An improved synthesis of 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI): a simplified analog of the CC-1065 alkylation subunit
摘要:
A concise and improved synthesis of 11, the immediate precursor to N-BOC-CBI and related analogues of CC-1065 incorporating the 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one alkylation subunit, is detailed based on a direct 5-exo-trig aryl radical-alkene cyclization for 3-hydroxymethylindoline generation.
描述了类似物1(CC-1065)及其与抗体的结合物的磷酸盐前药的合成和生物学评估。1,2,9,9a-四氢环丙烷[ c ]苯并[ e化合物的] indol-4-one(CBI)部分赋予其在水溶液中增强的溶解度和稳定性。在磷酸酶存在下,这些化合物转化为活性DNA烷基化剂。通过将CBI与双吲哚基部分偶合,然后连接含硫醇的连接基,并将CBI的羟基转化为磷酸酯前药,依次实现前药的合成。结合到前药中的接头使得在含有少至5%有机助溶剂的水性缓冲溶液中,可以通过稳定的二硫键或硫醚键与抗体偶联,从而产生单体和稳定的抗体-细胞毒性前药偶联物。在抗体缀合物中使用了两个在空间位阻上不同的含二硫键的接头,以测试不同速率的细胞内二硫键裂解和效应物释放对生物活性的影响。前药可通过内源磷酸酶的作用转化为活性细胞毒性化合物。抗体-前药结合物在体外和体内均显示出有效的抗原选择性细胞毒活性。
CHEMICAL LINKERS AND CLEAVABLE SUBSTRATES AND CONJUGATES THEREOF
申请人:Sufi Bilal
公开号:US20100145036A1
公开(公告)日:2010-06-10
The present disclosure provides drug-ligand conjugates and drug-cleavable substrate conjugates that are potent cytotoxins. The disclosure is also directed to compositions containing the drug-ligand conjugates, and to methods of treatment using them.
NOVEL TETRACARBOXYLIC DIANHYDRIDE, POLYIMIDE RESIN AND METHOD FOR PRODUCING THE SAME, PHOTOSENSITIVE RESIN COMPOSITIONS, PATTERNING PROCESS, METHOD FOR FORMING CURED FILM, INTERLAYER INSULATING FILM, SURFACE PROTECTIVE FILM, AND ELECTRONIC PARTS
申请人:SHIN-ETSU CHEMICAL CO., LTD.
公开号:US20190169211A1
公开(公告)日:2019-06-06
The present invention has been made in view of the circumstances herein. An object of the present invention is to provide: a tetracarboxylic dianhydride which can lead to a polyimide usable as a base resin of a photosensitive resin composition capable of forming a fine pattern and obtaining high resolution without impairing excellent characteristics such as mechanical strength and adhesiveness; a polyimide resin obtained by using the tetracarboxylic dianhydride; and a method for producing the polyimide resin. The tetracarboxylic dianhydride is shown by the following general formula (1).
Role of substituents on the reactivity and product selectivity in reactions of naphthalene derivatives catalyzed by the orphan thermostable cytochrome P450, CYP175A1
substrate selectivity of this enzyme, the biocatalytic activities of CYP175A1 on different substituted naphthalenes have been studied in oxidative pathway, and the effect of the substituent on the reaction has been determined. The enzyme first acts as a peroxygenase to convert these substituted naphthalenes to the corresponding naphthols, which subsequently undergo in-situ oxidative dimerization to form
Compounds of the formula I:
or pharmaceutically acceptable salts thereof, wherein A, D, E, G, J, X, Y, Z R
6
, R
7
and R
8
are as defined herein. Also provided are methods of using the compounds for treating diseases mediated by a P2X
3
and/or a P2X
2/3
receptor antagonist and methods of making the compounds.
NOVEL COMPOUND, POLYIMIDE RESIN AND METHOD OF PRODUCING THE SAME, PHOTOSENSITIVE RESIN COMPOSITION, PATTERNING METHOD AND METHOD OF FORMING CURED FILM, INTERLAYER INSULATING FILM, SURFACE PROTECTIVE FILM, AND ELECTRONIC COMPONENT
申请人:International Business Machines Corporation
公开号:US20210317270A1
公开(公告)日:2021-10-14
Provided is a compound that can be used as a base resin for a photosensitive resin composition. The photosensitive resin can form a fine pattern and can achieve high resolution without impairing mechanical strength and solubility. The compound is represented by the general formula (1):
wherein Z represents a linear, branched or cyclic divalent hydrocarbon group having 2 to 30 carbon atoms; X
1
to X
3
represent any of —CO
2
—, —CONR
X1
—, —O—, —NR
X1
—, —S—, —SO
2
—, —SO
3
— and —SO
2
NR
X1
— and may be the same as or different from each other, provided that R
X1
is a hydrogen atom or a monovalent hydrocarbon group having 1 to 30 carbon atoms; Ar represents a divalent aromatic group having 2 to 30 carbon atoms; L
1
and L
2
independently represent a divalent hydrocarbon group having 1 to 30 carbon atoms; and x and y are each independently 0 or 1.