UA67715C2

UA67715C2 - Peptides derivatives, a method for the preparation thereof, pharmaceutical composition and a method for inhibition of thrombine of mammals

Peptides derivatives, a method for the preparation thereof, pharmaceutical composition and a method for inhibition of thrombine of mammals Download PDF

Info

Publication number: UA67715C2
Authority: UA; Ukraine
Prior art keywords: denotes; сно; hydrogen; compound; unsubstituted
Prior art date: 1994-03-04

Application number

UA96093453A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Astrazeneca Ab

Priority date

1994-03-04

Filing date

1995-03-03

Publication date

2004-07-15

1995-03-03 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2004-07-15 Publication of UA67715C2 publication Critical patent/UA67715C2/uk

Links

238000000034 method Methods 0.000 title claims abstract description 267
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
241000124008 Mammalia Species 0.000 title claims description 10
238000002360 preparation method Methods 0.000 title description 104
108090000765 processed proteins & peptides Proteins 0.000 title description 12
230000005764 inhibitory process Effects 0.000 title description 11
102000004196 processed proteins & peptides Human genes 0.000 title description 8
150000001875 compounds Chemical class 0.000 claims abstract description 225
108090000190 Thrombin Proteins 0.000 claims abstract description 53
229960004072 thrombin Drugs 0.000 claims abstract description 53
230000002401 inhibitory effect Effects 0.000 claims abstract description 12
-1 homoprolinyl Chemical group 0.000 claims description 141
229910052739 hydrogen Inorganic materials 0.000 claims description 105
239000001257 hydrogen Substances 0.000 claims description 97
125000000217 alkyl group Chemical group 0.000 claims description 61
150000003839 salts Chemical class 0.000 claims description 57
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 55
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 53
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
150000002431 hydrogen Chemical class 0.000 claims description 42
229910052757 nitrogen Inorganic materials 0.000 claims description 29
239000012453 solvate Substances 0.000 claims description 29
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 28
125000006239 protecting group Chemical group 0.000 claims description 27
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
229910052760 oxygen Inorganic materials 0.000 claims description 24
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 23
125000005842 heteroatom Chemical group 0.000 claims description 23
239000001301 oxygen Substances 0.000 claims description 23
125000003118 aryl group Chemical group 0.000 claims description 21
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 20
239000002253 acid Substances 0.000 claims description 20
229910052717 sulfur Inorganic materials 0.000 claims description 19
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 18
125000004429 atom Chemical group 0.000 claims description 18
230000015572 biosynthetic process Effects 0.000 claims description 18
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125000001424 substituent group Chemical group 0.000 claims description 18
239000011593 sulfur Substances 0.000 claims description 18
150000001412 amines Chemical class 0.000 claims description 14
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
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125000000623 heterocyclic group Chemical group 0.000 claims description 13
125000000753 cycloalkyl group Chemical group 0.000 claims description 12
JIDDDPVQQUHACU-YFKPBYRVSA-N (2s)-pyrrolidine-2-carbaldehyde Chemical group O=C[C@@H]1CCCN1 JIDDDPVQQUHACU-YFKPBYRVSA-N 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
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239000003085 diluting agent Substances 0.000 claims description 9
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125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
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PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical group NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims description 4
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125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
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GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
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239000000460 chlorine Substances 0.000 claims description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
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125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
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125000001041 indolyl group Chemical group 0.000 claims description 2
239000011630 iodine Chemical group 0.000 claims description 2
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125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
125000001786 isothiazolyl group Chemical group 0.000 claims description 2
125000000842 isoxazolyl group Chemical group 0.000 claims description 2
125000006431 methyl cyclopropyl group Chemical group 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000002971 oxazolyl group Chemical group 0.000 claims description 2
229910052700 potassium Inorganic materials 0.000 claims description 2
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
125000003373 pyrazinyl group Chemical group 0.000 claims description 2
125000003226 pyrazolyl group Chemical group 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
125000000168 pyrrolyl group Chemical group 0.000 claims description 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
229910052709 silver Inorganic materials 0.000 claims description 2
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 2
125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
239000005864 Sulphur Substances 0.000 claims 2
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 2
125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
235000010469 Glycine max Nutrition 0.000 claims 1
244000068988 Glycine max Species 0.000 claims 1
125000002947 alkylene group Chemical group 0.000 claims 1
125000006242 amine protecting group Chemical group 0.000 claims 1
235000015111 chews Nutrition 0.000 claims 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
238000007327 hydrogenolysis reaction Methods 0.000 claims 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
239000003795 chemical substances by application Substances 0.000 abstract description 10
229940122388 Thrombin inhibitor Drugs 0.000 abstract description 8
239000003868 thrombin inhibitor Substances 0.000 abstract description 8
239000003130 blood coagulation factor inhibitor Substances 0.000 abstract 1
230000009424 thromboembolic effect Effects 0.000 abstract 1
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