In 1998 he was presented with the Mullard Award from the Royal Society
for his work on the development of computational methods for molecular
design and their application.
Professor Graham
Richards, Chairman of Chemistry at Oxford and Director of the Centre for
Drug Discovery, said: "One in four people throughout the world contract
some form of cancer, so nearly everyone will have a relative, friend or
colleague who has suffered or is suffering from the disease. People now
have the opportunity to make a positive impact on the disease by donating
their unused computer power, which will enable us to accelerate our programme
of research, and come up with many new molecular candidates that could
be developed into cancer drugs."
Selected recent
publications
Books
- Computational Chemistry, G.H. Grant and W.G. Richards, Oxford University
Press (1995).
- Computer-aided
molecular design, ed. W.G. Richards, IBC Press, (1989).
- QuantumPharmacology,
W.G. Richards, Butterworths, London, 2nd edn. (1983).
Articles
Pattern
recognition techniques in drug discovery. Richards,
W. Graham; Robinson, Daniel D. Department of Chemistry, Oxford University,
Oxford OX1 3QT, UK. Abstr. Pap. - Am. Chem. Soc. (2001), 221st
COMP-027. CODEN: ACSRAL ISSN: 0065-7727. Journal; Meeting Abstract
written in English. AN 2001:199812 CAPLUS (Copyright 2001 ACS)
Abstract
Techniques
developed in the area of artificial intelligence such as computer vision
and object recognition can be adapted for use in computational chem.
and drug discovery. We present two examples. Mol. alignment is a crucial
first step in many deign projects. This is particularly difficult if
the structures are very diverse particularly with respect to size.
Nonetheless computer vision methods can handle the problem. Another
adaptation from medical imaging using a multiscale approach permits
us to find binding sites on proteins.
Similarity
Calculations Using Two-Dimensional Molecular Representations. Allen,
Benjamin C. P.; Grant, Guy H.; Richards, W. Graham. New Chemistry Laboratory,
University of Oxford, Oxford, UK. J. Chem. Inf. Comput. Sci. (2001),
41(2), 330-337. CODEN: JCISD8 ISSN: 0095-2338. Journal written in
English. AN 2001:156265 CAPLUS (Copyright 2001 ACS)
Abstract
Mol.
similarity calcns. are important for rational drug design. Time constraints
prevent these techniques being used on large data sets or on large mols.
By reducing the mol. representation to a two-dimensional form, the alignment
of the mols. can be greatly speeded up. The accuracy of the resulting
similarity values can be improved by using a neural network.
Partial
Molecular Alignment via Local Structure Analysis. Robinson,
Daniel D.; Lyne, Paul D.; Richards, W. Graham. Physical and Theoretical
Chemistry Laboratory, University of Oxford, Oxford, UK. J. Chem.
Inf. Comput. Sci. (2000), 40(2), 503-512. CODEN: JCISD8 ISSN: 0095-2338.
Journal written in English. CAN 132:202562 AN 2000:44083 CAPLUS
(Copyright 2001 ACS)
Abstract
Mol.
alignment remains as one of the most problematic aspects of mol. design.
A technique is introduced that facilitates the alignment of a range
of structures that could not be handled easily using existing alignment
procedures. The flexibility of the method is illustrated with a series
of test sets. First, an alignment is performed on a series of mols.
from a typical 3D-quant. structure-activity relation data set. The
results of this test show the technique to outperform many existing
alignment methodologies based upon the optimization of mol. similarity
or mol. overlaps. This test set is then extended to consider the alignment
of more structurally diverse inhibitors of HIV-1 reverse transcriptase
and HIV-1 protease. Finally, in the most challenging test, a large
protein-based inhibitor is matched with a small-mol. mimic. It is believed
that the existence of such a versatile alignment technique will prove
invaluable in the fields of mol. design and chem. information handling.
Molecular
similarity. Richards, W. Graham; Robinson, Daniel D.
New Chemistry Laboratory, Oxford University, Oxford, UK. IMA Vol.
