A compound of Formula (I), (II), (III), (IV), (V), (VI) (VII), (VIII), (IX), (X), (XI), (XII) or (XIII), or a pharmaceutically acceptable salt thereof;
- wherein the compound of Formula (I) is:
- 44
- wherein
- A is S(O)o;
- W1 is —C—NR87R87′, —CH or nitrogen;
- W2 is:
- 45
- J is CH or nitrogen;
- o is an integer from 0 to 2;
- R1 is a hydrogen, an alkoxy group, a lower alkyl group, or an alkylthio group;
- R2 is a hydrogen, a halogen, an alkoxy group, a lower alkyl group, an alkylthio group, a haloalkoxy group, an alkoxyalkyl group, —NR87R87′, —OX, or —SX;
- or R2 and R3 taken together with the carbon atoms to which they are attached form a cycloalkyl ring, an aryl group or a heterocyclic ring, and with the proviso that R2 must be OX, or —SX in W2;
- R3 and R11 are each independently a hydrogen, an alkoxy group, a lower alkyl group, or an alkylthio group;
- or R3 and R11 taken together with the carbon chain to which they are attached form a cycloalkyl ring, an aryl group or a heterocyclic ring;
- R32 and R47 are each independently a hydrogen, an alkyl group, a halo group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cyano group, an aryl group, a heterocyclic ring, —NR87R87′, —OX, or —CO2R12;
- or R32 and R47 taken together are:
- 46
- wherein
- R86 is oxygen or N═O—R87;
- R87 and R87′ are each independently hydrogen, a lower alkyl group, D1 or X;
- or R87 and R87′ taken together with the nitrogen to which they are attached form a heterocyclic ring;
- R10 is a hydrogen;
- or R10 and R1 taken together with the carbon chain to which they are attached form a cycloalkyl ring;
- R12 is a lower alkyl group or X, with the proviso that Y in the definition of X must be oxygen or sulfur (—S—);
- D1 is:
- (i) —C(R6R6′)—T—C(O)—X;
- (ii) —C(O)—X;
- (iii) —S(O)2—X;
- (iv) —C(R6R6′)—T—S(O)2—X;
- (v) —C(R6R6′)—X;
- or
- (vi) an inorganic cation;
- R6 and R6′ are each independently a hydrogen, a lower alkyl group, an aryl group;
- X is:
- (1) —Y—(CR4R4′)p—T—(CR4R4′)p—ONO2;
- (2) —Y—(CR4R4′)p—ONO2;
- 47
- wherein T is ortho, meta or para;
- 48
- (5) —Y—(CR4R4′)p—V—B—T—(CR4R4′)p—ONO2;
- (6) —Y—(CR4R4′)p—T—C(O)—(CR4R4′)o—(CH2)—ONO2;
- (7) —Y—(CR4R4′)p—C(Z)—(CH2)q—T—(CR4R4′)q—(CH2)—ONO2;
- (8) —Y—(CR4R4′)p—T—(CH2)q—V—(CR4R4′)q—(CH2)—ONO2;
- (9) —Y—(CR4R4′)p—V—(CH2)q—V—(CR4R4′)q—(CH2)—ONO2;
- (10) —Y—(CR4R4′)o—(W)q—(CR4R4′)o—(CH2)—ONO2;
- (11) —NRj—O—(CH2)o—V—(CR4R4′)q—(CH2)—ONO2;
- (12) —NRj—O—(CH2)o—(W)q—CR4R4′)q—(CH2)—ONO2;
- (13) —O—NRj—(CH2)o—(W)q—CR4R4′)q—(CH2)—ONO2;
- (14) —Y—(CH2)o—(W)q—(CH2)o—V—(CR4R4′)o—Q′—(CR4R4′)o—(CH2)—ONO2;
- (15) —Y—(CR4R4′)p—V—(CH2)o—(W)q—CR4R4′)q—(CH2)—ONO2;
- (16) —O—NRj—(CH2)o—V—(CR4R4′)q—CH2)—ONO2;
- (17) —Y—(CR4R4′)o—Q′—(CR4R4′)o—V—(CR4R4′)o—(CH2)—ONO2;
- (18) —Y—(CR4R4′)o—Q′—(CR4R4′)o—(W)q—(CR4R4′)o—(CH2)—ONO2;
- (19) —Y—(CR4R4′)p—T—(CR4R4′)p—Q′—(CR4R4′)o—(CH2)—ONO2;
- (20) —Y—(CR4R4′)q—C(Z)—(CR4R4′)o—(CH2)—ONO2;
- (21) —Y—(CR4R4′)p—Q′—(CR4R4′)o—(CH2)—ONO2;
- (22) —Y—(CR4R4′)q—P(O)MM′;
