The present invention provides a novel macrocyclic prodrug compound of general Formula (I), a pharmaceutical composition comprising a compound of Formula (I), and a method for treating diseases mediated by HDAC enzymes by administering a compound of Formula (I), wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, A and Z are defined herein.

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The present invention provides compounds as PPAR agonists and their application, involving a new class of peroxisome proliferator-activated receptor (PPAR) gamma receptor agonist, which can inhibit the production of mitochondrial reactive oxygen species, and most of which can readily cross the blood-brain barrier. The present invention also includes pharmaceutical uses of the compounds.

The present disclosure generally relates to compounds and pharmaceutical compositions that may be used in methods of treating cancer.

Disclosed herein are salt and solvate forms of. (1S,3′R,6′R,7′S,8′E,11′S,12′R)-6-chloro-7′-methoxy-11′,12′-dimethyl-3,4-dihydro-2H,15′H-spiro[naphthalene-1,22′-[20]oxa[13]thia[1,14]diazatetracyclo[14.7.2.0.sup.3,6.0.sup.19,24]pentacosa[8,16,18,24]tetraen]-15′-one 13′,13′-dioxide (AMG 176):

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such as crystalline salt and solvate forms thereof. Also disclosed are methods of making the salt and solvate forms, and methods of treating diseases and disorders with the salt and solvate forms.

Disclosed herein are salt and solvate forms of. (1S,3′R,6′R,7′S,8′E,11′S,12′R)-6-chloro-7′-methoxy-11′,12′-dimethyl-3,4-dihydro-2H,15′H-spiro[naphthalene-1,22′-[20]oxa[13]thia[1,14]diazatetracyclo[14.7.2.0.sup.3,6.0.sup.19,24]pentacosa[8,16,18,24]tetraen]-15′-one 13′,13′-dioxide (AMG 176):

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such as crystalline salt and solvate forms thereof. Also disclosed are methods of making the salt and solvate forms, and methods of treating diseases and disorders with the salt and solvate forms.

The present disclosure provides methods for preparing MCL1 inhibitors or a salt thereof and related key intermediates.

An objective of the present invention is to provide methods of producing a cyclic organic compound using a continuous stirred tank reactor(s) (CSTR), the methods being capable of achieving excellent impurity-suppressing effects (quality improvement), reduction in reaction-tank size, continuous production, and such. The present inventors conducted studies on cyclization reactions using a CSTR(s), which had not been conventionally used for cyclization reactions for cyclic compounds. As a result, the inventors have found that the present methods can achieve excellent impurity-suppressing effects (quality improvement), reduction in reaction-tank size, continuous production, and such, as compared with conventional cyclization methods. Furthermore, the present inventors have also found that the above-mentioned improvement effects can efficiently be achieved even in the production of cyclic peptides and heterocyclic compounds by applying simulation methods that had been conventionally used mainly at the fine chemicals plant level to the cyclization reactions of the present invention, thereby experimentally predicting the reaction rate of a cyclization reaction, and setting the flow volume (residence time), the concentrations of precursor and cyclic organic compound, and the temperature for the cyclization reaction and such which affect these conditions, in the cyclization reaction using a CSTR(s).

The present disclosure generally relates to compounds of Formula (I) and pharmaceutical compositions that may be used in methods of treating cancer.

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The present disclosure generally relates to compounds of Formula (I) and pharmaceutical compositions that may be used in methods of treating cancer.

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Provided herein are processes for synthesizing mcl-1 inhibitors and intermediates such as compound Z that can be used to prepare them. In particular, provided herein are processes for synthesizing compound A1, and salts or solvates thereof and compound A2, and salts and solvates thereof.

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