Paul D Schwartz

US Patent:

42062080, Jun 3, 1980

Filed:

Dec 22, 1978

Appl. No.:

5/972354

Inventors:

Glen R. Gale - Charleston SC
Paul Schwartz - Charleston SC

Assignee:

The United States of America as represented by the Department of Health,
Education and Welfare - Washington DC

International Classification:

A61K 31675
A61K 31505
A61K 3128

US Classification:

424200

Abstract:

##STR1## 4-Carboxyphthalato(1,2-diaminocyclohexane)platinum(II) (and alkali metal salts thereof) has shown antileukemic activity in mice against murine leukemia L1210. It is effective in dosages of 5-60 mg/kg of body weight and is potentiated in a treatment with cyclophosphamide (CY) (50 mg/kg of body weight) to which may be added 5-fluorouracil (5-FU) (75 mg/kg of body weight) or hydroxyurea (HU) (1000 mg/kg of body weight). Some previous platinum chelate compounds show dosage limitation due to renal impairment but the free carboxyl of the present Pt compound offers a possible route of oral administration and absorption by the stomach. The Pt compound may be prepared by reacting the known dichloro(1,2-diaminocyclohexane)platinum(II) (NSC 194814) with silver nitrate to replace chloro with nitro. Subsequently, benzene tricarboxylic acid is added to form an off-white precipitate (2 hrs, dark, 5. degree. C. ) of the desired product which is preferably utilized as the alkali metal salt.

US Patent:

41372484, Jan 30, 1979

Filed:

Aug 29, 1977

Appl. No.:

5/828926

Inventors:

Glen R. Gale - Charleston SC
Paul Schwartz - Charleston SC

Assignee:

The United States of America as represented by the Department of Health,
Education and Welfare - Washington DC

International Classification:

C07F 1500

US Classification:

260429R

Abstract:

##STR1## 4-Carboxyphthalato (1,2-diaminocyclohexane)platinum(II) (and alkali metal salts thereof) has shown antileukemic activity in mice against murine leukemia L1210. It is effective in dosages of 5-60 mg/kg of body weight and is potentiated in a treatment with cyclophosphamide (CY) (50 mg/kg of body weight) to which may be added 5-fluorouracil (5-FU) (75 mg/kg of body weight) or hydroxyurea (HU) (1000 mg/kg of body weight). Some previous platinum chelate compounds show dosage limitation due to renal impairment but the free carboxyl of the present Pt compound offers a possible route of oral administration and absorption by the stomach. The Pt compound may be prepared by reacting the known dichloro(1,2-diaminocyclohexane)platinum(II) (NSC 194814) with silver nitrate to replace chloro with nitro. Subsequently, benzene tricarboxylic acid is added to form an off-white precipitate (2 hrs, dark, 5. degree. C) of the desired product which is preferably utilized as the alkali metal salt.

US Patent:

42062071, Jun 3, 1980

Filed:

Dec 22, 1978

Appl. No.:

5/972338

Inventors:

Glen R. Gale - Charleston SC
Paul Schwartz - Charleston SC

Assignee:

The United States of America as represented by the Department of Health,
Education and Welfare - Washington DC

International Classification:

A61K 31675
A61K 3128

US Classification:

424200

Abstract:

##STR1## 4-Carboxyphthalato(1,2-diaminocyclohexane)platinum(II) (and alkali metal salts thereof) has shown antileukemic activity in mice against murine leukemia L1210. It is effective in dosages of 5-60 mg/kg of body weight and is potentiated in a treatment with cyclophosphamide (CY) (50 mg/kg of body weight) to which may be added 5-fluorouracil (5-FU) (75 mg/kg of body weight) or hydroxyurea (HU) (1000 mg/kg of body weight). Some previous platinum chelate compounds show dosage limitation due to renal impairment but the free carboxyl of the present Pt compound offers a possible route of oral administration and absorption by the stomach. The Pt compound may be prepared by reacting the known dichloro(1,2-diaminocyclohexane)platinum(II) (NSC 194814) with silver nitrate to replace chloro with nitro. Subsequently, benzene tricarboxylic acid is added to form an off-white precipitate (2 hrs, dark, 5. degree. C. ) of the desired product which is preferably utilized as the alkali metal salt.

US Patent:

42062268, Jun 3, 1980

Filed:

Jul 19, 1978

Appl. No.:

5/926035

Inventors:

Glen R. Gale - Charleston SC
Paul Schwartz - Charleston SC

Assignee:

The United States of America as represented by the Department of Health,
Education and Welfare - Washington DC

International Classification:

A61K 3128

US Classification:

424287

Abstract:

##STR1## Y=H, alk met 4-Carboxyphthalato(1,2-diaminocyclohexane) platinum(II) (and alkali metal salts thereof) has shown antileukemic activity in mice against murine leukemia L1210. It is effective in dosages of 5-60 mg/kg of body weight and is potentiated in a treatment with cyclophosphamide (CY) (50 mg/kg of body weight) to which may be added 5-fluorouracil (5-FU) (75 mg/kg of body weight) or hydroxyurea (HU) (1000 mg/kg of body weight). Some previous platinum chelate compounds show dosage limitation due to renal impairment but the free carboxyl of the present Pt compound offers a possible route of oral administration and absorption by the stomach. The Pt compound may be prepared by reacting the known dichloro(1,2-diaminocyclohexane) platinum(II) (NSC 194814) with silver nitrate to replace chloro with nitro. Subsequently, benzene tricarboxylic acid is added to form an off-white precipitate (2 hrs, dark, 5. degree. C. ) of the desired product which is preferably utilized as the alkali metal salt.

US Patent:

42028906, May 13, 1980

Filed:

Dec 22, 1978

Appl. No.:

5/972336

Inventors:

Glen R. Gale - Charleston SC
Paul Schwartz - Charleston SC

Assignee:

The United States of America as represented by the Department of Health,
Education and Welfare - Washington DC

International Classification:

A61K 31675
A61K 3128
A61K 3117

US Classification:

424200

Abstract:

##STR1## 4-Carboxyphthalato(1,2-diaminocyclohexane)platinum(II) (and alkali metal salts thereof) has shown antileukemic activity in mice against murine leukemia L1210. It is effective in dosages of 5-60 mg/kg of body weight and is potentiated in a treatment with cyclophosphamide (CY) (50 mg/kg of body weight) to which may be added 5-fluorouracil (5-FU) (75 mg/kg of body weight) or hydroxyurea (HU) (1000 mg/kg of body weight). Some previous platinum chelate compounds show dosage limitation due to renal impairment but the free carboxyl of the present Pt compound offers a possible route of oral administration and absorption by the stomach. The Pt compound may be prepared by reacting the known dichloro(1,2-diaminocyclohexane)platinum(II) (NSC 194814) with silver nitrate to replace chloro with nitro. Subsequently, benzene tricarboxylic acid is added to form an off-white precipitate (2 hrs, dark, 5. degree. C. ) of the desired product which is preferably utilized as the alkali metal salt.