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31:, the purpose of exchanging one bioisostere for another is to enhance the desired biological or physical properties of a compound without making significant changes in chemical structure. The main use of this term and its techniques are related to pharmaceutical sciences. Bioisosterism is used to reduce toxicity, change
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group or by a cyano -Cā”N group. Depending on the particular molecule used, the substitution may result in little change in activity, or either increased or decreased affinity or efficacy - depending on what factors are important for ligand binding to the target protein. Another example is aromatic
139:
Non-classical bioisosteres may differ in a multitude of ways from classical bioisosteres, but retain the focus on providing similar sterics and electronic profile to the original functional group. Whereas classical bioisosteres commonly conserve much of the same structural properties, nonclassical
79:
in a drug candidate may prevent such metabolism from taking place. Because the fluorine atom is similar in size to the hydrogen atom the overall topology of the molecule is not significantly affected, leaving the desired biological activity unaffected. However, with a blocked pathway for
140:
bioisosteres are much more dependent on the specific binding needs of the ligand in question and may substitute a linear functional group for a cyclic moiety, an alkyl group for a complex heteroatom moiety, or other changes that go far beyond a simple atom-for-atom switch.
107:
atom. Procainamide is a classical bioisostere because the valence electron structure of a disubstituted oxygen atom is the same as a trisubstituted nitrogen atom, as
Langmuir showed.
27:
are chemical substituents or groups with similar physical or chemical properties which produce broadly similar biological properties in the same chemical compound. In
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which may improve efficacy, change specificity of binding or reduce metabolically labile sites on the molecule, resulting in better pharmacokinetic properties.
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131:
221:, wherein a carbon center has been replaced by isosteric silicon, and in addition, one hydrogen atom is replaced by isosteric fluorine atom.
469:
317:
48:
255:
118:
433:
Showell, G. A.; Mills, J. S. (2003). "Chemistry
Challenges in Lead Optimization: Silicon Isosteres in Drug Discovery".
115:. By modifying certain substituents, the pharmacological activity of the chalcone and its toxicity are also modified.
329:
Meanwell, Nicholas A. (2011). "Synopsis of Some Recent
Tactical Application of Bioisosteres in Drug Design".
557:
503:
239:
480:
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35:, or modify the activity of the lead compound, and may alter the metabolism of the lead.
20:
187:. Alloxanthine is considered a non-classical bioisostere because of the scaffold change.
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Chemical groups which can be substituted to enhance therapeutic activity of drugs
423:
Comprehensive
Pharmacy Review, 6th edition, Leon Shargel, Alan H. Mutnick, p.264
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Comprehensive
Pharmacy Review, 6th edition, Leon Shargel, Alan H. Mutnick, p.264
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For example, a chloride -Cl group may often be replaced by a trifluoromethyl -CF
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Classical bioisosterism was originally formulated by James Moir and refined by
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284:, 2nd ed. (the "Gold Book") (1997). Online corrected version: (1998) "
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as a response to the observation that different atoms with the same
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375:"Chalcone Derivatives: Promising Starting Points for Drug Design"
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compounds can be discovered automatically and used to circumvent
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ring can often be replaced by a different aromatic ring such as
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100:
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470:"Beyond Markush ā Protecting Activity not Chemical Structure"
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88:
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metabolism, the drug candidate may have a longer half-life.
432:
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Silafluofen is an isostere of pyrethroid insecticides.
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Another example is seen in a series of anti-bacterial
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135:
A phenyl for methylthiophene bioisosteric replacement
99:, because of the isosteric replacement of the ester
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258:, an early hypothesis to describe bioisosterism
238:patent claims. It has been proposed that key
126:
64:structure had similar biological properties.
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467:
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43:
328:
192:
52:A table of common classical bioisosteres
91:, has a longer duration of action than
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461:
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122:Example of bioisosterism in chalcones
306:Bioisosteres in Medicinal Chemistry
13:
281:Compendium of Chemical Terminology
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117:
67:For example, the replacement of a
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14:
569:
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256:Grimm's hydride displacement law
183:, the normal substrate for the
468:Gardner, Steve; Vinter, Andy.
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417:
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1:
447:10.1016/S1359-6446(03)02726-0
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179:. It is also an isostere of
7:
249:
38:
10:
574:
373:Gomes, Marcelo N. (2017).
127:Non-classical bioisosteres
392:10.3390/molecules22081210
294:10.1351/goldbook.BT06798
246:, be patented instead.
242:features, that is the
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123:
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44:Classical bioisosteres
230:Bioisosteres of some
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134:
121:
51:
435:Drug Discovery Today
558:Medicinal chemistry
175:is an inhibitor of
77:metabolic oxidation
21:medicinal chemistry
226:Other applications
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137:
124:
75:atom at a site of
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343:10.1021/jm1013693
318:978-3-527-33015-7
236:Markush structure
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540:
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479:. Archived from
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337:(8): 2529ā2591.
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177:xanthine oxidase
62:valence electron
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486:on 4 March 2016
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58:Irving Langmuir
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33:bioavailability
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477:Cresset Group
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488:. Retrieved
481:the original
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331:J. Med. Chem
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211:analogue of
173:Alloxanthine
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110:
85:Procainamide
71:atom with a
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55:
25:bioisosteres
24:
18:
385:(8): 1210.
286:bioisostere
240:force field
216:insecticide
205:Silafluofen
166:naphthalene
29:drug design
312:, p. 237.
263:References
219:Etofenprox
213:pyrethroid
518:Chemistry
379:Molecules
162:thiophene
113:chalcones
552:Category
530:Medicine
455:12821303
411:28757583
351:21413808
250:See also
232:patented
181:xanthine
105:nitrogen
93:Procaine
73:fluorine
69:hydrogen
39:Examples
542:Science
504:Portals
402:6152227
103:with a
490:15 Jan
453:
409:
399:
349:
316:
207:is an
185:enzyme
150:phenyl
101:oxygen
484:(PDF)
473:(PDF)
276:IUPAC
97:ester
95:, an
89:amide
87:, an
492:2015
451:PMID
407:PMID
347:PMID
314:ISBN
310:2012
443:doi
397:PMC
387:doi
339:doi
290:doi
288:".
164:or
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