NZ732771B2 - Cgrp antagonist peptides - Google Patents
Cgrp antagonist peptides Download PDFInfo
- Publication number
- NZ732771B2 NZ732771B2 NZ732771A NZ73277116A NZ732771B2 NZ 732771 B2 NZ732771 B2 NZ 732771B2 NZ 732771 A NZ732771 A NZ 732771A NZ 73277116 A NZ73277116 A NZ 73277116A NZ 732771 B2 NZ732771 B2 NZ 732771B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- cys
- val
- phe
- 3pal
- gly
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
Abstract
This disclosure relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof: in which m, p, A, Ar1, Ar2, Ar3, R1, R2, and R3 are defined in the specification. The compounds of formula (I) can be used as CGRP antagonists and can be used to treat migraine.
Claims (17)
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein 5 m is 0, 1, 2, 3, 4, or 5; p is 0, 1, 2, or 3;
2. A is single or double carbon-carbon bond; Ar1 is aryl or 5- or ered heteroaryl, each of which is optionally substituted with one or more substituents, each substituent independently being halogen, nitro, C1-C4 10 alkyl, C1-C4 hydroxyalkyl, ORa, or N(RaRa’), in which each Ra, independently, is H or C1- C4 alkyl and each Ra’, independently, is H or C1-C4 alkyl; Ar2 is aryl or 5- or 6-membered heteroaryl, each of which is optionally substituted with one or more substituents, each substituent independently being halogen, cyano, nitro, C1-C4 alkyl, C1-C4 aminoalkyl, C1-C4 yalkyl, ORb, ’), C(O)- 15 N(RbRb’), or NH-C(O)-N(RbRb’), in which each Rb, independently, is H or C1-C4 alkyl and each Rb’, ndently, is H or C1-C4 alkyl; Ar3 is aryl or 5- or 6-membered heteroaryl, each of which is optionally substituted with one or more substituents, each substituent independently being halogen, C1-C4 alkyl, C1-C4 hydroxyalkyl, ORc, or N(RcRc’), in which each Rc, independently, is H or C1-C4 20 alkyl and each Rc’, independently, is H or C1-C4 alkyl; each R1, independently, is C1-C4 alkyl, C1-C4 aminoalkyl, C1-C4 hydroxyalkyl, ORd, or C(O)-N(RdRd’), in which each Rd, independently, is H or C1-C4 alkyl and each Rd’, independently, is H or C1-C4 alkyl; R2 is -(CH2)n-R, in which n is 0, 1, 2, or 3 and R is N(CH3)2, NH(CH(CH3)2), NH- 5 H(NH2)-(CH2)4-N(CH3)2, NH-C(O)-CH2-(OCH2CH2)2-NH2, 3-amino-1,2,4- triazolyl, N(CH2CH3)2, or guanidino substituted with CH3; and each R3, ndently, is halogen, C1-C4 alkyl, or ORf, in which each Rf, independently, is H or C1-C4 alkyl. 10 2. The compound of claim 1, wherein Ar1 is phenyl, pyridinyl, oxazolyl, thiazolyl, olyl, pyrimidinyl, pyrolyl, or triazolyl, each of which is optionally substituted with one or more substituents, each substituent independently being F, Cl, NO2, CH3, CH2OH, or NH2. 15
3. The compound of claim 1, wherein Ar2 is phenyl or pyridinyl, each of which is optionally substituted with one or more substituents, each substituent independently being CH2NH2, C(O)NH2, OH, CN, CH2OH, NH2, or NH-C(O)-NH2.
4. The compound of claim 1, n Ar3 is pyridinyl.
5. The compound of claim 1, wherein m is 1.
6. The compound of claim 5, n R1 is OH, C(O)NH2, or CH2NH2. 25
7. The compound of claim 1, wherein n is 0, 1, or 2.
8. The compound of claim 1, wherein p is 0.
9. The compound of claim 1, wherein the compound is Oxazolecarbonyl- 30 D-Val-Phe(2-Cbm)-c(Cys-Orn(iPr)-Asp-Val-Gly-Pro-Phe-Cys)-3Pal-NH2.
