ライフサイエンスコーパス: isostere

1 bic side-chains of identical size and shape (isosteres).

2 into the (R)-(hydroxyethylamino)sulfonamide isostere.

3 into the (R)-(hydroxyethylamino)sulfonamide isostere.

4 nocyclobutyl group as a potential ethylamine isostere.

5 minal imidazole substituent as an amide bond isostere.

6 corporate a silicon atom as a side chain-C25 isostere.

7 chorismate with a stable C-linked propionate isostere.

8 nctionalities into the (R)-hydroxyethylamine isostere.

9 ex regardless of the position on the Phe-Phe isostere.

10 ffective anticancer agents than their sulfur isosteres.

11 ereoselective route to various ketomethylene isosteres.

12 to alpha-substituted gamma-lactam dipeptide isosteres.

13 nor were synthesized and evaluated as phenol isosteres.

14 than comparable benzamidines and benzamidine isosteres.

15 in the literature to act as carboxylic acid isosteres.

16 t are destabilizing, relative to hydrophobic isosteres.

17 access to an array of valuable aniline-like isosteres.

18 keto l-proline methyl ester led to two other isosteres.

19 ofluoroalkenes that are valuable amide group isosteres.

20 actions, leading to two of the four intended isosteres.

21 and dynamics, functioning as true tryptophan isosteres.

22 n-containing ring of hemiboronic "naphthoid" isosteres.

23 id moiety is replaced with a series of known isosteres.

24 rior to that of the trioxolane or tetraoxane isosteres.

25 lane, 1,2,4-trioxane, and 1,2,4,5-tetraoxane isosteres.

26 taining bis-THF in non-sulfonamide dipeptide isosteres.

27 ity for the duplexes containing the nonpolar isosteres.

28 in combination with hydroxyethylsulfonamide isosteres.

29 nated bases has been examined using nonpolar isosteres.

30 e synthesis of the hydroxyethylene dipeptide isostere 1 is described.

31 The cis isostere 1 was 23 times more potent (K(i) = 1.74 +/- 0.0

32 t that known (Z)-Ala-psi[CF=C]-Pro dipeptide isosteres 1 and 2, which contain O-acylhydroxylamines, w

33 In particular, a synthesis of the Pro-Gly isostere (1) is reported.

34 oquine (CQ), its two 4-aminoquinoline carbon isosteres (1, 2) are monoprotic at physiological pH.

35 The peptide isosteres (10 and 11) of the naturally occurring and pot

36 could be replaced with a thiazole-4(5H)-one isostere (19, IC((5)(0)(dyn I)) = 7.7 muM), reduced unde

37 ituted with the non-hydrogen-bonding thymine isostere 2,4-difluoro-5-methylbenzene (F).

38 iciently insert A opposite the hydrophobic T isostere 2,4-difluorotoluene (F) and vice versa, resulti

39 omparison of polar thymidine with a nonpolar isostere, 2,4-difluorotoluene deoxyriboside, as substrat

40 Swapping 2-methyl-3-pentanone with a close isostere, 2-methylcyclohexanone, causes a fundamental ch

41 ural comparison to a well-established biaryl isostere, 2-phenylphenol, through X-ray crystallographic

42 nucleosides, based on the parent OG nonpolar isostere 2Cl-4F-indole, were tested as possible direct s

43 shown to be partial agonists, whereas the O isostere 4-[2-(3-(trifluoromethyl)phenoxy)ethyl]-1H-imid

44 henylthio)propyl]-1H-imidazole and its CH(2) isostere 4-[4-(3-(trifluoromethyl)phenyl)butyl]-1H-imida

45 at position 73 substituted by its non-polar isostere 4-methylindole (M).

46 eadily extended to the preparation of indole isosteres, 4- and 6-azaindoles and thienopyrroles, obvia

47 The photoactivatible cross-linking thymine isostere, 5-iodoracil, was incorporated at a single site

48 inhibition by the K9 DON peptide (with the Q isostere 6-diazo-5-oxo-norleucine) and iodoacetamide wer

49 eries, the gamma-tetrazole bearing glutamate isostere 7d is the most potent inhibitor with a K(i) of

50 s more than 12 kcal.mol(-1) smaller than its isostere 9-(2-methylnaphthalen-1-yl)phenanthrene.

