5-OXYGENATED-2,4,6-TRIAMINOPYRIMIDINES

Abstract: The present invention discloses 5-oxygenated amino substituted pyrimidines (X), where R1 is (1) steroid substituent of formula (Steroid), (2) trolox substituent of formula (trolox), (3) an alkyl substituent selected from the group consisting of (A)Q2-(CH2)n2. Also disclosed are the oxygenated N,N-disubstituted pyrimidines (XIII) all of which are useful for treating a number of conditions including head injury, stroke, spinal cord injury, etc. Useful intermediates including the protected 5-oxygenated pyrimidines (VII) and the 5-oxygenated pyrimidines (VIII) are also disclosed. Further disclosed are 5-hydroxy amino substituted pyrimidines (XI).

Description: 5-OXYGENATED-2.4.6-TRIAMINOPYRIMIDINES BACKGROUND OF THE INVENTION 1. Field of the Invention The 5-oxygenated-2,4,6-triaminopyrimidines are inhibitors of lipid peroxidation arid therefore are useful pharmaceutical agents. 2. Description of the Related Art Non-oxygenated compounds similar to the oxygenated pyrimidine substituted piperazine compounds of formula (X) of the present invention are known. When R λ is a steroid, see International Publication No. WO 87/01706, published March 26, 1987 based on International Publication No. PCT/US86/01797. When Rj is trolox (vitamin E), see International Publication No. WO 88/08424, published November 3, 1988 based on International Publication No. PCT/US88/0I212, in particular, see the compounds of formula (III). When j is alkyl, see International Publication No. WO 88/-08424, published November 3, 1988 based on International Publication No. PCT/US88/01212, in particular, see the compounds of formula (II) and see US Patent application Serial No. 07/427,143. 5-Hydroxypyrimidines are known, see J. Chem. Soc., 2033 (1956) and Synthesis 443 (1975). Non-oxygenated N,N-disubstituted pyrimidines corresponding to the oxygenated N,N-disubstituted pyrimidines (XIII) of the present invention are known, see US Patent application Serial No. 07/427,143. SUMMARY OF INVENTION Disclosed are the 5-oxygenated amino substituted pyrimidines of formula (X) where R γ is (1) steroid substituent (steroid) where (A-I) Q 6 is c--Q 6-1 : β -Q 6 . 2 , Q ]0 is anc * Q7 is α-H: β -H, where one of Qe., and Qe- 2 is _ H» and tne other is -H, -F, or C,-C 3 alkyl, Q ιr 2 is -CH 3 , Q 10 ., and Q 5 taken together are -(CH 2 ) 2 -C(=Q 3 . 3 )-CH= or -CH =CH-CO-CH= , where Q 3 . 3 is =O or -H:β-OQ M or α-OQ w :β-H, where Q 3 _, is -H, -CO-CH 3 , -CO-C 2 H 5 , -CO-C 6 H 5 , -CO-O- CH 3 or -CO-0-C 2 H 5 ; (A-II) Qs is Q 10 is α-Q 10 , 3 : β -Qιr an d Q 7 is α;-H:β-H, where one of Q 6 . 3 and Q 6^ , is -H, and the other taken together with one of Q 5 _ 3 and Q^ forms a second bond between C 5 and C 6 , Q 10 - 4 is -CH 3 , Q ι o. 3 and the other of Qs. 3 and Q^ taken together is -(CH 2 ) 2 -C(H)(OH)-CH 2 -; <A-πi) Qio and O taken together are where Qj is -H, C r C 3 alkyl, -CO-H, C 2 -C 4 alkanoyl or benzyl, Q 6 is -Q^.R-Q^ where one of Q^ s and Q M is -H, and the other is -H, -F, or C r C 3 alkyl and Q, is α-H:β-H; (A-IV) Qj is α-Q^β-Q^, Q 6 is a-Q^iϋ-Q M , Q 7 is α-H:β-H and Q 10 is α-Q 10-7 : β-Qιo- 8 . where one of Oj., and Q 5 . g is -H, Qιo. and the other of Q 5-7 and Q 5 . g taken together are -(CH^-C^Q^-CH^ where Oj^ is as defined above, Qιo. 8 is -CH 3 , where one of Qe.- ? and is -H and the other is -H, -F, or C C 3 alkyl; (A-V) Q 6 is Q 7 is QM'-QI-IO, Qio is where one of Q M and Qe-io is -H and the other taken together with one of Qj_ 9 and Q O forms a second bond between C 6 and C 7 , and the other of Qη. 9 and Q 7 . 10 is -H, Q ]0- ιo is -CH 3 , Q 10 . 9 and Q 5 taken together are -(CH 2 ) 2 -C(=Q 3 . 3 )-CH= or -CH=CH-CO-CH = , where Q 3 . 3 is as defined above; (C-I) Q n is α-Qι 1 . 1 :β-Qι ι . 2 , where one of Q u-1 and Q u-2 is taken together with Q 9 to form a second bond between G, and C u and the other of Q π-1 and Q u . 2 is -H; (C-II) Q 9 is -Cl and Q„ is =O or α-H:β-Q lw where Q 1W is -Cl or -OH; (C-III) Q 9 is -H or -F and Q u is where one of Q u . 5 and Q π ^ is -H, and the other of Q n-5 and Q π . 6 is -H, -OH or Cι-C ϊ2 alkoxy; (C-rV) Q 9 is -H or -F and Q„ is o O-CO-Q π-7 :β-H, where Q n-7 is (A) C,-C 3 alkyl, (B) C r C 12 alkoxy, (D) -NQ I22 Qi 3 , where one of Q 122 and Q m is -H, methyl or ethyl and the other is -H, C,-C 4 alkyl or phenyl, (E) -O J -Q J , where Oj is -O- or a valence bond, where Qj is phenyl optionally substituted with 1 through 2 -Cl, -Br, C r C 3 alkoxy, -COOH, -NH 2 , C r C 3 alkylamino, di(C 1 -C 3 )alkylamino, where the alkyl groups are the same or different, 1- pyrrolidinyl-, 1-piperidinyl, 1-hexamethylenimino-, 1-heptamethylenimino-, C 2 -C 4 acylamino and -NH-CHO or with 1 -F or -CF 3 ; where: (D-I) Qj 6 is Qi 6 -ι:Qι« and Q, 7 is Q 17-1 :Q 17 - 2 , where one of Q^ and Q 16 . 2 is -H or -CH 3 and the other taken together with one of Q 17-1 and Q π-2 forms a second bond between C 16 and C π , and the other of Q 17- ι and Q 17 . 2 is -C(=Q 20 )-(CH 2 ) n -[attached to the piperazine of the 2,4,6-triaminopyrimidine], where Cjo is =0, =CH 2 or Q 17 . 9 :-H where Q 17 . 9 is -H or -CH 3 , where n is 0 through 6, where (D-II) Qι 6 is where one of Q 16 . 3 and Q 1M is -H and the other is -H, -F, -CH 3 or -OH, and Q 17 is =CH , (CH 2 ) p -[attached to the piperazine of the 2,4,6- triaminopyrimidine], where p is 1 or 2; (D-ffl) Q 16 is α-Q 16 . 5 :β-Q 16 . 6 and Q 17 is c.-Q n . 5 : -Q 17 ^, where Q 16-5 is -H, -OH, -F or -CH 3 and Q, w is -H, -OH, -P, or -CH 3 , with the proviso that at least one of Q 16 _ 5 and Q 1<μ6 is -H, where Q 17 . 5 is -H, -OH, -CH 3 , -CH 2 CH 3 , C 2 -C 7 alkahoyloxy or -O-CO-Qj, where Q t is as defined above, and where Q I7 ^ is -C(=Q 2 o)-(CH 2 ) n -[attached to the piperazine of the 2,4,6-triarninopyrimidine], where Q 20 and n are as defined above; (D-IV) the 16,17-acetonide of a compound where Q 16-5 is -OH, Q 16 . 6 is -H, Q 17 . 5 is -OH and Q, 7-6 is -C(=Q 20 )-(CH 2 ) n -[attached to the piperazine of the 2,4,6-triamino- pyrimidine], where O^o and n are as defined above; with the following overall provisos that: (I) one of Q l6 ., or Q 16 . 2 is taken together' with one of Q 17-1 or Q 17 . 2 to form a second bond between C 16 and C 17 , only when Q l0 is c.-Q 10 . I : β -Q 10-2 , c--Q 10 . 3 : β -Qι M , α- Qιo-7: β -Qιo-s or α-Qιo- 9 : β -Qιo.ιo, (II) Q 17 is =CH-(CH 2 ) p -[attached to the piperazine of the 2,4,6- triaminopyrimidine], only when Q 10 is α-Q 10-3 : β -Q KM , α-Q 10 . 7 : β -Qιo-8 or (Tfl) Qj and Q 10 taken together are =CH-CH=C(OQ 3 )-CH=, only when Q 17 is c.-Q 17 . 5 :β-Q 1M or the 16,17-acetonide of a compound where Q 16 is α-OH:β-H and Qπ is o;-OH:β-C(=Q 20 )-(CH 2 ) n -[attached to the piperazine of the 2,4,6-triamino- pyrimidine], and (IV) Oj is α-Q 5 . 7 :β-Qs. 8 , only when Q 17 is α-Qι 7 . 5 :β-Q 17-6 or α-OH:β-C- (=Q 2 o)-(CH 2 ) n -[att ched to the piperazine of the 2,4,6-triaminopyrimidine], or the 16, 17- acetonide thereof; (2) a trolox substituent (trolox) where W 2 is -O-, -S-, -NQ 54 - where Q^ is -H or C,-C 3 alkyl, r^ is 0, 1 or 2, Q 7 is -H or - -C 4 alkyl, -CO-(C,-C 4 alkyl), -CO-ό or -prodrug where prodrug -po 2 -α- -CO-CH 2 -CO-NH-CH 2 -S0 2 -0- -CO-^H^ Qs ! where n 2I is 1-7 and Q 51 is -COO " - -NQ I . I ^ where Q 5 ,.ι and Cjj.j are the same or different and are -H or C r C 3 alkyl, -N + Q i Q 5 , -2 Q 5 ι- 3 halide " where Qsi-iQsi-iQsi are the same or different and are -H or C { -C 3 alkyl, and where halide is -Cl or -Br, -CO-CH=CH-CO-O - -CO-N * -CH=CH-N=CH * where the atoms marked with an asterisk ( * ) are bonded to each other resulting in the formation of a ring, -CO-C * =C[(CH 2 ) n22 -NH 2 ]-CH=CH-CH=CH' where n 22 is 1 or 2 and where the atoms marked with an asterisk ( * ) are bonded to each other resulting in the formation of a ring, -CO-C , =CH-CH=C(-NQ 52 )-CH=CH * where Q^ is -H or C,-C 3 alkyl and where the atoms marked with an asterisk ( * ) are bonded to each other resulting in the formation of a ring, -CO-(CR 7 ) n21 -CO-0-[C 6 U l2 0 6 sugars], -CO-O-CH(CH 2 -O-CO-Q 53 ) 2 where the Gj s are the same or different and -CO-(CH 2 ) 6 -CO-N(CH 3 )-CH 2 -CH 2 -SO 3 -cation + where cation + is sodium, potassium or trialkylammonium where alkyl is C ! -C 3 , where n 21 , Q SM and Q 51 . 2 are as defined above, -CO-NH- H 4 -Q 55 where Q 55 is -H or C,-C 3 alkyl, -NO 2 , -NQ 5 i., . Q 51-2 where Q 51 - 1 and Q 51-2 are as defined above and Q 11 is -H or -CH 3 , Q 12 is -H or -CH 3 , (18-1) Q 16 is α-Qiβ- -Qi M where one of Q 16 ., and lM is -H, -CH 3 , -CH 2 CH 3 or -φ and the other is -^-[attached to the piperazine of the 2,4,6-triaminopyrimidine], where Cj is -CO-, -(CH 2 ) nl6 -CO- where n 16 is 1 or 2, -(CH^- where n 3 is 1-6, or -CO-0-(CH 2 ) nl5 - where n I5 is 2-6, Q 25 and Q 26 are -H:-H; (18-2) n < ; is 0, Q, 6 is Q 16-3 :Q ι6 - 4 where one of Q^ 3 and Q 1(M is taken together with Q M to form a second bond between the carbon atoms to which Q 16 and Q 25 are attached and the other of Qi 6 . 3 and Q 1(M is -Q 3 -[attached to the piperazine of the 2,4,6-triamino- pyrimidine], where Oj is as defined above, (18-3) r^ is 1, Q^ and Q 26 are taken together to form a second bond between the carbon atoms to which Q^ and Q 26 are attached; (3) an alkyl substituent selected from the group consisting of (A) QHCH^- where: n 2 is 1-14; Qj is -H, -OH, -O-CO-(C r C 4 alkyl), -O-CO-H, -O-CO-O-(C r C 4 alkyl), (C,-C 4 ) alkoxycarbonyl, -O-CO-aryl where aryl is φ optionally substitued with -OH, -OCH 3 , -F, -Cl, -Br, -CF 3 , -C r C 3 alkyl, and -CO-Qi where Oj is -OH, -NH 2 , -NHQ 6 where Q 6 is φ or Cι-C 3 alkyl, and -N(Qι 4 )(Qι 5 ) where Q 14 and Q 15 are the same or different and are C r C 3 alkyl; (B) is -H, C r C 3 alkyl, -CO-Q 3 . 2 where Q 3 , 2 is -H, C,-C 3 alkyl or -φ, (C) Q 5-3 -CO-(CH 2 ) n9 - where n 9 is 1 thru 3 and Q 3 . 3 is -OH, -O-Q 3 where Q w is C r C 4 alkyl or -CH 2 -φ, C r C 3 alkyl, -φ optionally substituted with 1 or 2 -F, -Cl, -Br, -NO 2 , C r C 3 or -OGj. 6 where Q^ is C r C 3 alkyl, (D) Q^ O-(CE 2 CB 2 -O l0 -C 2 CR 7 - where n 10 is 1 or 2 and where Q 3-! is as defined above, (E) Q 3 _ 3 -CO-CH=CH-CH 2 - where Q„ is as defined above, (F) -SO 2 Q 3 .j where Q 3 . 5 is C r C 3 alkyl; (G) 'CH^CH^-C'H- where the atoms marked with an asterisk ( * ) are bonded to each other resulting in the formation of a ' ring and where t, is 1 thru 6; R 2 and R 3 are the same or different and are -H, C,-C 4 alkyl and where R 2 and R 3 are taken with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-morpholinyl, 1-piperazinyl and 1- piperazinyl substituted in the 4- position with C,-C 4 alkyl with the proviso that R 2 and R 3 are not both -H; R 7 is (1) -CO-R 4 , where R 4 is -H, C 1 -C 4 alkyl, ->φ optionally substituted with 1, 2 or 3 -C 4 alkyl, -OH, C,-C 3 alkoxy, -F, -Cl, -Br, -NO 2 , where R 4 _ ! and R 4-2 are the same or different and are -H or C r C 4 alkyl, -S-R 4-3 where R 4-3 is -H or C r C 4 alkyl, -COOR 4 where R 4 is -H or C r C 4 alkyl, -(CH 2 ) D -N(R 4 .,)(R 4-2 ) where n 4 is 1-6, P^ and R 4 . 2 are as defined above, -(CH 2 ) n5 -O-(R 4 . ι ) where n 5 is 1-6 and R^ is as defined above, -(CH 2 ) n7 -CH 2 -COOH where n 7 is 1-6, -CH=CH-COOH, -(CH^^-N R,,.,)^.^ where n 4 , R^, and R^ are as defined above, -(CH 2 ) n5 -O-(R 4 . 