USRE37686EExpiredUtilityPatentIndex 63
Azahydroxybenzotriazoles and derivatives thereof for peptide coupling reactions
Est. expirySep 28, 2012(expired)· nominal 20-yr term from priority
Inventors:CARPINO LOUIS A
C07K 1/082C07K 1/084C07K 1/10C07F 9/6561C07D 513/04C07D 495/04C07D 491/04C07D 471/04
63
PatentIndex Score
3
Cited by
36
References
136
Claims
Abstract
This invention relates to a process for forming an amide or an ester from a reaction between an amine or an alcohol, respectively and an acylating derivative of a carboxylic acid, in the presence of an effective amount of a compound having the formula: and N-oxides thereof and salts thereof.
Claims
exact text as granted — not AI-modifiedWhat is claimed:
1. A compound of the formula:
or N-oxides thereof or salts thereof wherein
D is CR 16 or N;
E is CR 17 or N;
A is CR 15 or N;
G is CR 18 or N;
provided that one and only one of A, E, D or G is N;
R 15 , R 16 , R 17 and R 18 are independently hydrogen, lower alkyl or an electron donating group;
X is CR 7 or N;
Y is N or CR 5 ;
R 7 and R 5 are independently hydrogen or lower alkyl;
R 3 is SO 2 R 14 , lower alkyl carbonyl, aryl carbonyl, aryl lower alkyl carbonyl, a positively charged electron withdrawing group of the formula P⊕ ( NR 12 R 13 ) 3 , or AA 1 -BLK 1 ;
R 12 and R 13 are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5 - or 6 - membered heterocyclic ring containing up to a total of 5 ring carbon atoms;
R 14 is lower alkyl, aryl or aryl lower alkyl; BLK 1 is an amino acid protecting group; and AA 1 is an amino acid or peptide less a hydrogen on the N-terminus and an OH on the C-terminus.
2. The compound according to claim 1 wherein A or G is N.
3. The compound according to claim 1 wherein Y is CH or N and X is CH or N.
4. The compound according to claim 1 wherein the electron donating group is amino, lower alkylamino, diloweralkylamino, hydroxy, lower alkoxy, lower aralkoxy, halo, aryl, mercapto, or lower alkylthio.
5. The compound according to claim 4 wherein the electron donating group is lower dialkylamino or lower alkoxy.
6. The compound according to claim 1 having the formula
in which Y is N or CH and
X is N or CH.
7. The compound according to claim 6 wherein R 3 is OSO 2 R 14 SO 2 R 14 , lower alkylcarbonyl, aryl carbonyl, or aryl lower alkyl carbonyl.
8. The compound according to claim 6 wherein R 3 is AA 1 -BLK 1 .
9. The compound according to claim 6 wherein R 3 is a positively charged electron withdrawing group.
10. The compound according to claim 9 6 wherein R 3 is
wherein R 10 , R 11 , R 12 and R 13 are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or
R 10 and R 11 taken together with the nitrogen atom to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 10 and R 12 taken together with the atoms to which they are attached from a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocyclic ring containing up to a total of 5 ring carbon atoms.
11. The compound according to claim 10 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl, hydrogen or lower alkoxy lower alkyl.
12. The compound according to claim 11 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl.
13. The compound according to claim 12 wherein R 10 , R 11 , R 12 and R 13 are methyl.
14. The compound according to claim 10 wherein R 3 is
and m is 0 or 1.
15. The compound according to claim 14 wherein R 11 and R 12 are independently hydrogen, methyl, ethyl, propyl, butyl, pentyl or CH 2 —CH 2 O—CH 2 —CH 3 .
16. The compound according to claim 6 wherein R 3 is
wherein U is N-ALK, CH 2 or O, and ALK is lower alkyl or hydrogen.
17. The compound according to claim 16 wherein U is CH 2 .
18. The compound according to claim 6 wherein the compound has the formula:
19. The compound according to claim 18 wherein R 3 is OSO 2 R 14 SO 2 R 14 , lower alkylcarbonyl, aryl carbonyl, or aryl lower alkyl carbonyl.
