455264-31-0

Basic information

• Product Name: N-(2-Bromo-3-oxospiro[3.5]non-1-en-1-yl)-4-(2,7-naphthyridin-1-ylamino)-L-phenylalanine
• Synonyms: N-(2-Bromo-3-oxospiro[3.5]non-1-en-1-yl)-4-(2,7-naphthyridin-1-ylamino)-L-phenylalanine;Zaurategrast;CDP 323;CDP323;CDP-323;(S)-3-(4-((2,7-Naphthyridin-1-yl)amino)phenyl)-2-((2-bromo-3-oxospiro[3.5]non-1-en-1-yl)amino)pro;Zaurategrast (CDP323);(S)-3-(4-((2,7-Naphthyridin-1-yl)amino)phenyl)-2-((2-bromo-3-oxospiro[3.5]non-1-en-1-yl)amino)
• CAS NO: 455264-31-0
• Molecular Formula: C₂₆H₂₅BrN₄O₃
• Molecular Weight: 521.41
• Mol File: 455264-31-0.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 714.2±60.0 °C(Predicted)
• Appearance: /
• Density: 1.53
• PKA: 3.96±0.10(Predicted)
• CAS DataBase Reference: N-(2-Bromo-3-oxospiro[3.5]non-1-en-1-yl)-4-(2,7-naphthyridin-1-ylamino)-L-phenylalanine(CAS DataBase Reference)
• NIST Chemistry Reference: N-(2-Bromo-3-oxospiro[3.5]non-1-en-1-yl)-4-(2,7-naphthyridin-1-ylamino)-L-phenylalanine(455264-31-0)
• EPA Substance Registry System: N-(2-Bromo-3-oxospiro[3.5]non-1-en-1-yl)-4-(2,7-naphthyridin-1-ylamino)-L-phenylalanine(455264-31-0)

Safety Data

• Hazardous Substances Data: 455264-31-0(Hazardous Substances Data)

Usage

General Description

N-(2-Bromo-3-oxospiro[3.5]non-1-en-1-yl)-4-(2,7-naphthyridin-1-ylamino)-L-phenylalanine is a complex chemical compound with a unique, intricate structure. It contains a spiro ring with a bromo and oxo functional group, as well as an amino acid (L-phenylalanine) and a naphthyridine ring. N-(2-Bromo-3-oxospiro[3.5]non-1-en-1-yl)-4-(2,7-naphthyridin-1-ylamino)-L-phenylalanine likely displays a range of biological activities due to its diverse structure, and it may have applications in medicinal chemistry as a potential drug candidate or biological probe. The compound's multiple functional groups and complex three-dimensional structure make it a fascinating target for further research and potential therapeutic development.

Synthetic route

zaurategrast ethyl (455264-30-9) → zaurategrast (455264-31-0)

Conditions	Yield
With lithium hydroxide; water In tetrahydrofuran at 20℃; for 2h;	64%
With human carboxylesterase 1, recombinant In aq. phosphate buffer at 37℃; for 1h; pH=7.4; Reagent/catalyst; Enzymatic reaction;

methanol (67-56-1) + zaurategrast ethyl (455264-30-9) → zaurategrast (455264-31-0) + C27H27BrN4O3

Conditions	Yield
With human liver microsomes In aq. phosphate buffer at 37℃; for 0.166667h; pH=7.4; Enzymatic reaction;

zaurategrast ethyl (455264-30-9) + ethanol-d5 (1859-08-1) → zaurategrast (455264-31-0) + C28H24(2)H5BrN4O3

Conditions	Yield
With human liver microsomes In aq. phosphate buffer at 37℃; for 1h; pH=7.4; Enzymatic reaction;

zaurategrast (455264-31-0) + isopropyl alcohol (67-63-0) → isopropyl (2S)-2-(2-bromo-3-oxospiro[3,5]non-1-en-1-ylamino)-3-[4-([2,7]naphthyridin-1-ylamino)phenyl]propanoate

Conditions	Yield
With hydrogenchloride at 20 - 25℃; for 16h;	77.4%

zaurategrast (455264-31-0) + ethylene glycol (107-21-1) → 2-hydroxyethyl (2S)-2-(2-bromo-3-oxospiro[3,5]non-1-en-1-ylamino)-3-[4-([2,7]naphthyridin-1-ylamino)phenyl]propanoate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In DMF (N,N-dimethyl-formamide) at 20℃;	66%

Upstream product

• 455264-30-9 zaurategrast ethyl 
• 1859-08-1 ethanol-d5 
• 67-56-1 methanol 

Relevant articles and documents

In vitro hydrolysis and transesterification of CDP323, an α4β1/α4β7 integrin antagonist ester prodrug

We identified the enzyme(s) involved in the hydrolysis of the ethyl ester prodrug CDP323 (C28H29BrN403) and characterized its transesterification in the presence of ethanol with special emphasis on the risks of drug-drug interaction. The hydrolysis of CDP323 was evaluated in vitro using human liver and intestinal microsomes and recombinant human carboxylesterases (hCES1 and 2) and was shown to be approximately 20-fold higher in human liver microsomes when compared with human intestinal microsomes and in hCES1 when compared with hCES2. Nonspecific inhibitors of carboxylesterases significantly inhibited the hydrolysis of CDP323 (>80% inhibition) while specific inhibitors of CES2, acetylcholine esterase, arylesterase, and butyrylcholinesterase did not impair the hydrolysis reaction. The effect of ethanol on the kinetic parameters for hydrolysis was investigated, demonstrating that at high concentration (2%), Michaelis-Menten constant (Km), maximum velocity (Vmax), and intrinsic clearance (CLint) for the formation of the hydrolyzed product were decreased (～40%). The use of deuterated ethanol allowed more mechanistic investigations of the transesterification mechanism and showed that the intrinsic clearance based on parent loss was not impaired in the presence of alcohol. Overall, our data demonstrate that CDP323 is mainly hydrolyzed by hCES1 and is prone to transesterification in the presence of ethanol. Transesterification mechanisms compete with hydrolysis without impairing the overall clearance of the ester prodrug. Based on in vitro results, the risk of a clinically significant drug-drug interaction with ethanol is anticipated to be low. Copyright

Phenylalanine enamide derivatives

Phenylalanine enamide derivatives of formula (1) are described: wherein R1 is a group Ar1L2Ar2Alk- in which: Ar1 is an optionally substituted aromatic or heteroaromatic group; L2 is a covalent bond or a linker atom or group; Ar2 is an optionally substituted arylene or heteroarylene group; and Alk is a chain —CH2—CH(R)13 , —CH═C(R)— or ?in which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof; X is an —O— or —S— atom or —N(R2)— group in which: Rx, Ry and Rz which may be the same or different is each a hydrogen atom or an optional substituent; or Rz is an atom or group as previously defined and Rx and Ry are joined together to form an optionally substituted spiro linked cycloaliphatic or heterocycloaliphatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of integrins to their ligands and are of use in the prophylaxis and treatment of immuno or inflammatory disorders or disorders involving the inappropriate growth or migration of cells.