ES2553154T3

ES2553154T3 - Derivado de la insulina

Derivado de la insulina Download PDF

Info

Publication number: ES2553154T3
Authority: ES; Spain
Prior art keywords: insulin; group; amino acid; chain; amide
Prior art date: 2006-05-09
Legal status : Active

Application number

ES07728892.6T

Other languages

English (en)

Spanish (es)

Inventor

Ib Jonassen

Patrick William Garibay

Janos Tibor Kodra

Current Assignee

Novo Nordisk AS

Original Assignee

Novo Nordisk AS

Priority date

2006-05-09

Filing date

2007-05-08

Publication date

2015-12-04

2007-05-08 Application filed by Novo Nordisk AS filed Critical Novo Nordisk AS

2015-12-04 Application granted granted Critical

2015-12-04 Publication of ES2553154T3 publication Critical patent/ES2553154T3/es

Status Active legal-status Critical Current

2027-05-08 Anticipated expiration legal-status Critical

Links

NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims abstract description 541
239000004026 insulin derivative Substances 0.000 title claims abstract description 189
102000004877 Insulin Human genes 0.000 claims abstract description 165
108090001061 Insulin Proteins 0.000 claims abstract description 165
229940125396 insulin Drugs 0.000 claims abstract description 157
-1 - (CH2) 1-6COOH Chemical group 0.000 claims abstract description 83
150000001413 amino acids Chemical class 0.000 claims abstract description 50
125000000539 amino acid group Chemical group 0.000 claims abstract description 43
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 41
125000001424 substituent group Chemical group 0.000 claims abstract description 37
239000001257 hydrogen Substances 0.000 claims abstract description 30
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 30
125000003118 aryl group Chemical group 0.000 claims abstract description 24
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 22
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 18
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 18
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 17
125000000729 N-terminal amino-acid group Chemical group 0.000 claims abstract description 16
229910006069 SO3H Inorganic materials 0.000 claims abstract description 13
229910018828 PO3H2 Inorganic materials 0.000 claims abstract description 11
150000001412 amines Chemical class 0.000 claims abstract description 10
125000002843 carboxylic acid group Chemical group 0.000 claims abstract description 9
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 8
229910052736 halogen Inorganic materials 0.000 claims abstract description 7
150000002367 halogens Chemical class 0.000 claims abstract description 7
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 6
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 5
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PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 56
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150000001408 amides Chemical class 0.000 claims description 16
150000002431 hydrogen Chemical class 0.000 claims description 12
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
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235000001014 amino acid Nutrition 0.000 abstract description 49
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
150000001875 compounds Chemical class 0.000 description 34
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CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 25
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CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 22
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JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
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