Abstract: This invention relates to novel derivatives of camptothecin, and will, particularly to derivatives having a substitution at the C-7 position, or at one of the C-9, C-10, C-11 or C-12 positions, or to disubstituted derivatives having a first substitution at C-7 and a second at one of C-9, C-10, C-11 or C-12. The invention also includes methods of using the compounds as Topoisomerase I inhibitors to treat patients with cancer. The invention also includes pharmaceutical formulations which consist of the novel compounds in solution or suspension with one or more pharmaceutical excipients or dilutes.

Abstract: This invention relates to novel compositions of matter which either terminate in a sulfhydryl moiety or are disulfides. The compounds also include a terminal sulfonate or phosphonate moiety, and have many uses, such as toxicity reducing agents when administered with many antineoplastic agents.

Abstract: Derivatives of Camptothecin are disclosed, particularly derivatives having multiple substitutions at the `A`, `B` and `E` rings thereof. The novel compounds are useful in treating a wide variety of susceptible tumors and are potent inhibitors of Topoisomerase I.

Abstract: To reduce the toxic effect of carboplatin, particularly myelosuppression and emesis, a dithioether having the formula R.sub.1 -(CH.sub.2).sub.n --S--S--(CH.sub.2).sub.m --R.sub.2 (I) wherein:each of R.sub.1 and R.sub.2 individually is SO.sub.3 H or PO.sub.3 H.sub.2 ; andeach of m and n is individually 1, 2, 3 or 4;or a pharmaceutically acceptable salt thereof, preferably disodium 2,2'-dithiobis(ethane sulfonate) (dimesna), is administered in combination with carboplatin to a patient, at substantially the same time or sequentially, whereby the dithioether and the carboplatin become co-present in the blood of the patient. Compositions comprising carboplatin and the dithioether are included in the invention.

Abstract: Novel compounds, formulations and methods of treating patients with cancer are provided for in this invention. The compounds are derivatives of camptothecin, and specifically relate to compounds having novel substitutions at the C-7 position of the camptothecin scaffold B-ring. The formula I compounds are highly lipophilic, lactone stable, do not require metabolic activation, and are potent antineoplastic compounds.

Abstract: A- and/or B-ring substituted camptothecin derivatives, which are poorly water soluble (less than 5 micrograms per milliliter of water), are highly lipophilic camptothecin derivatives (HLCD) and are very active against a variety of human cancers. Because of their very poor water solubility, HLCD have not been used to treat human patients with cancer due to the inability to administer sufficient quantities of the HLCD dissolved in a pharmaceutical formulation. This invention overcomes these limitations by teaching novel pharmaceutically acceptable HLCD formulations for the direct administration of HLCD to human patients with cancer. The claimed invention also describes the methods to create solutions of HLCD and antitumor compositions of HLCD to allow the administration of HLCD in sufficient amounts to treat human patients with various types of cancer.

Abstract: A- and/or B-ring substituted camptothecin derivatives, which are poorly water soluble (less than 5 micrograms per milliliter of water), are highly lipophilic camptothecin derivatives (HLCD) and are very active against a variety of human cancers. Because of their very poor water solubility, HLCD have not been used to treat human patients with cancer due to the inability to administer sufficient quantities of the HLCD dissolved in a pharmaceutical formulation. This invention overcomes these limitations by teaching novel pharmaceutically acceptable HLCD formulations for the direct administration of HLCD to human patients with cancer. The claimed invention also describes the methods to create solutions of HLCD and antitumor compositions of HLCD to allow the administration of HLCD in sufficient amounts to treat human patients with various types of cancer.

Abstract: Pharmaceutical formulations of highly lipophilic, poorly water soluble derivatives of Camptothecin are disclosed. The formulations include an effective amount of the HLCD dissolved or suspended in an appropriate amount of N-methyl-2-pyrrolidinone (NMP), and one or more pharmaceutically acceptable excipients.

Abstract: A process for synthesizing disulfides and sulfhydryl compounds which are useful pharmaceuticals. The process includes a two step, single pot process for preparing disulfides from an alkenyl sulfonate salt. The disulfides are useful as toxicity mitigating agents of chemotherapeutic drugs, such as certain platinum complexes, and as use therapeutic drugs for a variety of conditions in mammals.The two step process involves first the conversion of the starting reagent to a mercaptane sulfonate, then an oxidation to the desired disulfide.

Abstract: Novel compounds, formulations and methods of treating patients with cancer are provided for in this invention. The compounds are derivatives of camptothecin, and specifically relate to compounds having novel substitutions at the C-7 position of the camptothecin scaffold B-ring. The formula I compounds are highly lipophilic, lactone stable, do not require metabolic activation, and are potent antineoplastic compounds.

Abstract: This invention describes novel formulations containing a water soluble disulfide, 2,2'-dithio-bis-ethane sulfonate, with or without cis-diammine dichloro platinum present in the same formulation, wherein the parenteral or oral administration of 2,2'-dithio-bis-ethane sulfonate is used to reduce the risk or prevent or retard the development of cisplatin induced nephrotoxicity, myelosuppression, and neurotoxicity, and wherein the parenteral or oral administration of 2,2'-dithio-bis-ethane sulfonate potentiates the antitumor activity of cisplatin when treating human patients with cancer. This invention also teaches novel formulations containing 2,2'-dithio-bis-ethane sulfonate alone or in combination with cisplatin in lyophilized or dissolved in an aqueous formulations which can be administered to patients with cancer who are being treated with cisplatin.