51 degrees C, while the peptide containing the isostere, Ac-(Gly-Pro-Hyp)3-Gly-psi[(E)CH C]-Pro-Hyp-(Gl

52 to find applications for the synthesis of BN-isostere analogues in medicinal chemistry, and the mecha

53 itors feature a hydroxyethyl secondary amine isostere and a novel aromatic ring replacement for the C

54 rk, the synthesis of a constrained dipeptide isostere and insertion in the short peptide epitope EDLF

55 red in which both the Cys-Val methyleneamine isostere and the Tic replacement were incorporated.

56 idines as potent, isoform-selective arginine isosteres and (b) possess chemical properties more condu

57 al, although it could be substituted by acid isosteres and amides.

58 as a class of meta-substituted aromatic ring isosteres and rigidified cyclohexanes.

59 Aromatic ring isosteres and rigidified saturated hydrocarbons are impo

60 iented synthesis, the preparation of peptide isosteres and the development of protease inhibitors as

61 able phosphotyrosine surrogate, a methionine isostere, and a C-terminal amide.

62 We utilized a 2'-fluoro isostere approach to stabilize this lesion and synthesiz

63 Here, we employed a 2'-fluoro isostere approach to synthesize an oligonucleotide conta

64 is-THF) in a pseudo-C(2)-symmetric dipeptide isostere are described.

65 bis)biguanides, and their urea- and thiourea isosteres are potent inhibitors of LSD1 and induce the r

66 ry programs where bioisosteres and geometric isosteres are sought.

67 tential of the new Phe-Pro dihydroxyethylene isostere as a core unit of powerful HIV-1 PR inhibitors.

68 lar selective TNKSs inhibitor working as NAD isostere as ascertained by crystallographic analysis.

69 hylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2' ligands.

70 Our findings highlight base isosteres as valuable tools for the analysis of proteins

71 g replacements such as heterocycles as amide-isosteres as well as alpha-F-acrylamides, two compounds

72 atic inhibitory values were similar for both isosteres, as were structure-activity relationships with

73 bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a posi

74 strate, and having either a thymine or a DFT isostere at the templating base position.

75 locking a new platform to introduce carbonyl isosteres at saturated hydrocarbon sites.

76 , acylsulfonamides were incorporated as acid isosteres at the C-2 position.

77 Our inhibitors contain glutamine isosteres at the P(1) position, including 2-pyridon-3-yl

78 esis and evaluation of nonhydrolyzable amide isosteres based on this class, leading to highly potent

79 n appears to be the right choice as a carbon isostere because of the similarity in chemical propertie

80 Attachment of the arginine isostere (benzamidine) to the supporting nucleus can be

81 istinguishing features from its carbonaceous isostere benzene: its ability to serve as an NH hydrogen

82 ition is dependent on (1) hydrophobic lysine isosteres blocking the active site, (2) proximal residue

83 should not be perceived as a simple aromatic isostere but rather as a readily interacting moiety of d

84 oluene nucleobase (dF) as a nonpolar thymine isostere by Kool and colleagues challenged the Watson-Cr

85 rovides a unique opportunity to develop core isosteres by inserting B-N units in place of C horizonta

86 Mutation of Arg11 to the uncharged isostere citrulline gives peptide homologues that assemb

87 The AE isostere class represents a promising advance in the dev

88 [2,1-f][1,2,4]triazin-4(3H)-one as a guanine isostere, conserving the biologically important HBA-HBD-

89 Two nonpolar deoxynucleoside isosteres containing 2,4-difluorotoluene (F) and 4-methy

90 The isosteres, containing four stereogenic centers, were syn

91 the corresponding cis-cyclopropane dipeptide isosteres could stabilize a reverse turn.

