ISOSORBIDE DERIVATIVES AND THEIR USE AS FLAVOR MODIFIERS, TASTANTS, AND TASTE ENHANCERS

• US 20090220662A1
• Filed: 03/03/2009
• Published: 09/03/2009
• Est. Priority Date: 03/03/2008
• Status: Active Grant

• Current Assignee: Senomyx Inc (DSM-Firmenich AG)
• Original Assignee: Senomyx Inc (DSM-Firmenich AG)
• Inventors: Yamamoto, Jeffrey M., Servant, Guy, Karanewsky, Donald S., TACHDJIAN, Catherine, Adamski-Werner, Sara L.
• Granted Patent: US 8,420,145 B2
• Time in Patent Office: Days
• US Class Current: 426/536
• CPC Class Codes: A23L 2/60 Sweeteners
• CPC Class Codes: A23L 27/205 Heterocyclic compounds
• CPC Class Codes: A23L 27/2052 having oxygen or sulfur as the only hetero atoms
• CPC Class Codes: C07D 493/04 Ortho-condensed systems

Abstract

The present invention provides isosorbide derivatives having the formula shown below and certain subgenera or species thereof, as flavor or taste modifiers, particularly, savory (“umami”) taste modifiers, savory flavoring agents and savory flavor enhancers in foods, beverages, and other comestible compositions,

Claims

1. A compound having structural formula (I)

or the salt, solvate, ester, or N-oxide thereof, wherein:

A is aryl, heteroaryl, or a covalent bond;

Y is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, carbocyclyl, substituted carbocyclyl, acyl, halo, —

CN, —

NO₂, —

OR¹, —

S(O)R¹, —

S(O)₂R¹, —

OC(O)R¹, —

N(R¹)C(O)R², —

NR¹R², —

C(O)NR¹R², —

C(O)OR¹, —

S(O)₂NR¹R², —

COR¹, —

N(R¹)S(O)₂R², —

SR¹, —

C(R¹R²R⁶), —

C(S)—

R¹, —

C(═

NR²)—

R¹, —

N(R¹)—

C(═

N—

OR²)R⁶, —

N(R¹)C(S)NR²R⁶, —

C(═

N—

OR¹)R², —

C(═

NR¹)—

NR²R⁶, —

N(R¹)C(═

NR²)NR⁶R⁷, —

N(R¹)C(S)R², —

N(R¹)—

C(O)—

C(O)R², —

C(S)—

NR¹R², —

N(R¹)C(═

NR²)OR⁶, —

C(═

NR¹)O—

NR²R⁶, —

N(R¹)N(R²)C(O)OR⁶, —

N(R¹)C(O)OR², —

N(R¹)C(O)NR²R⁶, —

N(R¹)—

C(O)—

C(O)—

NR²R⁶, —

C(O)—

C(O)—

NR¹R², —

P(O)(OR¹)(OR²), —

P(O)(OR¹)(R²), or —

P(O)R¹R²;

X is —

O—

, —

S—

, —

S(O)—

, —

S(O)₂—

, —

C(R³R⁴)—

, —

C(O)—

, —

C(S)—

, —

C(═

NR³)—

, —

C(O)O—

, —

N(R³)—

, —

OC(O)—

, —

N(R³)C(O)—

, —

C(O)N(R³)—

, —

N(R³)—

C(═

N—

OR⁴)—

, —

C(═

N—

OR³)—

, —

C(═

NR³)—

NR⁴—

, —

N(R³)C(S)N(R⁴)—

R⁵, —

N(R³)C(O)N(R⁴)—

R⁵, —

N(R³)C(═

NR⁴)—

, —

N(R³)C(S)—

, —

N(R³)—

C(O)—

C(O)—

, —

C(S)—

N(R³)—

, —

N(R³)S(O)₂—

, —

S(O)₂—

N(R³)—

, —

N(R³)C(═

NR⁴)O—

, —

C(═

NR⁴)O—

N(R³)—

, —

N(R³)—

C(═

NR⁴)—

N(R⁵)—

, —

N(R³)N(R⁴)C(O)O—

, —

N(R³)C(O)O—

, —

N(R³)C(O)N(R⁴)—

, —

N(R³)—

C(O)—

C(O)—

NR⁴—

, —

C(O)—

C(O)—

NR⁴—

, —

P(O)(OR³)—

, or —

P(O)R³—

;

Z is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, carbocyclyl, or substituted carbocyclyl;

R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are each independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, carbocyclyl, substituted carbocyclyl, heteroarylalkyl, or substituted heteroarylalkyl; and

with the following provisos;

(a) when A is triazole or tetrazole;

then —

X-Z is not —

O-alkyl, —

O-acyl, or sulfonamido;

(b) when A is tetrazole, and Z is cyclohexyl;

then X is not —

NH—

C(O)—

, —

NH—

C(O)—

NH—

; and

(c) when A is a covalent bond, then Y is not hydrogen.

