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SM-319777, AG-1776, KNI-764, JE-2147

(4R)-3-{(2S,3S)-2-羟基-3-[(3-羟基-2-甲基苯甲酰)氨基]-4-苯基丁酰}-5,5-二甲基-N-(2-甲基苯甲基)-1,3-噻唑烷-4-甲酰胺Chemical Name: 3-[2(S)-Hydroxy-3(S)-(3-hydroxy-2-methylbenzamido)-4-phenylbutanoyl]-5,5-dimethyl-N-(2-methylbenzyl)thiazolidine-4(R)-carboxamide
CAS No. 186538-00-1
项目整合开发状态: Phase I
项目研究机构: Japan Energy (Originator), Agouron (Licensee)
合成路线:Treatment of penicillamine (I) with formaldehyde produced thiazolidine (II),which was then protected with Boc2O to give carbamate (III).Coupling of (III) with 2-methylbenzylamine (IV) by means of either diphenylphosphoryl chloride (DPPCl),1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl (EDC) or dicyclohexylcarbodiimide (DCC) afforded the corresponding amide (V).After acid cleavage of the Boc group of (V),the deprotected thiazolidine (VI) was coupled with N-Boc-(S,S)-3-amino-2-hydroxy-4-phenylbutyric acid (VII) using EDC to give diamide (VIII).Further acid deprotection of the Boc group of (VIII) yielded (IX).This was finally coupled with 3-hydroxy-2-methylbenzoic acid (X) to furnish the title compound.Alternatively,amine (IX) was coupled with 3-acetoxy-2-methylbenzoic acid (XI) to afford (XII),which was then deacetylated using NaOH in MeOH.

合成路线:Treatment of penicillamine (I) with formaldehyde produced thiazolidine (II),which was then protected with Boc2O to give carbamate (III).Coupling of (III) with 2-methylbenzylamine (IV) by means of either diphenylphosphoryl chloride (DPP-Cl) or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl (EDC) afforded the corresponding amide (V).After acid cleavage of the Boc group of (V),the deprotected thiazolidine (VI) was coupled with N-Boc-(S,S)-3-amino-2-hydroxy-4-phenylbutyric acid (VII) using EDC to give diamide (VIII).Further acid deprotection of the Boc group of (VIII) yielded (IX).This was finally coupled with 2-ethyl-3-hydroxybenzoic acid (X) to furnish the title compound.Alternatively,amine (IX) was coupled with 3-acetoxy-2-ethylbenzoic acid (XI) to afford (XII),which was then deacetylated using NaOH in MeOH.
📌 参考资料/链接:
参考文献标题:HIV-protease inhibitors
文献作者:Kato,R.; Mimoto,T.; Fukazawa,T.; Morohashi,N.; Kiso,Y.(Japan Energy Corp.)
参考来源:CA 2179935; EP 0751145; JP 1998025242

📄 详细内容


合成路线:Treatment of penicillamine (I) with formaldehyde produced thiazolidine (II),which was then protected with Boc2O to give carbamate (III).Coupling of (III) with 2-methylbenzylamine (IV) by means of either diphenylphosphoryl chloride (DPPCl),1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl (EDC) or dicyclohexylcarbodiimide (DCC) afforded the corresponding amide (V).After acid cleavage of the Boc group of (V),the deprotected thiazolidine (VI) was coupled with N-Boc-(S,S)-3-amino-2-hydroxy-4-phenylbutyric acid (VII) using EDC to give diamide (VIII).Further acid deprotection of the Boc group of (VIII) yielded (IX).This was finally coupled with 3-hydroxy-2-methylbenzoic acid (X) to furnish the title compound.Alternatively,amine (IX) was coupled with 3-acetoxy-2-methylbenzoic acid (XI) to afford (XII),which was then deacetylated using NaOH in MeOH.

合成路线:Treatment of penicillamine (I) with formaldehyde produced thiazolidine (II),which was then protected with Boc2O to give carbamate (III).Coupling of (III) with 2-methylbenzylamine (IV) by means of either diphenylphosphoryl chloride (DPP-Cl) or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl (EDC) afforded the corresponding amide (V).After acid cleavage of the Boc group of (V),the deprotected thiazolidine (VI) was coupled with N-Boc-(S,S)-3-amino-2-hydroxy-4-phenylbutyric acid (VII) using EDC to give diamide (VIII).Further acid deprotection of the Boc group of (VIII) yielded (IX).This was finally coupled with 2-ethyl-3-hydroxybenzoic acid (X) to furnish the title compound.Alternatively,amine (IX) was coupled with 3-acetoxy-2-ethylbenzoic acid (XI) to afford (XII),which was then deacetylated using NaOH in MeOH.

参考文献标题:Structure-activity relationship of small-sized HIV protease inhibitors containing allophenylnorstatine
文献作者:Mimoto,T.; Kato,R.; Takaku,H.; Nojima,S.; Terashima,K.; Misawa,S.; Fukazawa,T.; Ueno,T.; Sato,H.; Shintani,M.; Kiso,Y.; Hayashi,H.
参考来源:J Med Chem 1999,42(10),1789


合成路线:Treatment of penicillamine (I) with formaldehyde produced thiazolidine (II),which was then protected with Boc2O to give carbamate (III).Coupling of (III) with 2-methylbenzylamine (IV) by means of either diphenylphosphoryl chloride (DPPCl),1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl (EDC) or dicyclohexylcarbodiimide (DCC) afforded the corresponding amide (V).After acid cleavage of the Boc group of (V),the deprotected thiazolidine (VI) was coupled with N-Boc-(S,S)-3-amino-2-hydroxy-4-phenylbutyric acid (VII) using EDC to give diamide (VIII).Further acid deprotection of the Boc group of (VIII) yielded (IX).This was finally coupled with 3-hydroxy-2-methylbenzoic acid (X) to furnish the title compound.Alternatively,amine (IX) was coupled with 3-acetoxy-2-methylbenzoic acid (XI) to afford (XII),which was then deacetylated using NaOH in MeOH.

合成路线:Treatment of penicillamine (I) with formaldehyde produced thiazolidine (II),which was then protected with Boc2O to give carbamate (III).Coupling of (III) with 2-methylbenzylamine (IV) by means of either diphenylphosphoryl chloride (DPP-Cl) or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl (EDC) afforded the corresponding amide (V).After acid cleavage of the Boc group of (V),the deprotected thiazolidine (VI) was coupled with N-Boc-(S,S)-3-amino-2-hydroxy-4-phenylbutyric acid (VII) using EDC to give diamide (VIII).Further acid deprotection of the Boc group of (VIII) yielded (IX).This was finally coupled with 2-ethyl-3-hydroxybenzoic acid (X) to furnish the title compound.Alternatively,amine (IX) was coupled with 3-acetoxy-2-ethylbenzoic acid (XI) to afford (XII),which was then deacetylated using NaOH in MeOH.
参考文献标题:Design and synthesis of a covalently linked HIV-1 protease dimer analog and peptidomimetic inhibitors
文献作者:Kiso,Y.
参考来源:Yuki Gosei Kagaku Kyokaishi 1998,56(11),896


产品链接: CAS No. 186538-00-1››