- (23) —Y—(CR4R4′)o—Q′—(CR4R4′)o—(CH2)—ONO2;
- (24) —Y—(CR4R4′)o—Q′—(CR4R4′)o—T—(CR4R4′)o—(CH2)—ONO2;
- (25) —Y—(CR4R4′)q—(W)q—(CR4R4′)o—Q′—(CR4R4′)o—(CH2)—ONO2;
- (26) —Y—(CR4R4′)q—V—(CR4R4′)o—Q′—(CR4R4′)o—(CH2)—ONO2;
- (27) —Y—(CR4R4′)p—(T)o—(W)q—(CR4R4′)o—(CH2)—ONO2;
- (28) —Y—(CR4R4′)p—(W)q—(T)o—(CR4R4′)o—(CH2)—ONO2;
- (29) —Y—(CR4R4′)q—C(Z)—V—(CR4R4′)q—CH2)—ONO2;
- (30) —Y—(CR4R4′)o—C(R4)(ONO2)—(CR4R4′)q—(T)o—(W)q—(T)o—(CR4R4′)o—R5;
- (31) —Y—(CR4R4′)o—V—(CR4R4′)o—Q′—(CR4R4′)o—(CH2)—ONO2;
- (32) —Y—(CR4R4′)q—C(Z)—Q′—(CR4R4′)o—(CH2)—ONO2;
- (33) —Y—(CR4R4′)p—V—(CR4R4′)p—(CH2)—ONO2;
- (34) —Y—(CR4R4′)p—V—(CH2)q—(T)o—(CR4R4′)q—(CH2)—ONO2;
- (35) —Y—(CR4R4′)p—(T)o—Q′—(T)o—(CR4R4′)q—CH2)—ONO2;
- (36) —Y—(CR4R4′)q—C(Z)—(CR4R4′)q—V—(CR4R4′)o—Q′—(CR4R4′)o—(CH2)—ONO2;
- (37) —Y—(CR4R4′)q—C(Z)—(CR4R4′)q—(W)q—(CR4R4′)o—Q′—(CR4R4′)o—(CH2)—ONO2;
- (38) —NRj—O—(CH2)o—V—(CR4R4′)o—Q′—(CH2)—ONO2;
- (39) —NRj—O—(CH2)o—(W)q—(CR4R4′)o—Q′—(CH2)—ONO2;
- (40) —O—NRj—(CH2)o—(W)q—(CR4R4′)o—Q′—(CH2)—ONO2;
- (41) —O—NRj—(CH2)o—V—(CR4R4′)o—Q′—(CH2)—ONO2;
- (42) —NRj—NRj—(CR4R4′)p—(W)q—(T)o—(CR4R4′)o—(CH2)—ONO2;
- or
- (43) —Y—(CR4R4′)o—Q′—(CR4R4′)o—ONO2;
- or
- (44) —Y—(CR4R4′)o—V—(CR4R4′)o—Q—(CR4R4′)o—ONO2;
- R4 and R4′ at each occurrence are independently a hydrogen, lower alkyl group, —OH, —CH2OH, —ONO2, —NO2 or —CH2ONO2;
- or R4 and R4′ taken together with the carbon atom to which they are attached are a cycloalkyl group or a heterocyclic ring;
- V is —C(O)—T—, —T—C(O)—, —T—C(O)—T or T—C(O)—CO)—T;
- W is a covalent bond or a carbonyl group;
- T at each occurrence is independently an oxygen, (S(O)o)o or NRj;
- Rj is a hydrogen, an alkyl group, an aryl group, a heterocyclic ring, an alkylcarbonyl group, an alkylaryl group, an alkylsulfinyl group, an alkylsulfonyl group, an arylsulfinyl group, an arylsulfonyl group, a sulfonamido group, a N-alkylsulfonamido group, a N,N-diarylsulfonamido group, a N-arylsulfonamido group, a N-alkyl-N-arylsulfonamido group, a carboxamido group or a hydroxyl group;
- p at each occurrence is independently an integer from 1 to 6;
- q at each occurrence is independently an integer from 1 to 3;
- Y is oxygen, sulfur (—S—), NRj or a covalent bond;
- B is either phenyl or (CH2)o;
- Q′ is a cycloalkyl group, a heterocyclic ring or an aryl group;
- Z is (═O), (═N—OR5), (═N—NR5R′5) or (═CR5R′5);
- M and M′ are each independently —O− H3N+—(CR4R′4)q—CH2ONO2 or —T—(CR4R′4)o—CH2ONO2;
- R5 and R5′ at each occurrence are independently a hydrogen, a hydroxyl group, an alkyl group, an aryl group, an alkylsulfonyl group, an arylsulfonyl group, a carboxylic ester, an alkylcarbonyl group, an arylcarbonyl group, a carboxamido group, an alkoxyalkyl group, an alkoxyaryl group, a cycloalkyl group or a heterocyclic ring;
- o is as defined herein;
- and
- with the proviso that the compounds of Formula (I) must contain at least one nitrate group, and
- with the further proviso for compounds of Formula (I):
