This invention relates to butyrate prodrugs derived from lactic acid and pharmaceutical compositions and methods employing them, either alone or in combination with other agents, for increasing gamma globin and fetal hemoglobin in a patient. These compounds, compositions and methods are particularly effective in treating .beta.-hemoglobinopathies, including sickle cell syndromes and .beta.-thalassemia syndromes. This invention relates to the use of these prodrugs, alone or in combination with other agents, to stimulate cell differentiation which prevents proliferation of malignant cells. These methods are particularly useful in treating cancer, especially malignant hematological disorders. In addition, this invention relates to the use of these prodrugs in treating inflammatory bowel diseases.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of co-pending U.S. application Ser. No. 08/640,260, filed Apr. 30, 1996, which is a continuation-in-part of co-pending U.S. application Ser. No. 08/540,345, filed Oct. 6, 1995.
This invention relates to the use of butyrate prodrugs derived from lactic acid for treating inflammatory bowel disease. The invention also relates to the use of those prodrugs for the treatment of a chemotherapy-induced mucocutaneous side effect in a patient. The invention further relates to the use of butyrate prodrugs for treating lung, colo-rectal or prostate cancer. And the invention also relates to the use of butyrate prodrugs to treat cystic fibrosis and to enhance the efficiency of gene therapy.
Amidomethyl esters, carbonylmercaptomethyl esters, keto-containing esters, amidomethyl thioesters, amidomethyl amides, and methylene dithioesters are disclosed. The novel compounds have two carbonyl groups connected by a linking moiety having an oxygen, sulfur or nitrogen attached to a methylene group, to which is further attached a sulfur, nitrogen or CH.sub.2 group. Methods of treating illnesses and conditions, such as cancer, hemological disorders, inherited metabolic disorders and others, using these compounds are also disclosed.
Amidomethyl esters, carbonylmercaptomethyl esters, keto-containing esters, amidomethyl thioesters, amidomethyl amides, and methylene dithioesters are disclosed. The novel compounds have two carbonyl groups connected by a linking moiety having an oxygen, sulfur or nitrogen attached to a methylene group, to which is further attached a sulfur, nitrogen or CH.sub.2 group. Methods of treating illnesses and conditions, such as cancer, hemological disorders, inherited metabolic disorders and others, using these compounds are also disclosed.