20. The compound according to claim 18 wherein R 3 is AA 1 -BLK 1 .
21. The compound according to claim 18 wherein R 3 is a positively charged electron withdrawing group.
22. The compound according to claim 21 18 wherein R 3 is
wherein R 10 , R 11 , R 12 and R 13 are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or
R 10 , R 11 taken together with the nitrogen atom to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 10 and R 12 taken together with the atoms to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 12 and R 13 taken together with the nitrogen atoms to which they are attached form a 5- or 6-membered heterocyclic ring containing up to a total of 5 ring carbon atoms.
23. The compound according to claim 22 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl, hydrogen or lower alkoxy lower alkyl.
24. The compound according to claim 23 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl.
25. The compound according to claim 24 wherein R 10 , R 11 , R 12 and R 13 are methyl.
26. The compound according to claim 22 wherein R 3 is
and m is 0 or 1.
27. The compound according to claim 26 wherein R 11 and R 12 are independently hydrogen, methyl, ethyl, propyl, butyl, pentyl or CH 2 —CH 2 O—CH 2 —CH 3 .
28. The compound according to claim 18 wherein R 3 is
wherein U is N-ALK, CH 2 or O, and ALK is lower alkyl or hydrogen.
29. The compound according to claim 28 wherein U is CH 2 .
30. A compound of the formula:
or N-oxides thereof or salts thereof wherein
D is CR 16 or N;
E is CR 17 or N;
A is CR 15 or N;
G is CR 18 or N;
and at least two of A, E, D and G are N;
R 15 , R 16 , R 17 and R 18 are independently hydrogen, lower alkyl or an electron donating group;
R 3 is hydrogen lower alkyl carbonyl, aryl carbonyl, aryl lower alkyl carbonyl, SO 2 R 14 , a positively charged electron withdrawing group of the formula P⊕ ( NR 12 R 13 ) 3 , or AA 1 -BLK 1 ;
R 12 and R 13 are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5 - or 6 - membered heterocyclic ring containing up to a total of 5 ring carbon atoms,
R 14 is lower alkyl, aryl, or aryl lower alkyl;
BLK 1 is an amino acid protecting group, ; and
AA 1 is an amino acid or peptide less a hydrogen on the N-terminus and an OH on the C-terminus.
31. The compound of claim 30 wherein two of A, D, E and G are N.
32. The compound of claim 30 wherein the electron donating group is amino, lower alkylamino, diloweralkylamino, hydroxy, lower alkoxy, lower aralkoxy, halo, aryl, mercapto, or lower alkylthio.
33. The compound of claim 32 wherein the electron donating group is lower dialkylamino or lower alkoxy.
34. The compound of claim 30 wherein R 3 is hydrogen.
35. The compound of claim 30 wherein R 3 is OSO 2 R 14 SO 2 R 14 , lower alkylcarbonyl, aryl carbonyl, or aryl lower alkyl carbonyl.
36. The compound of claim 30 wherein R 3 is BLK 1 -AA 1 .
37. The compound of claim 30 wherein R 3 is a positively charged electron withdrawing group.
38. The compound of claim 37 30 wherein R 3 is
wherein R 10 , R 11 , R 12 and R 13 are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or
R 10 and R 11 taken together with the nitrogen atom to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total 5 ring carbon atoms or R 10 and R 12 taken together with the atoms to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocyclic ring containing up to a total of 5 ring carbon atoms.
39. The compound according to claim 38 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl, hydrogen or lower alkoxy lower alkyl.
40. The compound of claim 38 wherein R 3 is
and m is 0 or 1.
41. The compound according to claim 30 wherein R 3 is
wherein U is N-ALK, CH 2 or O, and ALK is lower alkyl or hydrogen.
