The invention provides compounds having the general Formula (I); ##STR00001##
and pharmaceutically acceptable salts thereof; wherein the variables R.sup.A, R.sup.AA, subscript n, subscript q, ring A, X.sup.2, L, subscript m, X.sup.1, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, D and E have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.

The present invention provides, in part a novel class of nonoate compounds which exhibit nitric oxide releasing activity and their pharmaceutically acceptable salts, esters and prodrugs. The compounds release nitric oxide upon activation by contact with plasma. The present invention also relates to the use of the disclosed compounds to deliver nitric oxide to treat disorders arising from nitric oxide dysregulation.

To provide a chiral reagent or a salt thereof. The chiral reagent has following chemical formula (I). In the formula (I), G.sup.1 and G.sup.2 are independently a hydrogen atom, a nitro group (—NO.sub.2), a halogen atom, a cyano group (—CN), a group of formula (II) or (III), or both G.sup.1 and G.sup.2 taken together to form a group of formula (IV). ##STR00001##

To provide a chiral reagent or a salt thereof. The chiral reagent has following chemical formula (I). In the formula (I), G.sup.1 and G.sup.2 are independently a hydrogen atom, a nitro group (—NO.sub.2), a halogen atom, a cyano group (—CN), a group of formula (II) or (III), or both G.sup.1 and G.sup.2 taken together to form a group of formula (IV). ##STR00001##

The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)-butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.

Disclosed herein are non-natural amino acids and dolastatin analogs that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The dolastatin analogs can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid dolastatin analogs and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology use.

Disclosed herein are non-natural amino acids and dolastatin analogs that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The dolastatin analogs can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid dolastatin analogs and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology use.

The present invention is directed to a process for preparing a compound of formula I-11 through multiple-step reactions: ##STR00001##

The present invention is directed to a process for preparing a compound of formula I-11 through multiple-step reactions: ##STR00001##

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.