92 ir is replaced by difluorotoluene (a thymine isostere) creating a G-F pair.

93 tency comparable to evolved transition state isostere derived inhibitors of BACE-1.

94 presents the hydroxyethylene tansition-state isostere), designed from the consensus residues, was fou

95 onal analysis of a hydroxyethylamine peptide isostere developed as an aspartic protease inhibitor sho

96 criminating, being inactive when the thymine isostere difluorotoluene (DFT) is present in the templat

97 we study the effects of nonpolar pyrimidine isosteres difluorotoluene (F) and monofluorotoluene (D)

98 wever, when paired opposite another nonpolar isostere, difluorotoluene (F), a mimic of thymine, the p

99 uation of reader proteins for a neutral Kme3 isostere, experimental and computational mechanistic stu

100 typically added across pai-bonds or pai-bond isosteres, followed by subsequent coupling to another ty

101 Triazole is a well-recognized bio-isostere for peptide bonds, and peptides with one or mor

102 up has been long considered a potential (bio)isostere for tert-butyl and trifluoromethyl groups, yet

103 le heterocycle has been widely adopted as an isostere for the amide bond.

104 ine-4-carboxylic acid fragment as a suitable isostere for the anthranilic acid appendage of 4, which

105 phinic acid moiety (P(O)(OH)R) behaves as an isostere for the C(1) carboxylic acid in the human prost

106 the 2-aminobenzophenone moiety as a suitable isostere for the chemically labile enaminone moiety in c

107 observation that an aromatic ring is a good isostere for the terminal isoprene of FPP.

108 of these nortricyclanes makes them plausible isosteres for meta disubstituted aromatic rings.

109 Investigation of heterocyclic amide isosteres for the labile amide moiety revealed distinct

110 of assays with Mg(2+) and offer new catechol isosteres for use in integrase inhibitors.

111 VEK-30 contains a "through-space isostere" for C-terminal lysine, wherein Arg and Glu sid

112 ytic enantioselective syntheses of candidate isosteres from readily available precursors.

113 ex show that, like other nonpolar nucleoside isosteres, H is destabilizing and nonselective when pair

114 For the OZ277 series, the trioxane isostere had the best ADME profile, but its overall anti

115 of stereodefined hydroxyethylamine dipeptide isosteres has been developed, utilizing a syn-selective

116 riction of pyridone 4 into bicyclic pyridone isosteres has led to compounds with high in vitro and in

117 denotes the hydroxyethylene transition-state isostere) has been determined at 2.1 A resolution.

118 Although these dipeptide isosteres have been employed to orient amino acid side c

119 itors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated.

120 in the catalytic groove, whereas the reduced isostere hexapeptide MVT-101 binds in a single orientati

121 des, but not their urea, amide, or carbamate isosteres, impaired ATP production, enhanced caspase-3 a

122 plet were replaced by a Pro-trans-Pro alkene isostere in the host-guest peptide, H-(Pro-Pro-Gly)(10)-

123 ubstrate was replaced by cis and trans amide isosteres in Ac-Phe-Phe-pSer-Psi[(Z and E)CH=C]-Pro-Arg-

124 reaction to assemble the innovative guanine isosteres in moderate to good yields.

125 Conformationally and sterically modified isosteres included N-containing spirocyclic (6-9), fused

126 eak inhibitor of hemozoin formation, neither isostere inhibited P. falciparum in vitro.

127 mplex with this hydroxyethyl secondary amine isostere inhibitor is also presented.

128 tension reaction to a functionalized peptide isostere is reported.

129 ning pharmaceuticals and their dehalogenated isosteres is described.

130 The development of meta-arene (bio)isosteres is much less explored due to the challenge of

131 ic acid with a surrogate structure, or (bio)-isostere, is a classical strategy in medicinal chemistry

132 HF), a P2'-methoxybenzene, and a sulfonamide isostere, is highly active against laboratory and primar

133 With a thymine isostere lacking hydrogen-bonding ability in the nascent

134 Here we describe a series of Man84 isosteres (ligands 2-11) that maintain or improve on thi

135 + 2] cyclobutane adducts with its biological isosteres like toluene upon UV irradiation, resulting in

136 st examples of readers that bind the neutral isostere more tightly than Kme3.