1 ) where n 5 and R^. are as defined above, -(CH 2 ) nr CO-N(CH 3 )-CH 2 -CH 2 -SO 2 -OH where n, is 1 thru 6, (2) -R 5 , where R 5 is C r C 3 alkyl, Q-C, cycloalkyl, (3) -SO 2 -OH, (4) -PO(OH) 2) (5) -PO(OR 7-1 ) 2 where R 7 is C r C 4 alkyl, (6) -SO-OR 7-1 where R 7 _, is as defined above, (7) -[C 6 H, 2 O 6 ] nI2 where n 12 is 1 thru 3, and pharmaceutically acceptable salts thereof. Also disclosed are the protected 5-oxygenated pyrimidines of formula (VII) where R« is t-butoxycarbonyl (t-BOC), benzyloxycarbonyl (CBZ), CH 3 -CO-, φ-CO- and CHO- and where R 2 , R 3 and R 7 are as defined above and pharmaceutically acceptable salts thereof. Further disclosed are the 5-oxygenated pyrimidines of formula (VIII) where R 2 , R 3 and R 7 are as defined above and pharmaceutically acceptable salts thereof. Additionally disclosed are the 5-hydroxypyrimidines of formula (XI) where R 2 and R 3 are as defined above. Additionally disclosed are the oxygenated N,N-disubstituted pyrimidines of formula (XIII) where Oj is C r C 3 alkyl, -O-CH 3 , -O-CH,CH 3 , -(CH J H -O-Q,. ! where n, is 2 or 3 and Q^ is -H, C r C 3 alkyl, -CO-Q ι-2 where Gj. 2 is -H, C r C 3 alkyl or -φ, -CH 2 -CH(OQ )-CH 3 where Q M is as defined above, where n 2 is 1 or 2 and where Q M is as defined above, -(CH 2 ) n3 -CO-Q 1 - -3 where n 3 is 1 thru 3 and Q,. 3 is -OH, -O-Q M. where Q M is C r C 4 alkyl or -CH 2 -φ, C r C 3 alkyl, . -φ optionally substituted with 1 or 2 -F, -Cl, -Br, -NO 2 , C r C 3 or -O-Qι- 7 where Oj. 7 is C r C 3 alkyl, -CH 2 -CH=CH-CO-Q 1-3 where Gj. 3 is as defined above, -(CH 2 ) D4 -N(Q 1-5 )(Q 1-6 ) where " n 4 is 2 or 3 and Q,. 5 and Q^ are the same or different and are -H and Cι-C 3 alkyl, Q 2 is -H, C r C 3 alkyl, where n 5 is 2 or 3 and Q 2 is -H, C r C 3 alkyl, -CO-Q 2 . 2 where Q 2 , 2 is -H, C,-C 3 alkyl or -φ, 4 . -CH 2 -CH(OQ 2 .ι)-CH 3 where Q 2 .ι is as defined above, -CH 2 CH 2 -(0-CH 2 CH 2 ) n6 -0-Q 2-I where r^ is 1 or 2 and where Q 2 ., -is as defined above, -(CH 2 ) n7 -CO-Q 2 . 3 where n 7 is 1 thru 3 and Q 2 . 3 is -OH, -O-Q 2 where Q 2 ^ is C r C 4 alkyl or -CH 2 -φ; C r C 3 alkyl, -φ optionally substituted with 1 or 2 -F, -Cl, -Br, -NO 2 , C r C 3 or -OOjj where Gj.j is C,-C 3 alkyl; where R 2 , R 3 and R 7 are as defined - above and the pharmaceutically acceptable salts thereof. DETAILED DESCRIPTION OF THE INVENTION The 5-oxygenated amino substituted pyrimidines (X) , the protected 5-oxygenatged pyrimidines (VII) and 5-oxygenated pyrimidines (VIII) are prepared from known compounds by methods known to those skilled in the art. The 5-oxygenated amino substituted pyrimidines (X) include the ester substituted pyrimidines (II) R 7 is -CO-R,,, the ether substituted pyrimindines (III) R 7 is -R 5 , the sulfate substituted pyrimidines (IV) R 7 is -SO 2 -OH. The 5-oxygenated amino substituted pyrimidines (X) are produced by a number of known methods. One method involves oxidizing substituted pyrimidines (I) with the appropriate reagent to form the desired ester substituted pyrimidines (II), the ether sub¬ stituted pyrimindines (HI) or the sulfate substituted pyrimidines (IV) directly; see CHART A. Alternatively, one can start with the pyrimidine (V)., protect the piperazinyl hydrogen with an appropriate blocking group to form the protected piperazinyl pyrimidine (VI), oxidize it to the protected 5-oxygenated pyrimidine (VII) and then remove the protecting group to give the desired 5-oxygenated pyrimidine (VIII); see CHART B. The 5-oxygenated pyrimidine (VIII) is then coupled with the desired non- amine portion (IX) to form the desired 5-oxygenated amino substituted pyrimidines (X); see CHART C. The 5-hydroxy compound (XI) can be prepared from the substituted pyrimidine (I) by contacting the appropriate substituted pyrimidine (I) with hydrogen peroxide, see EXAMPLE 30. The substituted pyrimidines (I) are known to those skilled in the art. When R { is a steroid, see International Publication No. WO 87/01706, published March 26, 1987 based on International Patent application PCT/US86/01797. When R, is a steroid, it is preferred that Q 6 is α-H:β-H, Q 7 is α-H:β-H, Q ιr 2 is -CH 3 , Q 10- ι and Oj taken together are -CH=CH-CO-CH=. It is preferred that Q n is α Q π .ι: -Qπ- , where one of Q 1 and Q π . 2 is taken together with Q 9 to form a second bond between G, and C π and the other of Q π .j and Q u-2 is -H. It is also preferred that Q 16 is c.-Q 16 . 5 :β-Gj 6 . 6 and Q 17 is . -9- [attached to the piperazine of the 2,4,6-triaminopyrimidine], where Qa 0 is =O and n is 1. When R, is trolox, see International Publication Nθs WO 88/08424, published November 3, 1988 based on International Patent application PCT/US88/01212, in particular, see the compounds of formula (III). When Rj is trolox, the trolox portion contains an asymmetric center and therefore the desired 5-oxygenated amino substituted pyrimidines (X), produced when Ri is trolox, will be either optically active or racemic. Both enantiomers are pharmacologically active and useful in the same manner and same way as the racemic form. It is to be understood that the 5-oxygenated amino substituted pyrimidines (X) include both the racemic from as well as both enantiomeric forms. When j is trolox it isφreferred that Q 7 is -H and Q 10 , Q n and Q 12 are all C, alkyl, it is also preferred that W 2 is -O-, n 6 is 1, R 25 is -H:-H and R 26 is -H:-H. When R, is alkyl, see International Publication No. WO 88/08424, in particular, see the compounds of formula (II) and see US Patent application Serial No. 07/427,143. When Rj is alkyl it is preferred that R, is ■' * (1) where Oj is -H and n 2 is 2 thru 8 and (2) * CH 2 -(CH 2 ) t i-C * H- where the atoms marked with an asterisk ( * ) are bonded to each other resulting in the formation of a ring and "Where tj is 1 thru 5. It is preferred that R 2 and R^'are each C 2 alkyl and where R 2 and R 3 are taken with the attached nitrogen atom to forrii a heterocyclic ring which is 1-pyrrolidinyl or 1- piperidinyl; it is more preferred that R 2 and R 3 are taken together with the attached nitrogen atom to form a heterocyclic ring which is 1-pyrrolidinyl. When the desired 5-oxygenated amino substituted pyrimidine (X) is the ester substituted pyrimidine (II), the substituted pyrimidine (I) is contacted with the appropriate diacyl peroxide in an appropriate solvent at about 0° for 1-10 hours. The reaction mixture is then permitted to warm to about 20-25° and stirred for about 10-100 hr. The mixture is then worked up by extraction from an aqueous mixture with an organic solvent such as methylene chloride. It is preferred that the extracting solvent is the same as the reaction mixture solvent. The organic extract is dried over an appropriate reagent such as magnesium sulfate and concentrated. The concentrate is chromatographed to purify the ester substituted pyrimidine. It is preferred that Fv, is -CH 3 or -φ; it is more preferred that 4 is -φ. When the desired 5-σxygenated amino substituted pyrimidine (X) is the ether substituted pyrimidine (III), the substituted pyrimidine (I) is contacted with tert-butyl peroxybenzoate in an . inert nonpolar aprotic solvent at about 0° to about 25°. The reaction mixture is worked up similar to that as described for the ester substituted pyri idines (II) above. It is preferred that R 5 is (claim 14) -CH 3 or -C 2 H S ; it is more preferred that R 5 is -CH 3 . When the desired 5-oxygenated amino substituted pyrimidine (X) is the sulfate substituted pyrimidine (TV), the substituted pyrimidine (I) is contacted with ammonium persulfate in a solvent such as methylene chloride at about 20-25° for 10-100 hr. The mixture is worked up as previously described for the ester substituted pyrimidines (II). The second method of producing the 5-oxygenated amino substituted pyrimidines (X) is to first oxygenate- the protected piperaziny pyrimidines (VI) to form the 5- oxygenated pyrimidine (VIII), CHART B, and then couple it with the appropriate non- amine portion, R, (TX), to form the desired 5-oxygenated amino substituted pyrimidine (X), see CHART C. Using this method the pyrimidine (V) first has the piperazinyl hydrogen atom protected by an appropriate protecting group, R^. Suitable protecting groups include t-butoxycarbonyl [(CH 3 ) 3 C-O-CO-, t-BOC], benzyl carbamate [φ-CH 2 -O- CO-, CBZ], CH 3 -CO-, ό-CO- and CHO-. The preferred protecting group is t-BOC and CBZ, more preferred is t-BOC. After the piperazinyl hydrogen is protected, the protected piperazinyl pyrimidine (VI) is oxygenated as described above where R, is a drug such as a steroid, trolox or an alkyl group, rather than a blocking group, P^ to produce the protected 5-oxygenated pyrimidine (VII). Next the protecting group is removed by methods known to those skilled in the art to give the 5-oxygenated pyrimidine (VIII). The 5-oxygenated pyrimidine (VIII) is then coupled with the appropriate non- amine portion, R r Z (IX) to give the desired 5-oxygenated amino substituted pyrimidine (X). Z includes -Cl, -Br, -I, -CHO, -CO-C1, mesylate, tosylate and carboxylic acids activated by coupling agents such as 1,1-carbonyldiimidazole (CDI), and diethyl- pyrocarbonate (DEPC). The preferred Z depends on the particular type of R, group involved. The 5-hydroxy pyrimidines (XI) are produced by basic hydrolysis of the 5- oxygenated amino substituted pyrimidines (X), the ester substituted pyrimidines (II) and the sulfate substituted pyrimidines (IV). Alternatively the 5-hydroxy pyrimidines (XI) can be produced by reaction of the substituted pyrimidines (I) with hydrogen peroxide in solvents such as acetonitrile between about 0 and about 25° and from about 1 to about 96 hr, see EXAMPLE 30. The oxygenated N,N-disubstituted pyrimidines (XIII) are produced from the corresponding known N,N-disubstituted pyrimidines (XII) in the same way as the 5- oxygenated amino substituted pyrimidines (X) are produced from the corresponding substituted pyrimidines (I). The N,N-dιsubstituted pyrimidines (XII) are known, see US Patent application Serial No. 07/427,143. With the oxygenated N,N-disubstituted pyrimidines (XIII) it is preferred that R 7 is -CO-R 4 . It is preferred that Q, is C r C 3 alkyl, -0-CH 3 , -(CH^-O-Oj.,, -(CH 2 ) n3 -CO-Q 1 . 3 and -CH 2 -CH=CH-CO-Q 1-3 and Q 2 is -H, C r C 3 alkyl and -(CH^^-O-Q M ; it is more preferred that Gj is -CH 3 and Q 2 is where n 5 is 2 and Gj., is -H. The 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N- disubstituted pyrimidines (XIII) of the p' esent indention are useful pharmaceutical agents in treating a number of different medical conditions in humans and useful warm blooded animals. Since the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) of the present invention are amines, they readily form salts when reacted with acids of sufficient strength to produce the corresponding salts. Pharmaceutically acceptable salts include salts of both inorganic and organic acids. The anions of preferred pharmaceutically acceptable salts include acetate, benzoate, bromide, chloride, citrate, fumarate, mesylate, maleate, phosphate, nitrate, succinate, sulfate and tartrate. In humans, the 5-oxygenated amino substituted, pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) of the present invention are useful in treating spinal trauma, mild and/or moderate to severe head injury, subarachnoid hemorrhage and subsequent cerebral vasospasm, ischemic (thromboembolic) stroke, global ischemia, resuscitation (CPR), excess mucous secretion, asthma, muscular dystrophy, adriamycin-induced cardiac toxicity, brain tumor (neuroprotective), Parkin- sonism, Alzheimer's disease, Bells Palsy, other degenerative neurological disorders, multiple sclerosis, organ damage during reperfusion after transplant, skin graft rejection, hepatic necrosis (e.g. from viral hepatitis, hemorrhagic, traumatic and septic shock, and conditions such as severe burns, ARDS, inflammatory diseases such as osteo- or rheumatoid arthritis, nephrotic syndrome (immunological), systemic lupus erythematosis, allergic reactions, atherosclerosis, inflammation (for example dermatological, inflam¬ matory and psoriasis conditions), emphysema, stress induced