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 nocyclobutyl group as a potential ethylamine isostere.

4 minal imidazole substituent as an amide bond isostere.

5 chorismate with a stable C-linked propionate isostere.

6 nctionalities into the (R)-hydroxyethylamine isostere.

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

8 ereoselective route to various ketomethylene isosteres.

9 to alpha-substituted gamma-lactam dipeptide isosteres.

10 nor were synthesized and evaluated as phenol isosteres.

11 than comparable benzamidines and benzamidine isosteres.

12 in the literature to act as carboxylic acid isosteres.

13 t are destabilizing, relative to hydrophobic isosteres.

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

15 rior to that of the trioxolane or tetraoxane isosteres.

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

17 ity for the duplexes containing the nonpolar isosteres.

18 in combination with hydroxyethylsulfonamide isosteres.

19 nated bases has been examined using nonpolar isosteres.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

47 ry programs where bioisosteres and geometric isosteres are sought.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

66 The isosteres, containing four stereogenic centers, were syn

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

95 tension reaction to a functionalized peptide isostere is reported.

96 ning pharmaceuticals and their dehalogenated isosteres is described.

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

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

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

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

101 5, the latter was replaced by the amino acid isostere, norleucine (Ahx), giving [Ahx35]Abeta-(25-35)-

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

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

104 1,3-dihydro-1,3-azaborine, a long-sought BN isostere of benzene.

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

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

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

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

109 2-ketoGlc, which is the C(2)-carbon isostere of GlcNAc, is a novel GlcNAc analogue with a ke

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

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

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

113 1,2-azaborine derivatives, including the BN isostere of phenyl phenylacetate and BN1 triphenylmethan

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

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

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

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

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

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

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

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

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

123 1,3-dihydro-1,3-azaborines (see scheme), BN isosteres of arenes with potential for application in bi

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

148 Phenylheterocyclic isosteres replacing a critical charge-charge interaction

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

172 The derivatized isosteres were expected to be biotransformed by esterase

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

174 [[(4-Nitrophenyl)X]alkyl]imidazole isosteres (where X = NH, S, CH2S, O) of previously descr

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

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

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

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

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

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

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

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

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