42. A compound of the formula:
or N-oxides thereof or salts thereof; wherein
X is CR 7 or N;
Y is CR 5 or N; with the proviso that X and Y cannot both represent N simultaneously;
R 5 and R 7 are independently hydrogen or lower alkyl;
D is CR 16 or N;
E is CR 17 or N;
A is CR 15 or N;
G is CR 18 or N;
with the further proviso that one and only one of A, E, D and G is N;
R 15 , R 16 , R 17 and R 18 are independently hydrogen, lower alkyl or an electron donating group;
R 3 is hydrogen, SO 2 R 14 , lower alkyl carbonyl, aryl carbonyl, aryl lower alkyl carbonyl, a positively charged electron withdrawing group of the formula P ⊕ ( NR 12 R 13 ) 3 , or AA 1 -BLK 1 ;
R 12 and R 13 are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5 - or 6 - membered heterocyclic ring containing up to a total of 5 ring carbon atoms;
R 14 is lower alkyl, aryl or aryl lower alkyl;
BLK 1 is an amino acid protecting group; and
AA 1 is an amino acid or peptide less an hydrogen on the N-terminus and an OH on the C-terminus.
43. The compound according to claim 42 wherein R 3 is hydrogen.
44. The compound according to claim 42 having the formula:
45. The compound according to claim 44 wherein Y is CR 5 and X is N.
46. The compound according to claim 45 wherein Y is CH.
47. The compound according to claim 44 wherein X is CR 7 and Y is N.
48. The compound according to claim 47 wherein X is CH.
49. The compound according to claim 44 wherein X is CR 7 and Y is CR 5 .
50. The compound according to claim 49 wherein X and Y are both CH.
51. A compound of the formula:
wherein
D is CR 16 or N;
E is CR 17 or N;
A is CR 15 ;
G is CR 18 ;
provided that one and only one of D and E is N;
R 15 , R 16 , R 17 and R 18 are independently hydrogen, lower alkyl or an electron donating group,
R 3 is hydrogen, SO 2 R 14 , lower alkyl carbonyl, aryl carbonyl, aryl lower alkyl carbonyl, a positively charged electron withdrawing group of the formula P ⊕ ( NR 12 R 13 ) 3 , or AA 1 -BLK 1 ;
R 12 and R 13 are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5 - or 6 - membered heterocyclic ring containing up to a total of 5 ring carbon atoms;
R 14 is lower alkyl, aryl or aryl lower alkyl;
BLK 1 is an amino acid protecting group; and
AA 1 is an amino acid or peptide less ana hydrogen on the N-terminus and an OH on the C-terminus.
52. The compound according to claim 51 wherein D is N.
53. The compound according to claim 51 wherein E is N.
54. The compound according to claim 51 wherein D is N and A and G are CH.
55. The compound according to claim 54 wherein R 3 is hydrogen.
56. The compound according to claim 51 wherein E is N and A and G are CH.
57. The compound according to claim 56 wherein R 3 is hydrogen.
58. A compound of the formula:
or N-oxides thereof or salts thereof wherein
D is CR 16 or N;
E is CR 17 or N;
A is CR 15 or N;
G is CR 18 or N;
provided that one and only one of D, E, A, and G is N;
at least one of R 15 , R 16 , R 17 and R 18 is an electron donating group, and the remainder is independently hydrogen, lower alkyl or an electron donating group;
X is CR 7 or N;
Y is N or CR 5 ;
R 7 and R 5 are independently hydrogen or lower alkyl;
R 3 is hydrogen, SO 2 R 14 , lower alkyl carbonyl, aryl carbonyl, aryl lower alkyl carbonyl, a positively charged electron withdrawing group of the formula: P ⊕ ( NR 12 R 13 ) 3 , or AA 1 -BLK 1 ;
R 12 and R 13 are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5 - or 6 - membered heterocyclic ring containing up to a total of 5 ring carbon atoms;
R 14 is lower alkyl, aryl or aryl lower alkyl;
BLK 1 is an amino acid protecting group and
AA 1 is an amino acid or peptide less a hydrogen on the N-terminus and an OH on the C-terminus.