Math. Its Appl. (1999), 108(Rational Drug Design), 39-49. CODEN: IVMAFU
Journal; General Review written in English. CAN 131:53425 AN 1999:259233
CAPLUS (Copyright 2001 ACS)
Abstract
A review
with 19 refs. Mol. similarity aims to give a quant. answer to the question
of how similar two given mols. are. Such indexes are of use in drug
design as aids to the creation of mol. mimics and in structure- activity
studies or measures of mol. diversity. Similarity is most often computed
in terms of mol. shape or electrostatic potential. The advent of combinatorial
techniques and the use of high throughput synthesis have created a need
for ever faster methods of computation. Numerical calcn. has been superceded
by anal. evaluation of integrals, but even faster methods are urgently
needed. This is esp. so if we can ever hope to take thousands of mols.
and calc. the similarity between all pairs. A promising technique is
to use two-dimensional mol. representations and to utilize methodologies
perfected in optical character recognition.
The
design of novel acetylcholinesterase inhibitors using the multiple copy
simultaneous search method. Castro, Ana; Richards, W. Graham;
Lyne, Paul D. New Chemistry Laboratory, Oxford, UK. Med. Chem.
Res. (1999), 9(2), 98-107. CODEN: MCREEB ISSN: 1054-2523. Journal
written in English. CAN 131:53572 AN 1999:248892 CAPLUS (Copyright
2001 ACS)
Abstract
A novel
series of imidazole derivs. are designed by application of the multiple
copy simultaneous search technique as acetylcholinesterase inhibitors.
The resulting compds. are predicted to interact simultaneously with
the catalytic site and a peripheral site. Interaction energies are
compared between existing inhibitors and the designed ligands, suggesting
that these new compds. could bind better than known inhibitors.
Self-organizing
molecular field analysis: a tool for structure-activity studies.
Robinson, Daniel D.; Winn, Peter J.; Lyne, Paul D.; Richards,
W. Graham. Physical and Theoretical Chemistry Laboratory, Oxford University,
Oxford, UK. J. Med. Chem. (1999), 42(4), 573-583. CODEN: JMCMAR
ISSN: 0022-2623. Journal written in English. CAN 130:276227 AN
1999:65866 CAPLUS (Copyright 2001 ACS)
Abstract
Self-organizing
mol. field anal. (SOMFA) is a novel technique for three-dimensional
quant. structure-activity relations (3D-QSAR). It is simple and intuitive
in concept and avoids the complex statistical tools and variable selection
procedures favored by other methods. Our calcns. show the method to
be as predictive as the best 3D-QSAR methods available. Importantly,
steric and electrostatic maps can be produced to aid the mol. design
process by highlighting important mol. features. The simplicity of
the technique leaves scope for further development, particularly with
regard to handling mol. alignment and conformation selection. Here,
the method has been used to predict the corticosteroid-binding globulin
binding affinity of the "benchmark" steroids, expanded from
the usual 31 compds. to 43 compds. Test predictions have also been
performed on a set of sulfonamide endothelin inhibitors.
Explicit
calculation of 3D molecular similarity. Good, Andrew C.;
Richards, W. Graham. Glaxo Wellcome Medicines Research Center, Stevenage,
UK. Perspect. Drug Discovery Des. (1998), 9/10/11(3D QSAR in Drug
Design: Ligand/Protein Interactions and Molecular Similarity), 321-338.
CODEN: PDDDEC ISSN: 0928-2866. Journal; General Review written in English.
CAN 129:81233 AN 1998:442468 CAPLUS (Copyright 2001 ACS)
Abstract
A review
with 86 refs. is given on techniques for quantifying explicit 3-dimensional
mol. similarity, detailing their application, merits, and pitfalls including
mol. properties, indexes, and protocols, from the comparison of MEP
and shape for quant. structure activity relationship construction, through
to the rapid anal. of pharmacophore triplet descriptors for diversity
anal.
Use
of reduced representations of proteins and small molecules. Richards,
W. Graham; Robinson, Daniel D. Physical and Theoretical Chemistry Laboratory,
Oxford, UK. Alfred Benzon Symp. (1998), 42(Rational Molecular Design
in Drug Research), 139-150. CODEN: ABSYB2 ISSN: 0105-3639. Journal
written in English. CAN 129:75978 AN 1998:274058 CAPLUS (Copyright
2001 ACS)
Abstract
The
2D methods in mol. drug design are discussed. In general, there is
a good agreement between the 2D methods and a high correlation with
the 3D results. This confirms that the 2D methods are adequate for
similarity studies. It does not take too much imagination to envisage
a database of mols. being searched for similarity to some lead being
conducted with a similar rapidity providing a powerful tool to exploit
combinatorial chem.
