Abstract: A method of treating cancer is described. The method includes administering a therapeutically effective amount of a TET2 activating compound or pharmaceutically acceptable salt thereof to a subject in need of treatment. The TET2 activating compounds are ?-ketoglutarate derivatives. A method of treating or preventing cancer in a subject that includes the step of analyzing a biological sample to determine if cells of the biological sample exhibit a TET2 mutation in addition to administering a TET2 activator is also described.

Abstract: Compounds that can be used to increase NAD levels are described by inhibiting NAD+ degrading enzymes such as CD38 are described. The compounds have a structure according to formula I or Formula II, as described herein, or pharmaceutically acceptable salts thereof, wherein the attached groups are as defined in the specification. Methods of increasing intracellular NAD+ levels in a subject by administering an effective amount of a compound according to formula I or formula II to the subject are also described.

Abstract: Compounds according to formula (I) are described wherein R1 is an amino acid or a modified amino acid linked to the compound through a peptide bond, R2 is selected from CN, SO2CH3, NO2, CO2R3, CONHR3, NH2, NMe2 and CF3, and R3 is selected from H or lower alkyl, X is O or S, and Y is C—H or N, or a pharmaceutically acceptable salt thereof. The compounds can be used as protein disulfide isomerase inhibitors. The compounds can also be used in a method of treating or cancer in a subject.

Abstract: Imidazopyridine derivatives according to formula I are described wherein X is selected from CH, N, S, and O, Y is selected from S, CO, and O, R1 and optional R2 are independently selected from H, OH, substituted or unsubstituted C1-C6 alkyl, and substituted or unsubstituted C4-C6 cycloalkyl or cycloheteroalkyl, R3 is selected from H, OH, substituted or unsubstituted C1-C6 alkyl, and optional Z is selected from OH, NH2, NH(CO)R4, NH(SO2)R4, guanidine, alkylguanidine, and fluoroguanidine, R4 is polyethylene glycol or substituted or unsubstituted C1-C6 alkyl, and pharmaceutically acceptable salt thereof. The imidazopyridine derivatives can be used for treatment of cancer in a subject.

Abstract: Imidazopyridine derivatives according to formula I are described wherein X is selected from CH, N, S, and O, Y is selected from S, CO, and O, R1 and optional R2 are independently selected from H, OH, substituted or unsubstituted C1-C6 alkyl, and substituted or unsubstituted C4-C6 cycloalkyl or cycloheteroalkyl, R3 is selected from H, OH, substituted or unsubstituted C1-C6 alkyl, and optional Z is selected from OH, NH2, NH(CO)R4, NH(SO2)R4, guanidine, alkylguanidine, and fluoroguanidine, R4 is polyethylene glycol or substituted or unsubstituted C1-C6 alkyl, and pharmaceutically acceptable salt thereof. The imidazopyridine derivatives can be used for treatment of cancer in a subject.

Abstract: Autophagy inhibitors useful for the treatment of cancer and other diseases are described. The autophagy inhibitors are a compound of formula: I wherein R1 is a group selected from lower alkyl, lower alkyl amide, lower alkyl ester, lower alkyl ketone, and lower alkyl ether; R2 and R3 are H or a group selected from cycloalkyl, lower alkyl, lower alkyl amide, lower alkyl ester, lower alkyl ketone, and lower alkyl ether; R4 is a heteroaryl group; and L is a —(CH2)n—X—(CH2)n— group, wherein n is 1, 2, 3, or 4, X is absent, O, S, or N—R5, wherein R5 is H or a lower alkyl group, or a pharmaceutically acceptable salt thereof.