- when D1 is —C(R6R6′)—T—C(O)—X, T is oxygen, R6 and R6′ are each independently a hydrogen or a lower alkyl group, X is Formula 1, R4 and R4′ are both hydrogen, Y cannot be oxygen, NRj or a covalent bond when T is oxygen;
- when D1 is —C(R6R6′)—X, R6 and R6′ are each independently a hydrogen or a lower alkyl group, X is Formula 2, R4 and R4′ are both hydrogen, Y cannot be a covalent bond or oxygen;
- and
- with the proviso that the compounds of Formula (I) are not ACS registry numbers 384339-54-2, 384339-53-1, 326850-42-4, 302543-91-5 or 301669-76-1;
- wherein the compound of Formula (II) is:
- 49
- wherein
- Rx is hydrogen or
- 50
- Ry is hydrogen or
- 51
- R8 is a lower alkyl group, an alkoxyalkyl group, an alkylaryl group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group, an alkylaryl group, or X;
- R9 at each occurrence is independently a hydrogen, a lower alkyl group, an akylthio group, a halogen, a cyano group an alkanoyl group, a haloalkyl group, a carbamoyl group, —NR87X, —OX, or —CO2R12;
- R71 is a hydrogen, a lower alkyl group, an alkoxy group, or —OX;
- d is an integer from 1 to 5;
- and
- wherein o, X, D1, R12, R87, R87′ and o are as defined herein;
- and
- with the proviso that the compounds of Formula (II) must contain at least one nitrate group;
- wherein the compound of Formula (III) is:
- 52
- wherein
- R13 and R14 are each independently a hydrogen a lower alkyl group, an alkoxyalkyl, or a lower alkyl-OX;
- or R13 and R14 taken together along with the carbon atoms to which they are attached form a cycloalkyl group or an aryl group;
- R17 is a hydrogen or a lower alkyl group;
- Y3 is:
- 53
- wherein
- R15 is a hydrogen or a lower alkyl group;
- R16 is a hydrogen, a halogen, or a lower alkyl group;
- R63 is a lower alkyl group or a phenyl group;
- A1, A2 and A3 comprise the other subunits of a 5- or 6-membered monocyclic aromatic ring and A1, A2 and A3 are each independently:
- (i) CRo, wherein Ro at each occurrence is hydrogen or —OX;
- (ii) N—Rp, wherein Rp at each occurrence is independently a covalent bond to an adjacent ring atom in order to render the ring aromatic, a hydrogen, or X;
- (iii) a sulfur atom;
- (iv) an oxygen atom;
- or (v) Ba═Bb, wherein Ba and Bb are each independently a nitrogen atom or CRo;
- wherein Ro at each occurrence is hydrogen or —OX;
- D1 and X are as defined herein, and
- with the proviso that the compound of Formula (III) must contain at least one nitrate group;
- wherein the compound of Formula (IV) is:
- 54
- wherein
- R18 and R19 at each occurrence are each independently a hydrogen, a lower alkyl group, a halogen, a nitro group, an alkoxy group, —OX, —NR20R21, —O(O)CR20, —O(O)COR20, —O(O)CNR20R21, —N(R20)C(O)R21, —N(R20)C(O)NR20R21, or —N(R20)C(O)OR21;
- or R18 and R19 when taken together along with the carbons to which they are attached form a heterocyclic ring or a phenyl ring optionally substituted with up to four substituents selected from a hydrogen, a lower alkyl group, a halogen, a nitro group, an alkoxy group, —OD1, —NR20R21, —O(O)CR20, —O(O)COR20, —O(O)CNR20R21, —N(R20)C(O)R21, —N(R20)C(O)NR20R21 or —N(R20)C(O)OR21;