59. The compund compound according to claim 58 wherein R 3 is hydrogen.
60. The compound according to claim 58 wherein R 3 is AA 1 -BLK 1 .
61. The compound according to claim 58 wherein R 3 is a positively charged electron withdrawing group.
62. The compound according to claim 58 wherein A or G is N.
63. The compound according to claim 58 wherein Y is CH or N and X is CH or N.
64. The compound according to claim 58 wherein the electron donating group is diloweralkylamino, lower alkoxy, lower aralkoxy, halo, aryl or lower alkylthio.
65. The compound according to claim 64 wherein the electron donating group is lower dialkylamino or lower alkoxy.
66. The compound according to claim 58 having the formula:
wherein R 15 is lower alkyl or an electron donating group, and R 17 is lower alkyl, hydrogen or an electron donating group.
67. The compound according to claim 66 wherein R 3 is hydrogen.
68. The compound according to claim 66 wherein R 3 is OSO 2 R 14 SO 2 R 14 , lower alkyl carbonyl, aryl carbonyl or aryl lower alkyl carbonyl.
69. The compound according to claim 66 wherein R 3 is AA 1 -BLK 1 .
70. The compound according to claim 66 wherein R 3 is a positively charged electron withdrawing group.
71. The compound according to claim 70 66 wherein R 3 is
wherein R 10 , R 11 , R 12 and R 13 are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or
R 10 and R 11 taken together with the nitrogen atom to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 10 and R 12 taken together with the atoms to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocyclic ring containing up to a total of 5 ring carbon atoms.
72. The compound according to claim 71 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl, hydrogen or lower alkoxy lower alkyl.
73. The compound according to claim 72 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl.
74. The compound according to claim 73 wherein R 10 , R 11 , R 12 and R 13 are methyl.
75. The compound according to claim 71 wherein R 3 is
wherein m is 0 or 1.
76. The compound according to claim 70 wherein R 3 is
wherein U is N-ALK, CH 2 or O, and ALK is lower alkyl or hydrogen.
77. The compound according to claim 66 wherein R 15 is an electron donating group and R 17 is hydrogen or an electron donating group.
78. The compound according to claim 77 wherein the electron donating group is diloweralkylamino or lower alkoxy.
79. An N-oxide of a compound of the formula:
or a salt thereof, wherein
D is CR 16 or N;
E is CR 17 or N;
A is CR 15 or N;
G is CR 18 or N;
provided that one and only one of A, E, D or G is N;
R 15 , R 16 , R 17 and R 18 are independently hydrogen, lower alkyl and or electron donating group, ;
X is CR 7 or N;
Y is CR 5 or N;
R 7 and R 5 are independently hydrogen or lower alkyl;
R 3 is hydrogen, SO 2 R 14 , lower alkyl carbonyl, aryl carbonyl, aryl lower alkyl carbonyl, a positively charged electron withdrawing group of the formula P ⊕ ( NR 12 R 13 ) 3 , or BLK 1 -AA 1 AA 1 - BLK 1 ;
R 12 and R 13 are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5 - or 6 - membered heterocyclic ring containing up to a total of 5 ring carbon atoms;
R 14 is lower alkyl, aryl or aryl lower alkyl;
BLK 1 is an amino acid protecting group; and
AA 1 is an amino acid or peptide less a hydrogen on the N-terminus and an OH on the C-terminus.
80. The compound according to claim 79 wherein R 3 is hydrogen.
81. The compound according to claim 79 wherein R 3 is OSO 2 R 14 SO 2 R 14 , lower alkyl carbonyl, aryl carbonyl, or lower alkyl carbonyl.
82. The compound according to claim 79 wherein R 3 is a positively charged electron withdrawing group.
83. The compound according to claim 82 79 wherein R 3 is
wherein R 10 , R 11 , R 12 and R 13 are independently halogen, hydrogen, lower alkyl or lower alkoxy lower alkyl or
R 10 and R 11 taken together with the nitrogen atom to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 10 and R 12 taken together with the atoms to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 1 R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocyclic ring containing up to a total of 5 ring carbon atoms.