Theoretical
calculation of partition coefficients. Richards, W. Graham.
Physical and Theoretical Chemistry, Oxford University, Oxford, UK.
Methods Princ. Med. Chem. (1996), 4(Lipophilicity in Drug Action and
Toxicology), 173-180. CODEN: MPMCE3 Journal; General Review written
in English. CAN 127:214415 AN 1997:535905 CAPLUS (Copyright
2001 ACS)
Abstract
A review,
with 10 refs. on tools for calcg. partition coeffs. Statistical thermodn.,
equil. consts., free energy perturbation calcns., partition coeffs.,
and membrane simulations are discussed.
Molecular
similarity and dissimilarity. Richards, W. Graham. Phys.
Chemistry Lab., Oxford Univ., Oxford, UK. Mol. Eng. (1995), 5(1-3),
229-323. CODEN: MOLEEV Journal; General Review written in English.
CAN 123:131789 AN 1995:697130 CAPLUS (Copyright 2001 ACS)
Abstract
A review
with 12 refs. Mol. similarity provides a quant. measure of the resemblance
of mols. It is of use in the design of mimetics and in finding relationships
between biol. activity and mol. properties which incorporate three-dimensional
features. Dissimilarity between enantiomeric forms can rationalize
the relative potencies of optical isomers.
Molecular
similarity and dissimilarity. Richards, W. Graham. Physical
Chemistry Laboratory, Oxford University, Oxford, UK. Jerusalem Symp.
Quantum Chem. Biochem. (1995), 27 365-9. CODEN: JSQCA7 ISSN: 0075-3696.
Journal; General Review written in English. CAN 123:101836 AN 1995:690595
CAPLUS (Copyright 2001 ACS)
Abstract
A review
with 12 refs. Mol. similarity provides a quant. measure of the resemblance
of mols. It is of use in the design of mimetics and in finding relationships
between biol. activity and mol. properties which incorporate three-dimensional
features. Dissimilarity between enantiomeric forms can rationalize
the relative potencies of optical isomers.
Shape
similarity as a single independent variable in QSAR. Seri-Levy,
A.; Salter, R.; West, S.; Richards, W. G.. Phys. Chem. Lab., Oxford,
UK. Eur. J. Med. Chem. (1994), 29(9), 687-94. CODEN: EJMCA5 ISSN:
0223-5234. Journal written in English. CAN 122:23232 AN 1995:239258
CAPLUS (Copyright 2001 ACS)
Abstract
The
use of shape similarity as a single independent variable in QSAR equations
is demonstrated for the inhibition of dihydrofolate reductase (DHFR)
and for central hypotensive activity. The predictive ability of these
shape similarity QSAR equations is higher than that of the equiv. multivariate
QSAR equations.
Theoretical
chemistry in drug discovery. Richards, W. Graham. Phys.
Chem. Lab., Oxford Univ., UK. Editor(s): Nascimento, Marco Antonio
Chaer. Mol. Model. Chem. XXI Century, [Mater. Meet.] (1994), Meeting
Date 1992, 43-56. Publisher: World Sci., Singapore, Singapore CODEN:
60KZAX Conference; General Review written in English. CAN 121:291716
AN 1994:691716 CAPLUS (Copyright 2001 ACS)
Abstract
A review
with 18 refs. The role of theor. chem. (quantum mechanics, etc.) in
drug disign is discussed. Cases in which the drug receptor structure
is known (from e.g. crystallog.), in which the receptor structure is
predicted from theor. methods, an in which the receptor remains an unknown
macromol. are sep. considered.
Predictive
modeling of the 3-D structure of interleukin-13. Bamborough,
Paul; Duncan, David; Richards, W. Graham. Physical Chemistry Laboratory,
Oxford Centre for Molecular Science, Oxford, UK. Protein Eng. (1994),
7(9), 1077-82. CODEN: PRENE9 ISSN: 0269-2139. Journal written in
English. CAN 121:253376 AN 1994:653376 CAPLUS (Copyright 2001
ACS)
Abstract
Several
at. structures are now available for the family of helical cytokines,
which includes growth hormone as well as many of the interleukins.
