Excitatory amino acid receptor antagonists

• US 5,675,008 A
• Filed: 06/01/1995
• Issued: 10/07/1997
• Est. Priority Date: 09/03/1992
• Status: Expired due to Term

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Martinelli, Michael J., Ornstein, Paul L., Huff, Bret, Bertsch, Carl F.
• Primary Examiner(s): NORTHINGTON DAVIS, ZINNA
• Application Number:
  US08/457,766
• Time in Patent Office: 859 Days
• Field of Search: 546/146, 546/147
• US Class Current: 546/147
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 217/26 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07F 9/6524 : having four or more nitrogen atoms as the only ring hetero atoms

Abstract

This invention provides novel decahydroisoquinoline compounds which are useful as excitatory amino acid receptor antagonists and in the treatment of neurological disorders. This invention also provides synthetic methods for preparing decahydroisoquinolines, as well as, novel intermediates in the synthesis thereof.

Claims

1. A process for the preparation of a compound of the formula ##STR87## wherein:

R⁹ is acyl or alkoxycarbonyl; and

R¹⁰ is hydrogen, C₁ -C₆ alkyl, or aryl;

which comprises the steps of;

(1) stereoselectively reducing a compound of formula ##STR88## wherein R⁹ and R¹⁰ are as defined previously, with a hydrogenation catalyst and hydrogen wherein the hydrogenation catalyst is rhodium on carbon, to produce a compound of the formula ##STR89## wherein R⁹ and R¹⁰ are as defined previously; and

(2) oxidizing said formula VII compound.

2. The process of claim 1 wherein the formula VII compound is oxidized with ruthenium (III) chloride and periodic acid or ruthenium (III) chloride and sodium periodate.

3. The process of claim 2 wherein the formula VII compound is oxidized with ruthenium (III) chloride and periodic acid.

4. The process of claim 2 wherein the formula VII compound is oxidized with ruthenium (III) chloride and sodium periodate.

5. A process as claimed in claim 1, in which the reduction is carried out at a hydrogen pressure of about 30 psi to about 200 psi and at a temperature of about 70°

C. to about 90°

C.

6. A process as claimed in claim 5, in which the reduction is carried out at a hydrogen pressure of about 100 psi and a temperature of about 85°

C.

7. A process as claimed in claim 1, in which the reduction is carried out in a polar organic solvent.

8. A process as claimed in claim 7, in which the polar organic solvent is selected from ethyl acetate, methanol, and ethanol.

9. A process as claimed in claim 1, in which the reduction is carried out at a hydrogen pressure of about 30 psi to about 200 psi and a temperature of about 70°

C. to about 90°

C. in a polar organic solvent, and the formula VII compound is oxidized with ruthenium (III) chloride and periodic acid or ruthenium (III) chloride and sodium periodate.