84. The compound according to claim 79 wherein A or G is N.
85. The compound according to claim 79 wherein Y is CH or N and X is CH or N.
86. The compound according to claim 79 having the formula:
87. The compound according to claim 86 wherein R 3 is hydrogen.
88. The compound according to claim 86 wherein R 3 is OSO 2 R 14 SO 2 R 14 , lower alkyl carbonyl, aryl carbonyl, or lower alkyl carbonyl.
89. The compound according to claim 86 wherein R 3 is a positively charged electron withdrawing group.
90. The compound according to claim 89 86 wherein R 3 is
wherein R 10 , R 11 , R 12 and R 13 are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or
R 10 and R 11 taken together with the nitrogen atom to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 10 and R 12 taken together with the atoms to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocyclic ring containing up to a total of 5 ring carbon atoms.
91. The compound according to claim 1 of the formula:
wherein R 3 is
wherein U is CH 2 , O or N-ALK and ALK is H or lower alkyl.
92. The compound according to claim 1 of the formula:
wherein U is CH 2 , O or N-ALK is H or lower alkyl. Ar is aryl.
93. The compound according to claim 91 wherein U is CH 2 .
94. A compound prepared from the reaction of R 3 L with
under substitution reaction conditions wherein
D is CR
16
or N;
E is CR
17
or N;
A is CR
15
or N;
G is CR
18
or N;
provided that one and only one of A, E, D or G is N;
R
15
, R
16
, R
17
and R
18
are independently hydrogen, lower alkyl or an electron donating group;
X is CR
7
or N;
Y is N or CR 5 ;
R
7
and R
5
are independently hydrogen or lower alkyl;
R 3 is SO 2 R 14 , lower alkyl carbonyl, aryl carbonyl, aryl lower alkyl carbonyl, a positively charged electron withdrawing group or AA 1 - BLK 1 ;
R
14
is lower alkyl, aryl or aryl lower alkyl;
L is a leaving group;
BLK
1
is an amino acid protecting group; and
AA 1 is an amino acid or peptide less a hydrogen on the N - terminus and an OH on the C - terminus.
95. The compound according to claim 94 wherein A or G is N.
96. The compound according to claim 94 wherein Y is CH or N and X is CH or N.
97. The compound according to claim 94 wherein R 3 is a positively charged electron withdrawing group.
98. The compound according to claim 97 wherein R 3 is
wherein
R
10
, R
11
, R
12
and R
13
are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or
R 10 and R 11 taken together with the nitrogen atom to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 10 and R 12 taken together with the atoms to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms, or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5 - or 6 - membered heterocyclic ring containing up to a total of 5 ring carbon atoms.
99. The compound according to claim 98 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl, hydrogen or lower alkoxy lower alkyl.
100. The compound according to claim 99 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl.
101. The compound according to claim 100 wherein R 10 , R 11 , R 12 and R 13 are methyl.
102. The compound according to claim 98 wherein R 3 is
and m is 0 or 1 .
103. The compound according to claim 102 wherein R 11 and R 12 are independently hydrogen, methyl, ethyl, propyl, butyl, pentyl or CH 2 —CH 2 O—CH 2 CH 3 .
104. The compound according to claim 94 wherein R 3 is
wherein U is N - ALK, CH 2 or O and ALK is lower alkyl or hydrogen.
105. The compound according to claim 104 wherein U is CH 2 .
106. The compound according to claim 94 prepared from the reaction of R 3 L with
107. The compound according to claim 106 wherein A or G is N.
108. The compound according to claim 106 wherein R 3 is a positively charged electron withdrawing group.
109. The compound according to claim 108 wherein R 3 is
wherein
R
10
, R
11
, R
12
and R
13
are independently hydrogen, lower alkyl or lower alkoxy lower alkyl or
R 10 and R 11 taken together with the nitrogen atom to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 10 and R 12 taken together with the atoms to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5 - or 6 - membered heterocyclic ring containing up to a total of 5 ring carbon atoms.
110. The compound according to claim 109 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl, hydrogen or lower alkoxy lower alkyl.