Abstract: Imidazopyridine derivatives according to formula I are described wherein X is selected from CH, N, S, and O, Y is selected from S, CO, and O, R1 and optional R2 are independently selected from H, OH, substituted or unsubstituted C1-C6 alkyl, and substituted or unsubstituted C4-C6 cycloalkyl or cycloheteroalkyl, R3 is selected from H, OH, substituted or unsubstituted C1-C6 alkyl, and optional Z is selected from OH, NH2, NH(CO)R4, NH(SO2)R4, guanidine, alkylguanidine, and fluoroguanidine, R4 is polyethylene glycol or substituted or unsubstituted C1-C6 alkyl, and pharmaceutically acceptable salt thereof. The imidazopyridine derivatives can be used for treatment of cancer in a subject.

Abstract: Autophagy inhibitors useful for the treatment of cancer and other diseases are described. The autophagy inhibitors are a compound of formula: I wherein R1 is a group selected from lower alkyl, lower alkyl amide, lower alkyl ester, lower alkyl ketone, and lower alkyl ether; R2 and R3 are H or a group selected from cycloalkyl, lower alkyl, lower alkyl amide, lower alkyl ester, lower alkyl ketone, and lower alkyl ether; R4 is a heteroaryl group; and L is a —(CH2)n—X—(CH2)n— group, wherein n is 1, 2, 3, or 4, X is absent, O, S, or N—R5, wherein R5 is H or a lower alkyl group, or a pharmaceutically acceptable salt thereof.

Abstract: Naphthalenyl benzamide derivatives according to formula I are described, wherein Ar is an aryl or heteroaryl group, and R1-R4 are independently selected from H, halogen, CF3, hydroxyl, C1-C4 alkyl, and C1-C4 oxyalkyl, or a pharmaceutically acceptable salt thereof. The naphthalenyl benzamide derivatives can be used for the treatment of cancer in a subject.

Abstract: A system for use in borehole completion is provided and includes a perforating sub, a firing sub having a first port and an interior and including a firing assembly disposable within the interior and operably coupled to the perforating sub and a drilling fluid barrier, which is formed with a second port and is displaceable toward a position at which the first and second ports align to form a fluid path through the interior that is sufficiently pressurizable to actuate the firing assembly, a drop plug selectively engageable with the drilling fluid barrier to enable displacement thereof to the position in response to applied pressures and an isolation sub, into which the drop plug is receivable following disengagement thereof from the drilling fluid barrier.

Abstract: A system for use in borehole completion is provided and includes a perforating sub, a firing sub having a first port and an interior and including a firing assembly disposable within the interior and operably coupled to the perforating sub and a drilling fluid barrier, which is formed with a second port and is displaceable toward a position at which the first and second ports align to form a fluid path through the interior that is sufficiently pressurizable to actuate the firing assembly, a drop plug selectively engageable with the drilling fluid barrier to enable displacement thereof to the position in response to applied pressures and an isolation sub, into which the drop plug is receivable following disengagement thereof from the drilling fluid barrier.

Abstract: The present invention provides, in its principal aspect, compounds of the general formula: where A is —NHCO—, —N(CH3)—CO—, —NHCH2—, —N(CH3)—CH2—, —COCH2—, —CH2CH2—, or —CH(OH)CH2—, X is H, CH3, NH2, NH(CH3), N(CH3)2, OCH3, or SH; R2 is hydrogen or a methyl or ethyl group; R3 is hydrogen or a methyl or ehtyl group; n is 0, 1, 2, 3, 4, 5 or 6; R1 is selected from the group consisting of (a) alkyl; (b) C3 to C8 cycloalkyl; (c) phenyl or substituted phenyl; (d) heterocyclic; (e) decahydronaphthalene and (f) octahydroindane; or R1 and X may be taken together to denote a 5,6 or 6,6 saturated bicycle ring structure. The compounds of the present invention have H3 histamine receptor antagonist activity. This invention also provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier in combination with an effective amount of a compound of formula 1.0.

