Disubstituted amino acids and methods of preparation and use thereof
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07C-271/34
C07C-269/08
C07K-001/00
C07C-271/22
출원번호
US-0278824
(2016-09-28)
등록번호
US-9845287
(2017-12-19)
발명자
/ 주소
Darlak, Krzysztof
Kawahata, Noriyuki
Athamneh, Sameer Ahmed
출원인 / 주소
AILERON THERAPEUTICS, INC.
대리인 / 주소
Wilson Sonsini Goodrich & Rosati
인용정보
피인용 횟수 :
8인용 특허 :
299
초록▼
Provided are crystalline α, α-disubstituted amino acids and their crystalline salts containing a terminal alkene on one of their side chains, as well as optionally crystalline halogenated and deuterated analogs of the α, α-disubstituted amino acids and their salts; methods of making these, and metho
Provided are crystalline α, α-disubstituted amino acids and their crystalline salts containing a terminal alkene on one of their side chains, as well as optionally crystalline halogenated and deuterated analogs of the α, α-disubstituted amino acids and their salts; methods of making these, and methods of using these.
대표청구항▼
1. A crystalline composition comprising a crystalline compound of Formula (I): wherein: R1 is C1-C3 alkyl, C1-C3 deuteroalkyl, or C1-C3 haloalkyl;* is a stereocenter;n is an integer from 3 to 11;R2 is 9-Fluorenylmethoxycarbonyl (Fmoc); andR3 is —H;and wherein the crystalline composition further comp
1. A crystalline composition comprising a crystalline compound of Formula (I): wherein: R1 is C1-C3 alkyl, C1-C3 deuteroalkyl, or C1-C3 haloalkyl;* is a stereocenter;n is an integer from 3 to 11;R2 is 9-Fluorenylmethoxycarbonyl (Fmoc); andR3 is —H;and wherein the crystalline composition further comprises hexane and chloroform. 2. The crystalline composition of claim 1, wherein R1 is C1-C3 alkyl. 3. The crystalline composition claim of 1, wherein R1 is methyl. 4. The crystalline composition of claim 1, wherein n is selected from the group consisting of: 3 and 6. 5. The crystalline composition of claim 1, wherein the stereocenter * is (S). 6. The crystalline composition of claim 1, wherein the stereocenter * is (R). 7. The crystalline composition of claim 1, wherein the crystalline compound has a chemical purity ranging from about 90% to 100%. 8. The crystalline composition of claim 1, wherein the crystalline compound has an optical purity ranging from about 90% to 100%. 9. The crystalline composition of claim 1, wherein the crystalline compound has an optical purity ranging from about 95% to 100%. 10. The crystalline composition of claim 1, wherein the crystalline compound has an enantiomeric excess ranging from about 90% to 100%. 11. The crystalline composition of claim 1, wherein the crystalline compound has an enantiomeric excess ranging from about 95% to 100%. 12. The crystalline composition of claim 1, wherein the crystalline compound has a Formula (IIa): 13. The crystalline composition of claim 1, wherein the crystalline compound has a Formula (IIb): 14. The crystalline composition of claim 1, wherein the crystalline compound has a Formula (IIIa): 15. The crystalline composition of claim 1, wherein the crystalline compound has a Formula (IIIb): 16. The crystalline composition of claim 12, wherein the crystalline compound has an enantiomeric excess ranging from about 95% to 100%. 17. The crystalline composition of claim 13, wherein the crystalline compound has an enantiomeric excess ranging from about 95% to 100%. 18. The crystalline composition of claim 14, wherein the crystalline compound has an enantiomeric excess ranging from about 95% to 100%. 19. The crystalline composition of claim 15, wherein the compound or its crystalline salt has an enantiomeric excess ranging from about 95% to 100%. 20. The crystalline composition of claim 1, wherein n is 3. 21. A crystalline compound of Formula (I): wherein: R1 is C1-C3 alkyl, C1-C3 deuteroalkyl, or C1-C3 haloalkyl;* is a stereocenter;n is an integer from 3 to 11;R2 is 9-Fluorenylmethoxycarbonyl (Fmoc); andR3 is —H;wherein the crystalline compound is obtained by crystallization of a compound of Formula (I) with a solvent comprising hexane and chloroform. 22. A method of making a peptide, the method comprising reacting the crystalline composition of claim 1 with an amino acid building block in presence of a coupling agent, thereby forming a peptide bond. 23. The method of claim 1, wherein the peptide comprises an α-helix. 24. The method of claim 1, further comprising crosslinking a pair of terminal alkene side chains of at least two amino acids of the peptide. 25. The method of claim 24, wherein the crosslinking comprises a metal-catalyzed olefin metathesis reaction.
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