2. The compound of claim 1, wherein Y is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbocyclyl, or substituted carbocyclyl.

3. The compound of claim 1, wherein A is monocyclic five- or six-membered heteroaryl.

4. The compound of claim 1, wherein:

A is monocyclic five-membered heteroaryl;

Y is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, carbocyclyl, substituted carbocyclyl, heteroarylalkyl, or substituted heteroarylalkyl;

X is —

O—

, —

S—

, —

S(O)—

, —

S(O)₂—

, —

C(R³R⁴)—

, —

C(O)—

, —

C(S)—

, —

C(═

NR³)—

, —

C(O)O—

, —

N(R³)—

, —

OC(O)—

, —

N(R³)C(O)—

, —

C(O)N(R³)—

, —

C(═

N—

OR³)—

, —

C(═

NR³)—

NR⁴—

, —

N(R³)C(═

NR⁴)—

, —

N(R³)C(S)—

, —

C(S)—

N(R³)—

, —

N(R³)S(O)₂—

, —

S(O)₂—

N(R³)—

, —

N(R³)C(═

NR⁴)O—

, —

C(═

NR⁴)O—

N(R³)—

, —

N(R³)—

C(═

NR⁴)—

N(⁵)—

, —

N(R³)N(R⁴)C(O)O—

, —

N(R³)C(O)O—

, —

N(R³)C(O)N(R⁴)—

, —

NR³—

C(O)—

C(O)—

NR⁴—

, —

C(O)—

C(O)—

NR⁴—

, —

P(O)(OR³)—

, or —

P(O)(R³)—

;

Z is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, carbocyclyl, substituted carbocyclyl, heteroarylalkyl, or substituted heteroarylalkyl; and

R³, R⁴, and R⁵ are each independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, carbocyclyl, or substituted carbocyclyl.

5. The compound of claim 1, having a structural formula (Ia):

or the salt, solvate, ester, or N-oxide thereof, wherein

X^a is —

S(O)—

, —

S(O)₂—

, —

C(R³R⁴)—

, —

C(O)—

, —

C(O)O—

, —

C(O)N(R³)—

, —

C(═

N—

OR³)—

, —

C(═

NR³)—

NR⁴—

, —

C(═

NR³)—

, —

C(S)—

N(R³)—

, —

C(S)—

, —

NR³—

C(O)—

C(O)—

NR⁴—

, —

C(O)—

C(O)—

NR⁴—

, or —

S(O)₂—

N(R³)—

;

Y is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbocyclyl, or substituted carbocyclyl;

Z is alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, carbocyclyl, or substituted carbocyclyl; and

R hydrogen, alkyl, or substituted alkyl.

6. The compound of claim 1, having a structural formula selected from the group consisting of

or the salt, solvate, ester, or N-oxide thereof

7. The compound of claim 1 wherein

A is a covalent bond;

Y is —

OR¹, —

S(O)R¹, —

S(O)₂R¹, —

OC(O)R¹, —

N(R¹)C(O)R², —

NR¹R², —

C(O)NR R², —

C(O)OR¹, —

S(O)₂NR¹R², —

N(R¹)S(O)₂R², —

SR¹, —

C(R¹R²R⁶), —

C(S)—

R¹, —

C(═

NR²)—

R¹, —

N(R¹)—

C(═

N—

OR²)R⁶, —

C(═

N—

OR¹)R², —

C(═

NR¹)—

NR²R⁶, —

N(R¹)C(═

NR²)R⁶, —

N(R¹)C(S)R², —

N(R¹)—

C(O)—

C(O)R², —

N(R¹)C(S)N(R²)—

R⁶, —

C(S)—

NR¹R², —

N(R¹)C(═

NR²)OR⁶, —

C(═

NR¹)O—

NR²R⁶, —

N(R¹)—

C(═

NR²)—

N(R⁶)R⁷, —

N(R¹)N(R²)C(O)OR⁶,—

N(R¹)C(O)OR², —

N(R¹)C(O)NR²R⁶, —

N(R¹)—

C(O)—

C(O)—

NR²R⁶, —

C(O)—

C(O)—

NR¹R², —

P(O)(OR¹)(OR²), —

P(O)(OR¹)(R²), or —

P(O)R R²; and

R¹, R², R⁶ and R⁷ are each independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, carbocyclyl, substituted carbocyclyl, heteroarylalkyl, or substituted heteroarylalkyl.

