Studies of cross-resistance, synergistic combinations and blocking of activity of platinum derivatives

Burchenal, Joseph H.; Kalaher, Kathleen; Dew, Kimberly; Lokys, L.; Gale, Glen R.

doi:10.1016/s0300-9084(78)80582-3

Cited by 164 publications

(79 citation statements)

References 4 publications

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“…Some analogues of cisplatin are undoubtedly active against cisplatin-resistant tumours in experimental systems and it would appear that it is those derivatives possessing either a 1,2-diaminocycloheptane or a 1,2-diaminecyclohexane group that exhibit this property (Burchenal et al, 1979). One compound in the latter group, 4-carboxyphthalato (1,2-diaminocyclohexane) platinum (II), has now entered clinical trial and there has been one partial response out of eight patients with ovarian cancer, all of whom had previously received cisplatin (Kelsen et al, 1983).…”

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confidence: 99%

Cisplatin/carboplatin cross-resistance in ovarian cancer

Gore

Fryatt²,

Wiltshaw³

et al. 1989

Br J Cancer

107

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confidence: 99%

Cisplatin/carboplatin cross-resistance in ovarian cancer

Gore

Fryatt²,

Wiltshaw³

et al. 1989

Br J Cancer

107

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“…Preparative HPLC was performed on a Waters Associates Prep LC/System 500 liquid chromatograph using Prep PAK-500/silica cartridge (5.7 X 30 cm) containing 325 g of silica gel. (6) A suspension of trans-2-cyclohexene-1,4-diol 5 (1 14 mg, 1 mmol) and dihydropyran (0.56 mL, 6 mmol) in dry CH2Cl2 (5 mL) containing a catalytic quantity of pyridiniurn p-toluenesulfonate (PPTS) was stirred for 7 h at room temperature. The reaction mixture was diluted with 20 mL ether, then washed with half-saturated brine (2 X 5 mL), dried with Na2S04, and evaporated to give a colorless syrup, which was applied to a silica gel column.…”

Section: Methodsmentioning

confidence: 99%

“…Elution with EtOAc-hexane (1 : 2) gave 22 (1.35 g, 58%) as a mixture of the THP isomers, which was used for the next reaction without further purification: IR (film): 2105 (N,), 1800, 1775, 1720 (C=O) cms-'; 'H NMR (300 MHz, CDC1,) 6: 0.85-2.05 (m, 16H), lH),2H),lH),2H),lH),lH),2H),2H,ArH),2H,ArH) ,: C 55.62, H 4.67, N 18.54;found: C 55.68, H 5.08, N 18.27. For 24: mp 161-163°C;IR (film): 3480 (OH), 3410 (OH), 2260, 2105, 1780, 1720 (C=O) cm-l; 'H NMR (300 MHz, CD30D) 2H,6), 2H,6),3.55 (ddd,lH,J = 4.3 Hz,9.3 Hz,10.8 Hz,3.80 (dd,lH,J = 10.1 Hz,11.3 Hz,4.02 (dd,lH,J = 9.3 Hz,11.3 Hz,4.31 (dt,lH,J = 4.2 Hz,10.4 Hz,4H,ArH); ',c NMR (75 MHz,CD,OD) 6: 3 1.33,3 1.48,59.73,66.83,68.80,74.16,124.09,124.39,135.53,135.62,169.74,170.13 H 5.49, N 16.96; found: C 57.99, H 5.19, N 16.86<...>…”

Section: (Dl)-(ia2a3/34/3)-2-atnino-3-azidocyclohexa11e-l4-diol(13)mentioning

confidence: 99%

“…Since the molecule is chiral, the relevance of stereochemical issues has been addressed by a number of investigators (4). In spite of conflicting views (5), the consensus is that the (R,R) isomer is generally more active than the (S,S) isomer (6), although activity has also been demonstrated with the (R,S) isomer (7). With regard to the stereochemistry of the complexes, the trans isomer is more active than the cis isomer (8).…”

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confidence: 99%

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Hydrophilic analogs of (R,R)-diaminocyclohexane dichloroplatinum (DACH) and the influence of relative stereochemistry on antitumor activity

Hanessian¹,

Wang²

1993

Can. J. Chem.

