- Preparation method of trans 4 - (tert-butyloxycarbonylamino) cyclohexanecarboxylic acid and intermediate thereof
-
The invention provides a preparation method of trans 4 - (tert-butyloxycarbonylamino) cyclohexanecarboxylic acid and an intermediate thereof. The preparation method is characterized by comprising the following steps of 4 - oxocyclohexane carboxylic ester and chiral ligand reagent tert-butyl sulfinamide as a raw material, reducing amination to obtain trans -4 -tert-butyl sulfinyl sulfenamide cyclohexane carboxylic acid ester by virtue of chiral ligand reagent tert-butyl sulfinamide and 4 - 95% -oxocyclohexane carboxylic ester, and is stable in basic conditions and easy to leave under an acidic condition. Reaction conditions are mild, operation is simple and convenient, yield is high, and industrial production is easy.
- -
-
-
- BIFUNCTIONAL DEGRADERS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASES AND THERAPEUTIC USE THEREOF
-
The present disclosure provides bifunctional compounds as IRAK4 degraders via ubiquitin proteasome pathway, and method for treating diseases modulated by IRAK4.
- -
-
Page/Page column 56-57
(2021/08/27)
-
- Compound serving as protein kinase inhibitor and application of compound
-
The invention discloses a compound used as a protein kinase inhibitor and application of the compound, the compound has an obvious inhibition effect on protein kinase activity, can be used as a BTK inhibitor for preparing medicines for treating BTK-mediated diseases such as malignant tumors, autoimmune diseases and the like, and has wide application prospect.
- -
-
Paragraph 0330-0333
(2021/04/07)
-
- Discovery of Hydroxyamidine Derivatives as Highly Potent, Selective Indoleamine-2,3-dioxygenase 1 Inhibitors
-
In this study, a series of novel hydroxyamidine derivatives were identified as potent and selective IDO1 inhibitors by structure-based drug design. Among them, compounds 13-15 and 18 exhibited favorable enzymatic and cellular activities. Compound 18 showed improved bioavailability in mouse, rat, and dog (F% = 44%, 58.8%, 102.1%, respectively). With reasonable in vivo pharmacokinetic properties, compound 18 was further evaluated in a transgenic MC38 xenograft mouse model. The combination of compound 18 with PD-1 monoclonal antibody showed a synergistic antitumor effect. These data indicated that compound 18 as a potential cancer immunotherapy agent should warrant further investigation.
- Jin, Fangfang,Hu, Qiyue,Fei, Hongbo,Lv, Hejun,Wang, Shenglan,Gui, Bin,Zhang, Junzhen,Tu, Wangyang,Zhang, Yun,Zhang, Lei,Wan, Hong,Zhang, Limin,Hu, Bin,Yang, Fanglong,Bai, Chang,He, Feng,Zhang, Lianshan,Tao, Weikang
-
supporting information
p. 195 - 201
(2021/02/06)
-
- Generation of highly potent DYRK1A-dependent inducers of human β-Cell replication via Multi-Dimensional compound optimization
-
Small molecule stimulation of β-cell regeneration has emerged as a promising therapeutic strategy for diabetes. Although chemical inhibition of dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is sufficient to enhance β-cell replicat
- Allegretti, Paul A.,Horton, Timothy M.,Abdolazimi, Yassan,Moeller, Hannah P.,Yeh, Benjamin,Caffet, Matthew,Michel, Guillermina,Smith, Mark,Annes, Justin P.
-
supporting information
(2019/12/09)
-
- Preparation method of trans-4-N-Bocaminocyclohexylamine carboxylic acid
-
The invention discloses a preparation method of trans-4-N-Bocaminocyclohexylamine carboxylic acid, and belongs to the technical field of organic synthesis. 4-oxocyclohexane carboxylic acid triphenyl methanol ester is taken as the raw material, and the pro
- -
-
Paragraph 0042-0047; 0048; 0052-0054
(2019/07/04)
-
- Synthesis of Novel Tetrahydroisoquinoline CXCR4 Antagonists with Rigidified Side-Chains
-
A structure-activity relationship study of potent TIQ15-derived CXCR4 antagonists is reported. In this investigation, the TIQ15 side-chain was constrained to improve its drug properties. The cyclohexylamino congener 15a was found to be a potent CXCR4 inhi
- Jecs, Edgars,Miller, Eric J.,Wilson, Robert J.,Nguyen, Huy H.,Tahirovic, Yesim A.,Katzman, Brook M.,Truax, Valarie M.,Kim, Michelle B.,Kuo, Katie M.,Wang, Tao,Sum, Chi S.,Cvijic, Mary E.,Schroeder, Gretchen M.,Wilson, Lawrence J.,Liotta, Dennis C.
-
supporting information
p. 89 - 93
(2018/02/19)
-
- ANIMAL AND HUMAN ANTI-TRYPANOSOMONAL AND ANTI-LEISHMANIA AGENTS
-
Provided herein are Aminopurine compounds of Formula I: or pharmaceutically acceptable salts, tautomers, isotopologues, or stereoisomers thereof, wherein R1, R2, and R3 are as defined herein, compositions comprising an eff
- -
-
Paragraph 0400
(2018/01/11)
-
- SUBSTITUTED (AZA) -1-METHYL-1H-QUIN0LIN-2-0NES AS ANTIBACTERIALS
-
Bicyclic nitrogen containing compounds and their use as antibacterials (Formula I).
- -
-
Page/Page column 43-44
(2010/05/13)
-
- Synthesis and structure-activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores
-
Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(α-methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the α-methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50 = 5.8 mg kg-1, TD50 = 36.4 mg kg-1, PI = 6.3). Replacement of the piperidine ring of 1 by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man.
- Ho, Bin,Michael Crider,Stables, James P
-
p. 265 - 286
(2007/10/03)
-