111. The compound according to claim 110 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl.
112. The compound according to claim 111 wherein R 10 , R 11 , R 12 and R 13 are methyl.
113. The compound according to claim 94 wherein R 3 is
and m is 0 or 1 .
114. The compound according to claim 113 wherein R 11 and R 12 are independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, or CH 2 —CH 2 O—CH 2 CH 3 .
115. The compound according to claim 107 wherein R 3 is
wherein U is N - ALK, CH 2 or O and ALK is lower alkyl or hydrogen.
116. The compound according to claim 115 wherein U is CH 2 .
117. The compound according to claim 106 wherein
is prepared by reacting
with hydrazine under conditions effective to form said compound wherein
R
1
is halogen, NH—NH
2
or OR
11
and
R
11
is lower alkyl.
118. The compound according to claim 94 which is formed by reacting 1 - hydroxy - 7 - aza - benzotriazole with R 3 L, wherein R 3 is 1 , 1 , 3 , 3 - tetramethyluronium salt and L is a leaving group.
119. The compound according to claim 118 wherein the leaving group is a halide.
120. A compound of the formula:
or N - oxides thereof or salts thereof wherein
D is CR
16
or N;
E is CR
17
or N;
A is CR
15
or N;
G is CR
18
or N;
provided that one and only one of A, E, D or G is N;
R
15
, R
16
, R
17
, R
18
are independently hydrogen, lower alkyl or an electron donating group;
X is CR
7
or N;
Y is CR 5 ;
R
7
and R
5
are independently hydrogen or lower alkyl;
R 3 is SO 2 R 14 , lower alkyl carbonyl, aryl carbonyl, aryl lower alkyl carbonyl, a positively charged electron withdrawing group or AA 1 - BLK 1 ;
R 14 is lower alkyl, aryl or aryl lower alkyl; BLK 1 is an amino acid protecting group; and AA 1 is an amino acid or peptide less a hydrogen on the N - terminus and an OH on the C - terminus.
121. The compound according to claim 120 wherein A or G is N.
122. The compound according to claim 120 wherein Y is CH and X is CH or N.
123. The compound according to claim 120 wherein the electron donating group is amino, lower alkylamino, diloweralkylamino, hydroxy, lower alkoxy, lower aralkoxy, halo, aryl, mercapto, or lower alkylthio.
124. The compound according to claim 123 wherein the electron donating group is lower dialkylamino or lower alkoxy.
125. The compound according to claim 120 having the formula:
in which Y is CH and
X is N or CH.
126. The compound according to claim 125 wherein R 3 is SO 2 R 14 , lower alkylcarbonyl, aryl carbonyl, or aryl lower alkyl carbonyl.
127. The compound according to claim 125 wherein R 3 is AA 1 - BLK 1 .
128. The compound according to claim 125 wherein R 3 is a positively charged electron withdrawing group.
129. The compound according to claim 125 wherein R 3 is
wherein R
10
, R
11
, R
12
and R
13
are independently hydrogen, lower alkyl or lower alkoxy lower alkyl; or
R 10 and R 11 taken together with the nitrogen atom to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 10 and R 12 taken together with the atoms to which they are attached form a heterocyclic ring containing up to 6 ring atoms and up to a total of 5 ring carbon atoms or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 5 - or 6 - membered heterocyclic ring containing up to a total of 5 ring carbon atoms.
130. The compound according to claim 129 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl, hydrogen or lower alkoxy lower alkyl.
131. The compound according to claim 130 wherein R 10 , R 11 , R 12 and R 13 are independently lower alkyl.
132. The compound according to claim 130 wherein R 10 , R 11 , R 12 and R 13 are methyl.
133. The compound according to claim 129 wherein R 3 is
and m is 0 or 1 .
134. The compound according to claim 133 wherein R 11 and R 12 are independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, or CH 2 —CH 2 O—CH 2 —CH 3 .
135. The compound according to claim 125 wherein R 3 is
wherein U is N - ALK, CH 2 or O, and ALK is lower alkyl or hydrogen.
136. The compound according to claim 16 wherein U is CH 2 .Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.