AR081471A1 - Profarmacos de peptido de la superfamilia de glucagon basado en amida - Google Patents
Profarmacos de peptido de la superfamilia de glucagon basado en amidaInfo
- Publication number
- AR081471A1 AR081471A1 ARP110102184A ARP110102184A AR081471A1 AR 081471 A1 AR081471 A1 AR 081471A1 AR P110102184 A ARP110102184 A AR P110102184A AR P110102184 A ARP110102184 A AR P110102184A AR 081471 A1 AR081471 A1 AR 081471A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- glucagon superfamily
- peptide
- group
- nhr6
- Prior art date
Links
- 102000051325 Glucagon Human genes 0.000 title abstract 5
- 108060003199 Glucagon Proteins 0.000 title abstract 5
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 title abstract 5
- 229960004666 glucagon Drugs 0.000 title abstract 5
- 108090000765 processed proteins & peptides Proteins 0.000 title abstract 4
- 125000000217 alkyl group Chemical group 0.000 abstract 8
- 229940002612 prodrug Drugs 0.000 abstract 3
- 239000000651 prodrug Substances 0.000 abstract 3
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 abstract 2
- 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 abstract 2
- 125000003342 alkenyl group Chemical group 0.000 abstract 2
- 125000003277 amino group Chemical group 0.000 abstract 2
- 125000004429 atom Chemical group 0.000 abstract 2
- 125000001072 heteroaryl group Chemical group 0.000 abstract 2
- 230000004962 physiological condition Effects 0.000 abstract 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 abstract 1
- 125000001963 4 membered heterocyclic group Chemical group 0.000 abstract 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 abstract 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 abstract 1
- 108010016626 Dipeptides Proteins 0.000 abstract 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
- 125000001931 aliphatic group Chemical group 0.000 abstract 1
- 150000001408 amides Chemical class 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 238000002144 chemical decomposition reaction Methods 0.000 abstract 1
- 238000006911 enzymatic reaction Methods 0.000 abstract 1
- 238000009472 formulation Methods 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 125000005842 heteroatom Chemical group 0.000 abstract 1
- 125000005343 heterocyclic alkyl group Chemical group 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 230000002035 prolonged effect Effects 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 229910052717 sulfur Inorganic materials 0.000 abstract 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/605—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Child & Adolescent Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
Se proporcionan formulaciones de profármacos de péptidos de la superfamilia de glucagón en donde el péptido de la superfamilia de glucagón ha sido modificado por la unión de un dipéptido a la superfamilia de glucagón a través de una ligadura de unión amida. Los profármacos divulgados en el presente han prolongado las semividas y son convertidos a la forma activa en condiciones fisiológicas a través de una reacción no enzimática dirigida por inestabilidad química.Reivindicación 1: Un profármaco que comprende la estructura: A-B-Q en donde Q es un péptido de la superfamilia de glucagón, en donde A-B comprende la estructura de fórmula (1), en donde R1 y R2 son independientemente seleccionados del grupo que consiste en H, alquilo C1-18, alquenilo C2-18, alquilo C1-18-OH, alquilo C1-18-SH, alquilo C2-3-SCH3, alquilo C1-4-CONH2, alquilo C1-4-COOH, alquilo C1-4-NH2, alquilo C1-4-NHC(NH2+)NH2, alquilo C0-4-cicloalquilo C3-6, alquilo C0-4-heterocíclico C2-5, alquilo C0-4-arilo C6-10-R7, alquilo C1-4-heteroarilo C3-9 y alquilo C1-12(W1)alquilo C1-12, en donde W1 es un heteroátomo seleccionado del grupo que consiste en N, S y O, o R1 y R2 junto con los átomos a los cuales están unidos forman un cicloalquilo C3-12; R3 es alquilo C1-18; R4 y R8 son, cada uno, H; R5 es NHR6, o R5 y R2 junto con los átomos a los cuales están unidos forman un anillo heterocíclico de 4, 5 ó 6 miembros; R6 es H, o alquilo C1-4; y, R7 es seleccionado del grupo que consiste en H, OH, halo, alquilo C1-7, alquenilo C2-7, OCF3, NO2, CN, NC, O-alquilo C1-7, CO2H, CO2-alquilo C1-7, NHR6, arilo y heteroarilo; en donde A-B está unido a Q a través de una unión amida entre A-B y un grupo amino alifático de Q; en donde la semivida de descomposición química (t1/2) de A-B desde Q es al menos, aproximadamente, de 1 hora a, aproximadamente, 1 semana, en PBS bajo condiciones fisiológicas; con la condición de que cuando A-B está unido al grupo amino a en el extremo N de Q y (i) tanto R1 como R2 son H, y (ii) R3 es metilo, entonces Q no es F7GLP-1(8-37).
