The invention is a process for manufacturing a chemical product which may be later identified and distinguished from similar chemical products, and comprises the steps of (i) forming a reaction mixture comprising chemical intermediate A, chemical intermediate B and marker chemical M (ii) providing the conditions which enable chemical intermediate A and chemical intermediate B to react together to form chemical product C, and for marker chemical M to react either with chemical intermediate A to form a marker product AM or with chemical product C to form a marker product CM (iii) after said reactions have taken place, separating a mixture of product C with product AM and/or a mixture of product C with marker product CM from the reaction mix tune wherein product AM and product CM are both distinguishable from product C by analysis. By using the method of the invention, the marked product is formed in situ and in a mixture with unmarked product.

The invention is a process for manufacturing a chemical product which may be later identified and distinguished from similar chemical products, and comprises the steps of (i) forming a reaction mixture comprising chemical intermediate A, chemical intermediate B and marker chemical M (ii) providing the conditions which enable chemical intermediate A and chemical intermediate B to react together to form chemical product C, and for marker chemical M to react either with chemical intermediate A to form a marker product AM or with chemical product C to form a marker product CM (iii) after said reactions have taken place, separating a mixture of product C with product AM and/or a mixture of product C with marker product CM from the reaction mix tune wherein product AM and product CM are both distinguishable from product C by analysis. By using the method of the invention, the marked product is formed in situ and in a mixture with unmarked product.

Compounds which directly inhibit IRE-1 activity in vitro, prodrugs, and pharmaceutically acceptable salts thereof. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response and can be used as single agents or in combination therapies.

Compounds which directly inhibit IRE-1 activity in vitro, prodrugs, and pharmaceutically acceptable salts thereof. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response and can be used as single agents or in combination therapies.

A process for making certain spiroheterocyclic pyrrolidine dione derivatives.

A process for making certain spiroheterocyclic pyrrolidine dione derivatives.

The present invention provides a compound having the structure:

##STR00001## wherein R.sub.1 is halogen, NR.sub.5R.sub.6, NR.sub.5C(O)R.sub.6, NHC(O)OR.sub.7, OR.sub.7, NO.sub.2, CN, SR.sub.7, SO.sub.2R.sub.7, CO.sub.2R.sub.7, CF.sub.3, SOR.sub.7, POR.sub.7, C(S)R.sub.7, C(O)NR.sub.5R.sub.6, CH.sub.2C(O)NR.sub.5R.sub.6, C(NR.sub.5)R.sub.6, P(O)(OR.sub.5)(OR.sub.6), P(OR.sub.5)(OR.sub.6), C(S)R.sub.7, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R.sub.5, R.sub.6, and R.sub.7 and are each, independently, H, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, heteroalkyl, hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C.sub.1-5 alkyl-aryl, or C.sub.1-5 alkyl-NH-aryl; Ar.sub.1 is phenyl or thiophene; wherein when Ar.sub.1 is phenyl, then R.sub.1 is other than C(O)NR.sub.5R.sub.6, where one of R.sub.5 or R.sub.6 is phenyl or quinoline and the other of R.sub.5 or R.sub.6 is hydroxyalkyl, or where one of R.sub.5 or R.sub.6 is quinoline and the other of R.sub.5 or R.sub.6 is H; and wherein when Ar.sub.1 is phenyl, then R.sub.1 is other than NR.sub.5C(O)R.sub.6, where one of R.sub.5 is H and R.sub.6 is quinoline,
or a pharmaceutically acceptable salt thereof.

The present invention provides a compound having the structure:

##STR00001## wherein R.sub.1 is halogen, NR.sub.5R.sub.6, NR.sub.5C(O)R.sub.6, NHC(O)OR.sub.7, OR.sub.7, NO.sub.2, CN, SR.sub.7, SO.sub.2R.sub.7, CO.sub.2R.sub.7, CF.sub.3, SOR.sub.7, POR.sub.7, C(S)R.sub.7, C(O)NR.sub.5R.sub.6, CH.sub.2C(O)NR.sub.5R.sub.6, C(NR.sub.5)R.sub.6, P(O)(OR.sub.5)(OR.sub.6), P(OR.sub.5)(OR.sub.6), C(S)R.sub.7, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R.sub.5, R.sub.6, and R.sub.7 and are each, independently, H, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, heteroalkyl, hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C.sub.1-5 alkyl-aryl, or C.sub.1-5 alkyl-NH-aryl; Ar.sub.1 is phenyl or thiophene; wherein when Ar.sub.1 is phenyl, then R.sub.1 is other than C(O)NR.sub.5R.sub.6, where one of R.sub.5 or R.sub.6 is phenyl or quinoline and the other of R.sub.5 or R.sub.6 is hydroxyalkyl, or where one of R.sub.5 or R.sub.6 is quinoline and the other of R.sub.5 or R.sub.6 is H; and wherein when Ar.sub.1 is phenyl, then R.sub.1 is other than NR.sub.5C(O)R.sub.6, where one of R.sub.5 is H and R.sub.6 is quinoline,
or a pharmaceutically acceptable salt thereof.

Disclosed are 5-nitrobenzoate derivatives of Formula I, ##STR00001##
and the preparation method therefor, wherein R is referred to hydrogen (H), unsubstituted, mono-substituted, di-substituted or tri-substituted benzoyl moiety. 5-Nitrobenzoare derivatives of Formula I do not affect the platelet aggregation, possesses the inhibitory activity related to the tumor cell-induced platelet aggregation (TCIPA), and further specifically inhibits podoplanin-induced platelet aggregation. Therefore, 5-nitrobenzoates of the invention are applicable in its therapeutic use as the novel therapeutic agent in preventing tumor metastasis.

The disclosure provides methods of use of certain compounds that are useful for treating certain symptoms of endocrine disturbances, and in particular those associated with hot flashes.