ulcers, migrane cluster headaches, complications from brain tumors, some forms of radiation damage (for example during reaiation treatment or from accidental exposure to radiation), damage after MI, pre-birth infant strangulation and infant hypoxia syndrome, such opthalmic disorders as uveitis and optic neuritis, malignant hyperthermia and ischemic bowel syndrome. In humans, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are useful in preventing damage following cardiopulmonary resuscitation, neurological or cardiovascular surgery and from cardiac infarction, occular damage after opthalmic surgery (e.g. catratic surgery). Further, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are useful as anticancer agents. The 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N- disubstituted pyrimidines (XIII) are useful in irrigation solutions used in eye surgery. Generally, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are used like the glucocorticoid phar¬ maceuticals for the treatment of the above human conditions as well as the animal condi¬ tions listed below. While the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are useful in both humans and animals in treating many of the same conditions and preventing damage from the same problems as the glucocorticoids, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are useful in treating a number of conditions and preventing damage from conditions where the glucocorticoids are not useful. The 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N- disubstituted pyrimidines,, (XIII) have no glucocorticoid activity and therefore, unlike the glucocorticoids, they can be given daily for long periods of time (used chronically) without the side effects associated with the glucocorticoids. This is a distinct advantage. It is to be understood that each of the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) is useful to a different degree for treating each of the conditions above. However, as is known to those skilled in the art, some of the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are better for treating some conditions and others are better for treating other cpnditions. In order to determine which com¬ pounds are better than others for a particular condition one can utilize known tests that do not require expermentation but only routine analysis. For example, the fertile egg or chick embryo assay of Folkman, Nature 288, 551 (1980) or Science 221, 719 (1983), discloses an assay to determine antiangiogenic activity which is indicative of inhibition of tumor growth and anti-cancer utility. Because of the ability of the compounds which are active in the Folkman embryo test to inhibit tumor growth, they are useful in . the treatment of various diseases and conditions, especially various forms of cancer. Accordingly, they are administered to animals and humans to prolong survival or reduce pain and/or discomfort secondary to tumor growth and the alike. Further, the arachidonic acid LD 50 test of Kohler, Thrombosis Res., 9, 67 (1976), identifies compounds whi vare-antioxidants, which inhibit lipid peroxidation, and/or which inhibit the prostaglandin Cascade and are useful in treating spinal trauma, mild and/or moderate to severe head injury, degenerative neurological disorders, etc. Another method useful for determining which particular compounds inhibit lipid peroxidation and which are therefore useful in treating spinal trauma, mild and/or moderate to severe head injury, degenerative neurological disorders, etc is described by Pryor in Methods of Enzymology 105, 293 (1984). Further, the mouse head injury assay of Hall, J. Neurosurg., 62, 882 (1980) discloses an assay from which one skilled in the art can readily determine which of the particular amines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are useful in the acute treatment of spinal trauma or mild and/or moderate to severe head injury. Additionally, the cat 48 hr motor nerve degeneration model of Hall et al, Exp. Neurol., 79, 488 (1983) discloses a routine assay from which one skilled in the art can readily determine which particular 5-oxygenated amino substituted pyrimidines (X) arid the oxygenated N,N-disubstituted pyrimidines (Xπi) are useful in treating chronic degenerative neurological disorders such as Parkinsonism, Alzheimer's disease etc. H. Johnson in Int. ,Arch. Allergy Appl. Im¬ munol., 70, 169 (1983) has described the ascarias sensitized rhesus monkey assay for anti-asthma drugs. The standard conditions for treatment are to give the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) orally or parenterally, e.g. IV (that is by injection, infusion or continuous drip) or IM, with a standard dose of about 0.05 to about 10 mg/kg/day IV or about 0.5 to about 50 mg/kg/day, one to four times daily by mouth. For treating spinal trauma, mild and moderate to severe head injury, damage following cardiopulmonary resuscitation, cardiac infarction, organ damage during reperfusion after transplant, hemorrhagic, traumatic and septic shock, severe burns, ARDS, and nephrotic syndrome and preventing skin graft rejection, the standard conditions are used. Typical treatment will involve an initial loading dose, e.g. an IV dose of 0.01 mg to 2 mg/kg followed by maintenance dosing e.g. IV infusion for a day to a week depending on the particular condition of the patient and the particular compound used. This may be supplemented with IM or oral dosing for days, weeks or months to prevent delayed neuronal degeneration in neurological applications (eg spinal trauma, head injury). In treating subarachnoid hemorrhage and subsequent cerebral vasospasm or ischemic (thromboembolic) stroke the standard conditions are used and patients at risk are pre-treated orally. In treating excess mucous secretion and asthma, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are administered orally, IV and by inhalation in the standard dose. In treating excess mucous secretions the oral dose of the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) used is from about 0.5 to about 50 mg/kg/day. The frequency of administration is one through 4 times daily. The oral administration of the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) to treat excess mucous secretions may go on for months or even years. The susceptible individuals can be pre-treated a few hours before an expected problem. The IV dose is about 0.05 to about 20 mg/kg/day. The aerosol formulation contains about 0.05 to about 5.0% of the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) and is admin¬ istered or used about four times daily as needed. In treating muscular dystrophy, Parkinsonism, Alzheimer's disease and other degenerative neurological disorders (amyotrophic lateral sclerosis; multiple sclerosis) amines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are administered orally using a dose of about 0.5 to about 50 mg/kg/day j administered or used one to four times a day. The treatment may go on for years. In addition, utility in disorders or physiological phenomena dependent on -15- angiogenesis or neovascularization such as embryo implantation (antifertility), arthritis, and atherosclerosis is exhibited with the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) with or without co-administer¬ ed oral heparin or systemic heparin fragments, see Science 221, 719 (1983). In treating adriamycin-induced ' cardiac toxicity, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are administered orally or IV using a dose of about 0.05 to about 50 mg/kg/day, preferrably about 0.5 to about 10 mg/kg/day. The 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIH) are preferably, given concomitantly with IV adriamycin or the individual is pre-treated with the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII). For prophylaxis prior to and preventing damage after neurological or cardiovascu¬ lar surgery the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N- disubstituted pyrimidines (XIII) are used according to the standard conditions. The patient can be pretreated with a single IV or IM dose just prior to surgery or orally before and after surgery. In treating osteo- or rheumatoid arthritis and other inflammatory diseases, the 5- oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are given orally or IM in doses of about 0.5 to about 50 mg/kg/day, one to four times daily. Orally the drug- will be given over a period of months or years alone or with other steroidal or nonsteroidal antiinflammatory agents. The initial dose with some severe rheumatoid patients may be given IV and followed with an IV drip for up to 24 hr or more. In addition, intra-arterial administration may be employed. In treating drug allergic reactions, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XU1) are given in a dose of about 0.5 to 50 mg/kg/day, administered one to four times daily orally and IV. Typical treat¬ ment would be an initial IV loading dose followed by oral dosing for a few days or more. In treating atherosclerosis and emphysema, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are given orally in a dose of about 0.5 to about 50 mg/kg/day, one to four times daily for months or years. In treating dermatological inflammatory conditions including psoriasis, the 5- oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are given orally in a dose of about 0.5 to about 50 mg/kg/day, one ' to four times daily or applied topically as a cream, ointment or lotion or equivalent dosage form in a concentration of about 0.05 to about 5 % as long as needed. In treating these conditions the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) can be used with steroidal agents. For use in eye surgery, an isoosmolar solution containing about 0.001 to about 1 % of the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N- disubstituted pyrimidines (XIII) is used. In treating ophthalmic disorders the 5- oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIU) are given orally in a dose of about 0.5 to about 50 mg/kg/day, one to four times daily or applied topically as a cream, ointment or lotion or equivalent dosage form in a concentration of about 0.001 to about 1% as long as needed. The 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N- disubstituted pyrimidines (XIII) are useful in the prevention and treatment of stress ulcers and of gastric intolerance caused by drugs such as nonsteroidal anti-inflammatory compounds (NOS AC). Stress ulcers are ulcers that develop after exposure to severe conditions such as trauma, burns, sepsis, extensive surgery, acute illnesses, and the like. Patients in intensive care units are particularly prone to develop stress ulcers. Stress ulcers also include lesions that can lead to upper gastrointestinal bleeding; such bleeding is likely to be prevented by these compounds. NOS AC includes drugs such as ibuprofen, aspirin, indomethacin, naproxen, piroxicam and the like that are usually taken for analgesia, and that are often associated with gastrointestinal intolerance characterized by pain and lesions that may lead to bleeding. The 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) will be admini¬ stered preferentially by the oral route either as tablets, capsules or liquids, in doses ranging from about 5 to about 500 mg, two to four times a day. The treatment would be either preventive, i.e., starting before ulcers have formed in patients at risk of developing such lesions, or therapeutic, i.e., once the ulcers have formed. In patients whose clinical condition precludes swallowing the oral dosage forms, the amines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) would be given either through a nasogastric tube, or