Cannabinergic nitrate esters and related analogs

摘要

The present technology relates to novel cannabinergic nitrate esters and related analogs, process of preparation, pharmaceutical compositions and their methods of use as medicaments, pharmacological tools and/or biomarkers. The novel cannabinergic nitrate ester compounds provide medicaments useful in treating a variety of diseases and medical disorders.

主权项

1. A compound of formula (I): or a pharmaceutically acceptable salt thereof; wherein:
ring C has zero, one, two or three double bonds;X is carbon, CH, N, NH, C(CH2)2, S, O, SO, SO2, or CF2;R1 is H, OH, alkyl-OH, ═O, halogen, alkyl, COOH, C(O)Oalkyl, O(CO)alkyl, nitro, ONO2, or optionally substituted alkyl, haloalkyl, alkenyl, alkynyl, acyl, aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, heteroarylalkyl, heteroalkoxy, heteroaryloxy, alkenyl, amino, thio, cyano, thiocynato, isothiocynato, carboxyl, formyl, carbamyl, amino, acylamino, amido, imido, aminoalkyl, aminoaryl, heteroarylamino, heterocyclylamino, sulfonate, sufonamide, sulfonyl, thioalkyl, thioaryl, heteroarylthio, heterocyclylthio, phosphonate, phosphate, or acetate;W is C(CH3)2, CH(CH3), C═O, CF2, C═S, C═CH2, spirocyclic ring, S, SO, SO2, or C[CH3(R4)];R4 is an optionally substituted alkyl, alkenyl, or alkynyl group;Z is O, S, SO, SO2, NH, or N-alkyl;R2 is H, OH, SH, NH2, CF3, COOH, alkoxy, halogen, ONO2, alkyl-ONO2, or optionally substituted alkyl, haloalkyl, amine, amide, imide, alkoxy, alkoxy thio, phosphate, phosphonate, carboxyl, formyl, carbamyl, amino, acylamino, amido, imido, aminoalkyl, aminoaryl, heteroarylamino, heterocyclylamino, sulfonate, sufonamide, sulfonyl, thioalkyl, thioaryl, heteroarylthio, heterocyclylthio, phosphonate, phosphate, or acetate;Y is a bond, C(CH3)2, CF2, C═O, CH(alkyl), C(alkyl)2, C(O)O, NHCO, CONH, alkyl, C(O)Oalkyl, OC(O)alkyl, cycloalkyl, heterocyclyl, lactone, lactam, sultam, O, S, SO, SO2, OSO2, amine, diazine, alkenyl, or alkynyl group;R3 is absent, or is O, S, SO2, SO2NH, NHSO2, OSO2, OSO2alkyl, C(O)Oalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, a carbocyclic, a spirocyclic, heterocyclyl, aryl, heteroaryl, carboxyl, acetate, amine, amide, or imide;V is V1 or ONO2, wherein when any of rings A, B or C comprises a group comprising ONO2, V is V1, otherwise V is ONO2; andV1 is H, F, Cl, Br, I, haloalkyl, N3, NCS, CN, NO2, OH, alkoxy, amino, alkylamino, dialkylamino, trialkylamino, aryl, cycloalkyl, alkyl, alkenyl, alkynyl, —C(O)aryl, —C(O)alkyl, C(O)Oalkyl, —C(O)heteroaryl, —C(O)amino, —C(O)(dialkylamino), C(O)(trialkylamino), C(O)(heterocyclyl), C(O)heteroaryl, —OC(O)alkyl, OSO2H, OSO2(alkyl), OSO2(aryl), OSO2NO2, OSO2(alkyl)CN, OSO2(alkyl)OH, OSO2alkylamino), —SC(O)alkyl, —SO2alkyl, —SO-alkyl, —SC(CH3)2C(O)Oalkyl, —SC(CH3)2C(O)Oaryl, —SC(CH3)2C(O)Oheteroaryl, —SC(CH3)2C(O)Oheterocyclyl, Si(alkyl)3, —OC(O)aryl, NHC(O)alkyl, NHC(O)aryl, —C(O)H, C(O)Oalkyl, SO2(amino), SO2(heterocyclyl), SO2(trialkylamino), SO2(dialkylamino), carbocyclic, a spirocyclic ring, heterocyclyl, heteroaryl, alkylthio, alkylamino, dialkylamino, alkylsulfinyl, alkylsulfonyl, boronic acid, boronate ester, BF3K, or a biotin group tethered via an amide bond.