137 Upon evaluating these "hybrid isostere" motifs in the solid state, we measured excepti

138 e compounds and was replaced with the better isostere, N-beta-neopentyl asparagine.

139 5, the latter was replaced by the amino acid isostere, norleucine (Ahx), giving [Ahx35]Abeta-(25-35)-

140 ed by the formal total synthesis of a CHF(2) isostere of a TRPV1 inhibitor.

141 avage on such a substrate, but the uncharged isostere of Arg, citrulline, does not.

142 ompounds possess a hydroxyethylene dipeptide isostere of aspartyl protease transition state analogs,

143 1,3-dihydro-1,3-azaborine, a long-sought BN isostere of benzene.

144 We report that BirA also accepts a ketone isostere of biotin as a cofactor, ligating this probe to

145 und, which is the first reported parental BN isostere of cyclohexane featuring two BN units, is therm

146 ion of the parent 1,2-BN cyclohexane, the BN-isostere of cyclohexane.

147 d to synthesize a previously inaccessible BN isostere of ethylbenzene, a compound of interest in biom

148 2-ketoGlc, which is the C(2)-carbon isostere of GlcNAc, is a novel GlcNAc analogue with a ke

149 An alkene isostere of Gly-trans-Pro was synthesized and incorporat

150 We further demonstrate that the structural isostere of HMGSH, S-nitrosoglutathione, is an ideal hCB

151 F of darunavir on either side of the Phe-Phe isostere of lopinavir in combination with hydrophobic am

152 Isonicotinamide (INAM) is an isostere of NAM that stimulates yeast Sir2 deacetylase a

153 1,2-azaborine derivatives, including the BN isostere of phenyl phenylacetate and BN1 triphenylmethan

154 e diazomethyl-1,2-azaborine 1, which is a BN isostere of phenyldiazomethane, is significantly more st

155 ate, a weak partial agonist with a sulfonium isostere of the ammonium pharmacophore.

156 ppreciable interaction between a nonreactive isostere of the lead 2,2'-dithiobis[benzamide] and NCp7

157 hemical centers of the core transition-state isostere of the linear HIVPR inhibitors and cyclization

158 acrylate intermediate with benzimidazole, an isostere of the natural substrate indole, shows benzimid

159 : the alcohol 9a, the acetate 11a (an oxygen isostere of thiocolchicine), and the isonicotinoate 15a.

160 analogue 5-methyldeoxycytidine (5-Me-dC), an isostere of thymidine, can indeed be phosphorylated by w

161 -difluoro compound (1), which is the closest isostere of thymidine, had a value within 2.5-fold.

162 (F) nucleotide analogue that is an excellent isostere of uracil but possesses no hydrogen bond donor

163 The nonpolar isosteres of 2'-deoxyadenosine, 4-methylbenzimidazole be

164 These compounds are potential isosteres of 2,3-dihydrobenzofuran pharmacophores and co

165 Nonperoxidic 1,3-dioxolane isosteres of 3 were inactive as were trioxolanes without

166 demonstrated in the concise syntheses of BN isosteres of a PD-1/PD-L1 inhibitor and pyrethroid insec

167 the synthesis of a complete set of triazole-isosteres of ADP-ribosylated histidine to serve as probe

168 1,3-dihydro-1,3-azaborines (see scheme), BN isosteres of arenes with potential for application in bi

169 1,2-Azaborines, a unique class of BN-isosteres of benzene, have attracted great interest acro

170 various drug-like molecules and fluorinated isosteres of biologically active compounds.