parenterally , i . e. , IV or IM. The parenteral doses would range from -17- about 1 to about 100 mg and be administered one to four times a day or by IV. In dogs, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) trauma, intervertebral diseases (slipped disk), traumatic shock, flea bite and other allergies. In horses, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are useful in treating endotoxic or septic shock which follows colic, pretreatment before surgery for colic and treatment of Founder (laminitis). In cattle, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are useful in treating acute coliform mastitis, bovine mastitis, acute allergic reaction to feed lot vaccination and shipping fever. In pigs, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) are useful in treating porcine stress syndrome and thermal stress syndrome. The term treatment or treating as used in this patent is used broadly and includes both treatment of an existing condition as well as preventing the same condition from occurring where such is possible as is well known to those skilled in the art. For example, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N- disubstituted pyrimidines (XITI) can be used to treat existing asthma conditions and to prevent future ones from occurring. For example, the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) treat spinal trauma and prevent rejection of skin grafts. The 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N- disubstituted pyrimidines (XIII) can be used with other pharmaceutical agents in treat- ment of the conditions listed above as is known to those skilled in the art. The exact dosage and frequency of administration depends on the particular 5- oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) used, the particular condition being treated, the severity of the condition being treated, the age, weight, general physical condition of the particular patient, other medication the individual may be taking as is well known to those skilled in the art and can be more accurately determined by measuring the blood level or concentration of the 5-oxygenated amino substituted pyrimidines (X) and the oxygenated N,N-disubstituted pyrimidines (XIII) in the patient's blood and/or the patients response to the particular condition being treated. The 5-hydroxy pyrimidines (XI) are very potent inhibitors of lipid peroxidation and therefore are useful in the treatment of the above conditions, there usefulness being limited by the very short half-life. Because of their potency they are also useful as stan- dards in the malonyldialdehyde (MDA) formation assay, see Buege, and Aust, Methods in Enzymology, Fleisher and Packer Editors, Academic Press, 1978, New York, Vol Lπ f p 302-310 and Kohn and Liversedge, J. Pharmacol. Txpl Ther. 82, 292 (1944). The 5-hydroxy pyrimidines (XI) are also useful as intermediates in the preparation of the ester substituted pyrimidines (II) by acylation of the 5-hydroxy pyrimidines (X) with the appropriate acid halide. DEFINITIONS AND CONVENTIONS The definitions and explanations below are for the terms as used throughout this entire document including both the specification and the claims. I. CONVENTIONS FOR FORMULAS AND DEFINITIONS OF VARIABLES The chemical formulas representing various compounds or molecular fragments in the specification and claims may contain variable substituents in addition to expressly defined structural features. These variable substituents are identified by a letter or a letter followed by a numerical subscript, for example, "Zj" or "Rj" where "i" is an integer. These variable substituents are either monovalent or bivalent, that is, they represent a group attached to the formula by one or two chemical bonds. For example, a group T would represent a bivalent variable if attached to the formula CH 3 -C(=Zj)H. Groups j and j would represent monovalent variable substituents if attached to the formula CH 3 -CH 2 -C(Ri)(R j )H 2 . When chemical formulas are drawn in a linear fashion, such as those above, variable substituents contained in parentheses are bonded to the atom immediately to the left of the variable substituent enclosed in parenthesis. When two or more consecutive variable substituents are enclosed in parentheses, each of the consecutive variable substituents is bonded to the immediately preceding atom to the left which is not enclosed in parentheses. Thus, in the formula above, both R; and R j are bonded to the preceding carbon atom. Also, for any molecule with an established system of carbon atom numbering, such as steroids, these carbon atoms are designated as Q, where "i" is the integer corresponding to the carbon atom number. For example, C 6 represents the 6 position or carbon atom number in the steroid nucleus as traditionally designated by those skilled in the art of steroid chemistry. Likewise the term "Rή" represents a variable substituent (either rnonovalent or bivalent) at the C 6 position. Chemical formulas or portions thereof drawn in a linear fashion represent atoms in a linear chain. The symbol "-" in general represents a bond between two atoms in the chain. Thus CH 3 -0-CH 2 -CH(R,)-CH 3 represents a 2-substituted-l-methoxypropane compound. In a similar fashion, the symbol " = " represents a double bond, e.g. , CH 2 =C(R,)-O-CH 3 , and the symbol " ≡" represents a triple bond, e.g., HC ≡C-CH(RJ- CH 2 -CH 3 . Carbonyl groups are represented in either one of two ways: -CO- or -C(=0)-, with the former being preferred for simplicity. Chemical formulas of cyclic (ring) compounds or molecular fragments can be represented in a linear fashion. Thus, the compound 4-chloro-2-methylpyridine can be represented in linear fashion by N * =C(CH 3 )-CH=CC1-CH=C * H with the convention that the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring. Likewise, the cyclic molecular fragment, 4-(ethyl)-l-piperazinyl can be represented by -N * -(CH 2 ) 2 - N(C 2 H 5 )-CH 2 -CΗ 2 - A rigid cyclic (ring) structure for any compounds herein defines an orientation with respect to the plane of the ring for substituents attached to each carbon atom of the rigid cyclic compound. For saturated compounds which have two substituents attached to a carbon atom which is part of a cyclic system, -C(X,)(X 2 )- the two substituents may be in either an axial or equatorial position relative to the ring and may change between axial/equatorial. However, the position of the two substituents relative to the ring and each other remains fixed. While either " substituent at times may lie in the plane of the ring (equatorial) rather than above or below the plane (axial), one substituent is always above the other. In chemical structural formulas depicting such compounds, a substituent (X,) which is "below" another substituent (X^ will be identified as being in the alpha (α) configuration and is identified by a broken, dashed or dotted line attachment to the carbon atom, i.e., by the symbol " — " or "...". The corresponding substituent attached "above" (X 2 ) the other (X,) is identified as being in the beta (β) configuration and is indicated by an unbroken line attachment to the carbon atom. When a variable substituent is bivalent, the valences may be taken together or separately or both in the definition of the variable. For example, a variable R, attached to a carbon atom as -C(=R,)- might be bivalent and be defined as oxo or keto (thus forming a carbonyl group (-CO-) or as two separately attached monovalent variable substituents α-R^ j and β-Rj. k . When a bivalent variable, Rj, is defined to consist of two monovalent variable substituents, the convention used to define the bivalent variable is of the form "c.-Rj. j :β-Rj -k " or some variant thereof. In such a case both α-R^ and β-R;„ k are attached to the carbon atom to give -C(α-R i-j )(β-R i . k )-. For example, when the bivalent variable ^, -C(=R < ;)- is defined to consist of two monovalent variable substit¬ uents, the two monovalent variable substituents are α-R 6 .,:β-R 6 . 2 , .... etc, giving -C(c.-R 6-1 )( β -R 6-2 )-. •••• -C(c.-R 6-9 )( β -R 6-10 )-, etc. Likewise, for the bivalent variable R u , -C(=R n )-, two monovalent variable substituents are α-R„.,:β-R u . 2 . For a ring substituent for which separate a and β orientations do not exist (e.g. due to the presence of a carbon carbon double bond in the ring), and for a substituent bonded to a carbon atom which is not part of a ring the above convention is still used, but the α and β designations are omitted. Just as a bivalent variable may be defined as two separate monovalent variable substituents, two separate monovalent variable substituents may be defined to be taken together to form a bivalent variable. For example, in the formula (C, and C 2 define arbitrarily a first and second carbon atom, respectively) j and j may be defined to be taken together to form (1) a second bond between C, and C 2 or (2) a bivalent group such as oxa (-O-) and the formula thereby describes an epoxide. When Rj and R j are taken together to form a more complex entity, such as the group -X-Y-, then the orientation of the entity is such that C, in the above formula is bonded to X and C 2 is bonded to Y. Thus, by convention the designation "... Rj and R j are taken together to form -CH 2 -CH 2 -O-CO- ... " means a lactone in which the carbonyl is bonded to C 2 . However, when designated "... j and R ; are taken together to form -CO-O-CH 2 -CH 2 -the convention means a lactone in which the carbonyl is bonded to . The carbon atom content of variable substituents is indicated in one of two ways. The first method uses a prefix to the entire name of the variable such as "C^C^', where both "1" and "4" are integers representing the minimum and maximum number of carbon atoms in the variable. The prefix is separated from the variable by a space. For example, "C 1 -C 4 alkyl" represents alkyl of 1 through 4 carbon atoms, (including isomeric forms thereof unless an express indication to the contrary is given). Whenever this single prefix is given, the prefix indicates the entire carbon atom content of the variable being defined. Thus C 2 -C 4 alkoxycarbonyl describes a group CH 3 -(CH 2 ) n -0-CO- where n is zero, one or two. By the second method the carbon atom content of only each portion of the definition is indicated separately by enclosing the " -C j " designation in parentheses and placing it immediately (no intervening space) before the portion of the definition being defined. By this optional convention (C r C 3 )alkoxycarbonyl has the same meaning as -C 4 alkoxycarbonyl " because' the "C C 3 " refers only to the carbon atom content of the alkoxy group. Similarly while both - s alkoxyalkyl and (C,- C 3 )alkoxy(C,-C 3 )alkyl define alkoxyalkyl groups containing from 2 to 6 carbon atoms, the two definitions differ since the former definition allows either the alkoxy or alkyl portion alone to contain 4 or 5 carbon atoms while the latter definition limits either of these groups to 3 carbon atoms. When the claims contain a fairly complex (cyclic) substituent, at the end of the phrase naming/designating that particular substituent will be a notation in (parentheses) which will correspond to the same name/designation in one of the CHARTS which will also set forth the chemical structural formula of that particular substituent. II. DEFINITIONS All temperatures are in degrees Centigrade. TLC refers to thin-layer chromatography. Saline refers to an aqueous saturated sodium chloride solution. IR refers to infrared spectroscopy. NMR refers to nuclear (proton) magnetic resonance spectroscopy, chemical shifts are reported in ppm (δ) downfield from tetramethylsilane. 