The hydrothermal reaction of 1,4-bis（imidazol-1-yl）butane （bimb） and 1,4-bis（2- methylimidazol-1＇-yl）butane （bmib） with CdBr2·4H2O gave rise to two coordination polymers, [Cd（bimb）2Br2]n （1） and [Cd...The hydrothermal reaction of 1,4-bis（imidazol-1-yl）butane （bimb） and 1,4-bis（2- methylimidazol-1＇-yl）butane （bmib） with CdBr2·4H2O gave rise to two coordination polymers, [Cd（bimb）2Br2]n （1） and [Cd（bmib）Br2]n （2）, respectively. Single-crystal X-ray diffraction analysis reveals that 1 and 2 crystallize in the monoclinic space group P21/n and the orthorhombic space group Pccn, respectively. In 1, bimb adopts an anti-anti-anti conformation and bridges adjacent Cd（Ⅱ） to form a two-dimensional （2D） network containing rhombohedral rings. The 2D layers are arranged in an offset ABCABC sequence to fill large void in the rhombohedral rings. In 2, bmib also exhibits an anti-anti-anti conformation, but it links neighboring Cd（Ⅱ） into a one-dimensional （1 D） chain. Br in 1 and 2 serves as a monodentate ligand to balance charge.展开更多
A short synthesis starting from 4-imidazolylmethanol(2)was developed for the phosphonoisostere of histidine,-amino-β-(4-imidazolyl)- ethylphosphosphonic acid,His(P)(1).The synthesis features Wittig-Horner reaction of...A short synthesis starting from 4-imidazolylmethanol(2)was developed for the phosphonoisostere of histidine,-amino-β-(4-imidazolyl)- ethylphosphosphonic acid,His(P)(1).The synthesis features Wittig-Horner reaction of aldehyde(4)with diphosphonate(5)followed by selective detritylation with 50% formic acid.展开更多
Imidazolyl amino cuboidal Mo_(3)(μ_(3)-S)(μ-S)_(3)clusters have been investigated as catalysts for the semihydrogenation of alkynes.For that purpose,three new air-stable cluster salts[Mo_(3)S_(4)Cl_(3)(ImNH_(2))_(3)...Imidazolyl amino cuboidal Mo_(3)(μ_(3)-S)(μ-S)_(3)clusters have been investigated as catalysts for the semihydrogenation of alkynes.For that purpose,three new air-stable cluster salts[Mo_(3)S_(4)Cl_(3)(ImNH_(2))_(3)]BF_(4)([1]BF_(4)),[Mo_(3)S_(4)Cl_(3)(ImNH(CH_(3)))_(3)]BF_(4)([2]BF_(4))and[Mo_(3)S_(4)Cl_(3)(ImN(CH_(3))_(2))_(3)]BF_(4)([3]BF_(4))have been isolated in moderate to high yields and fully characterized.Crystal structures of complexes[1]PF6 and[2]Cl confirm the formation of a single isomer in which the nitrogen atoms of the three imidazolyl groups of the ligands are located trans to the capping sulfur atom which leaves the three bridging sulfur centers on one side of the trimetallic plane while the amino groups lie on the opposite side.Kinetic studies show that the cluster bridging sulfurs react with diphenylacetylene(dpa)in a reversible equilibrium to form the corresponding dithiolene adduct.Formation of this adduct is postulated as the first step in the catalytic semihydrogenation of alkynes mediated by molybdenum sulfides.These complexes catalyze the(Z)-selective semihydrogenation of diphenylacetylene(dpa)under hydrogen in the absence of any additives.The catalytic activity lowers sequentially upon replacement of the hydrogen atoms of the N-H_(2)moiety in 1+without reaching inhibition.Mechanistic experiments support a sulfur centered mechanism without participation of the amino groups.Different diphenylacetylene derivatives are selectively hydrogenated using complex 1+to their corresponding Z-alkenes in excellent yields.Extension of this protocol to 3,7,11,15-tetramethylhexadec-1-yn-3-ol,an essential intermediate for the production of vitamin E,affords the semihydrogenation product in very good yield.展开更多
The bromodomain-containing protein 9(BRD9)is a core subunit of mammalian SWI/SNF chromatin remodeling complex termed ncBAF.BRD9 has emerged as a potential target for anticancer drugs,particularly in the treatment of a...The bromodomain-containing protein 9(BRD9)is a core subunit of mammalian SWI/SNF chromatin remodeling complex termed ncBAF.BRD9 has emerged as a potential target for anticancer drugs,particularly in the treatment of acute myeloid leukemia(AML).Herein,we reported 10m(Y22073)and 10t as new BRD9 selective bromodomain inhibitors.Crystallographic studies revealed that the key active imidazolyl group discovered from structure-activity relationship(SAR)can induce Phe163 flipping and significantly enhance the cellular potency of the compounds,making 