171 Three of the new analogues are better isosteres of bzbr that contain bulky groups adjacent to

172 Oxetanes have garnered further interest as isosteres of carbonyl groups and as molecular tools to f

173 covery that boron nitride nanotubes (BNNTs), isosteres of CNTs with unique physical properties, are i

174 ing single and pairwise non-hydrogen-bonding isosteres of cytosine (2-fluoro-4-methylbenzene deoxyrib

175 e applied to access the first examples of BN isosteres of dihydrobenzofurans and benzofurans, classes

176 alpha-Aryl-substituted beta-oxa isosteres of fosmidomycin with a reverse orientation of

177 l investigation of enantioenriched methylene isosteres of Hayashi-Jorgensen catalysts, and their appl

178 sive electronic structure analysis of two BN isosteres of indole using a combined UV-photoelectron sp

179 d amino acids as carbocyclic hydroxyethylene isosteres of inhibitor molecules, in which the stereodef

180 afforded predominantly the desired E-olefin isosteres of L-glutamyl-gamma-D-glutamate and L-glutamyl

181 osphonate amidines and sulfonate amidines as isosteres of pArg and then use these mimics as haptens t

182 [3.3.0] octane carboxylic acids as possible isosteres of piperazine 2S-carboxylic acid.

183 Four 3-((hetera)cyclobutyl)azetidine-based isosteres of piperidine, piperazine, and morpholine were

184 Imidazo[5,1-f][1,2,4]triazinones, as isosteres of purine, are of interest for pharmaceutical

185 rboxylic acid, and CH-acidic ketosulfoxides, isosteres of pyrazinoic and nicotinic acids, which shoul

186 unds were compared with the unmodified polar isosteres of pyrazinoic and nicotinic acids.

187 s were more active than the unmodified polar isosteres of pyrazinoic and nicotinic acids.

188 cles revealed these derivatives as effective isosteres of rigidified piperidines.

189 Two new amide isosteres of Ser-cis-Pro and Ser-trans-Pro dipeptides we

190 Trends and conclusions from BN isosteres of simple monocyclic aromatic systems such as

191 In particular, using pyridine or thiazole as isosteres of the carboxylic acid moiety resulted in very

192 point to access either thioamide or amidine isosteres of the native amide (peptide bond).

193 bitors based on four novel dihydroxyethylene isosteres of the Phe-Pro and Pro-Pro dipeptides.

194 is important to quantify the impact of this isostere on DNA stability.

195 The Pro-trans-Pro alkene isostere peptide had a T(m) value 3.9 degrees C higher t

196 The resulting alkene isostere peptide had a T(m) value 53.6 degrees C lower t

197 the previously reported Pro-trans-Gly alkene isostere peptide that did not involve cis-trans Pro isom

198 the previously reported Gly-trans-Pro alkene isostere peptide that retained the backbone interchain h

199 Ring opening of a P-B-containing cyclobutene isostere provided access to unique 1,4-boraphosphabutadi

200 In this approach, the carboxylic isostere, quinoline N-oxide, plays a vital role by shift

201 affolds allow comparison of ring systems for isostere replacement studies.

202 rmed from dATP and gapped DNA in which a DFT isostere replaces thymine at the templating base positio

203 Phenylheterocyclic isosteres replacing a critical charge-charge interaction

204 ycol (PEG) extension as well as peptide bond isosteres resist KLKB1 cleavage but that only the PEG-ex

205 MR-based search for heterocyclic isothiourea isosteres resulted in several distinct classes of BACE-1

206 and testing of a variety of carboxylic acid isosteres resulted in several new compounds with improve

207 t, the argument that relative to hydrophobic isosteres, salt bridges destabilise proteins, may no lon

208 oxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initia

209 We identify a conserved oxindole isostere, shared between three structurally diverse modu

210 Compared to 2, these heterocyclic phenol isosteres showed much better pharmacokinetic profiles as

211 of the carboxylic acid with carboxylic acid isosteres such as tetrazole or triazole greatly improves

212 synthesis will add to the toolbox of guanine isostere syntheses.

