Alkaloids

Details Alkaloids Alkaloids

2001-05-22

2004-09-28

Celsa, Bennett (Department: 1639)

Organic compounds -- part of the class 532-570 series

Organic compounds

Unsubstituted hydrocarbyl chain between the ring and the -c-...

C540S546000, C540S581000

Reexamination Certificate

active

06797819

ABSTRACT:

BACKGROUND OF THE INVENTION
The identification of small organic molecules that affect specific biological functions is an endeavor that impacts both biology and medicine. Such molecules are useful as therapeutic agents and as probes of biological function. In but one example from the emerging field of chemical genetics, in which small molecules can be used to alter the function of biological molecules to which they bind, these molecules have been useful at elucidating signal transduction pathways by acting as chemical protein knockouts, thereby causing a loss of protein function. (Schreiber et al.,
J. Am. Chem. Soc.,
1990, 112, 5583; Mitchison,
Chem. and Biol.,
1994, 1, 3) Additionally, due to the interaction of these small molecules with particular biological targets and their ability to affect specific biological function, they may also serve as candidates for the development of therapeutics. One important class of small molecules, natural products, which are small molecules obtained from nature, clearly have played an important role in the development of biology and medicine, serving as pharmaceutical leads, drugs (Newman et al.,
Nat. Prod. Rep.
2000, 17, 215-234), and powerful reagents for studying cell biology (Schreiber, S. L.
Chem. and Eng. News
1992 (Oct. 26), 22-32).
Because it is difficult to predict which small molecules will interact with a biological target, intense efforts have been directed towards the generation of large numbers, or libraries, of small organic compounds. These libraries can then be linked to sensitive screens to identify the active molecules. Of particular interest has been the development of libraries based upon existing natural products. To date, however, libraries based on natural products have been synthesized primarily for the purpose of improving the known biological and pharmacokinetic properties of the parent natural products (Hall, D. G.; Manku, S.; Wang, F.
J. Comb. Chem.
2001, 3(2), 125-150; Nicolaou, K. C.; Vourloumis, D.; Li, T.; Pastor, J.; Winssinger, N.; He, Y.; Ninkovis, S.; Sarabia, F.; Vallberg, H.; Roschanger, F.; King, N. P.; Finlay, R. V.; Giannakakou, P.; Verdier-Pinard, P.; Hamel, E.
Angew. Chem., Int. Ed. Engl.
1997, 36, 2097-2103; Nicolaou, K. C.; Winssinger, D.; Vourloumis, D.; Ohshima, T.; Kim, S.; Pfefferkoth, J.; Xu, J.-Y.; Li, T.
J. Am. Chem. Soc.
1998, 120, 10814-10826; Lee, K. J.; Angulo, A.; Ghazal, P.; Janda, K. D.
Org. Lett.
1999, 1, 1859-1862; Xu, R.; Greiveldinger, G.; Marenus, L. E.; Cooper, A.; Ellman, J. A.
J. Am. Chem. Soc.
1999,121, 4898-4899; Wipf, P.; Reeves, J. T.; Balachandran, R.; Giuliano, K. A.; Hamel, E.; Day, B. W.
J. Am. Chem. Soc.
2000, 122, 9391-9395; Boger, D. L.; Fink, B. E.; Hedrick, M. P.
J. Am. Chem. Soc.
2000, 122, 6382-6394; Nicolaou, K. C.; Pfefferkorn, J. A.; Barluenga, S.; Mitchell, H. J.; Roecker, A. J.; Cao, G.-Q.
J. Am. Chem. Soc.
2000, 122, 9968-9976 and references cited therein).
Clearly, as detailed above, a great deal of research has been conducted to optimize existing natural product leads, the development of compounds and libraries of compounds based upon natural products and/or emulating the structural and stereochemical diversity of natural products, but having different biological activities than the parent natural product, would also be useful. Additionally, the development of novel synthetic methodologies would assist in the development of new classes of complex compounds and libraries of compound. In order achieve greater diversity and complexity in the synthesis of compounds and particularly libraries of compounds, it would be desirable to develop such methods by either utilizing or emulating the rapid and stereoselective pathways that nature uses in the synthesis of natural products for the efficient production of complex compounds and libraries of compounds. Any resultant novel complex compounds and libraries based on biomimetic pathways will certainly be useful in the quest to discover either non-natural compounds having the binding affinities and specific characteristics of natural products, themselves the products of genetic recombination and natural selection, or will be particularly useful in the quest to discover compounds based upon natural products that exhibit novel biological properties.