10m the first BRD9 selective inhibitor with significant cellular activity against AML cells.We also validated the critical role of imidazolyl groups by modifying existing BRD9 inhibitors.The representative compounds 10m and 10t demonstrated potent binding affinity,outstanding selectivity toward BRD9 bromodomain,and significantly inhibited the proliferation of AML cell lines.10m also showed good metabolic stability,solubility and pharmacokinetic properties.Additionally,oral administration of compounds 10m and 10t exhibited potent anti-tumor efficacy in the MV4-11 xenograft mouse model.The potent,selective,and orally available BRD9 bromodomain inhibitors may address the challenges of weak cellular activity and limited phenotypic efficacy faced by BRD9 inhibitors,and serve as new lead compounds for the development of anticancer agents for the treatment of AML.展开更多
A new coordination complex, [Ag(IIMB)N 3], was prepared by self-assembly of asymmetric ligand 1-(1-imidazolyl)-4-(imidazol-1-ylmethyl)benzene(IIMB) with [Ag(NH 3) 2]N 3. The crystal structural analysis indicates that ...A new coordination complex, [Ag(IIMB)N 3], was prepared by self-assembly of asymmetric ligand 1-(1-imidazolyl)-4-(imidazol-1-ylmethyl)benzene(IIMB) with [Ag(NH 3) 2]N 3. The crystal structural analysis indicates that the structure of the complex contains fifty-two-membered macrometallacyclic rings, and the complex crystallizes in monoclinic system, space group of P2 1/c with a=0.739 8(1) nm, {b=}1.045 1(1) nm, c=1.812 4(2)nm, β=91.65(1)°, V=1.400 7(3) nm3, Z=4, D c=1.774 g/cm3, {F(000)=}744, R=0.050 5, wR=0.084 0. It is notable that the azide ion bridges two silver(Ⅰ) atoms in end-on fashion.展开更多
3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one(DEPBT) condensation developed by our group is an effective organophosphorus condensation reagent for the synthesis of protected peptides containing Tyr,Ser and Th...3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one(DEPBT) condensation developed by our group is an effective organophosphorus condensation reagent for the synthesis of protected peptides containing Tyr,Ser and Thr with unprotected hydroxyl group on their side chain.Thus,DEPBT is useful for the synthesis of peptide alcohols,which have attracted much attention not only as the ligands but also as the enzyme inhibitors.A side reaction of DEPBT was found in the synthesis of Boc-β-Ala-HisOMe with unprotected imidazolyl group.In this paper,the discovery of this side reaction and the confirmation of the structure of this side product were reported.In addition,the influence of different reaction conditions on the side reaction were studied.Imidazolyl group was a key factor to cause the side reaction,excess DEPBT and high reaction temperature promoted the side reaction.展开更多
基金Supported by NSFC (21001025)NSF of Fujian Province (2010J05017)SRF for ROCS, SEM
文摘The hydrothermal reaction of 1,4-bis（imidazol-1-yl）butane （bimb） and 1,4-bis（2- methylimidazol-1＇-yl）butane （bmib） with CdBr2·4H2O gave rise to two coordination polymers, [Cd（bimb）2Br2]n （1） and [Cd（bmib）Br2]n （2）, respectively. Single-crystal X-ray diffraction analysis reveals that 1 and 2 crystallize in the monoclinic space group P21/n and the orthorhombic space group Pccn, respectively. In 1, bimb adopts an anti-anti-anti conformation and bridges adjacent Cd（Ⅱ） to form a two-dimensional （2D） network containing rhombohedral rings. The 2D layers are arranged in an offset ABCABC sequence to fill large void in the rhombohedral rings. In 2, bmib also exhibits an anti-anti-anti conformation, but it links neighboring Cd（Ⅱ） into a one-dimensional （1 D） chain. Br in 1 and 2 serves as a monodentate ligand to balance charge.
文摘A short synthesis starting from 4-imidazolylmethanol(2)was developed for the phosphonoisostere of histidine,-amino-β-(4-imidazolyl)- ethylphosphosphonic acid,His(P)(1).The synthesis features Wittig-Horner reaction of aldehyde(4)with diphosphonate(5)followed by selective detritylation with 50% formic acid.
基金support of the Spanish Ministerio de Economía y Competitividad(grants PRE2019-088511,and PID2019-107006GB-C22)Generalitat Valenciana(grant CIAICO/2021/122)Universitat Jaume I(grants UJI-B2019-30,UJI-B2021-29 and UJI-B2022-56)is gratefully acknowledged.