Abstract: A- and/or B-ring substituted camptothecin derivatives, which are poorly water soluble (less than 5 micrograms per milliliter of water), are highly lipophilic camptothecin derivatives (HLCD) and are very active against a variety of human cancers. Because of their very poor water solubility, HLCD have not been used to treat human patients with cancer due to the inability to administer sufficient quantities of the HLCD dissolved in a pharmaceutical formulation. This invention overcomes these limitations by teaching novel pharmaceutically acceptable HLCD formulations for the direct administration of HLCD to human patients with cancer. The claimed invention also describes the methods to create solutions of HLCD and antitumor compositions of HLCD to allow the administration of HLCD in sufficient amounts to treat human patients with various types of cancer.

Abstract: Pharmaceutical formulations of Highly Lipophilic Camptothecin Derivatives (HLCD) include HLCD dissolved in N-methyl Pyrrolidinene (NMP). The formulations also include quantities of pharmaceutically acceptable excipients and diluents incorporated thereinto.

Abstract: This invention describes novel formulations containing a water soluble disulfide, 2,2'-dithio-bis-ethane sulfonate, with or without cis-diammine dichloro platinum present in the same formulation, wherein the parenteral or oral administration of 2,2'-dithio-bis-ethane sulfonate is used to reduce the risk or prevent or retard the development of cisplatin induced nephrotoxicity, myelosuppression, and neurotoxicity, and wherein the parenteral or oral administration of 2,2'-dithio-bis-ethane sulfonate potentiates the antitumor activity of cisplatin when treating human patients with cancer. This invention also teaches novel formulations containing 2,2'-dithio-bis-ethane sulfonate alone or in combination with cisplatin in lyophilized or dissolved in an aqueous formulations which can be administered to patients with cancer who are being treated with cisplatin.

Abstract: This invention describes novel formulations containing a water soluble disulfide, 2,2'-dithio-bis-ethane sulfonate, with or without cis-diammine dichloro platinum present in the same formulation, wherein the parenteral or oral administration of 2,2'-dithio-bis-ethane sulfonate is used to reduce the risk or prevent or retard the development of cisplatin induced nephrotoxicity, myelosuppression, and neurotoxicity, and wherein the parenteral or oral administration of 2,2'-dithio-bis-ethane sulfonate potentiates the antitumor activity of cisplatin when treating human patients with cancer. This invention also teaches novel formulations containing 2,2'-dithio-bis-ethane sulfonate alone or in combination with cisplatin in lyophilized or dissolved in an aqueous formulations which can be administered to patients with cancer who are being treated with cisplatin.

Abstract: This invention describes novel formulations containing a water soluble disulfide, 2,2'-dithio-bis-ethane sulfonate, with or without cis-diammine dichloro platinum present in the same formulation, wherein the parenteral or oral administration of 2,2'-dithio-bis-ethane sulfonate is used to reduce the risk or prevent or retard the development of cisplatin induced nephrotoxicity, myelosuppression, and neurotoxicity, and wherein the parenteral or oral administration of 2,2'-dithio-bis-ethane sulfonate potentiates the antitumor activity of cisplatin when treating human patients with cancer. This invention also teaches novel formulations containing 2,2'-dithio-bis-ethane sulfonate alone or in combination with cisplatin in lyophilized or dissolved in an aqueous formulations which can be administered to patients with cancer who are being treated with cisplatin.

Abstract: A- and/or B-ring substituted camptothecin derivatives, which are poorly water soluble (less than 5 micrograms per milliliter of water), are highly lipophilic camptothecin derivatives (HLCD) and are very active against a variety of human cancers. Because of their very poor water solubility, HLCD have not been used to treat human patients with cancer due to the inability to administer sufficient quantities of the HLCD dissolved in a pharmaceutical formulation. This invention overcomes these limitations by teaching novel pharmaceutically acceptable HLCD formulations for the direct administration of HLCD to human patients with cancer. The claimed invention also describes the methods to create solutions of HLCD and antitumor compositions of HLCD to allow the administration of HLCD in sufficient amounts to treat human patients with various types of cancer.

Abstract: A- and/or B-ring substituted camptothecin derivatives, which are poorly water soluble (less than 5 micrograms per milliliter of water), are highly lipophilic camptothecin derivatives (HLCD) and are very active against a variety of human cancers. Because of their very poor water solubility, HLCD have not been used to treat human patients with cancer due to the inability to administer sufficient quantities of the HLCD dissolved in a pharmaceutical formulation. This invention overcomes these limitations by teaching novel pharmaceutically acceptable HLCD formulations for the direct administration of HLCD to human patients with cancer. The claimed invention also describes the methods to create solutions of HLCD and antitumor compositions of HLCD to allow the administration of HLCD in sufficient amounts to treat human patients with various types of cancer.

Abstract: A process for synthesizing disulfides and sulfhydryl compounds which are useful pharmaceuticals. The process includes a two step, single pot process for preparing disulfides from an alkenyl sulfonate salt. The disulfides are useful as toxicity mitigating agents of chemotherapeutic drugs, such as certain platinum complexes, and as use therapeutic drugs for a variety of conditions in mammals.The two step process involves first the conversion of the starting reagent to a mercaptane sulfonate, then an oxidation to the desired disulfide.

Abstract: This invention describes a novel formulation containing both cis-diammine dichloro platinum and a water soluble disulfide, 2,2'-dithio-bis-ethane sulfonate in the same solution, wherein the presence of the disulfide and the parenteral administration of the formulation reduces the risk of cisplatin induced nephrotoxicity when treating human patients with cancer.