Abstract: The present invention provides, in its principal aspect, compounds of the general formula: ##STR1## when A is --NHCO--, --N(CH.sub.3)--CO--, --NHCH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --, --CH.dbd.CH--, --COCH.sub.2 --, CH.sub.2 CH.sub.2 --, --CH(OH)CH.sub.2 -- or --C.tbd.C--;X can be H, CH.sub.3, NH.sub.2, NH(CH.sub.3),N(CH.sub.3).sub.2, OH, OCH.sub.3, SH,R.sub.2 is hydrogen or a methyl or ethyl group;R.sub.3 is hydrogen or a methyl or ethyl group;n is 0, 1, 2, 3, 4, 5 or 6;R.sub.1 is selected from the group consisting of (a) alkyl; (b) C.sub.3 to C.sub.8 cycloalkyl; (c) phenyl or substituted phenyl; (d) heteroocyclic; and (f) decahydronaphthalene or octahydroindane; andWhen R.sub.1 and X taken together denote a 5, 6 or 6, 6 saturated bicyclic ring structure, X can be NH, O, S, SO.sub.2,When X is constrained in a 5, 6 or 6, 6, saturated bicyclic ring structure, then for example, when X.dbd.NH, R.sub.1 and X taken together mean an octahydroindole ring structure directly attached to A.

Abstract: The present invention is directed to 1H-4(5)-substituted imidazole derivates of formula (I), wherein A is (a); (b); or (c) ##STR1## wherein R.sub.1 is lower alkyl or lower alkoxy;R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.7 and R.sub.8 are each independently hydrogen or lower alkyl;R.sub.6 is hydrogen, lower alkyl or lower alkoxy and R.sub.5 and R.sub.6 can be joined to form a 4, 5 or 6 membered ring.The compounds of formula (I) have H.sub.3 histamine receptor agonist activity. The pharmaceutically acceptable salts, and individual stereoisomers of compounds of formula (I) above, as well as mixtures thereof, are also contemplated as falling within the scope of the present invention. The present invention also provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier in combination with an effective amount of a compound of formula (1). The present invention also provides a method of treating conditions in which activation of histamine H.sub.

Abstract: The present invention provides compounds having H.sub.3 histamine receptor antagonist activity of the general formula: ##STR1## R.sub.2 is a hydrogen or a methyl or ethyl group; R.sub.3 is a hydrogen or a methyl or ethyl group;n is 1, 2, 2, 3, 4, 5, or 6; andR.sub.1 is selected from the group consisting of (a) C.sub.3 to C.sub.8 cycloalkyl; (b) phenyl or substituted phenyl; (c) alkyl; (d) heterocyclic; (e) decahydronapthalene; and (f) octahydroindene;with the provisos thatwhen X is H, A can be --CH.sub.2 CH.sub.2 --,--COCH.sub.2 --,--CONH--,--CON(CH.sub.3), CH.dbd.CH, --c.ident.c--,--CH.sub.2 --NH--, --CH.sub.2 --N(CH.sub.3)--,--CH(OH)CH.sub.2 --,--NH--CH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --,--CH.sub.2 O--,--CH.sub.2 S--, and --NHCOO--;when X is NH.sub.2, NH(CH.sub.3), N(CH.sub.3).sub.2, OH, OCH.sub.3, CH.sub.3, SH, and SCH.sub.3 ; A can be --NHCO--, --N(CH.sub.3)--CO--, --NHCH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --, --CH.dbd.CH--; --COCH.sub.2, --CH.sub.2 CH.sub.2 --,--CH(OH)CH.sub.2, or --C.ident.