6 refers to phenyl (C 6 H 5 ). MS refers to mass spectrometry expressed as m/e or mass/charge unit. [M + H] + refers to the positive ion of a parent plus ' a hydrogen atom. El refers to electron impact. Cl refers to chemical ionization. ' FAB refers to fast atom bombardment. Ether refers to diethyl ether. Pharmaceutically acceptable refers to those- properties and/or substances which are acceptable to the patient from a pharmacological/toxicological point of view and to the manufacturing pharmaceutical chemist from a physical/chemical point of view regarding composition, formulation, stability, patient acceptance and bioavailability. When solvent pairs are used, the ratios of solvents used are volume/volume (v/v). When the solubility of a solid in a solvent is used the ratio of the solid to the solvent is weight volume (wt/v). EXAMPLES Without further elaboration, it is believed that. one skilled in the art can, using the preceding description,. practice the present invention to its fullest extent. The following detailed examples describe how to prepare the various compounds and/or perform the various processes of the invention and are to be construed as merely illustrative, and not limitations of the preceding disclosure in any way whatsoever. Those skilled in the art will promptly recognize appropriate variations from the procedures both as to reactants and as to reaction conditions and techniques. EXAMPLE 1 l-[5-(Hydroxy)-2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16α- methylpregna-l,4,9(l l)-trien-3,20-dione-21-yl]-piperazine 5- benzoate (II) Benzoyl peroxide (0.950 g) is added to a solution of 16α-methyl-21-[4-[2,6-di-(l- pyrrolidinyl)-4-pyrimidinyl]-l-piperazinyl]-pregna-l,4,9(l l)-triene-3,20-dionemethane- sulfonate monohydrate (I, International Publication No. WO 87/01706 Example 109, 2.22 g) and dichloromethane (4.10 ml) at 0°. The resultant solution is stirred at 0° for 4 hours and is then allowed to warm to 20-25°. After 72 hours, aqueous workup (methylene chloride, magnesium sulfate) and purification by flash chromatography (1/1, hexane/ethyl acetate) provides the title compound, IR (nujol) 2952, 2924, 2856, 1744, 1666, 1555, 1468, 1447, 1375, 1345, 1245, 1175, 1053, 1023 and 714 cm "1 ; NMR (300 MHz, CDC1 3 ) 8.15, 7.63, 7.50, 7.16, 6.28, 6.07, 5.48, 3.50, 3.01, 1.39, 0.90 and 0.62 δ; MS (El m/e) exact mass calcd for C 45 H 56 N 6 O 4 (744.4363), found 744.4393. The hydrochloride salt of the title compound is prepared in ether/ethyl acetate, mp 146-148°. EXAMPLE 2 4-[4-(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-l-benz- opyran-2-yl)methyl]-l-piperazinyl]-5-hydroxy-2,6-di-(l-pyr- rolidinyl)-4-pyrimidinyl 5-benzoate (H) Benzoyl peroxide (0.257 g) is added to a solution of 2-[[4-(2,6-di-(l-pyrrolidinyl)- 4-pyrimidinyl)-l-piperazinyl]methyrj-3,4-dihydro-2,5,7,8-tetramethyl-2H-l-benzopyran-6- ol (I, International Publication No. WO 88/08424 Example 21, 0.500 g) and methylene chloride (1.10 ml) at 0°. The resultant solution is allowed to stir for 4 hours at 0° and 48 hours at 20-25°. Basic workup (methylene chloride, sodium dicarbonate, magnesium sulfate) and purification by flash chromatography (1/1; hexane/ethyl acetate) provides the title compound, IR (nujol) 3524, 2925, 2856, 1744, 1556, 1448, 1345, 1246, 1090 and ' 713 cm- 1 ; NMR (300 MHz, CDC1 3 ) 8.15, 7.62, 7.49, 3.2-3.7, 2.14, 2.08, 1.98 and 1.18 -23- δ; MS (El m/e) 535, 435, 379, 12 and 105, exact mass calcd for C 37 H 4g N 6 O 4 (640.3737), found 640.3753. The hydrochloride salt of the title compound is prepared in ether, mp 152-156°. EXAMPLE 3 l-[5-(Hydroxy) J -2,'6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16α- memylpregna-l,4,9(ll)-trien-3,20-dione-21-yl]-piperazine 5-acetate (H) A solution of diacetyl peroxide (75/25 dimethyl phthalate/isobutyl isobutylrate, 0.65 ml) is added to a solution of 16α-methyl-21-[4-[2,6-di-(l-pyrrolidinyl)-4- pyrimidinyl]-l-piperazinyl]-pregna-r,4,9(l l)-triene-3,20-dione methanesulfonate monohydrate (I, 0.80 g) and methylene chloride (1.5 ml) at 0°. The solution is allowed to stir for 6 hours at 0° and 42 hours at 20-25°. Aqueous workup (methylene chloride/magnesium sulfate) and purification by flash chromatography (1/3, hexane/ethyl acetate) provides the title compound, IR (nujol) 2954, 2916, 2855, 1760, 1666, 1557, 1446, 1375, 1345, 1207, 1012 and 887 cm "1 ; NMR (300 MHz, CDC1 3 ) 7.17, 6.28, 6.08, 5.51, 3.47, 3.12, 2.18, 1.40, 0.95 and 0.67 δ; MS (El m/e) 639, 373, 359, 317, 291 and 246, exact mass calcd for C^NA (682.4206), found 682.4189. The hydrochloride salt of the title compound is prepared in ether, mp dec 215°. EXAMPLE 4 l-[5-(Hydroxy)-2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16α- methylpregna-1 ,4,9(1 l)-trien-3,20-dione-21-yl]-piperazine 5-(o- chlorobenzoate) (II) Di-o-chlorobenzoyl peroxide (479 mg) is added to a solution of 16α-methyl-21-[4- [2,6-di-(l-pyπOlidinyl)-4-pyrimidinyl]-l-piperazinyl]-pregna-l,4,9(l l)-triene-3,20-dione methanesulfonate monohydrate (I, 800 rjfg) and methylene chloride (1.50 ml) at 0°. The resultant solution is stirred for 4 hours at 0° and 48 hours at 20-25°. Aqueous workup (methylene chloride, magnesium sulfate,) anrj purification by flash chromatography (1/1 - 0/100, hexane/ethyl acetate) provides the title compound, IR (nujol) 2937, 2856, 1665, 1557, 1448, 1377, 1345, 1239 and 750 cm" 1 ; NMR (300 MHz, CDC1 3 ) 8.09, 7.1-7.6, 7.17, 6.29, 6.08, 5.4-5.6, 3.3-3.7, 1.39, 0.91 and 0.63 δ; MS (FAB m/e) 639, 260 and 139, exact mass calculated for C 45 H 56 N 6 O 4 Cl (779.4051), found 779.4030. The hydrochloride salt of the title compound is prepared in ether/ethyl acetate, mp dec 155°. EXAMPLE 5 l-[5-(Hydroxy)-2 5 6-dj-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16a- methylpregna-1 ,4,9(1 l)-trien-3,20-dione-21-yl]-piperazine 5-(p- methoxybenzoate) (II) Di-p-methoxybenzoyl peroxide (466 mg).is added to a solution of 16α-methyl-21- [4-[2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-l-piperazinyl]-pregna-l,4,9(ll)-triene-3,20- dione methanesulfonate monohydrate (I, 800 mg) and methylene chloride (1.5 ml) at 0°. The solution is stirred for 4 hours at 0° and 44 hours at 20-25°. Aqueous workup (methylene chloride, magnesium sulfate), flash chromatography (3/1, ethyl ace- tate/hexane) and acidic workup (ethyl acetate, methylene chloride, magnesium sulfate) to remove unreacted peroxide gives the title compound, IR (nujol) 2954, 2926, 2856, 1736, 1666, 1606, 1555, 1446, 1253 and 1164 cm "1 ; NMR (300 MHz, CDC1 3 ) 8.10, 7.17, 6.97, 6.28, 6.07, 5.48, 3.89, 3.3-3.7, 3.02, 1.39, 0.90 and 0.62 δ; MS (FAB m/e) 639, 135, exact mass calcd for C^H^N- (775.4547), found 775.4578. The hydrochloride salt of the title compound is prepared in ether/ethyl acetate, mp dec 150-152°. EXAMPLE 6 l-[5-(Hydroxy)-2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16α- methylpregna-1 , 4,9(1 l)-trien-3,20-dione-21-yl]-piperazine 5-(p- chlorobenzoate) (II) Di-p-chlorobenzoyl peroxide (439 mg) is added to a solution of 16α-methyl-21-[4- [2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-l-piperazinyl]-pregna-l,4,9(ll)-triene-3,20-dione methanesulfonate monohydrate (I, 800 mg) and methylene chloride (1.50 ml) at 0°. The solution is stirred for 6 hr at 0° and 26 hr at 20-25°. Aqueous workup (methylene chloride, magnesium sulfate) and purification by flash chromatography (2/1, ethyl acetate hexane) provides benzoate, IR (nujol) 2953, 2914, 2856, 1743, 1666, 1557, 1468, 1448, 1376, 1345, 1252, 1091, 1014 and 756 cm "1 ; NMR (300 MHz, CDC1 3 ) 8.09, 7.48, 7.18, 6.30, 6.07, 5.49, 3.2-3.7, 3.02, 1.39, 0.91 and 0.62 δ; MS (FAB m/e) 639, 469 and 260, exact mass calcd for C 45 H 56 N 6 O 4 Cl (779.4051), found 779.4015- The hydrochloride salt of the title compound is prepared in ether/ethyl acetate, mp 151-155°. EXAMPLE 7 l-[5-(Hydroxy)-2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16α- methylpregna-1 ,4,9(1 l)-trien-3,20-dione-21-yl]-piperazine 5- myristoate (II) Dimyristoyl peroxide (641 mg) is added to a solution of 16α-methyl-21-[4-[2,6-di- (l-pyrrolidinyl)-4-pyrimidinyl]-l-piperazinyl]-pregna-l ,4,9(l l)-triene-3,20-dione methanesulfonate monohydrate (I, 800 mg) and methylene chloride (1.50 ml) at 0°. An -25- additional 1.0 ml. of methylene chloride is added to the mixture which is stirred for 3 hr at 0° and 21 hr at 20-25°. Aqueous workup (methylene chloride, magnesium sulfate, and purification by flash chromatography (2/1, ethyl acetate/hexane) provides the title compound, IR (neat) 2927, 2855, 1763, 1719, 1667, 1557, 1447 and 1345 cm "1 ; NMR (300 MHz, CDC1 3 ) 7.17, 6.29, 6.08, 5.51, 3.47, 3.14, 1.40, 1.26, 0.95, 0.88 and 0.67 δ; MS (FAB m/e) 639, 541 and 260, exact mass calcd for Cj 2 H 79 N 6 O 4 (851.6162), found 851.6129. The hydrochloride salt of the title compound is prepared in ether/ethyl acetate, mp dec 119°. EXAMPLE 8 l-[5-(Hydroxy)-2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16α- methylpregna-l,4,9(ll)-trien-3,20-dione-21-yl]-piperazine 5-o- toluoate (II) A solution of di-o-toluoyl peroxide (381 mg) and methylene chloride (0.50 ml) is added to a solution of 16α-methyl-21-[4-[2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-l- piperazinyl] -pregna-1, 4, 9(1 l)-triene-3,20-dione methanesulfonate monohydrate (I, 800 mg) and methylene chloride- (1.25 ml) at 0°. The resultant solution is stirred for 4 hr at 0° and 23 hr at 20-25°. Aqueous workup (methylene chloride, magnesium sulfate) and purification by flash chromatography (2/1, ethyl acetate/hexane) gives the title com¬ pound, IR (nujol) 2954, 2914, 2856, 1716, 1664, 1625, 1569, 1455, 1416, 1378, 1338, 1236 and 743 cm" 1 ; NMR (300 MHz, CDC13) 8.11, 8.01, 7.2-7.5, 6.29, 6.08, 5.49, 3.3-3.7, 3.03, 2.64, 1.38, 0.89 and 0.61 δ. The hydrochloride salt of the title compound- is prepared in ether/ethyl acetate, mp 146-149°. EXAMPLE 9 l-[5-(Hydroxy)-2,6 ~ -di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16α- methylpregna-l,4,9(ll)-trien-3,20-dione-21-yl]-piperazine 5-sulfate (II) Water (8.5 ml) is added to a mixture of 16α-methyl-21-[4-[2,6-di-(l-pyrrolidinyl)- 4-pyrimidinyl]-l-piperazinyl]-pregna-l ,4,9(l l)-triene-3,20-dione methanesulfonate monohydrate (I, 1.14 g), ammonium persulfate (623 mg) and methylene chloride (8.5 ml). The mixture is stirred for 3 days at 20-25°. Aqueous workup (methylene chloride, magnesium sulfate) and trituration of the residue with ethyl acetate several times gives the title compound, mp. effr 223°; IR (nujol) 2929, 2870, 2855, 1665, 1626, 1555, 1454, 1377 and 1043 cm "1 ; NMR (300 MHz, CDC1 3 ) 7.15-7.25, 6.2-6.35, 6.06, 5.50, 1.39, 0.95 and 0.66 δ; MS (FAB m/e) 721, 641 and 247. EXAMPLE 10 4-[4-(t-Butoxycarbonyl)piperazin-l-yl]-2,6-di-(l-pyrrolidinyl)- pyrimidine (VI) A solution of di-tert-butyl dicarbonate (4.76 g) and methylene chloride (10.0 ml) is added dropwise over 10 minutes to a solution of 4-(l-piperazinyl)-2,6-di-(l-pyrrol- idinyl)pyrimidine (V, International Publication No. WO 87/01706 PREPARATION A- 22, 6.00 g), triethylamine (3.10 ml), 4-dimethylaminopyridine (20 mg) and methylene • chloride (20.0 ml) at 0°. The solution is allowed to stir at 0° for 1 hr and 16 hrs at 20- 25°. Basic workup (methylene chloride, sodium bicarbonate, magnesium sulfate) and purification by flash chromatography (2/1, hexane/ethyl acetate) provides the carbamate as a solid. An analytical sample is prepared by recrystallization from hot ethyl acetate to provide the title compound, mp 169-169.5°; IR (nujol) 2925, 2854, 1701, 1570, 1556, 1435, 1242 and 788 cm "1 ; NMR (300 MHz, CDC1 3 ) 4.85, 3.3-3.6, 1.8-2.0 and 1.47 δ; MS (El m/e) 402, 301 and 246. EXAMPLE 11 5-Hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6-di-(l- pyrrolidinyl)pyrimidine 5-benzoate (VII) Benzoyl peroxide (1.49 g) is added to a solution of the protected piperazinyl pyrimidine (VI, EXAMPLE 10, 2.26 g) and methylene chloride (5.60 ml) at 0°. The resultant solution is stirred for 6.5 hr at 0° and 72 hr at 20-25°. Basic workup (methylene chloride, sodium bicarbonate, magnesium sulfate) and purification by flash chromatography (3/1, hexane/ethyl acetate) provides the title compound, IR (nujol) 2952, 2924, 2856, 1747, 1698, 1559, 1468, 1345, 1247, 1172 and 712 cm "1 ; NMR (300 MHz, CDC1 3 ) 8.16, 7.64, 7.51, 3.2-3.7, 1.7-2.0 and 1.42 δ; MS (m/e) 417 and 361, exact mass calcd for C 28 H 38 N 6 O 4 (522.2954), found 522.2977. EXAMPLE 12 5-Hydroxy-4-(piperazinyl)-2,6-di-(l-pyrrolidinyl) pyrimidine 5-benzoate (VIII) Trifluoroacetic acid (2.1 ml) is added to a solution of the protected 5-oxygenated pyrimidine (VII, EXAMPLE 11, 286 mg) and methylene chloride (2.1 ml) at 0°. After stirring for 30 minutes at 0° the solution is concentrated. Basic workup (methylene chloride, potassium carbonate, magnesium sulfate) provides, the title compound, NMR (300 MHz, CDC1 3 ) 8.15, 7.62, 7.49, 3.3-3.7, 2.7-2.9 ' and 1.7-2.1 δ. The hydrochloride salt of the title compound is formed in ether, mp 78-82°; IR (nujol) 3396, 2955, 2921, 2856, 1734, 1711, 1631 , 1573, 1452, 1414, 1326 and 719 cm "1 ; MS (m/e) 317, 246 and 105, exact mass calcd for CisHao βOj (422.2430), found 422.2432. EXAMPLE 13 5-Hydroxy-4-(4-methyl-l-piperazinyl)-2,6-di-(l-pyrrolidinyl)- pyrimidine 5-benzoate (X) Formaldehyde (0.30 ml, 37% aqueous) is added to a solution of 5-hydroxy-4- (piperazinyl)-2,6-di-(l-pyrrolidinyl)pyrimidine 5-benzoate (VJJI, EXAMPLE 12, 0.72 g) and methanol (7.0 ml). Sodium cyanoborohydride (0.14 g) is added to the mixture followed by 1 drop of acetic acid 20 minutes later. After 1 hour, a solution is formed, which after 2 hours turns into a thick slurry. The mixture is stirred overnight and is then concentrated. Basic workup (chloroform, sodium bicarbonate, magnesium sulfate) and purification by flash chromatography (ethyl acetate — » 15/1 ethyl acetate/methanol) provides the title compound, IR (nujol) 2949, 2921, 2855, 1740, 1561, 1449, 1347, 1306, 1242, 1052 and 709 cm "1 ; NMR (300 MHz, CDC1 3 ) 8.16, 7.64, 7.51, 3.3-3.7, 2.2-2.5, 2.21 and 1.6-2.0 δ; MS (m/e) 366 and 331, exact mass calculated for C 24 H 32 N 6 O 2 (436.2587), found 436.2573. The hydrochloride salt of the title compound is formed in ether/ ethyl acetate, mp 106-109°. EXAMPLE 14 5-Hydroxy-4-(4-propyl-l-piperazinyl)-2,6-di-(l-pyrrolidinyl)- pyrimidine 5-benzoate (X) Sodium cyanoborohydride (0.14 g) is added to a solution of 5-hydroxy-4-(piper- azinyl)-2,6-di-(l-pyrrolidinyl)pyrimidine 5-benzoate (VJJI, EXAMPLE 12, 0.74 g), propionaldehyde (0.16 ml) and methanol (7.0 ml). After 20 minutes acetic acid (1 drop) is added and the solution stirred overnight. Methylene chloride (2.0 ml) is added to the mixture and the resultant solution stirred for an additional 3 hrs. Concentration, basic workup (chloroform, sodium bicarbonate, magnesium sulfate) and purification by flash chromatography (ethyl acetate) provides the title compound, IR (nujol) 2953, 2925, 1745, 1559, 1446, 1343, 1246, 1162, 1057 and 709 cm "1 ; NMR (300 MHz, CDC1 3 ) 8.16, 7.63, 7.51 , 3.3-3.7, 2.34, 2.22, 1.6-2.0, 1.35- 1.55 and 0.84 δ; MS (m/e) 359, 274, 260 and 247, exact mass calcd for C 26 H 36 N 6 O 2 (464.2900), found 464.2918. The hydrochloride salt of the title compound is formed in ether/ ethyl acetate, mp 99-101°. EXAMPLE 15 4-[[4-(3 ,4-dihydro-6-hydroxy-2,5 ,7,8-tetramethyl-2H-l-benzopyan- 2-yl)carbonyl]-l-piperazinyl]-5-hydroxy-2,6-di-(l-pyrrolidinyl)-4- pyrimidine 5-benzoate (X) l,r-Carbonyldiimidazole (0.454 g) is added to a solution of 2-[[4-(2,6-di-(l- pyrroUdiτιyl)-4-pyrimidinyl)-l-piperazinyl]carbonyl]-3,4-dihydro-2,5,7,8-tetramethyl-2H- l-benzopyran-6-ol (I, International Publication No. WO 88/08424, 0.701 g) and tetrahydrofuran (7.0 ml). After stirring for 40 minutes at 20-25°, a solution of 5- hydroxy-4-(piperazinyl)-2,6-di-(l-pyrrolidinyl)pyrimidine5-benzoate VIII, EXAMPLE 12, 2.54 mmol) and tetrahydrofuran (7.0 ml) are added. The reaction is allowed to stir for 16 hours at 20-25°. Basic workup (chloroform, sodium bicarbonate, magnesium sulfate) and purification by flash chromatography (1/2, ethyl acetate/hexane) provides the title compound, mp. 214-217°; IR (nujol) 3404, 2926, 2856, 1745, 1625, 1556, 1451, 1345, 1244, 1089 and 714 cm "1 ; NMR (300 MHz, CDC1 3 ) 8.14, 7.64, 7.51, 25, 3.3-3.6, 2.4-2.8, 2.08, 2.04 and 1.55 δ; MS (m/e) 549, 385, 371 and 205, exact mass calcd for (654.3529), found 654.3519. EXAMPLE 16 5-Hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6-di-(l- pyrrolidinyl)pyrimidine 5-acetate (VII) A solution of diacetyl peroxide (0.81 ml, 25%) is added to a solution of 4-[4-(t- butoxycarbonyl)piperazin-l-yl]-2,6-di-(l- pyrrolidinyl)pyrimidine (VI, EXAMPLE 10, 0.40 g) and methylene chloride (1.0 ml) at 0°. The solution is stirred for 3.5 hours at 0°C and 24 hours at 20-25°. Acidic workup (ether, chloroform, cold 3% hydrochloric acid, magnesium sulfate) and purification by flash chromatography (4/1, hexane/ethyl acetate) provides the title compound, IR (nujol) 2925, 2855, 1691, 1564, 1443, 1264, 1243, 1210, 1194 and 1180 cm "1 ; NMR (300 MHz, CDC1 3 ) 3.3-3.7, 2.20, 1.75-2.05 and ' 1.47 δ; MS (m/e) 417, 361 and 246, exact mass calcd for C^H^ , (460.2798), found 460.2803. EXAMPLE 17 5-Hydroxy-4-piperazinyl-2,6-l-di-(l-pyrrolidinyl)pyrimidine 5- acetate (VIII) Following the general procedure of EXAMPLE 12 and making non-critical variations but starting with 5-hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6-di-(l- pyrrolidinyl)pyrimidine 5-acetate (VII, EXAMPLE 16) the title compound is obtained, EXAMPLE 18 5-Hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6-di-(l- pyrrolidinyl)pyrimidine 5-o-chlorόbenzoate (VII) Di-o-chlorobenzoyl peroxide (0.179 g) is added to a solution of 4-[4-(t-butoxy- carbonyl)piperazin-l-yl]-2,6-di-(l-pyπ;olidinyl)pyrimidine(VI, EXAMPLE 10, 0.200 g) and methylene chloride (0.50 ml) at 0°. The solution is allowed to stir at 0° for 2 hours and at 20-25° for 72 hours. Aqueous workup (methylene chloride, magnesium sulfate) and purification by flash chromatography (3/1, hexane/ethyl acetate) gives the title compound, IR (nujol) 2954, 2926, 1757, 1698, 1558..1449, 1345, 1246, 1167, 1026 and 747 cm "1 ; NMR (300 MHz, CDC1 3 ) 8.10, 7.45-7.6, 7.3-7.4, 3.3-3.6, 1.7-2.0 and 1.44 δ; MS (m/e) mass calcd for (556.2565), found 556.2554. EXAMPLE 19 5-Hydroxy-4-piperazinyl-2,6-l-di-(l-pyrrolidiny)lpyrimidine 5-o- chlorobenzoate(VIII) Following the general procedure .of EXAMPLE 12 and making non-critical variations but starting with 5-hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6-di-(l- pyrrolidinyl)pyrimidine 5-o-chlorobenzoate (VII, EXAMPLE 18) the title compound is obtained. * EXAMPLE 20 5-Hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6-di-l- (pyrrolidinyl)pyrimidine 5-p-methoxybenzoate (VII) Di-p-methoxybenzoyl peroxide (188 mg) is added to a solution of 4-[4-(t-butoxy- carbonyl)piperazin-l-yl]-2,6-di-(l-pyrrolidinyl)pyrimidine(VI, EXAMPLE 10, 0.200 g) and methylene chloride (0.50 ml) at 0°. The resultant solution is stirred for 2 hours at 0° and 72 hours at 20-25°. Aqueous workup (methylene chloride, magnesium sulfate) and purification by flash chromatography (3/1, hexane/ethyl acetate) provides the title compound, mp. 215-217°; IR (nujol) 2925, 2856, 173 1681, 1607, 1560, 1446, 1255 and 1164 cm "1 ; NMR (300,MHz, CDC1 3 ) 8.11, 6.98, 3.90, 3.1-3.6, 1.6-2.0 and 1.42 δ; MS (m/e) calcd for C 29 H 40 N 6 O 5 (552.3060), found 552.3047. EXAMPLE 21 5-Hydroxy-4-piperazinyl-2,6-di-(l-pyrrolidinyl)pyrimidine 5-p- methoxybenzoat (VIII) Following the general procedure of EXAMPLE 12 and making non-critical variations but starting with 5-hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6-di-(l- pyrrolidinyl)pyrimidine 5-p-methoxybenzoate (VII, EXAMPLE 20) the title compound is obtained. EXAMPLE 22 5-Hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6-di-(l- pyrrolidinyl)pyrimidine 5-p-chlorobenzoate (VII) Di-p-chlorobenzoyl peroxide (f93 4 mg) is added to a solution of.4-[4-(t-butoxy- carbonyl)piperazin-l-yl]-2,6-di-(l-pyrtolidinyl)pyrimJ<line(VI, EXAMPLE 10, 0.200 g) and methylene chloride (0.50 ml) at 0°. The solution is stirred for 3 hours at 0° and 20 hours at 20-25°. Aqueous workup (methylene chloride, magnesium sulfate) and purifica¬ tion by flash chromatography (3/1, hexane/ethyl acetate) gives the tide compound, mp. 217-218°; IR (nujol) 2954, 2925, 1740, 1696, 1559, 1457, 1446, 1264, 1255, 1245, 1180, 1169, 1091 and 757 cm "1 ; NMR (300 MHz, CDC1 3 ) 8.09, 7.49, 3.2-3.7, 1.7-2.0 and 1.43. δ; MS (m/e) 417 and 361, exact mass calcd for C 28 H 37 N 6 O 4 Cl (556.2565), found 556.2573. EXAMPLE 23 5-Hydroxy-4-piperazinyl-2,6-l-di-(l-pyrrolidinyl)pyrimidine 5rp- chlorobenzoate (VIII) Following the. general procedure of EXAMPLE 12 and making non-critical variations but starting with 5-hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6-di-(l- pyrrolidinyl)pyrimidine 5-p-chlorobenzoate (VII, EXAMPLE 22) the title compound is obtained. EXAMPLE 24 5-Hydroxy-4-[4-(t-butoxycarbonyl)piperazin- 1 -yl]-2 , 6-di-( 1 - pyrrolidinyl)pyrimidine 5-myristoate (VII) Dimyristoyl peroxide (282 mg) is added to a solution of 4-[4-(t-butoxycarbonyl)- piperazin-l-yl]-2,6-di-(l-pyrrolidinyl)pyrimidine (VI, EXAMPLE 10, 0.200 g) and methylene chloride (0.50 ml) at 0°. Additional methylene chloride (0.50 ml) is added to the mixture which is stirred for 2 hours at 0° and 20 hours at 20-25°. Aqueous workup (methylene chloride, magnesium sulfate) and purification by flash chromatog¬ raphy (3/1, hexane/ethyl acetate) gives the title compound, mp 58-62°; IR (nujol) 2924, 2854, 1757, 1695, 1565, 1452, 1346, 1247, 1175 and 1162 cm "1 ; NMR (300 MHz, CDC1 3 ) 3.67, 3.2-3.6, 2.45, 2.31, 1.5-2.0, 1.47, 1.26 and 0.88 δ; MS (m/e) 417 and 361, exact mass calcd for (628.4676), found 628.4668. EXAMPLE 25 5-Hydroxy-4-piperazinyl-2,6-l-di-(l-pyrrolidinyl)-pyrimidine 5- πyyristoate (VIII) Following the general procedure of EXAMPLE 12 and making non-critical variations but starting with 5-hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6-di-(l- pyrrolidinyl)pyrimidine 5-myristoate (VII, EXAMPLE 24) the title compound is ob- tained. EXAMPLE 26 5-Hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6-di-(l- pyrrolidinyl)pyrimidine 5-o-toluoate (VII) Di-o-toluoyl peroxide (168 mg) is added to a solution of 4-[4-(t-butoxycarbonyl)- -31- piperazin-l-yl]-2,6-di-(l-pyrrolidinyl)pyrimidine (VI, EXAMPLE 10, 200 mg) and methylene chloride (0.50 ml) at 0°. The resultant solution is stirred for 2 hours at 0° and 16 hours at 20-25°. Aqueous worltup (methylene chloride, magnesium sulfate) and purification by flash chromatography (3/1, hexane/ethyl acetate) gives the title com- pound, mp. 147-150°; IR (nujol) 2965, 2926, 2859, 1744, 1687, 1552, 1470, 1451, 1422, 1262, 1251, 1236, 1171, 1030 and 742 cm "1 ; NMR (300 MHz, CDC1 3 ) 8.13, 7.48, 7.2-7.4, 3.2-3.6, 2.64, 1.7-2.0 and 1.43 δ; MS (m/e) 417 and 361, exact mass calcd for (536.3111), found 536,3102. EXAMPLE 27 5-Hydroxy-4-piperazinyl-2,6-l-di-(l-pyrrolidinyl)pyrimidine 5-o- toluoate (VIII) Following the general proc sedure of EXAMPLE 12 and making non-critical variations but starting with 5-Hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6-dι-(l- pyrrolidinyl)pyrimidine5-o-toluoate (VJJ, EXAMPLE 26) the title compound is obtained. EXAMPLE 28 5-Hydroxy-4- [4-(t-butoxycarbonyl)piperazin- 1 -yl]-2 , 6-di-( 1 - pyπolidinyl)pyrimidine 5-O-sulfate (VII) Water (2.0 ml) is added to a mixture of 4-[4-(t-butoxycarbonyl)piperazin-l-yl]- 