Using structural information from 5 members of this family, 2
alternative models of interleukin (IL)-13 are proposed. IL-13 has biol.
properties similar to those of IL-4 and, like the other interleukins,
is a potentially important pharmaceutical target. The model of IL-13
is discussed and compared with the known interleukin structures.
Theoretical
chemistry in drug discovery. Richards, W. G.. Phys.
Chem. Lab., Oxford Univ., Oxford, UK. Eur. J. Med. Chem. (1994),
29(7-8), 499-502. CODEN: EJMCA5 ISSN: 0223-5234. Journal; General
Review written in English. CAN 121:220874 AN 1994:620874 CAPLUS
(Copyright 2001 ACS)
Abstract
A review,
with 19 refs., of the application of theor. chem. in drug discovery.
Computer-aided
drug design. Richards, W. Graham. Phys. Chemistry Laboratory,
Oxford Univ., Oxford, UK. Pure Appl. Chem. (1994), 66(8), 1589-96.
CODEN: PACHAS ISSN: 0033-4545. Journal; General Review written in English.
CAN 121:220872 AN 1994:620872 CAPLUS (Copyright 2001 ACS)
Abstract
A review
with 21 refs. Two distinct approaches are possible in the area of computer-aided
drug design. If the mol. structure of the target macromol. is known
the methods are obvious and direct and have achieved a high level of
sophistication. That area may be extended by using computational techniques
to predict protein structure as illustrated here by the interleukin-4-receptor.
When the only led is a set of known active compds. or knowledge of a
biochem. transformation which is to be interrupted, then the path is
less direct. Currently favored tactics include the use of mol. similarity
methods and the employment of neural networks. Recent advances include
the prediction of the relative potency of different chiral forms of
drugs.
Molecular
Similarity, Quantitative Chirality, and QSAR for Chiral Drugs. Seri-Levy,
Alon; West, Susan; Richards, W. Graham. Physical Chemistry Laboratory,
Oxford, UK. J. Med. Chem. (1994), 37(11), 1727-32. CODEN: JMCMAR
ISSN: 0022-2623. Journal written in English. CAN 120:315184 AN
1994:315184 CAPLUS (Copyright 2001 ACS)
Abstract
The
current policy of drug regulatory authorities demanding that pharmaceutical
companies justify their reasons for preferring drugs contg. a mixt.
of enantiomers over one stereoisomer increases the importance of quant.
structure-activity relations (QSARs) for chiral drugs. The QSAR proposed
by Pfeiffer for chiral drug enantiomer potencies was brought into question
by the existence of sets obeying an anti-Pfeiffer rule. Using computer-aided
mol. design methods and treating chirality not as an existing/nonexisting
property but as a continuous one improve the QSAR proposed by Pfeiffer,
yielding higher correlation coeffs. and an independent ordinate. Calcd.
shape similarities reveal the details of the Pfeiffer behavior and the
source of the anti-Pfeiffer behavior. Consequently revised models for
the D2 and s receptor are suggested.
QSAR's
from similarity matrices. Technique validation and application in the
comparison of different similarity evaluation methods. Good,
Andrew C.; Peterson, Stephen J.; Richards, W. Graham. Phys. Chem. Lab.,
Univ. Oxford, Oxford, UK. J. Med. Chem. (1993), 36(20), 2929-37.
CODEN: JMCMAR ISSN: 0022-2623. Journal written in English. CAN 120:124107
AN 1994:124107 CAPLUS (Copyright 2001 ACS)
Abstract
It
has recently been shown that good quant. structure-activity relationships
can be obtained through statistical anal. of mol. similarity matrixes.
Here we extend the technique to seven addnl. mol. series, previously
studied using Comparative Mol. Field Anal. (CoMFA) methodol. The results
are used to confirm technique applicability across a wider range of
QSAR problems and to compare quant. the ability of various similarity
indexes to describe biol. systems. The relative merits of this technique
in comparison to CoMFA are discussed.
Chiral
drug potency: Pfeiffer's rule and computed chirality coefficients.