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35818810P | 2010-06-24 | 2010-06-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR081471A1 true AR081471A1 (es) | 2012-09-05 |
Family
ID=45372025
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP110102184A AR081471A1 (es) | 2010-06-24 | 2011-06-23 | Profarmacos de peptido de la superfamilia de glucagon basado en amida |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US8778872B2 (es) |
| EP (1) | EP2588126A4 (es) |
| JP (1) | JP2013540102A (es) |
| KR (1) | KR20130102470A (es) |
| CN (1) | CN103179979A (es) |
| AR (1) | AR081471A1 (es) |
| CA (1) | CA2796894A1 (es) |
| MX (1) | MX2012014576A (es) |
| RU (1) | RU2580317C2 (es) |
| TW (1) | TW201209062A (es) |
| WO (1) | WO2011163012A2 (es) |
Families Citing this family (76)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007056362A2 (en) | 2005-11-07 | 2007-05-18 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
| AU2008216265B2 (en) | 2007-02-15 | 2014-04-03 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
| ES2430067T3 (es) | 2007-03-28 | 2013-11-18 | President And Fellows Of Harvard College | Polipéptidos cosidos |
| JP5669582B2 (ja) | 2007-10-30 | 2015-02-12 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションＩｎｄｉａｎａ Ｕｎｉｖｅｒｓｉｔｙ Ｒｅｓｅａｒｃｈ Ａｎｄ Ｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐｏｒａｔｉｏｎ | グルカゴンアンタゴニスト |
| EP2214691B1 (en) | 2007-10-30 | 2015-09-30 | Indiana University Research and Technology Corporation | Compounds exhibiting glucagon antagonist and glp-1 agonist activity |
| AU2009210570B2 (en) | 2008-01-30 | 2014-11-20 | Indiana University Research And Technology Corporation | Ester-based insulin prodrugs |
| MX337038B (es) | 2008-06-17 | 2016-02-10 | Univ Indiana Res & Tech Corp | Co-antagonistas de receptor de glucagon/glp-1. |
| EP2300035B1 (en) | 2008-06-17 | 2015-08-12 | Indiana University Research and Technology Corporation | Gip-based mixed agonists for treatment of metabolic disorders and obesity |
| EP2376520B1 (en) | 2008-12-19 | 2014-02-12 | Indiana University Research&Technology Corporation | Insulin analogs |
| WO2010080609A1 (en) | 2008-12-19 | 2010-07-15 | Indiana University Research And Technology Corporation | Amide-based insulin prodrugs |
| SG172291A1 (en) | 2008-12-19 | 2011-07-28 | Univ Indiana Res & Tech Corp | Amide based glucagon superfamily peptide prodrugs |
| MX2011013625A (es) | 2009-06-16 | 2012-01-20 | Univ Indiana Res & Tech Corp | Compuestos glucagon activo de receptor de gip. |
| JP2013518115A (ja) * | 2010-01-27 | 2013-05-20 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーション | 代謝疾患及び肥満の治療のためのグルカゴンアンタゴニスト‐ｇｉｐアゴニスト複合体及び組成物 |
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| DK2603600T3 (da) | 2010-08-13 | 2019-03-04 | Aileron Therapeutics Inc | Peptidomimetiske makrocyklusser |
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| CA2838503C (en) | 2011-06-10 | 2020-02-18 | Hanmi Science Co., Ltd. | Novel oxyntomodulin derivatives and pharmaceutical composition for treating obesity comprising the same |
| ES2710356T3 (es) | 2011-06-17 | 2019-04-24 | Hanmi Science Co Ltd | Conjugado que comprende oxintomodulina y un fragmento de inmunoglobulina, y uso del mismo |
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2011
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- 2011-06-14 CN CN201180031415XA patent/CN103179979A/zh active Pending
- 2011-06-14 MX MX2012014576A patent/MX2012014576A/es not_active Application Discontinuation
- 2011-06-14 EP EP11798640.6A patent/EP2588126A4/en not_active Withdrawn
- 2011-06-14 RU RU2013103093/04A patent/RU2580317C2/ru not_active IP Right Cessation
- 2011-06-14 JP JP2013516609A patent/JP2013540102A/ja active Pending
- 2011-06-14 WO PCT/US2011/040330 patent/WO2011163012A2/en not_active Ceased
- 2011-06-14 KR KR1020127033177A patent/KR20130102470A/ko not_active Withdrawn
- 2011-06-14 US US13/697,021 patent/US8778872B2/en active Active
- 2011-06-23 AR ARP110102184A patent/AR081471A1/es unknown
- 2011-06-23 TW TW100121933A patent/TW201209062A/zh unknown
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| RU2580317C2 (ru) | 2016-04-10 |
| US8778872B2 (en) | 2014-07-15 |
| EP2588126A4 (en) | 2015-07-08 |
| MX2012014576A (es) | 2013-02-21 |
| KR20130102470A (ko) | 2013-09-17 |
| CN103179979A (zh) | 2013-06-26 |
| US20130123462A1 (en) | 2013-05-16 |
| RU2013103093A (ru) | 2014-07-27 |
| WO2011163012A2 (en) | 2011-12-29 |
| CA2796894A1 (en) | 2011-12-29 |
| JP2013540102A (ja) | 2013-10-31 |
| WO2011163012A3 (en) | 2013-07-11 |
| TW201209062A (en) | 2012-03-01 |
| EP2588126A2 (en) | 2013-05-08 |
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