Described herein are N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl) carbamoyl)-4,5,6,7-tetrahydrobenzofuran-2-sulfonamide derivatives and related compounds of formula (I) wherein R1 is formulae (II), (III), (IV), (V), (VI), (VII), (VIII) or (IX) and R2 is formulae (X) or (XI) as NLPR3 (pyrin domain-containing protein 3) modulators for the treatment of e.g. metabolic diseases (e.g. type 2 diabetes or obesity), liver diseases (e.g. NAFLD or cirrhosis), lung diseases (e.g. asthma or CORD), central nervous system diseases (e.g. Alzheimer's disease or multiple sclerosis), inflammatory or autoimmune diseases (e.g. rheumatoid arthritis or psoriasis), cardiovascular diseases (e.g. atherosclerosis or stroke). The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 67 to 90; examples 1 to 21; compounds 1 to 126; tables). An exemplary compound is e.g. N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-hydroxy-4-methyl-4,5,6,7-tetrahydrobenzofuran-2-sulfonamide (Example 1; compound (5))

##STR00001## ##STR00002##

Described herein are N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl) carbamoyl)-4,5,6,7-tetrahydrobenzofuran-2-sulfonamide derivatives and related compounds of formula (I) wherein R1 is formulae (II), (III), (IV), (V), (VI), (VII), (VIII) or (IX) and R2 is formulae (X) or (XI) as NLPR3 (pyrin domain-containing protein 3) modulators for the treatment of e.g. metabolic diseases (e.g. type 2 diabetes or obesity), liver diseases (e.g. NAFLD or cirrhosis), lung diseases (e.g. asthma or CORD), central nervous system diseases (e.g. Alzheimer's disease or multiple sclerosis), inflammatory or autoimmune diseases (e.g. rheumatoid arthritis or psoriasis), cardiovascular diseases (e.g. atherosclerosis or stroke). The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 67 to 90; examples 1 to 21; compounds 1 to 126; tables). An exemplary compound is e.g. N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-hydroxy-4-methyl-4,5,6,7-tetrahydrobenzofuran-2-sulfonamide (Example 1; compound (5))

##STR00001## ##STR00002##

The present invention relates to a process for the preparation of a chiral prostaglandin enol intermediate of formula 1, comprising the steps of: separating a compound of formula 16-(R,S)-10 into its diastereomers by fractional crystallisation, reducing the 15-oxo group of the compound of formula 16-(R)-10, thereby obtaining a compound of formula 15-(R,S), 16-(R)-11, followed by removing the protecting group of the compound of formula 15-(R,S), 16-(R)-11, and isolating the compound of formula 1, and optionally, crystallizing the compound of formula 1. Optionally, the undesired isomer formed during fractional crystallization can be epimerized and further amount of the desired isomer can be recovered from the resulting mixture. The present invention also provides novel intermediates useful in the process. The invention further relates to a process for fractional crystallization of the compound of formula 16-(R,S)-10.

##STR00001##

The present invention relates to a process for the preparation of a chiral prostaglandin enol intermediate of formula 1, comprising the steps of: separating a compound of formula 16-(R,S)-10 into its diastereomers by fractional crystallisation, reducing the 15-oxo group of the compound of formula 16-(R)-10, thereby obtaining a compound of formula 15-(R,S), 16-(R)-11, followed by removing the protecting group of the compound of formula 15-(R,S), 16-(R)-11, and isolating the compound of formula 1, and optionally, crystallizing the compound of formula 1. Optionally, the undesired isomer formed during fractional crystallization can be epimerized and further amount of the desired isomer can be recovered from the resulting mixture. The present invention also provides novel intermediates useful in the process. The invention further relates to a process for fractional crystallization of the compound of formula 16-(R,S)-10.

##STR00001##

The present disclosure relates to adhesive compositions, processes of forming adhesive compositions, and multi-layer films. The processes generally include contacting an olefin monomer with a catalyst system within a polymerization zone to form an olefin based polymer under polymerization conditions sufficient to form the olefin based polymer, the catalyst system including a metal component generally represented by the formula:

MR.sub.x;

wherein M is a transition metal, R is a halogen, an alkoxy, or a hydrocarboxyl group and x is the valence of the transition metal, wherein the catalyst system further includes an internal donor (ID) comprising a C.sub.3-C.sub.6 cyclic ether; and withdrawing the olefin based polymer from the polymerization zone; and melt blending the olefin based polymer with a graft (polyolefin/elastomer) copolymer to form a polyolefin based adhesive composition, wherein the process is an in-line process.

The present disclosure relates to adhesive compositions, processes of forming adhesive compositions, and multi-layer films. The processes generally include contacting an olefin monomer with a catalyst system within a polymerization zone to form an olefin based polymer under polymerization conditions sufficient to form the olefin based polymer, the catalyst system including a metal component generally represented by the formula:

MR.sub.x;

wherein M is a transition metal, R is a halogen, an alkoxy, or a hydrocarboxyl group and x is the valence of the transition metal, wherein the catalyst system further includes an internal donor (ID) comprising a C.sub.3-C.sub.6 cyclic ether; and withdrawing the olefin based polymer from the polymerization zone; and melt blending the olefin based polymer with a graft (polyolefin/elastomer) copolymer to form a polyolefin based adhesive composition, wherein the process is an in-line process.

Methods for the synthesis of a tricyclic-prostaglandin D.sub.2 metabolite methyl ester or a pharmaceutically acceptable salt thereof.

The present invention provides a method for producing a compound represented by Formula (1a), (1b), or (1c), comprising a step of reducing a compound represented by Formula (3) in the presence of a metal complex represented by Formula (5), an inorganic base, and a solvent under a hydrogen atmosphere to obtain a compound represented by Formula (4). In the formula, Ar.sup.1 is an aryl group, each Are is independently a phenyl group or the like, W is a biphenyl group or the like, Z is an ethylene group that is substituted with a phenyl group or the like, and L is a chlorine atom or if Z has a phenyl group or a C.sub.1-3 alkoxyphenyl group, L is one of carbon atoms constituting the phenyl group or the C.sub.1-3 alkoxyphenyl group.

##STR00001##

The present invention provides a method for producing a compound represented by Formula (1a), (1b), or (1c), comprising a step of reducing a compound represented by Formula (3) in the presence of a metal complex represented by Formula (5), an inorganic base, and a solvent under a hydrogen atmosphere to obtain a compound represented by Formula (4). In the formula, Ar.sup.1 is an aryl group, each Are is independently a phenyl group or the like, W is a biphenyl group or the like, Z is an ethylene group that is substituted with a phenyl group or the like, and L is a chlorine atom or if Z has a phenyl group or a C.sub.1-3 alkoxyphenyl group, L is one of carbon atoms constituting the phenyl group or the C.sub.1-3 alkoxyphenyl group.

##STR00001##

The present invention relates to the technical field of organic chemical engineering, and in particular to a key intermediate for synthesizing prostaglandin compounds and a preparation method therefor. When applied to the synthesis of prostaglandin compounds, the process flow is simplified, the yield and product purity are improved, the production costs are reduced, and the industrial application is easy.

##STR00001##