Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Patent
1997-08-04
2000-05-16
Burn, Brian M.
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
25218212, 560 27, 560 29, C07C20936
Patent
active
060639636
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The inhibition of various proteases has application in treating many medical conditions, such as Alzheimer's disease, retroviral infections, hypotension and hypertension. Many protease-inhibitor compounds have been identified. However, the methods for synthesizing these protease-inhibitor compounds are often complex and/or expensive. Consequently, methods are needed to produce protease-inhibitor compounds through simpler and/or less expensive processes.
SUMMARY OF THE INVENTION
The present invention relates to a method of forming a 1,3-diamino-3-substituted-2-propanol chemical intermediate represented by the following structural formula (structural formula I): ##STR1## and salts thereof, wherein R.sup.1 is a protecting group and R.sup.2 is selected from the group consisting of --H, C1-C18 alkyl, aryl, heteroaryl, acetyl and tosyl.
Additionally, R.sup.3 is the side-chain of an amino acid wherein the amino acid has the structural formula (structural formula II): ##STR2##
Some examples of suitable amino acids include natural and synthetic .alpha.-amino acids, such as alanine, cysteine, 3,5-dibromotyrosine, 3,5-diiodotyrosine, glutamine, glycine, histidine, hydroxylysine, isoleucine, leucine, methionine, phenylalanine, serine, threonine, thyroxine, tryptophane, tyrosine, valine and .alpha.-aminobutyric acid. In addition, wherein the amino acid has a chiral center, the side-chain may be from either the D or L isomer of the amino acid. Further, the amino acid may optionally be substituted with one or more substitutents, such as halogen, hydroxyl, sulfonate, C1-C3 alkyl, C1-C3 alkoxy and acyl.
Furthermore, R.sup.4 and R.sup.5 are each independently selected from the group consisting of --H, alkyl, aryl, nitrile and alkoxycarbonyl. However, it is preferred that R.sup.4 and R.sup.5 are not both alkoxycarbonyl groups.
This method includes contacting a nitromethyl amino acid compound with at least one reducing agent to form said chemical intermediate. A suitable nitromethyl amino acid compound is represented by the following structural formula (structural formula III): ##STR3## wherein R.sup.6 is either ##STR4##
The benefits of this invention include the ability to produce protease-inhibitor compounds, and other drugs, through simpler and/or less expensive synthetic processes.
DETAILED DESCRIPTION OF THE INVENTION
A chemical intermediate, as defined herein, comprises a compound from which various chemicals, such as selected protease-inhibitors and other drugs, as well as polymers, can be synthesized. In a preferred embodiment, the 1,3-diamino-3-substituted-2-propanol chemical intermediate is derived from phenylalanine and comprises a 1,3-diamino-3-benzyl-2-propanol compound.
Suitable protecting groups include protecting groups which generally prevent substitution or addition reactions from occurring with a protected amino group while producing said chemical intermediate according to the method of this invention. Examples of suitable protecting groups include benzyl, t-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), 9-fluorenylmethoxycarbonyl (f-moc), 2,2,2-trichloroethoxycarbonyl, 2-haloethoxycarbonyl, benzoyl, phthalimidyl, diphenylphosphinyl and benzenesulfonyl. Alternatively, R.sup.1 and R.sup.2 can be combined to form a protecting group, such as dibenzyl.
Alkyl groups of the present invention include straight-chained, branched and cyclic alkyl radicals containing up to about 18 carbons. Suitable alkyl groups may be saturated or unsaturated. Further, an alkyl group may also be substituted one or more times on one or more carbons with substitutents selected form the group consisting of C1-C6 alkyl, C3-C6 heterocycle, aryl, halo, hydroxy, amino, alkoxy and sulfonyl. Additionally, an alkyl group may contain up to 3 heteroatoms. Suitable heteroatoms include nitrogen, oxygen and sulfur.
Aryl groups of the present invention include aryl radicals which may optionally contain up to 3 heteroatoms. An aryl group may also be optionally substituted one or more times with an aryl group or a
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Al-Farhan Emile
Cai Bing
Gabriel Richard
Pal Biman
Ram Siya
Burn Brian M.
Pharm-Eco Laboratories, Inc.
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