SUMMARY OF THE INVENTION
In one aspect of the invention, novel compounds having the structure (I) are provided:
wherein R
1
is hydrogen or halogen, or is an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, alkylheteroaryl moiety or is SR
A
, N(R
A
)
2
, or OR
A
, wherein R
A
is hydrogen or is an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, and wherein each of the aliphatic and heteroaliphatic moieties may be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and wherein each of the aryl, heteroaryl, alkylaryl or alkylheteroaryl moieties may be substituted or unsubstituted;
wherein R
2
is hydrogen or is an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, alkylheteroaryl moiety, wherein each of the aliphatic and heteroaliphatic moieties may be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and wherein each of the aryl, heteroaryl, alkylaryl or alkylheteroaryl moieties may be substituted or unsubstituted, or R
2
is a solid support optionally attached through a linker moiety;
wherein R
3
is hydrogen or is an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, alkylheteroaryl moiety, wherein each of the aliphatic and heteroaliphatic moieties may be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and wherein each of the aryl, heteroaryl, alkylaryl, or alkylheteroaryl moieties may be substituted or unsubstituted; or wherein R
3
is —CN; —O(CN)R
x
; —C(O)R
x
; —CO
2
(R
x
); —CON(R
x
)
2
; —OC(O)R
x
; —OCO
2
R
x
; —OCON(R
x
)
2
; —N(R
x
)
2
; —S(O)
2
R
x
; wherein each occurrence of R
1
is aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, wherein any of the aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl substituents may be substituted or unsubstituted, branched or unbranched, cyclic or acyclic, and wherein any of the aryl or heteroaryl substituents may be substituted or unsubstituted;
wherein R
4
is is hydrogen or is an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, alkylheteroaryl moiety, wherein each of the aliphatic and heteroaliphatic moieties may be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and wherein each of the aryl, heteroaryl, alkylaryl or alkylheteroaryl moieties may be substituted or unsubstituted;
wherein R
5
is hydrogen, halogen, —NO
2
, —CN, —C(O)R
x
, —CO
2
(R
x
), —CON(R
x
)
2
, —OC(O)R
x
, —OCO
2
R
x
, —OCON(R
x
)
2
, —N(R
x
)
2
, —S(O)
2
R
x
, wherein each occurrence of R
x
independently includes, but is not limited to, aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, wherein any of the aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl substituents described above and herein may be substituted or unsubstituted, branched or unbranched, cyclic or acyclic, and wherein any of the aryl or heteroaryl substituents described above and herein may be substituted or unsubstituted; or R
5
is an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, alkylheteroaryl moiety, or is SR
A
, N(R
A
)
2
, or OR
A
, wherein R
A
is an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, and wherein each of the aliphatic and heteroaliphatic moieties may be substituted or unsubstituted, cyclic or acyclic, or branched or unbranched, and wherein each of the aryl, heteroaryl, alkylaryl or alkylheteroaryl moieties may be substituted or unsubstituted;
wherein X is O, S or NR
6
, wherein R
6
is OR
7
, NHR
7
, or NH(S(═O)
2
)R
7
, wherein R
7
is aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, wherein any of the aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl substituents described above and herein may be substituted or uns

Affiliated with

Also associated with

Rating

Alkaloids does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Alkaloids, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Alkaloids will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3203777