5'-ESTERS D'ARA-CYTIDINE ET LEUR PREPARATION

1,263,408. ara-Cytidine derivatives. UPJOHN CO. 21 April, 1970 [27 May, 1969; 16 Feb., 1970], No. 18999/70. Headings C2C and C2P. A process for preparing S1-O- esters of aracytidine or acid addition salts thereof by reacting ara-cytidine (1) or S1-trityl-ara-cytidine (2) with #,#,#-trihaloethoxycarbonyl halide, wherein halo is Cl or Br and halide is Cl, Br or I, to form the corresponding N4-trihaloethoxycarbonyl-ara-cytidines and in the case of the compounds formed from (2) removing the S1- trityl group, then reacting the thus protected compounds with acylating agents to form 51 O- esters, removing the #,#,#-trihaloethoxycarbonyl group, and optionally forming acid addition salts and novel compounds obtained by said process. Alternatively the S1-esters of aracytidine may be obtained by reacting acid chlorides or acid anhydrides with a protonated form of said ara-cytidine in an inert solvent. The novel compounds have the formula wherein R 1 is a radical selected from a C 1-20 aliphatic, C 6-10 aromatic, C 4-10 monocyclic aliphatic, C 7-12 araliphatic, C 4-10 monocyclic heterocyclic or where R 1 CO is an acyl radical of a C 3-8 aliphatic dicarboxylic acid, a radical of the formula A(N)CO-, wherein A and B each are H, C 1-10 aliphatic, C 4-10 monocyclic aliphatic or C 6-10 aromatic or A and B together can make up an aliphatic chain of from 3 to 6 carbon atoms; MSCO-, wherein M is C 1-10 aliphatic, C 4-10 monocyclic aliphatic, C 6-10 aromatic or C 7-12 aralkyl; M 1 S-CS- wherein M 1 is C 1-20 aliphatic, C 6-10 aromatic, or C 7-12 araliphatic; wherein A 1 and B 1 each are H 1 C 1-7 alkyl, C 6-10 aromatic; R 2 SO 2 -, wherein R 2 is C 1-7 alkyl, C 6-10 aromatic, or substituted C 6-12 aromatic; R 3 O-SO 2 -, wherein R 3 is H, C 1-20 aliphatic, C 6-10 aromatic, or C 7-12 araliphatic; wherein R 4 and R 5 each are H, C 1-7 alkyl or C 1-7 haloalkyl; R 6 OCO-, wherein R 6 is C 1-20 aliphatic, C 6-10 aromatic, or C 7-12 araliphatic; where A 2 and B 2 each are H or C 1-7 alkyl; or and acid addition salts thereof. Pharmaceutical compositions, suitable for oral or parenteral administration, contain the above novel compounds or acid addition salts thereof and acceptable carriers. The compounds may be used for controlling growth of certain kinds of cancer, especially leukaemia.