Seri-Levy, Alon; Richards, W. Graham. Phys. Chem. Lab.,
Oxford, UK. Tetrahedron: Asymmetry (1993), 4(8), 1917-23. CODEN:
TASYE3 ISSN: 0957-4166. Journal written in English. CAN 119:262014
AN 1993:662014 CAPLUS (Copyright 2001 ACS)
Abstract
Since
the thalidomide tragedy there has been an increased awareness of the
potential dangers of using racemic drugs. Pharmaceutical companies
are required to justify each decision to manuf. a racemic drug in preference
to its homochiral version. This process of justification is both time-consuming
and costly. Any method for its simplification would be most valuable.
The computer-aided mol. design method suggested here, based on the method
of C.C. Pfeiffer (1956), produces a sensitive quant. structure-activity
relation between the potency ratios of drug enantiomers and a computed
chirality coeff. defined as (1 - mol. similarity). The advantage of
this correlation is that it permits the explanation of previous exptl.
results and also the prediction of the potency of new drugs within a
series. The method is illustrated by using a series of muscarinic 1,3-dioxolanes
and a series of S-alkyl p-nitrophenyl methylphosphonothiolates which
react with cholinesterase receptors.
Computers
in drug design. Richards, W. Graham. Phys. Chem. Lab.,
Oxford, UK. Pure Appl. Chem. (1993), 65(2), 231-4. CODEN: PACHAS
ISSN: 0033-4545. Journal; General Review written in English. CAN
118:160346 AN 1993:160346 CAPLUS (Copyright 2001 ACS)
Abstract
A review
with 13 refs. Computational techniques may be used to aid the process
of drug discovery both when the target macromol. is of unknown structure
and when it is understood in at. detail. Methods include measures of
mol. shape; mol. similarity; quantum, statistical and mol. mechanics;
mol. dynamics; Monte Carlo calcns. and mol. graphics.
Computer-aided
drug discovery. Richards, W. Graham. Oxford Cent. Mol.,
Oxford, UK. Proc. - R. Soc. Edinburgh, Sect. B: Biol. Sci. (1992),
99(1-2), 105-11. CODEN: PRSSDP ISSN: 0269-7270. Journal; General Review
written in English. CAN 118:24 AN 1993:24 CAPLUS (Copyright
2001 ACS)
Abstract
A review
with 16 refs. The role of computers in drug discovery depends on just
how much is known about the target macromol. If at. detail of the receptor
is known, binding free energy differences between drug variants may
be computer. Major effort is being expended in extending the area of
applicability of such studies by predicting protein structure based
on homologies with known protein crystal data. Where no target structure
is available, computational methods can provide leads by defining transition
state structures and then using the approach of mol. similarity to define
stable mimics to act as blockers.
A
linear molecular similarity index. Reynolds, Christopher
A.; Burt, Catherine; Richards, W. Graham. Dep. Chem. Biol. Chem.,
Univ. Essex, Colchester, UK. Quant. Struct.-Act. Relat. (1992),
11(1), 34-5. CODEN: QSARDI ISSN: 0931-8771. Journal written in English.
CAN 117:19930 AN 1992:419930 CAPLUS (Copyright 2001 ACS)
Abstract
Mol.
similarity is a tool for rationalizing the biol. activities of potential
drug mols. The most useful form of mol. similarity calcns. are usually
based upon the mol. electrostatic potential and generally use formulae
due to Carbo or Hodgkin but these formulae do not give a similarity
index which varies linearly with mol. electrostatic potential. Consequently,
a new linear index has been proposed and the potential advantages of
this index are discussed.
Fast
drug-receptor mapping by site-directed distances: a novel method of predicting
new pharmacological leads. Smellie, Andrew S.; Crippen,
G. M.; Richards, W. G.. BioCAD Corp., Mountain View, CA, USA.
J. Chem. Inf. Comput. Sci. (1991), 31(3), 386-92. CODEN: JCISD8 ISSN:
0095-2338. Journal written in English. CAN 115:84822 AN 1991:484822
CAPLUS (Copyright 2001 ACS)
Abstract
The
searching and characterization of large chem. databases has recently
provoked much interest, particularly with respect to the question of
whether any of the compds. in the database could serve as new leads
to a compd. of pharmacol. interest. This study introduces a fast and
novel method of detg. whether any of a given series of compds. are able,
on geometrical grounds, to interact with an active site of interest.
The C program written to implement the method is able to make a qual.
prediction for a given compd. in about 1 s per structure (for drug-sized
mols.), while still permitting the compd. complete conformational freedom.
