(S, S)-NEPA is a well-known chemical intermediate in the pharmaceutical industry, which plays an important role in synthesizing Angiotensin-I Converting Enzyme (ACE) Inhibitors. ACE-inhibitors such as Delapril, Enalapril, Imidapril, Indolapril, Moexipril, Quinapril, Ramipril and Trandolapril can be synthesized by incorporating (S, S)-NEPA. The most important clinical application of ACE-Inhibitors is in the management of cardiovascular diseases, i.e. hypertension and  congestive heart failure (CHF).

To produce highly pure (S, S)-NEPA, it requires sophisticated technologies to separate three other optical isomers for the utmost optical purity. Everlight has succeeded in the key technologies of hydrogenation and asymmetric synthesis for producing (S, S)-NEPA.

Quality

The purity of our pharmaceutical intermediate, (S, S)-NEPA, is ≥ 98.5%. The (R, S)-isomer impurities are < 0.5%. More importantly, the impurity Cyclohexyl-NEPA is less than 0.2%. However, these optical and chemical isomers of (S, S)-NEPA, are available for our customers’ analytical and development needs.  

Table I. The Worldwide Sales of ACE Inhibitors¹         Unit:USD, millions

^{*  Estimated}

The demand of (S, S)-NEPA has been increasing during the past few years, and it will continue to grow in the near future. However, the quantity of ACE Inhibitor depends closely on the optical quality of this key intermediate. Although Enalapril Maleate^2,3 (Vasotec^® ) world sales are slipping, the combined formulations, Lexxel^®3 (Enalapril Maleate & Felodipine), Vaseretic^® (Enalapril Maleate & Hydrochlorothiazide)³, Teczem^® (Enalapril Maleate & Diltiazem Maleate)³ have been increasing in the treatment of hypertension & CHF due to lower side effects and better therapy results.

Another New Intermediate From Everlight --- NEPA-NCA

In addition, another key intermediate for ACE inhibitor,     NEPA-NCA (chemical name: N- [1-(S)- Ethoxycarbonyl -3-Phenylpropyl] -(S)- Alanine- N-Carboxyanhydride ), is also available commercially. The assay is between 98.0 ~ 102.0% with total impurities less than 0.5%. 

1. Med Ad News1998/1999

2. Martindale 31 Edition

3. Physicians’ Desk Reference  52 Edition, 1998

产  品

用  途

前列腺素原料药

Alprostadil(PG E₁)

先天性心脏动脉阻塞之治疗 

Misoprostol

消炎镇痛剂所造成的胃及十二指肠溃疡之治疗及预防 

Cloprostenol Sodium 

动物妊娠末期的催生

Dinoprostone (PG E₂)

人工引产

Latanoprost

Epoprostenol Sodium (PGI2)

治疗青光眼

治疗肺动脉高压

心血管原料药

Felodipine

抗高血压

中间体

心血管药ACE抑制剂中间体