213 overy and evaluation of a novel nicotinamide isostere that demonstrates selectivity over other PARP f

214 nc module were substituted by norleucine, an isostere that maintains the aliphatic portion of the sid

215 e of the challenge of synthesizing saturated isosteres that accurately reproduce substituent vectors(

216 nd better distinguished them from more polar isosteres that are not observed to bind.

217 ip between these azaborines and their carbon isosteres that changed based on boron connectivity.

218 hat VKK38 provides two conformational lysine isosteres that each interact with the lysine-binding sit

219 and of the bound structures of two inhibitor isosteres that form multicentered short hydrogen bond ar

220 aborines represent a unique class of benzene isosteres that have attracted interest for developing ph

221 or (1) with the goal of identifying catechol isosteres that support inhibition.

222 Conversely, the S(VI) aza-isosteres thereof, vinyl sulfoximines and sulfonimidamid

223 via cation-pai interactions and the neutral isostere through the hydrophobic effect in the same arom

224 dual approach: 1) using CF2 as a sulfone bio-isostere to exploit the unique properties of fluorine, a

225 By appending a nicotinamide isostere to the C9 position of the aTC D-ring, we genera

226 eported synthesis of ketomethylene dipeptide isosteres to allow for the preparation of derivatives su

227 these ends, including an exploration of urea isosteres to reduce hydrogen bond donor count and total

228 or using malonyl-CoA analogs with carboxyate isosteres to study the complicated structure-function re

229 pproach to the synthesis of dipeptide olefin isosteres using intermolecular olefin cross-metathesis i

230 The hydroxyethylene (HE) transition state isostere was developed as a scaffold to provide potent,

231 An alpha-TOH isostere was prepared by a Wittig coupling of a C16 side

232 The peptide containing the Pro-trans-Pro isostere was significantly less stable than the previous

233 ogue, using a monofluorostilbene as an amide isostere, was synthesized.

234 re-activity relationships of fluorinated LPA isosteres, we describe a series of monofluorinated LPA a

235 Using non-hydrogen-bonding nucleoside isosteres, we have now studied effects in both primer an

236 aminoethylene (AE) tetrahedral intermediate isostere were synthesized and evaluated in comparison to

237 Pivaloyloxymethyl derivatives of the isosteres were also prepared in order to increase their

238 Moreover, several drug isosteres were evaluated for anti-inflammatory and antic

239 The derivatized isosteres were expected to be biotransformed by esterase

240 Acids and acid isosteres were incorporated at the 5-pyridyl position of

241 ral aspects of these unique SF(5)-CB "hybrid isosteres" were then contextualized using SC-XRD.

242 [[(4-Nitrophenyl)X]alkyl]imidazole isosteres (where X = NH, S, CH2S, O) of previously descr

243 were rectified by introducing the nonpolar F isostere, whereas the requirement for the +1T base was n

244 mics that were used are cyclopropane-derived isosteres whereby a cyclopropane ring substitutes to the

245 furanyl urethane (bis-THF) and a sulfonamide isostere, which is extremely potent against a wide spect

246 -doped polycyclic aromatic hydrocarbon (PAH) isosteres, which expose BN mimics of the amidic NH funct

247 ently been explored by the use of nucleotide isosteres, which preserve the steric but not the electro

248 A second trans amide isostere with a C-terminal N-methylamide 3 was synthesiz

249 a potent non-nitrogen containing morpholine isostere with the ability to mimic this conformation and

250 d widespread binding of readers to a neutral isostere with the first examples of readers that bind th

251 SAR revealed tolerance for 4-Cl isosteres with 4-F (8), 3-F (9), 3-CH3 (22), and 4-C(CH3

252 he inhibitors were assembled by coupling the isosteres with suitable flanking groups and were screene

253 ly with two KR2 via the high-affinity lysine isosteres within the a1a2 motifs.

254 hysicochemical properties of carboxylic acid isosteres would be desirable to enable more informed dec

255 sis of the cyclopropane-containing dipeptide isosteres -XaaPsi[COcpCO]Yaa- and -XaaPsi[NHcpNH]Yaa-wer