Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

Provided herein are the K-Ras inhibitors of the formulae: ##STR00001##
Also provided are compositions comprising thereof for treating cancer.

Provided herein are the K-Ras inhibitors of the formulae: ##STR00001##
Also provided are compositions comprising thereof for treating cancer.

The present invention relates to use of an isobaric label in mass spectrometry (MS) analysis using data-independent acquisition (DIA), wherein said isobaric label comprises or consists of a group which fragments in the mass spectrometer (i) at an energy below the energy required for fragmenting analyte-derived precursor ions and/or a higher conversion rate than said precursor ions; and (ii) at said energy according to (i) and when coupled to a precursor ion, at a single site within said group, to yield a first moiety and a second moiety, said second moiety being coupled to said precursor ion.

The present invention relates to use of an isobaric label in mass spectrometry (MS) analysis using data-independent acquisition (DIA), wherein said isobaric label comprises or consists of a group which fragments in the mass spectrometer (i) at an energy below the energy required for fragmenting analyte-derived precursor ions and/or a higher conversion rate than said precursor ions; and (ii) at said energy according to (i) and when coupled to a precursor ion, at a single site within said group, to yield a first moiety and a second moiety, said second moiety being coupled to said precursor ion.

The present invention provides a compound represented by formula (1) (in formula (1), R.sup.1 and R.sup.2 each independently represent a group represented by formula (2) or NHR.sup.0 (where R.sup.1 and R.sup.2 are not simultaneously NHR.sup.0), R.sup.0 represents any one of hydrogen, an alkyl group having 1-20 carbon atoms, an alkenyl group having 2-30 carbon atoms, an aryl group having 6-30 carbon atoms, an alkylaryl group having 7-30 carbon atoms, and an arylalkyl group having 7-30 carbon atoms, each R.sup.3 independently represents hydrogen or a hydrocarbon group having 1-30 carbon atoms, l represents an integer of 0-4, m represents an integer of 1-4 (where m is an integer of 2-4 in the case where R.sup.1 and R.sup.2 are a group represented by formula (2)), and each n independently represents an integer of 0-4, and, in formula (2), R.sup.4 represents a hydrocarbon group having 6-24 carbon atoms, and X.sup.1 and X.sup.2 each independently represent an oxygen atom or a sulfur atom). ##STR00001##

The present invention provides a compound represented by formula (1) (in formula (1), R.sup.1 and R.sup.2 each independently represent a group represented by formula (2) or NHR.sup.0 (where R.sup.1 and R.sup.2 are not simultaneously NHR.sup.0), R.sup.0 represents any one of hydrogen, an alkyl group having 1-20 carbon atoms, an alkenyl group having 2-30 carbon atoms, an aryl group having 6-30 carbon atoms, an alkylaryl group having 7-30 carbon atoms, and an arylalkyl group having 7-30 carbon atoms, each R.sup.3 independently represents hydrogen or a hydrocarbon group having 1-30 carbon atoms, l represents an integer of 0-4, m represents an integer of 1-4 (where m is an integer of 2-4 in the case where R.sup.1 and R.sup.2 are a group represented by formula (2)), and each n independently represents an integer of 0-4, and, in formula (2), R.sup.4 represents a hydrocarbon group having 6-24 carbon atoms, and X.sup.1 and X.sup.2 each independently represent an oxygen atom or a sulfur atom). ##STR00001##

A conjugate of a potent cytotoxic agent with a cell-surface receptor binding molecule having a Formula (I), wherein T, L, m, n, 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, R.sup.12, and R.sup.13 are defined herein, can be used for targeted treatment of cancer, autoimmune disease, and infectious disease.

A conjugate of a potent cytotoxic agent with a cell-surface receptor binding molecule having a Formula (I), wherein T, L, m, n, 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, R.sup.12, and R.sup.13 are defined herein, can be used for targeted treatment of cancer, autoimmune disease, and infectious disease.

The present invention provides compounds of formula (I), ##STR00001##
wherein: R.sub.1 is unsubstituted C.sub.1-C.sub.6 alkyl; L.sub.a is substituted or unsubstituted C.sub.1-C.sub.6 alkyl linker, substituted or unsubstituted C.sub.3-C.sub.10 carbocycle, substituted or unsubstituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S; and R.sub.2 and R.sub.3 are each, independently, H, substituted or unsubstituted C.sub.1-C.sub.6 alkyl, or substituted or unsubstituted C.sub.6-C.sub.10 aryl; or alternatively, R.sub.2 and R.sub.3, together with the nitrogen atom to which they are attached, form a substituted or unsubstituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S or a substituted or unsubstituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S. The invention also provides pharmaceutical compositions and methods for treating neurological diseases, such as multiple sclerosis.