8. The compound of claim 7 wherein

Y is —

N(R¹)C(O)R², —

NR¹R², —

N(R¹)S(O)₂R², —

N(R¹)—

C(═

N—

OR²)R⁶, —

C(═

NR¹)—

NR²R⁶, —

N(R¹)C(═

NR²)R⁶, —

N(R¹)C(S)R², —

N(R¹)—

C(O)—

C(O)R², —

N(R¹)C(S)N(R²)—

R⁶, —

N(R¹)C(═

NR²)OR⁶, —

N(R¹)—

C(═

NR²)—

NR⁶R⁷, —

N(R¹)N(R²)C(O)OR⁶—

N(R¹)C(O)OR², —

N(R¹)C(O)NR²R⁶, or —

N(R¹)—

C(O)—

C(O)—

NR²R⁶;

X is —

N(R³)C(O)—

, —

N(R³)—

, —

N(R³)S(O)₂—

, —

N(R³)—

C(═

N—

OR⁴)—

, —

N(R³)C(═

NR⁴)—

, —

N(R¹)—

C(═

NR²)—

N(R⁶)—

, —

N(R³)C(S)—

, —

N(R³)C(S)N(R⁴)—

, —

N(R³)C(O)N(R⁴)—

, —

N(R³)C(═

NR⁴)O—

, —

N(R³)—

C(═

NR⁴)—

N(R⁵)—

, —

N(R³)N(R⁴)C(O)O—

, —

N(R³)C(O)O—

, or —

N(R³)C(O)N(R⁴)—

; and

R¹, R², R³, R⁵, R⁶, and R⁷ are each independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, substituted arylalkyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclyl, substituted heterocyclyl, carbocyclyl, or substituted carbocyclyl; and

Z is alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, substituted arylalkyl, heteroarylalkyl, substituted heteroarylalkyl, carbocyclyl, or substituted carbocyclyl.

9. The compound of claim 8 wherein Z is carbocyclyl or substituted carbocyclyl.

10. The compound of claim 8 wherein Z is alkyl or substituted alkyl.

11. A compound of formula (Ib):

or a salt, solvate, ester, or N-oxide thereof, wherein

M is O or S; and

W and Z are each independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, alkoxy, alkylamine, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, carbocyclyl, or substituted carbocyclyl.

12. The compound of claim 11 wherein

W and Z are each independently selected from alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkylamine, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, substituted arylalkyl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, carbocyclyl, or substituted carbocyclyl.

13. A composition comprising a compound having structural formula (I),

or the salt, solvate, ester, or N-oxide thereof, wherein:

A is aryl, heteroaryl, or a covalent bond;

Y is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, carbocyclyl, substituted carbocyclyl, acyl, halo, —

CN, —

NO₂, —

OR¹, —

S(O)R¹, —

S(O)₂R¹, —

OC(O)R¹, —

N(R¹)C(O)R², —

NR¹R², —

C(O)NR¹R², —

C(O)OR¹, —

S(O)₂NR¹R², —

COR¹, —

N(R¹)S(O)₂R², —

SR¹, —

C(R¹R²R⁶), —

C(S)—

R¹, —

C(═

NR²)—

R¹, —

N(R¹)—

C(═

N—

OR²)R⁶, —

N(R¹)C(S)NR²R⁶, —

C(═

N—

OR¹)R², —

C(═

NR¹)—

NR²R⁶, —

N(R¹)C(═

NR²)NR⁶R⁷, —

N(R¹)C(S)R², —

N(R¹)—

C(O)—

C(O)R², —

C(S)—

NR¹R², —

N(R¹)C(═

NR²)OR⁶, —

C(═

NR¹)O—

NR²R⁶, —

N(R¹)N(R²)C(O)OR⁶ , —

N(R¹)C(O)OR², —

N(R¹)C(O)NR²R⁶, —

N(R¹)—

C(O)—

C(O)—

NR²R⁶, —

C(O)—

C(O)—

NR¹R², —

P(O)(OR¹)(OR²), —

P(O)(OR¹)(R²), or —

P(O)R¹R²;