10. The compound of claim 1, wherein the compound is Picolinoyl-D-Val-Tyr-c(Cys-Dab(Et2)-Asp-Val-Gly-Pro-Phe-Cys)-3Pal-NH2; Picolinoyl-D-Val-Tyr-c(Cys-Dab(iPr)-Asp-Val-Gly-Pro-Phe-Cys)-3Pal-NH2; 5 noyl(5-F)-D-Val-Tyr-c(Cys-Orn(iPr)-Asp-Val-Gly-Pro-Phe-Cys)-3Pal-NH2; Picolinoyl-D-Val-Tyr-c(Cys-Orn(Et2)-Asp-Val-Gly-Pro-Phe-Cys)-3Pal-NH2; Picolinoyl(5-F)-D-Val-Phe(2-Cbm)-c(Cys-Orn(iPr)-Asp-Val-Gly-Dhp-3Pal-Cys)-3Pal- Picolinoyl(5-F)-D-Val-Phe(2-Cbm)-c(Cys-Orn(iPr)-Asp-Val-Gly-Pro-3Pal-Cys)-3Pal- 10 NH2; Oxazolecarbonyl-D-Val-Phe(2-Cbm)-c(Cys-Orn(iPr)-Asp-Val-Gly-Pro-3Pal-Cys)- 3Pal-NH2; Oxazolecarbonyl-D-Val-Phe(2-Cbm)-c(Cys-Orn(iPr)-Asp-Val-Gly-Dhp-Phe(3- )-Cys)-3Pal-NH2; 15 Oxazolecarbonyl-D-Val-Phe(2-Cbm)-c(Cys-Orn(iPr)-Asp-Val-Gly-Dhp-4Aph-Cys)- 3Pal-NH2; Oxazolecarbonyl-D-Val-Phe(2-Cbm)-c(Cys-Orn(iPr)-Asp-Val-Gly-Dhp-4Uph-Cys)- 3Pal-NH2; Picolinoyl(5-F)-D-Val-Tyr-c(Cys-Orn(iPr)-Asp-Val-Gly-Pro-Phe(4-CH2OH)-Cys)-3Pal- 20 NH2; Picolinoyl(3,5-F2)-D-Val-Tyr-c(Cys-Orn(iPr)-Asp-Val-Gly-Pro-Phe-Cys)-3Pal-NH2; Picolinoyl(5-F)-D-Val-Phe(2-Cbm)-c(Cys-Orn(iPr)-Asp-Val-Gly-Dhp-Phe(4-CH2OH)- Cys)-3Pal-NH2; Oxazolecarbonyl-D-Val-Phe(2-Cbm)-c(Cys-Orn(iPr)-Asp-Val-Gly-Pro-Phe(4- 25 CH2OH)-Cys)-3Pal-NH2; Oxazolecarbonyl-D-Val-Phe(2-Cbm)-c(Cys-Orn(iPr)-Asp-Val-Gly-Dhp-Phe(3-Cbm)- Cys)-3Pal-NH2; Picolinoyl(5-F)-D-Val-Phe(2-Cbm)-c(Cys-Orn(iPr)-Asp-Val-Gly-Dhp-Phe(2-Cbm)- Cys)-3Pal-NH2; Oxazolecarbonyl-D-Val-Tyr-c(Cys-Orn(iPr)-Asp-Val-Gly-Dhp-Phe(3-Cbm)-Cys)- 3Pal-NH2; Picolinoyl(5-F)-D-Val-Tyr-c(Cys-Orn(iPr)-Asp-Val-Gly-Dhp-Phe(3-Cbm)-Cys)-3Pal- NH2; or 5 Picolinoyl-D-Val-Tyr-c(Cys-Orn(iPr)-Asp-Val-Gly-Dhp-Phe(4-CH2OH)-Cys)-3Pal-NH2.
11. A pharmaceutical ition, comprising the compound of any of claims 1-10 and a pharmaceutically acceptable carrier. 10
12. The pharmaceutical composition of claim 11, wherein the ition comprises an aqueous solution.
13. The pharmaceutical composition of claim 12, wherein the composition comprises a sodium chloride aqueous solution.
14. The pharmaceutical composition of claim 13, wherein the aqueous solution comprises about 0.9 wt% of sodium chloride.
15. A compound of any of claims 1 to 10 for, or for use in, the treatment of 20 migraine.
16. Use of a compound of any of claims 1 to 10 in the cture of a medicament for the treatment of migraine. 25
17. A nd selected from: Picolinoyl-D-Val-Tyr-c(Cys-Orn-Asp-Val-Gly-Pro-Phe(4-CH2OH)-Cys)-3Pal-NH2; or Picolinoyl(3,5-F2)-D-Val-Tyr-c(Cys-Arg-Asp-Val-Gly-Pro-Phe-Cys)-3Pal-NH2
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562100371P | 2015-01-06 | 2015-01-06 | |
| PCT/EP2016/050110 WO2016110499A1 (en) | 2015-01-06 | 2016-01-06 | Cgrp antagonist peptides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ732771A NZ732771A (en) | 2024-07-05 |
| NZ732771B2 true NZ732771B2 (en) | 2024-10-08 |
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