The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, wherein: the group X—Y is —NHSO.sub.2— or —SO.sub.2NH—; Z is a monocyclic aryl or heteroaryl group, each of which is optionally substituted by one or more substituents selected from alkyl, cycloalkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.1 is H or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, C land alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, SO.sub.2NR.sub.12R.sub.13, heteroaryl, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.8 is selected from H, alkyl, haloalkyl and halo; and R.sub.9 is H, alkyl or halo; R.sub.10 and R.sub.11 are each independently H or alkyl; and R.sub.12 and R.sub.13 are each independently H or alkyl. Further aspects of the invention relate to such compounds for use in the field of immuno-oncology and related applications. Another aspect of the invention relates to compounds of formulae (la) and (lb).

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The present invention discloses a diphenylamine-linked chiral bis(oxazoline) ligand without C.sub.2-symmetry of formula 3 and its synthesis method and application in an asymmetric catalytic reaction, wherein C.sub.2-symmetry is lost by introducing different groups into the diphenylamine backbone to realize precise control of “electronic effect” of the ligand backbone. An anthranilic acid derivative and an orthochlorobenzoic acid derivative are used as starting materials to prepare a compound of formula 1, and then the compound of formula 1 is reacted with a chiral amino alcohol compound to prepare a β-bishydroxy amide compound of formula 2, and the compound of formula 2 is further subjected to condensation to obtain the diphenylamine-linked chiral bis(oxazoline) ligand without C.sub.2-symmetry of formula 3. The present invention also provides an application of a catalyst formed by coordination of the diphenylamine-linked chiral bis(oxazoline) ligand without C.sub.2-symmetry with copper salt, zinc salt, nickel salt, iron salt or rhodium salt, in an asymmetric catalytic reaction.

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The present invention discloses a diphenylamine-linked chiral bis(oxazoline) ligand without C.sub.2-symmetry of formula 3 and its synthesis method and application in an asymmetric catalytic reaction, wherein C.sub.2-symmetry is lost by introducing different groups into the diphenylamine backbone to realize precise control of “electronic effect” of the ligand backbone. An anthranilic acid derivative and an orthochlorobenzoic acid derivative are used as starting materials to prepare a compound of formula 1, and then the compound of formula 1 is reacted with a chiral amino alcohol compound to prepare a β-bishydroxy amide compound of formula 2, and the compound of formula 2 is further subjected to condensation to obtain the diphenylamine-linked chiral bis(oxazoline) ligand without C.sub.2-symmetry of formula 3. The present invention also provides an application of a catalyst formed by coordination of the diphenylamine-linked chiral bis(oxazoline) ligand without C.sub.2-symmetry with copper salt, zinc salt, nickel salt, iron salt or rhodium salt, in an asymmetric catalytic reaction.

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Chiral acetyl-protected aminoethyl quinoline (APAQ), pyridine and imazoline ligands are disclosed that enable Pd (II)-catalyzed enantioselective arylation or heteroarylation of ubiquitous prochiral β-methylene C—H bonds of aliphatic amides offers an alternative disconnection for constructing β-chiral centers. Systematic tuning of the ligand structure reveals that a six-membered instead of a five-membered chelation of these types of ligands with the Pd(II) is important for accelerating the C(sp.sup.3)-H activation thereby achieving enantioselectivity for quinoline and pyridine ligands.

Chiral acetyl-protected aminoethyl quinoline (APAQ), pyridine and imazoline ligands are disclosed that enable Pd (II)-catalyzed enantioselective arylation or heteroarylation of ubiquitous prochiral β-methylene C—H bonds of aliphatic amides offers an alternative disconnection for constructing β-chiral centers. Systematic tuning of the ligand structure reveals that a six-membered instead of a five-membered chelation of these types of ligands with the Pd(II) is important for accelerating the C(sp.sup.3)-H activation thereby achieving enantioselectivity for quinoline and pyridine ligands.

The invention provides for methods for the synthesis of various compounds through reaction of carboxamide, or carboxamide derivatives, with various substituted or unsubstituted haloalkanols in a one-step, single vessel, reaction mechanism. Preferably, but not exclusively, the reaction proceeds in the absence of any solvents, catalyst, base, or any further reagents.

The invention provides for methods for the synthesis of various compounds through reaction of carboxamide, or carboxamide derivatives, with various substituted or unsubstituted haloalkanols in a one-step, single vessel, reaction mechanism. Preferably, but not exclusively, the reaction proceeds in the absence of any solvents, catalyst, base, or any further reagents.

Peptidomimetic N5-methyl-N2-(nonanoyl-L-leucyl)-L-glutaminate derivatives, triazaspiro[4.14]nonadecane derivatives and similar compounds for use in methods of inhibiting the replication of noroviruses and coronaviruses in a biological sample or patient, for use in reducing the amount of noroviruses or coronaviruses in a biological sample or patient, and for use in treating norovirus and coronavirus in a patient, comprising administering to said biological sample or patient a safe and effective amount of a compound represented by formulae I or II, or a pharmaceutically acceptable salt thereof. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. page 99 to page 271; examples 1 to 3; compounds A1 to A104 and B1 to B66; tables A to E).

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The present invention discloses a method for preparing florfenicol and its intermediate (V), comprising an addition reaction, a ring closure reaction, a hydrolysis reaction, a ring opening reaction, a reduction reaction, a ring reaction, a fluorination reaction and a ring opening reaction. In the present method for preparing florfenicol, respective reaction steps can be continuously operated, therefore the methods of the present invention features simplified process and shorter synthetic route, and obtained florfenicol has high chiral purity and is of high yield. The method of the present invention for preparing florfenicol (TM) using the intermediate (V) avoids waste water pollution and reduces the cost for treating wastewater and alleviates environmental pollution. At the same time, the methods of the present invention eliminates a chiral resolution procedure, thus increasing the utilization rate of atoms in the reaction. As a result, cost is reduced and process is simplified.

The present disclosure provides compounds of Formula (I), Formula (I), Formula (II), Formula (II-A), Formula (III), and Formula (IV). The compounds described herein are MAX binders and/or modulators of Myc, Mad, or Mxi1 (e.g., inhibitors of Myc, Mad, or Mxi1), and may be useful in treating a subject with a disease associated with Myc, such as proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions and kits including the compounds described herein, as well as methods of using and uses of the compounds, compositions, and kits. ##STR00001##