- Amide compound and derivative thereof, preparation method, pharmaceutical composition and application thereof
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The invention discloses an amide compound and derivative thereof, a preparation method, a pharmaceutical composition and application thereof. The structure of the amide compound is shown as a formula (I). The derivatives of theamide compound relate to a stereoisomer, a tautomer, a metabolite, a metabolic precursor, a prodrug, a solvate, a salt of the solvate, a crystal, a pharmaceutically acceptable salt or a mixture of the above of theamide compound. The amide compound and the derivative thereof have an efficient inhibition effect on indoleamine 2, 3-dioxygenase 1, and can be used for preparing medicines for treating indoleamine 2, 3-dioxygenase 1 mediated immunosuppression related diseases, the prepared medicine can exert the medicine effect at the molecular level and is wide in application, and the synthesis method of the compound is simple, convenient and easy to operate.
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- Synthesis method of arylcyclobutane compound
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The present invention discloses a method for synthesizing an arylcyclobutane compound to 1eq phenylacetonitrile and 1.1eq 1-bromo-3-chloropropane as raw material, N,N- dimethylacetamide as a solvent, plus 2.5eq sodium hydride, under the protection of iner
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Paragraph 0130-0133; 0176-0178
(2022/01/10)
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- Short Synthesis of Oxetane and Azetidine 3-Aryl-3-carboxylic Acid Derivatives by Selective Furan Oxidative Cleavage
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Four-membered rings remain underexplored motifs despite offering attractive physicochemical properties for medicinal chemistry. Arylacetic acids bearing oxetanes, azetidines, and cyclobutanes are prepared in two steps: a catalytic Friedel-Crafts reaction from four-membered ring alcohol substrates, followed by mild oxidative cleavage. The suitability of the products as building blocks is reflected in their facile purification and amenability to derivatization. Examples include heteroaromatics and aryltriflates, as well as oxetane-derived profen drug analogues and a new endomorphin derivative containing an azetidine amino acid residue.
- Bull, James A.,Choi, Chulho,Dubois, Maryne A. J.,Lee Wei Jie, Alvin,Mousseau, James J.,Smith, Milo A.,White, Andrew J. P.
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p. 5279 - 5283
(2020/08/14)
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- Iridium-Catalyzed Enantioselective C(sp3)–H Borylation of Cyclobutanes
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We herein report the first example of iridium-catalyzed enantioselective C(sp3)–H borylation of cyclobutanes using benzoxazoline as the directing group. The combination of a chiral bidentate boryl ligand and an iridium precursor has found to effectively catalyze C(sp3)–H borylation to afford a variety of cyclobutylboronates with good to excellent enantioselectivities. We also demonstrate the synthetic utility of the current method by converting the stereogenic C—B bond to other functionalities.
- Chen, Xiang,Chen, Lili,Zhao, Hongliang,Gao, Qian,Shen, Zhenlu,Xu, Senmiao
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p. 1533 - 1537
(2020/09/09)
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- Cycloalkyl Amine Compounds
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Cycloalkyl amine compounds of Formula (I), wherein ring A is C3-C6 cycloalkyl, optionally substituted with one or more C1-C3 alkyl, and R5 is ORS2, in which RS2 is H or C1-C6 alkyl, or R5 and R6, together with the carbon atom to which they are attached, form C═O, for use in treating CNS disorders, including movement disorders, depressive disorders, sleep disorders, cognitive dysfunctions, obesity, sexual dysfunction and substance abuse.
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- Identification of A Novel Small-Molecule Binding Site of the Fat Mass and Obesity Associated Protein (FTO)
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N-(5-Chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide (N-CDPCB, 1a) is found to be an inhibitor of the fat mass and obesity associated protein (FTO). The crystal structure of human FTO with 1a reveals a novel binding site for the FTO inhibitor and defines the molecular basis for recognition by FTO of the inhibitor. The identification of the new binding site offers new opportunities for further development of selective and potent inhibitors of FTO, which is expected to provide information concerning novel therapeutic targets for treatment of obesity or obesity-associated diseases.