However, the algorithm is sufficiently flexible to permit distance constraints
to be placed on the mols. while docking. The test system studied was
a family of Baker's triazines docking into the active site of dihydrofolate
reductase (DHFR), as defined by a methotrexate-NADPH complex.
Relative
partition coefficients from partition functions: a theoretical approach
to drug transport. Essex, Jonathan W.; Reynolds, Christopher
A.; Richards, W. Graham. Phys. Chem. Lab., Oxford Cent. Mol. Sci.,
Oxford, UK. J. Chem. Soc., Chem. Commun. (1989), (16), 1152-4.
CODEN: JCCCAT ISSN: 0022-4936. Journal written in English. CAN 111:126410
AN 1989:526410 CAPLUS (Copyright 2001 ACS)
Abstract
The
free-energy perturbation method was applied to the calcn. of the difference
in partition coeffs. (P) between MeOH and EtOH partitioned between H2O
and CCl4. The calcd. and exptl. values agreed to within 0.06 log P
unit.
Rational
drug design: binding free energy differences of carbonic anhydrase inhibitors.
Menziani, M. Cristina; Reynolds, Christopher A.; Richards, W.
Graham. Phys. Chem. Lab., Oxford Univ., Oxford, UK. J. Chem.
Soc., Chem. Commun. (1989), (13), 853-5. CODEN: JCCCAT ISSN: 0022-4936.
Journal written in English. CAN 111:89800 AN 1989:489800 CAPLUS
(Copyright 2001 ACS)
Abstract
The
free energy perturbation method has been applied to calc. the binding
energy of sulfonamide inhibitors of carbonic anhydrase; agreement with
exptl. data gives further evidence for the reliability of this method
even for anionic inhibitors and supports its use in drug design.
Computer-aided
molecular design. Richards, W. Graham. Phys. Chem. Lab.,
Oxford Univ., Oxford, UK. Sci. Prog. (Oxford) (1988), 72(288),
481-92. CODEN: SCPRAY ISSN: 0036-8504. Journal written in English.
CAN 110:211665 AN 1989:211665 CAPLUS (Copyright 2001 ACS)
Abstract
In
the pharmaceutical industry and elsewhere, the role of computer-aided
mol. design has developed into a powerful set of methods involving both
the display of mols. and their properties on graphics devices and the
calcn. of mol. properties. Many mols. are designed to bind to specific
receptor sites on macromols. so the design aspect is simplest when the
mol. structures of both binding partners are known. In such cases,
questions of fit and of binding energy are paramount. Where the macromol.
structure is unknown, it may be inferred from a knowledge of transition
states which again can be derived from theor. calcns.
Molecular
similarity. Richards, W. Graham; Hodgkin, Edward E.
Phys. Chem. Lab., Univ. Oxford, Oxford, UK. Chem. Br. (1988),
24(11), 1141, 1143-4. CODEN: CHMBAY ISSN: 0009-3106. Journal; General
Review written in English. CAN 110:17901 AN 1989:17901 CAPLUS
(Copyright 2001 ACS)
Abstract
A review,
with 12 refs., discussing means for detg. how similar 1 mol. is to another,
e.g., for QSAR studies on drug design.
Quantum
chemistry in drug design. Richards, W. Graham. Phys.
Chem. Lab., Oxford, UK. Pure Appl. Chem. (1988), 60(2), 277-9.
CODEN: PACHAS ISSN: 0033-4545. Journal; General Review written in English.
CAN 108:142663 AN 1988:142663 CAPLUS (Copyright 2001 ACS)
Abstract
A review
with 11 refs. examg. the use of quantum chem. in the design of tumor-selective
antifolates and transition state analogs.
Molecular
similarity in terms of valence electron density. Bowen-Jenkins,
Philippa E.; Richards, W. Graham. Phys. Chem. Lab., Univ. Oxford,
Oxford, UK. J. Chem. Soc., Chem. Commun. (1986), (2), 133-5.
CODEN: JCCCAT ISSN: 0022-4936. Journal written in English. CAN 105:41963
AN 1986:441963 CAPLUS (Copyright 2001 ACS)
Abstract
Ab
initio comparison of the valence electron d. of mols. provides a quant.
measure of their similarity which conforms with qual. ideas of bioisosterism.
The technique may provide a useful criterion in mol. and pharmaceutical
design.
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