X is —

O—

, —

S—

, —

S(O)—

, —

S(O)₂—

, —

C(³R⁴)—

, —

C(O)—

, —

C(S)—

, —

C(═

NR³)—

, —

C(O)O—

, —

N(R³)—

, —

OC(O)—

, —

N(R³)C(O)—

, —

C(O)N(R³)—

, —

N(R³)—

C(═

N—

OR⁴)—

, —

C(═

N—

OR³)—

, —

C(═

NR³)—

NR⁴—

, —

N(R³)C(S)N(R⁴)—

R⁵, —

N(R³)C(O)N(R⁴)—

R⁵, —

N(R³)C(═

NR⁴)—

, —

N(R³)C(S)—

, —

N(R³)—

C(O)—

C(O)—

, —

C(S)—

N(R³)—

, —

N(R³)S(O)₂—

, —

S(O)₂—

N(R³)—

, —

N(R³)C(═

NR⁴)O—

, —

C(═

NR⁴)O—

N(R³)—

, —

N(R³)—

C(═

NR⁴)—

N(R⁵)—

, —

N(R³)N(R⁴)C(O)O—

, —

N(R³)C(O)O—

, —

N(R³)C(O)N(R⁴)—

, —

N(R³)—

C(O)—

C(O)—

NR⁴—

, —

C(O)—

C(O)—

NR⁴—

, —

P(O)(OR³)—

, or —

P(O)R³—

;

Z is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, carbocyclyl, or substituted carbocyclyl; and

R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are each independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, carbocyclyl, substituted carbocyclyl, heteroarylalkyl, or substituted heteroarylalkyl.

14. The composition of claim 13, which comprises an ingestible composition.

15. The composition of claim 13, which comprises a food or beverage.

16. A method for modulating the savory taste of a composition comprising combining the composition with at least one compound of formula (I):

or the salt, solvate, ester;

or N-oxide thereof, wherein;

A is aryl, heteroaryl, or a covalent bond;

Y is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, carbocyclyl, substituted carbocyclyl, acyl, halo, —

CN, —

NO₂, —

OR¹, —

S(O)R¹, —

S(O)₂R¹, —

OC(O)R¹, —

N(R¹)C(O)R², —

NR¹R², —

C(O)NR¹R², —

C(O)OR¹, —

S(O)₂NR¹R², —

COR¹, —

N(R¹)S(O)₂R², —

SR¹, —

C(R¹R²R⁶), —

C(S)—

R¹, —

C(═

NR²)-R¹, —

N(R¹)—

C(═

N—

OR²)R⁶, —

N(R¹)C(S)NR²R⁶, —

C(═

N—

OR¹)R², —

C(═

NR¹)—

NR²R⁶, —

N(R¹)C(═

NR²)NR⁶R⁷, —

N(R¹)C(S)R², —

N(R¹)—

C(O)—

C(O)R², —

C(S)—

NR¹R², —

N(R¹)C(═

NR²)OR⁶, —

C(═

NR¹)O—

NR²R⁶, —

N(R¹)N(R²)C(O)OR⁶, —

N(R¹)C(O)OR², —

N(R¹)C(O)NR²R⁶, —

N(R¹)—

C(O)—

C(O)—

NR²R⁶, —

C(O)—

C(O)—

NR¹R², —

P(O)(OR¹)(OR²), —

P(O)(OR¹)(R²), or —

P(O)R¹R²;

X is —

O—

, —

S—

, —

S(O)—

, —

S(O)₂—

, —

C(R³R⁴)—

, —

C(O)—

, —

C(S)—

, —

C(═

NR³)—

, —

C(O)O—

, —

N(R³)—

, —

OC(O)—

, —

N(R³)C(O)—

, —

C(O)N(R³)—

, —

N(R³)—

C(═

N—

OR⁴)—

, —

C(═

N—

OR³)—

, —

C(═

NR³)—

NR⁴—

, —

N(R³)C(S)N(R⁴)—

R⁵, —

N(R³)C(O)N(⁴)—

R⁵, —

N(R³)C(═

NR⁴)—

, —

N(R³)C(S)—

, —

N(R³)—

C(O)—

C(O)—

, —

C(S)—

N(R³)—

, —

N(R³)S(O)₂—

, —

S(O)₂—

N(R³)—

, —

N(R³)C(═

NR⁴)O—

, —

C(═

NR⁴)O—

N(R³)—

, —

N(R³)—

C(═

NR⁴)—

N(R⁵)—

, —

N(R³)N(R⁴)C(O)O—

, —

N(R³)C(O)O—

, —

N(R³)C(O)N(R⁴)—

, —

N(R³)—

C(O)—

C(O)—

NR⁴—

, —

C(O)—

C(O)—

NR⁴—

, —

P(O)(OR³)—

, or —

P(O)R³—

;

Z is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, carbocyclyl, or substituted carbocyclyl; and

R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are each independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, carbocyclyl, substituted carbocyclyl, heteroarylalkyl, or substituted heteroarylalkyl.