Abstract: The present invention provides compounds having H.sub.3 histamine receptor antagonist activity of formula (1.0) wherein R.sub.2 is a hydrogen or a methyl or ethyl group; R.sub.3 is a hydrogen or a methyl or ethyl group; n is 0, 1, 2, 3, 4, 5, or 6; and R.sub.1 is selected from the group consisting of (a) C.sub.3 to C.sub.8 cycloalkyl; (b) phenyl or substituted pneyly; (c) alkyl; (d) heterocyclic; (e) decahydronaphthalene; and (f) octahydroindene; with the proviso that when X is H, A can be --CH.sub.2 CH.sub.2, --COCH.sub.2 --CON(CH.sub.3)--, --CH.dbd.CH--, .alpha., --CH.sub.2 --NH--, --CH.sub.3 --N(CH.sub.3)--, --CH(OH)CH.sub.2 --, --NH--CH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --, --CH.sub.2 O--, --CH.sub.2 S--, and --NHCOO--; when X is NH.sub.2, HN(CH.sub.3), N(CH.sub.3).sub.2, OH, OCH.sub.3, CH.sub.3, SH and SCH.sub.3 ; A can be --NHCO--, --N(CH.sub.3)--CO--, --NHCH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --, --CH.dbd.XH--, --COCH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH( )H)CH.sub.2 --, or .beta.; and when R.sub.

Abstract: The present invention provides compounds having H.sub.3 histamine receptor antagonist activity of the general formula: ##STR1## where X is H, A is --CH.sub.2 CH.sub.2 --, --COCH.sub.2 --, --CONH--, --CON(CH.sub.3)--, --CH.dbd.CH--, --C.tbd.C--, --CH.sub.2 --NH--, --CH.sub.2 --NCH.sub.3 --, --CH(OH)CH.sub.2 --, --NH--CH.sub.2 --, --N(CH.sub.3) --CH.sub.2 --, --NHSO.sub.2 --, --CH.sub.2 O--, --CH.sub.2 S--, CH.sub.2 SO.sub.2 --, or --CH.sub.2 S(O)--;R.sub.2 is a hydrogen or a methyl or ethyl group;R.sub.3 is a hydrogen or a methyl or ethyl group;n is 0, 1, 2, 3, 4, 5, or 6; andR.sub.1 is selected from the group consisting of (a) C.sub.3 to C.sub.8 cycloalkyl; (b) H; (c) phenyl or substituted phenyl; (d) alkyl; (e) heterocyclic; and (f) bicyclic alkyl; andwhenX is NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, OH, OCH.sub.3, NHR.sub.4, OR.sub.4, SH, SR.sub.4, or SO.sub.2 R.sub.4 ; A is --NHCO--, --N(CH.sub.3)--CO--, --NHCH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --, --NHSO.sub.2 --, --CH.dbd.CH--, --CH.dbd.CHF--, --COCH.

Abstract: Indole compounds substituted at the 1- or 3-position by a (pyrid-3-yl)thiazolid-4-yl)alkyl-, (pyrid-3-yl)thiazolid-4-oyl)-, (pyrid-3-yl)dithiolan-4-yl)alkyl- or (pyrid-3-yl)dithiolan-4-oyl)- group are potent inhibitors of PAF and are useful in the treatment of PAF-related disorders including septic shock, respiratory distress syndrome, acute inflammation, delayed cellular immunity, parturtition, fetal lung maturation, and cellular differentiation.

Abstract: Benzoylphenyl derivatives of 2-(3-pyridinyl)-3-alkyl-4-thiazolidinecarboxamide, 2-(3-pyridinyl)-thiazolid-4-ylacetamide, 2-(3-pyridinyl)-4-dithiolanecarboxamide or 2-(3-pyridinyl)dithiolan-4-yl]urea-group are potent inhibitors of PAF and are useful in the treatment of PAF-related disorders including anaphylactic shock, respiratory distress syndrome, acute inflammation, delayed cellular immunity, parturtition, fetal lung maturation, and cellular differentiation.

Abstract: Indole compounds substituted at the 1- or 3 position by a (pyrid-3 yl)thiazolid-4-yl)alkyl-, (pyrid-3-yl)thiazolid-4-oyl)-, (pyrid-3-yl)dithiolan-4-yl)alkyl- or (pyrid-3-yl) dithiolan-4-ol)- group are potent inhibitors of PAF and are useful in the treatment of PAF-related disorders including anaphylactic shock, respiratory distress syndrome, acute inflammation, delayed cellular immunity, parturtition, fetal lung maturation, and cellular differentiation.