- R20 and R21 at each occurrence are each independently a hydrogen, a lower alkyl group, an aryl group, a lower alkylaryl group, or X;
- X4 is —C(═R86)R22, a heterocyclic ring, —NR20R21, a halogen, an alkoxy group, an arylalkoxy group, a cycloalkoxy group, a heterocyclicalkoxy group, an alkylsulfonyl group, an alkylsulfinyl group, an arylsulfonyl group, an arylsulfinyl group an arylalkylsulfonyl group, an arylalkylsulfinyl group, a heterocyclicsulfonyl group, or a heterocyclicsulfinyl group;
- R22 is a hydrogen, an alkyl group, an alkoxy group, an aryl group, an alkylaryl group, a heterocyclic ring, an —O-heterocyclic ring, or an alkylheterocyclic ring;
- D1, R86, and X are defined as herein, and
- with the proviso that the compound of Formula (IV) must contain at least one nitrate group;
- wherein the compound of Formula (V) is:
- 55
- wherein
- X15 is:
- 56
- wherein
- R23 is a hydrogen, a dialkylamino group, —NR87R87′, or a heterocyclic ring;
- R24 is a hydrogen or halogen;
- R25 is a hydrogen, —OX, or lower alkyl-OX;
- R27 at each occurrence is independently a hydrogen or an alkoxy group;
- R28, R29, and R30 are each independently a hydrogen, a lower alkyl group, a dialkylamino group, a heterocyclic ring, or a lower alkyl-OX;
- R31 is a hydrogen, a dialkylamino group, or an alkoxy group;
- R33 is a hydrogen or a lower alkyl group;
- g is an integer from 0 to 1;
- R87, R87′, X and d are as defined herein, and
- with the proviso that the compound of Formula (V) must contain at least one nitrate group;
- wherein the compound of Formula (VI) is:
- 57
- wherein
- A4, A5, and A6 are each independently a sulfur or CR34 with the proviso that at least one of A4, A5, or A6 is a sulfur atom and the other two are CR34;
- R34 at each occurrence is independently a hydrogen, a halogen, a cyano, a nitro, a trifluoromethyl, a lower alkyl group, a heterocyclic ring, a lower alkyl-OX, an alkoxy, a haloalkoxy, an alkylthio, an alkylsulfinyl, an alkylsulfonyl, an alkylcarbonyl, an alkoxycarbonyl, a carbamoyl, a N-alkylcarbamoyl, a N,N-di-alkylcarbamoyl, an ester, a cycloalkyl, an aryl, an alkylaryl, an aryloxy, an arylalkoxyoxy, an arylamino, a alkylarylamino, an arylthio, an arylsulfonyl, an arylsulfinyl, or a sulfonamido;
- R35 and R36 are each independently a hydrogen or a lower alkyl group;
- or R35 and R36 taken together with the carbon chain to which they are attached form a cycloalkyl ring;
- R26 is:
- 58
- wherein
- X6 is nitrogen, and Y6 is CR37;
- or
- X6 is CR37, and Y6 is nitrogen;
- R37 is a hydrogen, a halogen, a lower alkyl group, a trifluoromethyl, an alkoxy group, a haloalkoxy group, an aryl group, an arylalkoxy group, a heterocyclic ring, or an aryloxy;
- Z6 is —NR38R39, SR40, or an arylalkoxy group;