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A series of analogs of (R, R)-1,2-diaminocyclohexane dichloroplatinum(I1) (DACH) containing stereochemically defined hydroxy groups and appropriate acidic leaving groups were synthesized and tested as antitumor agents. The (la,2~,3a,4~)-1,4-dihydroxy-2,3-diaminocyclohexane analog showed the highest potency against P388 leukemia in mice. The results indicate that increasing the hydrophilicity of the platinum complex to a certain extent could improve the antitumor activity of the drug. It is also likely that the stereochemical disposition of the substituents on the cyclohexane ring affects the antitumor activity. STEPHEN HANESSIAN et JIANGUO WANG. Can. J. Chem. 71, 2102. Des analogues du (R,R)-1,2-diaminocyclohexane dichloroplatine(I1) (DACH) qui contiennent des groupes hydroxy et des groupes partant acides ont Ct C synthCtisCs en vue d'obtenir des substances antitumorales. L'analogue (la,2P,3a,4P)-1,4-dihydroxy-2,3-diaminocyclohexane s'est avCrC &tre le plus actif contre la IeucCmie P388 chez la souris. Les rCsultats indiquent que l'augmentation de I'hydrophilicitC de ces complexes pourrait aider B I'amClioration de I'activitC antitumorale. I1 est aussi possible que I'activitC puisse dependre sur la stCrCochimie des substituants sur le noyau cyclohexanique.[Traduit par la redaction]In spite of the multitude of structural analogs of the antitumor agent cis-diamine dichloroplatinum(II) (cisplatin) (1) only a few are presently used in clinical practice (2). Of these, trans-1,2-diaminocyclohexane dichloroplatinum(1l) (DACH) and its variants with different anionic counterparts appear to be the most effective (3) (Fig. 1). Since the molecule is chiral, the relevance of stereochemical issues has been addressed by a number of investigators (4). In spite of conflicting views (5), the consensus is that the (R,R) isomer is generally more active than the (S,S) isomer (6), although activity has also been demonstrated with the (R,S) isomer (7). With regard to the stereochemistry of the complexes, the trans isomer is more active than the cis isomer (8). As in the case of the parent cisplatin, the antitumor activity of DACH is accompanied by some toxicity. The emergence of resistance, and low water solubility that can affect the pharmacokinetics, are additional features that must be improved in the quest for a more effective analog. An obvious choice for platinum I1 complexes that can increase water solubility in this series is the introduction of hydrophilic groups such as the hydroxyl group into the molecule. Witiak and co-workers (9) as well as oiher groups (10) have reported on the synthesis and antitumor activity of a series of 4-mono-and 4,5-dihydroxy 1,2-diaminocyclohexane dichloroplatinum derivatives. Although these derivatives are sparingly soluble in water, the monohydroxy analogs are more active than the dihydroxy analogs. This enhanced potency was attributed to subtle differenies in crystalline structure, thus affecting drug dissolution and bio-availability (9).As part of a program aimed at the discovery of novel cis...

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“…One series of complexes, which shows promise, is based on the [(1,2-diaminocyclohexane)platinum(II)] 2÷ moiety and a number of complexes have been tested (Gale, Walker, Atkins, Smith & Meischen, 1974;Gale, Atkins, Meischen, Smith & Walker, 1976Gale, Atkins, Meischen & Schwartz, 1978;Gale, Smith & Schwartz, 1979;Ogawa, Gale, Meischen & Cooke, 1976;Ward, Young, Fauvie, Wolpert, Davis & Guarino, 1976;Ridgway, Speer, Hall, Stewart, Newman & Hill, 1977;Schwartz, Meischen, Gale, Atkins, Smith & Walker, 1977; 0567-7408/81/010045-05501.00 Ridgway, Stewart, Hall, Zapata & Hill, 1977;Hill et al, 1977;Burchenal, Kalaher, O'Toole & Chisholm, 1977;Burchenal, Kalaher, O'Toole & Chisholm, 1977;Burchenal, Kalaher, Dew, Lokys & Gale, 1978). In the early work it was not realized apparently that 1,2-diaminocyclohexane (dac) can exist as cis, RR, and SS isomers.…”

Section: Introductionmentioning

confidence: 99%