[4,5]-fused-3,6-disubstituted-pyridazines with sulfur-containing substituents in position three for the treatment of neoplasia

A method of treating a patient having neoplasia comprising administering a pharmacologically effective amount of a compound of Formula I to the patient with a neoplasia sensitive to such a compound:

• wherein
• Y1 and Y2 are independently selected from the group consisting of (CH2)n, —C(X)—NH—, —(CH2)n—C(X)—O—, and X is O or S;
• R1 is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, hydrogen and substituted or unsubstituted phenyl, pyridinyl, pyrrolyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolidinyl, piperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, morpholinyl, naphthyl, tetrazolyl, triazinyl, furfuryl and thiophenyl, wherein said substituents are one to three independently selected from the group consisting of halogen, lower alkyl, lower alkoxy, amino, lower alkylamino, di-lower alkylamino, hydroxy, nitro, cyano, carboxyl, lower alkyl mercapto, and lower alkyl sulfonyl;
• R2 is selected from the group consisting of substituted or unsubstituted phenyl, benzyl, pyridinyl, pyrrolyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolidinyl, piperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, tetrazolyl, morpholinyl, triazinyl, furfuryl and thiophenyl, wherein said substituents are one to three independently selected from the group consisting of halogen, lower alkyl, lower alkoxy, amino, lower alkylamino, di-lower alkylamino, hydroxy, nitro, cyano, carboxyl, aminosulfonyl, lower alkyl mercapto, and lower alkyl;
• “A” is a pyridine ring fused with the pyridazine ring;
• R3 is independently selected in each instance form the group consisting of halogen, lower alkyl, lower alkoxy, amino, lower alkylamino, di-lower alkylamino, hydroxy, nitro, cyano, carboxyl, lower alkyl mercapto, and lower alkyl sulfonyl;
• m is an integer from 0 to 4;
• n is an integer from 0 to 3;
• p is 0 or 1;
• x is an integer from 0 to 2;
• and
• pharmaceutically acceptable salts thereof.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of the formula:

• wherein
• Y1 and Y2 are independently selected from the group consisting of (CH2)n, —C(X)—NH—, —(CH2)n—C(X)—O—, and X is O or S;
• R1 is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, hydrogen and substituted or unsubstituted phenyl, pyridinyl, pyrrolyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolidinyl, piperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, morpholinyl, naphthyl, tetrazolyl, triazinyl, furfuryl and thiophenyl, wherein said substituents are one to three independently selected from the group consisting of halogen, lower alkyl, lower alkoxy, amino, lower alkylamnino, di-lower alkyl amino, hydroxy, nitro, cyano, carboxyl, lower alkyl mercapto, and lower alkyl sulfonyl;
• R2 is selected from the group consisting of substituted or unsubstituted phenyl, benzyl, pyrrolyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolidinyl, piperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, tetrazolyl, morpholinyl, triazinyl, furfuryl and thiophenyl, wherein said substituents are one to three independently selected from the group consisting of halogen, lower alkyl, lower alkoxy, amino, lower alkylamino, di-lower alkylamino, hydroxy, nitro, cyano, carboxyl, aminosulfonyl, lower alkyl mercapto, and lower alkyl;
• “A” is a pyridine ring fused with the pyridazine ring;
• R3 is independently selected in each instance form the group consisting of halogen, lower alkyl, lower alkoxy, amino, lower alkylamnino, di-lower alkylamino, hydroxy, nitro, cyano, carboxyl, lower alkyl mercapto, and lower alkyl sulfonyl;
• m is an integer from 0 to 4;
• n is an integer from 0 to 3
• p is 0 or 1;
• x is an integer from 0 to 2;
• and
• pharmaceutically acceptable salts thereof.