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US 2003/0195187 A1Published application
Guanidino compounds
AssigneeChiron Corporation
InventorsRustum S. Boyce, Daniel Chu
Life of this patent
Estimating the term…
Abstract
A variety of small, guanidino group-containing molecules capable of acting as MC4-R agonists are provided. The compounds have various structures provided herein. The compounds are useful in treating MC4-R mediated diseases and may be formulated into pharmaceutical formulations and compositions.
Claims64
A compound of formula A1-A2-A3-A4
- wherein
- A1 is a group of formula IIA or IIB;
- 48
- R1′ is selected from the group consisting of H, and substituted and unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, arylalkyl, heteroarylalkyl, and cycloalkylalkyl groups;
- R2′ is selected from the group consisting of substituted and unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, arylalkyl, heteroarylalkyl, and cycloalkylalkyl groups;
- or R1′ and R2′, together with the nitrogen to which they are bound, form a substituted or unsubstituted heterocyclyl or heteroaryl group;
- R3′ is selected from the group consisting of substituted and unsubstituted aryl, alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, heterocyclyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, and cycloalkylalkyl groups;
- R4′ is selected from the group consisting of H, and substituted and unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocyclyl, arylalkyl, and heteroarylalkyl groups;
- A2 is selected from the group consisting of substituted and unsubstituted aryl groups and substituted and unsubstituted heteroaryl groups;
- A3 is a covalent bond such that A2 is directly bonded to A4, or A3 is a linking group selected from the group consisting of O, S, —NRa—, —C(═O)—, —C(═O)O—, —NRaC(═O)—, —SO2NRa—, —C(═S)—, —C(═O)S—, —P(═O)Rb—, —SO2—, and —S(═O)—, wherein if A3 is a linking group, then it is bonded to A2 and A4 in a configuration selected from the group consisting of A2-O-A4, A2-S-A4, A2-NRa-A4, A2-C(═O)-A4, A2-C(═O)O-A4, A4-C(═O)O-A2, A2-NRaC(═O)-A4, A4-NRaC(═O)-A2, A2-SO2NRa-A4, A4-SO2NRa-A2, A2-C(═S)-A4, A2-(C═O)S-A4, A4-(C═O)S-A2, A2-(P═O)Rb-A4, A2-SO2-A4, and A2-S(═O)-A4 provided that if A3 is a linking group with the configuration A4-NRaC(═O)-A2, then A2 is not a substituted or unsubstituted phenyl group and is not a substituted or unsubstituted 6-membered N-containing heteroaryl group;
- A4 is selected from the group consisting of substituted and unsubstituted arylalkyl, heteroarylalkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, alkenyl, alkynyl, and alkyl groups;
- Ra is selected from the group consisting of H, and substituted and unsubstituted arylalkyl, heteroarylalkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, alkenyl, alkynyl, and alkyl groups;
- Rb is selected from the group consisting of substituted and unsubstituted arylalkyl, heteroarylalkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, alkenyl, alkynyl, and alkyl groups;
- and
- prodrugs thereof, pharmaceutically acceptable salts thereof, stereoisomers thereof, tautomers thereof, hydrates thereof, hydrides thereof, or solvates thereof.
12 more elements
A compound of formula I
- 49
- wherein
- Q, W, X, Y, and Z are independently selected from the group consisting of carbon atoms and nitrogen atoms;
- R1, R2, R3, R4, and R5 may be the same or different, and are each independently selected from the group consisting of H, Cl, I, F, Br, OH, NH2, CN, NO2, and substituted and unsubstituted aryl, alkoxy, amino, alkyl, alkenyl, alkynyl, alkylamino, dialkylamino, cycloalkyl, heterocyclylamino, heteroarylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, heterocyclylaminocarbonyl, heteroarylaminocarbonyl groups, and groups of formula IIA or IIB;
- 50
- wherein R1 may be absent if W is a nitrogen atom;
- wherein R2 may be absent if X is a nitrogen atom;
- wherein R3 may be absent if Z is a nitrogen atom;
- wherein R4 may be absent if Y is a nitrogen atom;
- wherein R5 may be absent if Q is a nitrogen atom;
- wherein one of R1, R2, R3, R4, or R5 is a group having the formula IIA or IIB;
- R1′ is selected from the group consisting of H, and substituted and unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, arylalkyl, heteroarylalkyl, and cycloalkylalkyl groups;
- R2′ is selected from the group consisting of substituted and unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, arylalkyl, heteroarylalkyl, and cycloalkylalkyl groups;
- or R1′ and R2′, together with the nitrogen to which they are bound, form a substituted or unsubstituted heterocyclyl or heteroaryl group;
- R3′ is selected from the group consisting of substituted and unsubstituted aryl, alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, heterocyclyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, and cycloalkylalkyl groups;
- R4′ is selected from the group consisting of H, and substituted and unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocyclyl, arylalkyl, and heteroarylalkyl groups;
- R6 is a group of formula IIIA, IIIB, IIIC, IIID, or IIIE
- 51
- m is an integer selected from 0, 1, or 2;
- n is an integer selected from 0, 1, or 2;
- R7, R8, R9, and R10 may be the same or different and are independently selected from the group consisting of H, Cl, l, F, Br, OH, NH2, CN, NO2, and substituted and unsubstituted alkoxy, amino, alkyl, aryl, alkenyl, alkynyl, alkylamino, dialkylamino, cycloalkyl, heterocyclylamino, heteroarylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, heterocyclylaminocarbonyl, and heteroarylaminocarbonyl groups;
- R7 and R8 may join together with the carbon atoms to which they are attached to form a substituted or unsubstituted 5 or 6 membered ring;
- R11 is selected from the group consisting of H, and substituted and unsubstitued alkyl groups;
- R12, R13, R14, and R15 may be the same or different and are each independently selected from the group consisting of H, Cl, I, F, Br, OH, NH2, CN, NO2, and substituted and unsubstituted alkoxy, amino, alkyl, aryl, alkenyl, alkynyl, alkylamino, dialkylamino, cycloalkyl, heterocyclylamino, heteroarylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, heterocyclylaminocarbonyl, and heteroarylaminocarbonyl groups;
- R12 and R14 may represent a second bond between the carbon bonded to R12 and the carbon bonded to R14 such that the bond between the carbon bonded to R12 and the carbon bonded to R14 is a double bond;
- and
- R16 is selected from the group consisting of H, and substituted and unsubstituted alkyl groups;
- R11 and R16 may represent a second bond between the carbon bonded to R16 and the nitrogen bonded to R11 such that the bond between the carbon bonded to R16 and the nitrogen bonded to R11 is a double bond;
- R17 is selected from the group consisting of H, and substituted and unsubstituted arylalkyl, heteroarylalkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, alkenyl, alkynyl, and alkyl groups;
- R18 is selected from the group consisting of H, and substituted and unsubstituted arylalkyl, heteroarylalkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, alkenyl, alkynyl, and alkyl groups;
- R19 is selected from the group consisting of substituted and unsubstituted arylalkyl, heteroarylalkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, alkenyl, alkynyl, and alkyl groups;
- and
- prodrugs thereof, pharmaceutically acceptable salts thereof, stereoisomers thereof, tautomers thereof, hydrates thereof, hydrides thereof, or solvates thereof.
30 more elements
Dependencies are inferred from the claim text.