2,6-di-(l-pyrrolidinyl)pyrimidine (VI, EXAMPLE 10, 200 mg), ammonium persulfate (170 mg) and methylene chloride (2.0 ml). The mixture is stured for 4 days at 20-25°. Aqueous workup (methylene chloride, magnesium sulfate) provides a foam which is triturated with ether several times to provide the title compound, IR (nujol) 2954, 2926, 2855, 1696, 1629, 1563, 1456, 1414, 1327, 1265, 1168 and 986 cm "1 ; NMR (300 MHz, CDC1 3 ) 3.4-4.4, 1.7-2.3 and 1.46 δ. EXAMPLE 29 5-Hydroxy-4-piperazinyl-2 , 6- 1 -di-( l-pyrrolidinyl)pyrimidine 5-O- sulfate (Vπi) Following the general procedure of EXAMPLE 12 and making non-critical variations (including an aqueous workup) and starting with 5-hydroxy-4-[4-(t-butoxy- carbonyl)piperazin-l-yl]-2,6-di-(l-pyrrolidinyl)pyrimidine5-sulfate(VII,EXAMPLE28), the title compound is obtained. EXAMPLE 30 l-[5-(Hydroxy)-2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16α- methylpregna-1, 4,9(1 l)-trien-3,20-dione-21-yl]-piperazine (XI) Hydrogen peroxide (30% , 71μl) is added to a solution of 16α-methyl-21-[4-[2,6- di-(l-pyrrolidinyl)-4-pyrimidinyl]-l-piperazinyl]-pregna-l ,4,9(l l)-triene-3,20-dione methanesulfonate monohydrate (I, 100 mg) and acetonitrile (50 ml) at 0°. The mixture is stirred for 3 hr at 0° and for 3 hr at 20-25°. Methyl sulfide (0.20 ml) is added and the reaction stirred for an additional 30 min. The mixture is concentrated, triturated with ether several times and purified by rapid flash chromatography, eluting with chloro- form/methanol/ammonia (375/25/5). The appropriate fractions are pooled and con- centrated to give the title compound., IR (nujol) 2954, 2925, 2856, 1664, 1606, 1574 and 1456 cm "1 . EXAMPLE 31 5-Hydroxy-4-(2-(hydroxyethyl)methylamino)-2,6-di-(l-pyrroli- dinyl)pyrimidine 5-acetate (XIII) Following the general procedure of EXAMPLE 3 but starting with 4-(2-(hy- droxyethyl)methylamino)-2,6-di-(l-pyrrolidinyl)pyrimidine (XJJ, US Patent application Serial No. 07/427,143), the title compound is obtained. EXAMPLE 32 5-Hydroxy-4-(2-(hydroxyethyl)methylamino)-2,6-di-(l-pyrroli- dinyl)pyrimidine 5-benzoate (XIII) Following the general procedure of EXAMPLE 1 but starting with 4-(2-(hyd- roxyethyl)methylamino)-2,6-di-(l-pyrrolidinyl)pyrimidine (XII, US Patent application Serial No. 07/427,143), the title compound is obtained. -33- CHART A R CHART B R 2 -35- CHART C Rτ-Z (IX) R 2 N R 3 N (X) R7° N-R 3 I R 2 CHART D CHART E (steroid) (trolox)

Claims: CLAIMS 1. A 5-oxygenated amino substituted pyrimidine of formula (X) where Rx is (1) steroid substituent of the formula (Steroid) where (A-I) Q 6 is cϋ-Q 6 .ι: β -Q 6 . 2 , Q 10 is α-Q 10 .ι:β-Q 10-2 and Q 7 is o;-H:B-H, where one of Qe. ! and Q^ is -H, and the other is -H, -F, or -C 3 alkyl, Q 10 _ 2 is -CH 3 , Q 1C and Q 5 taken together are -(CH 2 ) 2 -C(=Q 3-3 )-CH= or -CH=CH-CO-CH=, where Q 3-3 is =O or is -H, -CO-CH 3 , -CO-C 2 H 5 , -CO-C 6 H 5 , -CO- O-CH 3 or -CO-O-C 2 H 5 ; (A-II) Qj is Q 6 is α-Q 6 . 3 :β-Q (M , Q 10 is and Q 7 is α-H:β-H, where one of Q & . 3 and Q^ is -H, and the other taken together with one of Q 5 . 3 and Q 5 forms a second bond between C 5 and C 6 , Q 1(M is -CH 3 , Q 10 _ 3 and the other of Q 5 . 3 and Q ^ taken together is -(CH 2 ) 2 -C(H)(OH)-CH 2 -;. (A-III) Q JO and Q 5 taken together are =CH-CH=C(0Q 3i -CH.= where Q 3 is -H, C r C 3 alkyl, -CO-H, C 2 -C 4 alkanoyl or benzyl, Q 6 is α-Qβ-s: β-Qβ-e where one of Q 6 . 5 '» -39- and Q^ is -H, and the other is -H, -F, or C,-C 3 alkyl and Q 7 is α-H-.βΗ; (A-IV) Qj is α-Q^β-Q^, Q 6 is α-Q^ 7 :β-Q Mj Q 7 is α-H:β-H and Q 10 is α-Q ιr 7 : β-Qιo- 8 . where one of taken together are -(CH^-C^Q^-CH^ where Q 3 . 3 is as defined above, Q 10-g is -CH 3 , where one of is -H and the other is -H, -F, or C J -C J alkyl; (A-V) Q 6 is and and Q. i forms a second bond between C 6 and C 7 , and the other of Qj. 9 and Q 7 . 10 is -H, Q l0 . l0 is -CH 3 , Q 10 . 9 and Q 5 taken together are -(CH 2 ) 2 -C(=Q J-3 )- !H= or -CH=CH-CO-CH=, where Q 3-3 is as defined above; (C-I) Qπ is α-Qιu: -Qιι- 2 , where one of Q u . ! and Q 1I-2 is taken together with Q 9 to form a second bond between G, and C π and the other of Q n-1 and Q n-2 i -H; (C-II) Q 9 is -Cl and Q„ is =O or c.-H:β-Q n where Q 1M is -Cl or -OH; (C-III) Q 9 is -H or -F and Q α is =O or where one of Q n .j and Q ιW is -H, and the other of Q π . 5 and Q ^ is -H, -OH or C r C, 2 alkoxy; (C-IV) Q 9 is -H or -F and Q u is α-O-CO-Q n-7 :β-H, where Q π . 7 is (A) C r C 3 alkyl, (B) C Ci 2 alkoxy, (D) -NQi 22 Q 123 , where one of Q m and Q I23 is -H, methyl or ethyl and the other is -H, C,-C 4 alkyl or phenyl, (E) -Oj-Qu where Q 3 is -O- or a valence bond, where Q, is phenyl option¬ ally substituted with 1 through 2 -Cl, -Br, C r C 3 alkoxy, -COOH, -NH 2 , C r C 3 alkyl- amino, di(Cι-C 3 )alkylamino, where the alkyl groups are the same or different, 1- pyrrolidinyl-, 1-piperidinyl, 1-hexamethylenimino-, 1-heptamethylenimino-, C 2 -C 4 acylamino and -NH-CHO or with 1 -F or -CF 3 ; where: (D-I) Q 16 is Q IM .-Q JM and Q J7 is Qι 7 .ι:Q 17 . 2 , where one of Q 1W and Q 16 . 2 is -H or -CH 3 and the other taken together with? one of Q 17- ι and Q 17-2 forms a second bond be- tween C 16 and C 17 , and the other of Q 17 . ! and Q -2 is -C(=Q 20 )-(CH 2 ) n - [attached to the piperazine of the 2,4,6-triarninopyrimidine], where Q^o is =O, =CH 2 or Q I7 . 9 :-H where Q 17 . 9 is -H or -CH 3 , where n is 0 through 6, whefe (D-II) Q 16 is c.-Q 16-3 :β-Q 1& where one of Q 16-3 and Q 164 is -H and the other is -H, -F, -CH 3 or -OH, and Q π is = CH-(Ctϊ 2 ) p -[attached t0 tne piperazine of the 2,4,6-tri- aminopyrimidine], where p is 1 or 2; (D-πi) Q 16 is α-Q 16-5 :β-Q 1<i-6 and Q 17 is where Q 16 . 5 is -H, -OH, -F or -CH 3 and Q 1W is -H, -OH, -F, or -CH 3 , with the proviso that at least one of Q^ and is -H, where Q 17 . 5 is -H, -OH, -CH 3 , -CH 2 CH 3 , C 2 -C 7 alkanoyloxy or -O-CO-Q l5 where Q v is as defined above, and where Q 17 ^. is -C(=Q 20 )-(CH 2 ) n -[attached to the piperazine of the 2,4,6-triaminopyrimidine], where Q J Q and n are as defined above; (D-IV) the 16, 17-acetonide of a compound where Q ϊ6 . 5 is -OH, is -H, Q π . s is -OH and Q 17 ^ is -C(=Q 20 )-(CH 2 ) n -[attached to the piperazine of the 2,4,6-triam- inopyrimidine], where Q 20 and n are as defined above; with the following overall provisos that: (I) one of Q 16-1 or Q 16 _ 2 is taken together with one of Q m or Q 17 . 2 to form a second bond between C l6 and C π , only when Q 10 is c.-Q 1 o. 1 :β-Qι 0 - 2 , α-Q 10-3 :β-Q 1O - 4 , α- Qιo-7: β -Qιo-8 or α-Qio-gi β -Qio-io, (II) Q 17 is =CH-(CH 2 ) p -[attached to the piperazine of the 2,4,6-triamino- pyrimidine], only when Q 10 is α-Qιo.f. β -Qιo.21 (III) Q 5 and Q 10 taken together are =CH-CH=C(OQ 3 )-CH=, only when Q π is c.-Q 17 . 5 :β-Qι 7-6 or the 16,17-acetonide of a compound where Q i6 is o;-OH:β-H and Q 17 is α-OH:β-C(=Q 20 )-(CH 2 ) n -[attached to the piperazine of the 2,4,6-triaminopyrim- idine], and (TV) Qj is α-Q 5 . 7 :β-Q 5-g , only when Q 17 is α-Q 17 . 5 :β-Q 17 ^ or α-OH:β-C- (=Q 20 )-(CH 2 ) n -[attached to the piperazine of the 2,4,6-triaminopyrimidine], or the 16,17- acetonide thereof; (2) trolox substituent of the formula (trolox) where W 2 is -O-, -S-, -NQ 54 - where Q 54 is -H or C, T C 3 alkyl, n <5 is 0, 1 or 2, Q 7 is -H or -C r C 4 alkyl, -CO-(C r C 4 alkyl), -CO-φ or -prodrug where prodrug s -po 2 -α- -CO-CH 2 -CO-NH-CH 2 -SO 2 -O-- -CO-(CH 2 ) lfll -Q 5 j where n 21 is 1-7 and Q 5 ιis -COO • -NQ JI . J Q JLJ where Q;,. ! and where Q SM Q JJ . J Q JI . S are the same or different and are -H or C r C 3 alkyl, and where halide is -Cl or -Br, -CO-CH=CH-CO-O\ -CO-N * -CH==CH-N=CH * where the atoms marked with an asterisk ( * ) are bonded to each other resulting in the formation of a ring, -CO-C'^KCH^-NHJ-O^CH-CH^CH' where n n is 1 or 2 and where the atoms marked with an asterisk ( * ) are bonded to each other resulting in the formation of a ring, -CO-C * =CH-CH=C(-NQs 2 )-CH=CH' where Q^ is -H or C C 3 alkyl and where the atoms marked with an asterisk 0 are bonded to each other resulting in the formation of a ring, -CO-(CH 2 ) n2 ,-CO-O-[C 6 H 12 O 6 sugars], -CO-O-CH(CH 2 -O-CO-Qs 3 ) where the Qj 3 's are the same or different and -CO-(CH 2 ) 6 -CO-N(CH 3 )-CH 2 -CH 2 -SO 3 -cation + where cation + is sodium, potassium or trialkylammonium where alkyl is -C 3 , -CH 2 -O-CC CH 2 ) n21 -NQ 5 ι_ 1 Q 5 ι. 2 where i^,, Qsn and Q^ are as defined above, is -H or - alkyl, -NO 2 , -NQ JJ . I Q SI . J where Q 51 - 1 and Ojι- 2 are as defined above and Qu is -H or -CH 3 , Qι 2 is -H or -CH 3 , (18-1) Q l6 is α-Qwjtβ-Qj M where one of Q }( ϊ and Q 16 . 2 is -H, -CH 3 , -CH 2 CH 3 or -φ and the other is -Qj-jattached to the piperazine of the where Qj is -CO-, -(CHj ie-CO- where n 16 is 1 or 2, -(CHj) ώ - where n 3 is 1-6, or -CO-O-(CH 2 ) nlJ - where n 15 is 2-6, Q 25 and Q^ are -H:-H; (18-2) nβ is 0, Q 16 is Q K ^Q KHI where one of Q 16 . 3 and Q 1M is taken together with Q 25 to form a second bond between the carbon atoms to which Q J6 and Q JJ are attached and the other of Q 16-3 and Q 1M is -Oj-tattached to the piperazine of the 2,4,6-triamino- pyrimidine], where Oj is as defined above, (18-3) n^ is 1, Q 25 and Qjβ are taken together to form a second bond between the carbon atoms to which Q^ and jβ are attached; (3) an alkyl substituent selected from the group consisting of (A)Q 2 -(CH 2 ) n2 - where: n 2 is 1-14; Oj is -H, -OH, -O-CO-(C r C 4 alkyl), -O-CO-H, -O-CO-O-(C r C 4 alkyl), (C r C 4 ) alkoxycarbonyl, -O-CO-aryl where aryl is δ optionally substitued with -OH, -OCH 3 , -F, -Cl, -Br, -CF 3 , -C,-C 3 alkyl, and -CO-Q 5 where Qj is -OH, -NH 2 , - HQβ where Q 6 is φ or C r C 3 alkyl, and -N(Q M )(Qιs) where Q 14 and Qι 5 are the same or different and are C 1 -C 3 alkyl; (B) Q 3 -rO-(CH 2 ) B8 - where n 8 is 2 or 3 and where Q 3 . 1 is -H, Cj-Ca alkyl, -CO-Oj. 2 where Q 3 _ 2 is -H, C,-C 3 alkyl or -φ, (C) Q 3 _ 3 -CO-(CH 2 ) n9 - where n 9 is 1 thru 3 and Q„ is -OH, is C C 4 alkyl or -CH 2 - , C 1 -C 3 alkyl, - optionally substituted with or 2 -F, -Cl, -Br, -NC^, C,-C 3 or -OQ^ where Q^ is C r C 3 alkyl, (D) Q 3 . r O-(CH 2 CH 2 -O) nl o-CH 2 CH 2 - where n 10 is 1 or 2 and where Q^ is as defined above, (E) Q 3 . 3 -CO-CH=CH-CH 2 - where Q 3 . 3 is as defined above, (F) -SO 2 Q 3 . 5 where Q 3-s is C r C 3 alkyl; (G) "CH 2 -(CH 2 ) ll -C * H- where the atoms marked with an asterisk ( * ) are bonded to each other resulting in the formation of a ring and where t, is 1 thru 6; R 2 and R 3 are the same or different and are -H, Gι-C 4 alkyl and where R 2 and R 3 are taken with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-morpholinyl, 1-piperazinyl and 1- piperazinyl substituted in the 4- position with Cj-C 4 alkyl with the proviso that R 2 and R 3 are not both -H; R 7 is (1) -CO-R 4 , where R < is -H, C r C 4 alkyl, -φ optionally substituted with 1, 2 or 3 C.-C alkyl, -OH, Cj- alkoxy, -F, -Cl, -Br, -NO,, -N(R 4 .ι)(R 4 . 2 ) where R . l and ^ are the same or different and are -H or C,-C 4 alkyl, -S-R 4J where R^ 3 is -H or C1-C 4 alkyl, -COOR^ where R^ is -H or C^ alkyl, -(CH 2 ) D4 -N(R 4 .ι)(R 4-2 ) where n„ is 1-6, R . 1 and R^ are as defined above, where n 5 is 1-6 and R*., is as defined above, where n 7 is 1-6, -CH=CH-COOH, -(CH^-NCR^ f ^ ∑ ) where iu, R 4 . J and R^ are as defined above, -(CHjλr f -O-OR*.,) where n s and R 4 ., are as defined above, -(CH^-CO-N CH^-Cft-CHz-SCyOH where nj is 1 thru 6, (2) -R 5 , where R s is C r C 3 alkyl, -C, cycloalkyl, (4) -PO(OH) 2 , (5) -PO(OR 7 .ι) 2 where R 7-l is C r C 4 alkyl', (6) -SO-OR 7 .ι where R 7 .j is as defined above, (7) where n 12 is 1 thru 3, and pharmaceutically acceptable salts thereof. 2. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 1 where R ! is a steroid. 3. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 1 where Q 6 is cr-H:β-H, Q; is α-H:β-H, Q ιa . 2 is -CH 3 , Q 10 ., and Qj taken together are -CH=CH-CO-CH=. 4. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 1 where Qu is α-Q 1 :β-Qu -2 , where one of Q 1M and Q n _ 2 is taken together with Q 9 to form a second bond between G, and C n and the other of Q n- ι and Q n _ 2 is -H. 5. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 2 where Q 16 is α-Qi6- 5 : β -Qι« and Q π is o;-Qι 7- 5: β -Qπ-6, where is -CH 3 , Q lwi is -H, Q 17-5 is -H and Q I7 ^ is -C(=Q 20 )-(CH 2 ) n -[attached to the piperazine of the 2,4,6- triaminopyrimidine], where Q∞ is =O and n is 1. 6. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 1 where j is trolox. 7. A 5-oxygenated aminό substituted pyrimidine of formula (X) according to claim 6 where Q; is -H and Q 10 , Qu and Q 12 are all C x alkyl. 8. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 6 where W 2 is -O-, n^ is 1, Ry is -H:-H and R^ is -H:-H. 9. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 1 where R, is an alkyl group. 10. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 1 where Rj is s -45- (1) Q 2 -(CH 2 ) ll2 - where O^ is -H and n 2 is 2 thru 8 and (2) * CH 2 -(CH 2 ) tl -C * H- where the atoms marked with an asterisk ( * ) are bonded to each other resulting in the formation of a ring and where t t is 1 thru 5. 11. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 1 where R 7 is -CO-R^ 12. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 8 where R_; is -φ or -CH 3 . 13. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 1 where R 7 is -R 5 . 14. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 10 where R 5 is -CH 3 or -C 2 H 5 . 15. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 1 where R 7 is -SCyOH. 16. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 1 where R 2 and R 3 are each C 2 alkyl and where R 2 and R 3 are taken with the attached nitrogen atom to form a heterocyclic ring which is 1-pyrrolidinyl or 1-piperidinyl. 17. A 5-oxygenated amino substituted pyrimidine of formula (X) according to claim 1 which is l-[5-(hydroxy)-2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16α-methylpregna- 1 ,4,9(1 l)-trien-3,20-dione-21-yl]-piperazine 5-benzoate, 4-[4-(3,4-dihydro-6-hydroxy-2,5,7,8-tetrame yl-2H-l-berizopyιan-2-yl)me yl]-l- piperazmyl]-5-hydroxy-2,6^-(l-pyrroUdinyl)-4-pyrimidmyl5-benzoate, l-[5-(hydroxy)-2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16α-methylpregna- 1 ,4,9(1 l)-trien-3,20-dione-21-yl]-piperazine 5-acetate, 1 -[5-(hydroxy)-2 , 6-di-( 1 -pyrrolϊdinyl)-4-pyrimidinyl]-4-[ 1 όαmethylpregna- l,4,9(ll)-trien-3,20-dione-21-yl]-piperazine5-(o-chlorobenzoate), l-[5-(hydroxy)-2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16c--methylpregna- 1 ,4,9(ll)-trien-3,20-dione-21-yl]-φiperazine 5-(p-methoxybenzoate), l-[5-(hydroxy)-2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16c--methylpregna- 1,4,9(1 l)-trien-3 ,20-dione-21 -yl]-piperazine 5-(p-chlorobenzoate) , l-[5-(hydroxy)-2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16α-methylpregna- 1 ,4,9(1 l)-trien-3,20-dione-2 l-yl]-piperazine 5-myristoate, l-[5-(hydroxy)-2,6-di-(l-pyrrolidinyl)-4-pyrimidinyl]-4-[16a-methylpregna- 1 ,4,9(ll)-trien-3,20-dione-21-yl]-piperazine 5-o-toluoate, 1 -[5-(hydroxy)-2 , 6-di- ( 1 -pyrrolidinyl)-4-pyrimidinyl]-4-[l 6o;-methylpregna- 1 ,4,9(1 l)-trien-3,20-dione-21-yl]-piperazine 5-sulfate, 5-hydroxy^-(4-memyl-l-piperazinyl)-2,6-di-(l-pyrrolidinyl)pyrimidine5-benzo- ate, 5-hydroxy-4-(4-propyl-l-piperazinyl)-2,6-di-(l-pyιroUdmyl)pyrinύ 5-benzoate, 4-[[4-(3 ,4-dihydro-6-hydroxy-2,5 ,7, 8-tetramethyl-2H- l-benzopyan-2-yl) carbonyl]-l-piperazinyl]-2,6-di-(l-pyrrondinyl)-4-^^ 18. A protected 5-oxygenated pyrimidine of formula (VII) where R 2 and R 3 are the same or different and are -H, Cι-C 4 alkyl and where R 2 and R 3 are taken with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-morpholinyl, 1-piperazinyl and 1- piperazinyl substituted in the 4- position with C r C 4 alkyl with the proviso that R 2 and R 3 are not both -H; e is t-butoxycarbonyl (t-BOC), benzyloxycarbonyl (CBZ), CH 3 -CO-, φ-CO- and CHO-; -47- R 7 is (1) -CO-R^ where R 4 is -H, C,-C alkyl, -φ optionally substituted with 1, 2 or 3 C,-C alkyl, -OH, Ci- alkoxy, -F, -Cl, -Br, -NO,, -N^ C ^^ where R^, and ^ 2 are the same or different and are -H or C r C 4 alkyl, -S-R 4 where 4 . 3 is -H or C r C 4 alkyl, -COOR^ where ^ is -H or C 1 alkyl, -(CH 2 ) o4 -N(R 4 .ι)(R 4 . 2 ) where 11 4 is 1-6, are as defined above, where n 5 is 1-6 and R ., is as defined above, -(CHi r t -CH COOH where n 7 is 1-6, -CH=CH-COOH, are as defined above, where n 5 and R 4 .1 are as defined above, -(CH 2 ) nr CO-N(CH 3 )-CH 2 -CH 2 -SO 2 -OH where n, is 1 thru 6, (2) -Rj, where R 5 is C r C 3 alkyl, C 4 -C, cycloalkyl, (3) -SO 2 -OH, (4) -PO(OH) 2 , (5) -PC OR 7 .ι) 2 where R 1A is C r C 4 alkyl, (6) -SO-O - 7 . ! where R 7 .ι is as defined above, (7) where n 12 is 1 thru 3, and pharmaceutically acceptable salts thereof. 19. A protected 5-oxygenated pyrimidine (VET) according to claim 18 where R^ is t-BOC or CBZ. 20. A protected 5-oxygenated pyrimidine (VII) according to claim 18 where R 7 is -CO- R . 21. A protected 5-oxygenated pyrimidine (VII) according to claim 18 where R 2 and R 3 are each C^ alkyl and where R 2 and R 3 are taken with the attached nitrogen atom to form a heterocyclic ring which is l-pyrrolidinyl or 1-piperidinyl. 22. A protected 5-oxygenated pyrimidine (VII) according to claim 18 which is 5-hydroxy-4-[4-(t-butoxycarbonyl)piperazm^ 5-benzoate, 5-hydroxy-4-[4-(t-butoxycarbonyl)piperazin-l-yl]-2,6^ 5-acetate, 5-hydroxy-4-[4-(t-butoxycarbonyl)piperazm-l-yl]-2,6-di-(l-pyrroUdinyl)pyrirmdm 5-o-chlorobenzoate, 5-hydroxy-4-[4-(t-butoxycarbonyl)piperazm-l-yl]-2,6^-(l-pyrroUdinyl)pyrirmdm 5-p-methoxybenzoate, 5-hydroxy-4-[4-(t-butoxycarbonyI)piperazm-l-yl]-2,6^-(l-py^ 5-p-chlorobenzoate, 5-hydroxy-4-[4-(t-butoxycarbonyl)pipeiaz -l-yl]-2,6^ 5-myristoate, 5-hydroxy-4-[4-(t-butoxycarbonyl)piperazώ-l-yl]-2,6 5-o-toluoate, 5-hydroxy-4-[4-(t-butoxycarbonyl)piperazm-l-yl]-2,6^ 5-sulfate. 23. A 5-oxygenated pyrimidine of formula (VJJI) where R 2 and R 3 are the same or different and are -H, -C 4 alkyl and where R 2 and R 3 are taken with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidϊnyl, 1-pfperidinyl, 1-morpholinyl, 1-piperazinyl and 1- piperazinyl substituted in the 4- position with C C 4 alkyl with the proviso that R 2 and R 3 are not both -H; R 7 is (1) -CO-R 4 , wherein is - -H, * C,-C 4 alkyl, -φ optionally substituted with 1, 2 or 3 C r C 4 alkyl, -OH,. Cj-Cs alkoxy, -F, -Cl, -Br, -NO,, are the same or different and are -H or C r C 4 alkyl, -S-R 4 . 3 where R^ is -H or Cj-C 4 alkyl, -COOR^ where ^ is -H or C^ alkyl, -(CH^-N R^ R^) where r^ is 1-6, . 1 and ^ are as defined above, is as defined above, -CH=CH-COOH ? -(CH^-NC . ! )^^ where n«, 4 . 1 and R^ are as defined above, where n 5 are as defined above, where n, is 1 thru 6, (2) -Rj, where R 5 is C r C? 3 alkyl, C 4 -C 7 cycloalkyl, (4) -PO(OH) 2 , - (5) - O(OR l ) 2 where R 7 _, is C r C 4 alkyl, (6) -SO-OR 7 _ι where ^^is as. defined above, (7) -[CβHπOJ n wher n, 2 is 1 thru 3, and pharmaceutically acceptable salts thereof. 24. A 5-oxygenated pyrimidine (Viπ according'to * claim 23 where R 2 and R 3 are each C 2 alkyl and where R 2 and R 3 are taken with the attached nitrogen atom to form a hetero- cyclic ring which is 1-pyrrolidinyl or 1-piperidinyl. 25. A 5-oxygenated pyrimidine (VJJI) according to claim 23 which is 5-hydroxy-4-φiperazinyl)-2,6-di-(l-pyrrolidinyl)pyrimidine5-benzoate, 5-hydroxy-4-piperazinyl-2,6-di-(l-pyrrolidinyl)pyrimidine 5-acetate, 5-hydroxy-4-piperazmyl-2,6-di-(l-pyrroHdinyl)pyriπύdine5-o-chlorobenzoate, 5-hydroxy-4-piperazinyl-2,6-di-(l-pyπOUdmyl)pyriπύdine5-p-methoxybenzoate, 5-hydroxy-4-piperazinyl-2,6-di-(l-pyrroUd yl)pyrimidine 5-p-chlorobenzoate, 5-hydroxy-4-piperazinyl-2,6-di-(l-pyrrolidinyl)pyrimidine 5-myristoate, 5-hydroxy-4-piperazinyl-2,6-di-(l-pyrrolidinyl)pyrimidine5-o-toluoate, 5-hydroxy-4-piperazinyl-2,6-di-(l-pyrrolidinyl)pyrimidine 5-O-sulfate. 26. A 5-hydroxy pyrimidine of formula (XI) where R 2 and R 3 are the same or different and are -H, Cj-C alkyl and where R 2 and R 3 are taken with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-morpholinyl, 1-piperazinyl and 1- piperazinyl substituted in the 4- position with - alkyl with the proviso that R 2 and R 3 are not both -H, and where R, is as defined in claim 1. 27. A 5-hydroxy pyrimidine (XI) according to claim 26 which is l-[5-(hydroxy)-2,6-di- (1 -pyrrolidinyl)-4-pyrimidinyl]-4-[16α-methylpregna- 1 ,4,9(1 l) trien-3 ,20-dione-21-yl]- piperazine. 28. An oxygenated N,N-disubstituted pyrimidine of formula (XUJ) -51- where R 2 and R 3 are taken with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-morpholinyl, 1- piperazinyl and 1-piperazinyl substituted in the 4- position with - alkyl with the proviso that R 2 and R 3 are not both -H; R 7 is (1) -CO-R^ where R 4 is -H, Cj-C 4 alkyl, -φ optionally substituted with 1, 2 or 3 C,-C 4 alkyl, -OH, C,-C 3 alkoxy, -F, -Cl, -Br, -NO -N R^ ζR^ where R 4 . J and R^ are the same or different and are -H or C r C 4 alkyl, -S-R^ where R^ is -H or C r C 4 alkyl, -COOR. M where R^ is -H or C M * alkyl, are as defined above, is as defined above, where n 7 is 1-6, -CH=CH-COOH, are as defined above, -(CH 2 ) n5 -O-(R 4 .ι) where n 5 and. R 4 . are as defined above, -(CH 2 ) βl -CO-N(CH 3 )-CH 2 -CH 2 -Sθ 2 -OH where n, is 1 thru 6, (2) -Rj, where R 5 is C r C 3 alkyl, C 4 -C 7 cycloalkyl, (3) -SOrOH, (4) -PO(OH) 2 , (5) -PO(OR 7-1 ) 2 where R 7- , is C r C 4 alkyl, (6) -SO-OR 7-1 where R 7-1 is as defined above, (7) -[C f iHiAG n π where n 12 is 1 thru 3; Qi is Cr alkyl, -O-CH 3 , -O-CH 2 CH 3 , -(CH Z ^ I -O-Q LI where nj is 2 or 3 and Q M is -H, C,-C 3 alkyl, -CO- Qι. 2 where Q^ is -H, Ci- alkyl or -δ, -CH 2 -CH(OQj.ι)-CH 3 where Qu is as defined above, where n 2 is 1 or 2 and where Q is as defined above, -(CH 2 ) n3 -C Q 1-3 where n 3 is 1 thru 3 and Q,. 3 is -OH, -O-Q where Q M is C,-C 4 alkyl or -CH 2 -φ, -Cs alkyl, -φ optionally substituted with 1 or 2 -F, -Cl, -Br, -NO 2 , Cj- or -OQι. 7 where Q 1-7 is C r C 3 alkyl, -CH 2 -CH=CH-CO-Qι -3 where Q 1-3 is as defined above, -(CH 2 ) D -N(Q I-J )(Q I ^) where n, is 2 or 3 and Q l-5 and Q M are the same or different and are -H and C,-C 3 alkyl, Q 2 is -H, Cj-Cs alkyl, is -H, C r C 3 alkyl, -CO- Q 2 . 2 where Q 2 . 2 is -H, Ci- alkyl or -φ, is as defined above, -CK 2 CK 2 -(0-CK 2 CR 2 ) a6 -0-Q 2 . l where n^ is 1 or 2 and where Q 2 ,ι is as defined above, -(CH 2 ) n7 -CO-Q 2-3 where n 7 is 1 thru 3 and Q 2 _ 3 is -OH, -O-Qj. 4 where Q^ is C r C 4 alkyl or -CH 2 -φ; C 1 -C 3 alkyl, -φ optionally substituted with 1 or 2 -F, -Cl, -Br, -NO 2 , C r C 3 or -O-Qj.j where Q 2 . 5 is alkyl and pharmaceutically acceptable salts thereof. 29. An oxygenated N,N-disubstituted pyrimidine (XIII) according to claim 28 where R 7 is -CO-R,. 30. An oxygenated N,N-disubstituted pyrimidine (XUT) according to claim 28 where Q, is C r C 3 alkyl, -O-CH 3 , and Qj is -H, - alkyl and 31. An oxygenated N,N-disubstituted pyrimidine (Xm) according to claim 28 which is 5-hydroxy-4-(2-(hydroxyethyl)methylamino)-2,6-di-(l-pyrrolidinyl)pyrimidine 5-acetate, 5-hydroxy-4-(2-(hydroxyethyl)methylamino)-2,6-di-(l-pyrrolidinyl)pyrimidine 5-benzoate.

Inventors: JACOBSEN ERIC JON, MCCALL JOHN MICHAEL, JACOBSEN, ERIC, JON, MCCALL, JOHN, MICHAEL
Applicants: UPJOHN CO, THE UPJOHN COMPANY
Application year: 1991
Main classification: C07D403
IPC codes: A61K31, A61P3, A61P43, C07D239, C07D403, C07D405, C07J43