- He, Wu,Zhou, Bin,Liu, Weijia,Zhang, Meizi,Shen, Zhenhua,Han, Zhifu,Jiang, Qingwei,Yang, Qinghua,Song, Chuanjun,Wang, Ruiyong,Niu, Tianhui,Han, Shengna,Zhang, Lirong,Wu, Jie,Guo, Feima,Zhao, Renbin,Yu, Wenquan,Chai, Jijie,Chang, Junbiao
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p. 7341 - 7348
(2015/10/05)
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- PYRAZOLE DERIVATIVES AS MODULATORS OF CALCIUM RELEASE -ACTIVATED CALCIUM CHANNEL
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Disclosed are novel calcium release-activated calcium (CRAC) channel inhibitors, methods for preparing them, pharmaceutical compositions containing them, and methods of treatment using them. The present disclosure also relates to methods for treating non-small cell lung cancer (NSCLC) with CRAC inhibitors, and to methods for identifying therapeutics for treating and of diagnosing cancer.
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- IL-8 RECEPTOR ANTAGONISTS
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This invention relates to novel compounds, compositions and combinations thereof, useful in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).
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Page/Page column 52
(2008/12/06)
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- ACYCLIC HYDRAZIDES AS CANNABINOID RECEPTOR MODULATORS
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The acyclic hydrazides of the invention are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present inventio
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Page/Page column 49
(2010/11/08)
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- Substituted alkanoic acids
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The invention is directed to physiologically active compounds of general formula (I): wherein:- represents (i) a saturated 3 to 6 membered carbocycle, optionally substituted by one or more alkyl groups, (ii) indanyl or (iii) a saturated 4 to 6 membered heterocyclic ring; R1 represents R3Z1-Het- or R4N(R5)—C(═O)—NH—Ar1—; L1 represents an —R6—R7— linkage; R2 represents hydrogen, halogen, lower alkyl or lower alkoxy; L2 represents an alkylene linkage; Y is carboxy or an acid bioisostere; and their corresponding N-oxides or prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their corresponding N-oxides or prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (α4β1).
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- 1,1-DISUBSTITUTED CYCLOALKYL DERIVATIVES AS FACTOR XA INHIBITORS
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The present application describes 1,1-disubstituted cycloalkyl compounds and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.
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Page 316-317
(2010/02/05)
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- A polar substituent effect on the ring-cleavage rearrangement of 1-arylcyclobutylmethyl Grignard reagents
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The kinetics of the ring-cleavage rearrangements of 1-phenylcyclobutylmethylmagnesium chloride and its p-methyl and p-chloro analogs have been determined.The first-order rate constants are correlated by the Hammett equation, with ρ=-0.47.The results are consistent with a concerted mechanism with a cyclic transition state having significant polar character, although polar effects on the stabilities of reactant and product may also contribute.The phenyl group itself slows the reaction by a factor of 0.031, which is interpreted principally in terms of steric destabilization of the transition state.
- Hill, E. Alexander,Li, Baoju
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- Thermolabile Hydrocarbons, XXV. Relationships between Thermal Stability, Strain, and Structure of 1,1'-Diphenyl-1,1'-bicycloalkyls
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The products and activation parameters of the thermolysis reaction of the title hydrocarbons 1a (n = 4-8) and 1b (n = 12) were determined.Strain enthalpies and structural data of the compounds 1a and of the radicals 2a, which are generated on thermolysis, were obtained from force field calculations.For 1a (n = 8) a crystal structure analysis was carried out. - The importance of i-strain action is estimated from the relationship between ΔG% of the thermolysis reaction and the strain enthalpy of 1 from which the ring strain of the corresponding cycloalkane was substracted as a correction factor.In addition, a linear correlation between ΔG% and the change in strain enthalpy (MM2 results) in the course of the dissociation process was found.The large variation in ΔS% can be rationalized by consideration of the change in internal mobility (MM2 results) during the dissociation process.
- Bernloehr, Werner,Beckhaus, Hans-Dieter,Lindner, Hans-Joerg,Ruechardt, Christoph
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p. 3303 - 3319
(2007/10/02)
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