文摘Imidazolyl amino cuboidal Mo_(3)(μ_(3)-S)(μ-S)_(3)clusters have been investigated as catalysts for the semihydrogenation of alkynes.For that purpose,three new air-stable cluster salts[Mo_(3)S_(4)Cl_(3)(ImNH_(2))_(3)]BF_(4)([1]BF_(4)),[Mo_(3)S_(4)Cl_(3)(ImNH(CH_(3)))_(3)]BF_(4)([2]BF_(4))and[Mo_(3)S_(4)Cl_(3)(ImN(CH_(3))_(2))_(3)]BF_(4)([3]BF_(4))have been isolated in moderate to high yields and fully characterized.Crystal structures of complexes[1]PF6 and[2]Cl confirm the formation of a single isomer in which the nitrogen atoms of the three imidazolyl groups of the ligands are located trans to the capping sulfur atom which leaves the three bridging sulfur centers on one side of the trimetallic plane while the amino groups lie on the opposite side.Kinetic studies show that the cluster bridging sulfurs react with diphenylacetylene(dpa)in a reversible equilibrium to form the corresponding dithiolene adduct.Formation of this adduct is postulated as the first step in the catalytic semihydrogenation of alkynes mediated by molybdenum sulfides.These complexes catalyze the(Z)-selective semihydrogenation of diphenylacetylene(dpa)under hydrogen in the absence of any additives.The catalytic activity lowers sequentially upon replacement of the hydrogen atoms of the N-H_(2)moiety in 1+without reaching inhibition.Mechanistic experiments support a sulfur centered mechanism without participation of the amino groups.Different diphenylacetylene derivatives are selectively hydrogenated using complex 1+to their corresponding Z-alkenes in excellent yields.Extension of this protocol to 3,7,11,15-tetramethylhexadec-1-yn-3-ol,an essential intermediate for the production of vitamin E,affords the semihydrogenation product in very good yield.
基金supported in part by grants from the National Key R&D Program of China(Nos.2022YFE0210600 and 2019YFE0123700)the National Natural Science Foundation of China(Nos.22307116 and 82173745)+4 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2024A1515012186,China)the Science and Technology Program of Guangzhou(No.2025A04J4520,China)Guangdong Province Grant for Belt and Road Joint Laboratory(No.2022B1212050004,China)the Youth Innovation Promotion Association CAS(No.2023372,China)the Basic Research Project of Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences(Nos.GIBHBRP24-03 and GIBHBRP24-04,China).
文摘The bromodomain-containing protein 9(BRD9)is a core subunit of mammalian SWI/SNF chromatin remodeling complex termed ncBAF.BRD9 has emerged as a potential target for anticancer drugs,particularly in the treatment of acute myeloid leukemia(AML).Herein,we reported 10m(Y22073)and 10t as new BRD9 selective bromodomain inhibitors.Crystallographic studies revealed that the key active imidazolyl group discovered from structure-activity relationship(SAR)can induce Phe163 flipping and significantly enhance the cellular potency of the compounds,making 10m the first BRD9 selective inhibitor with significant cellular activity against AML cells.We also validated the critical role of imidazolyl groups by modifying existing BRD9 inhibitors.The representative compounds 10m and 10t demonstrated potent binding affinity,outstanding selectivity toward BRD9 bromodomain,and significantly inhibited the proliferation of AML cell lines.10m also showed good metabolic stability,solubility and pharmacokinetic properties.Additionally,oral administration of compounds 10m and 10t exhibited potent anti-tumor efficacy in the MV4-11 xenograft mouse model.The potent,selective,and orally available BRD9 bromodomain inhibitors may address the challenges of weak cellular activity and limited phenotypic efficacy faced by BRD9 inhibitors,and serve as new lead compounds for the development of anticancer agents for the treatment of AML.
文摘A new coordination complex, [Ag(IIMB)N 3], was prepared by self-assembly of asymmetric ligand 1-(1-imidazolyl)-4-(imidazol-1-ylmethyl)benzene(IIMB) with [Ag(NH 3) 2]N 3. The crystal structural analysis indicates that the structure of the complex contains fifty-two-membered macrometallacyclic rings, and the complex crystallizes in monoclinic system, space group of P2 1/c with a=0.739 8(1) nm, {b=}1.045 1(1) nm, c=1.812 4(2)nm, β=91.65(1)°, V=1.400 7(3) nm3, Z=4, D c=1.774 g/cm3, {F(000)=}744, R=0.050 5, wR=0.084 0. It is notable that the azide ion bridges two silver(Ⅰ) atoms in end-on fashion.
文摘3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one(DEPBT) condensation developed by our group is an effective organophosphorus condensation reagent for the synthesis of protected peptides containing Tyr,Ser and Thr with unprotected hydroxyl group on their side chain.Thus,DEPBT is useful for the synthesis of peptide alcohols,which have attracted much attention not only as the ligands but also as the enzyme inhibitors.A side reaction of DEPBT was found in the synthesis of Boc-β-Ala-HisOMe with unprotected imidazolyl group.In this paper,the discovery of this side reaction and the confirmation of the structure of this side product were reported.In addition,the influence of different reaction conditions on the side reaction were studied.Imidazolyl group was a key factor to cause the side reaction,excess DEPBT and high reaction temperature promoted the side reaction.