- R38 and R39 are each independently a hydrogen, a lower alkyl group, an aryl group, an alkylaryl group, or a cycloalkyl group;
- or R38 and R39 taken together with the nitrogen to which they are attached form a heterocyclic ring;
- R40 is a hydrogen, a halogen, a lower alkyl group, an alkylaryl group, an alkenyl group, or a haloalkyl group;
- R41, R42, R43, and R44 are each independently a hydrogen, a halogen, a lower alkyl group, an alkoxy group, a haloalkoxy group, an alkoxyaryl group, an alkylthio group, an alkysulfinyl group, an alkylsulfonyl group, a cyano group, B1—OX, B1—SX, —B1—NR20R21, —B1—O(O)CR20, —B1—O(O)CNR20R21, —B1—N(R20)C(O)R21, or —B1—N(R20)S(O)2R21;
- R45 and R46 are each independently a hydrogen, a lower alkyl group, a cycloalkyl group, an alkenyl group, or an alkynyl group;
- B1 is —C—NR87R87′ or nitrogen;
- D1, A, X, R20, R21, R87 and R87′ are as defined herein, and
- with the proviso that the compound of Formula (VI) must contain at least one nitrate group;
- wherein the compound of Formula (VII) is:
- 59
- wherein
- R60 is a lower alkyl group, an aryl group, a haloalkyl group, a lower alkyl-OX, or heterocyclic ring;
- A7 is oxygen, —CH═CH— or —ND1;
- X7 is a hydrogen or a halogen;
- Z7 is —CH2OD or —NDD1;
- D is hydrogen, —NO2 or D1;
- Y7 is:
- 60
- or X7, A7, and Y7 taken together along with the carbon atoms to which they are attached is:
- 61
- wherein
- R61 is a hydrogen, a halogen, a lower alkyl group, —OX, or —NHC(O)O-lower alkyl;
- R62 is a hydrogen, a halogen, or a lower alkyl group;
- and
- wherein D1 and X are as defined herein, and
- with the proviso that the compound of Formula (VII) must contain at least one nitrate group;
- wherein the compound of Formula (VIII) is:
- 62
- wherein D1 and D are as defined herein, and
- with the proviso that the compound of Formula (VIII) must contain at least one nitrate group;
- wherein the compound of Formula (IX) is:
- 63
- wherein
- R98 and R99 taken together are:
- 64
- wherein D1 and R87 are as defined herein;
- and
- with the proviso that the compound of Formula (IX) must contain at least one nitrate group;
- wherein the compound of Formula (X) is:
- 65
- wherein
- R100 at each occurrence is independently a hydrogen, a halogen, an alkoxy group or a haloalkoxy group;
- wherein D1 is as defined herein;
- and
- with the proviso that the compound of Formula (X) must contain at least one nitrate group;
- wherein the compound of Formula (XI) is:
- 66
- wherein R100, D and D1 are as defined herein;
- and
- with the proviso that the compound of Formula (XI) must contain at least one nitrate group;
- wherein the compound of Formula (XII) is:
- 67
- wherein R100, J and D1 are as defined herein;
- and
- with the proviso that the compound of Formula (XII) must contain at least one nitrate group;
- wherein the compound of Formula (XIII) is:
- 68
- wherein R1, R2, A and D1 are as defined herein;
- and
- with the proviso that the compound of Formula (XIII) must contain at least one nitrate group.