1. A compound of Formula I
43
an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug; wherein W is (a) O, (b) S, (c) SO, (d) SO2, (e) CH2, (f) CF2, (g) CHF,
44
(h) C(O), (i) CH(OH), (j) NRaor (k)
R0 is (a) hydrogen, (b) (C1-C6)alkyl substituted with zero or one substituent selected from the group consisting of (1) (C3-C6)cycloalkyl, (2) heterocycloalkyl and (3) phenyl substituted with zero or one substituent selected from the group consisting of (i) (C1-C4)alkyl, (ii) halogen, (iii) CF3 and (iv) OCF3; (c) C(O)Rh, (d) S(O)2Rh or (e) halogen;
R1, R2, R3 and R6 are each independently (a) hydrogen, (b) halogen, (c) (C1-C8)alkyl, (d) CF3, (e) OCF3, (f) O(C1-C8)alkyl, or (g) CN;
R4 is (a) (C1Cl2)alkyl substituted with zero to three substituents independently selected from Group V, (b) (C2-C12 )alkenyl, (c) (C2-C12)alkynyl, (d) halogen, (e) CN, (f) ORb, (g) aryl, (h) heteroaryl, (i) (C3-C10)cycloalkyl, (j) heterocycloalkyl, (k) C(O)ORc, (I) NRaC(O)Rd, (m) NRaC(O)NRcRd, (n) NRaS(O)2Rd, (o) NRaRd or (p) C(O)Rc;
or R3 and R4 are taken together along with the carbon atoms to which they are attached to form a carbocyclic ring of formula (CH2)i or a heterocyclic ring of formula (CH2)kQ(CH2)i wherein Q is O, Sor NRe; i is 3, 4, 5 or 6; k is 0, 1, 2, 3, 4 or 5; and I is 0, 1, 2, 3, 4 or 5; and wherein the carbocyclic ring and the heterocyclic ring are each substituted with zero to four substituents independently selected from (a) (C1-C4)alkyl, (b) ORb, (c) oxo, (d) CN, (e) phenyl or (f) NRaRg;
R5 is (a) OH, (b) O(C1-C6)alkyl, (c) OC(O)Rf, (d) F, or (e) C(O)ORc;
or R4 and R5 are taken together along with the carbon atoms to which they are attached to form a heterocyclic ring selected from the group consisting of CRcCRaNH, NCRaNH, CRcCRaO, CRcCRaS, CRcN-NH- and CRaCRaCRaN;
R7 is (a) hydrogen or (b) (C1-C6)alkyl;
R8 and R9 are each independently (a) hydrogen, (b) (C1-C6)alkyl, (c) aryl, or (d) halogen;
R10 is (a) (C0-C1)alkyl-C(O)OH, (b) (C0-C1)alkyl-C(O)ORf, (c) (C0-C1)alkyl-C(O)NRcRd, or (d) (C0-C1)alkyl-OH;
Ra for each occurrence is independently (a) hydrogen or (b) (C1-C6)alkyl substituted with zero or one (C3-C6)cycloalkyl or methoxy;
Rb for each occurrence is independently (a) hydrogen, (b) (C1-C12)alkyl substituted with zero to three substituents independently selected from Group V, (c) aryl, (d) heteroaryl, (e) (C3-C10)cycloalkyl, (f) heterocycloalkyl, (g) C(O)NRcRd, or (h) C(O)Rf;
Rc and Rd for each occurrence are each independently (a) hydrogen, (b) (C1-C12)alkyl substituted with zero to three substituents independently selected from Group VI, (c) (C2-C12)alkenyl, (d) (C2-C12)alkynyl, (e) aryl, (f) heteroaryl, (g) (C3-C10)cycloalkyl or (h) heterocycloalkyl;
or Rc and Rd are taken together along with the atom(s) to which they are attached to form a 3-10 membered heterocyclic ring which may optionally contain a second heterogroup selected from O, NRe or S; and wherein the heterocyclic ring is substituted with zero to four substituents independently selected from (a) (C1-C4)alkyl, (b) ORb, (c) oxo, (d) CN, (e) phenyl or (f) NRaRg;
Re for each occurrence is (a) hydrogen, (b) CN, (c) (C1-C10)alkyl substituted with zero to three substitutents independently selected from Group V, (d) (C2-C10)alkenyl, (e) (C2-C10)alkoxy, (f) (C3-C10)cycloalkyl, (g) aryl, (h) heteroaryl, (i) C(O)Rf, (j) C(O)ORf, (k) C(O)NRaR for (I) S(O)2Rf;
Rf for each occurrence is independently (a) (C1-C10)alkyl substituted with zero to three substituents independently selected from the Group VI, (b) (C2-C10)alkenyl, (c) (C2-C10)alkynyl, (d) (C3-C10)cycloalkyl, (e) aryl, (f) heteroaryl or (g) heterocycloalkyl;
R9 for each occurrence is independently (a) hydrogen, (b) (C1-C6)alkyl, (c) (C2-C6)alkenyl, (d) aryl, (e) C(O)Rf, (f) C(O)ORf, (g) C(O)NRaRf, (h) S(O)2Rf or (i) (C3-C8)cycloalkyl;
Rh is (a) (C1-C6)alkyl substituted with zero or one substituent selected from the group consisting of (1) (C3-C6)cycloalkyl, (2) heterocycloalkyl and (3) phenyl substituted with zero or one substituent selected from the group consisting of (i) (C1-C4)alkyl, (ii) halogen, (iii) CF3 and (iv) OCF3; (b) phenyl substituted with zero to two substituents independently selected from the group consisting of (1) (C1-C4)alkyl, (2) halogen, (3) CF3 and (4) OCF3; (c) (C3-C6)cycloalkyl or (d) heterocycloalkyl;
Group V is (a) halogen, (b) CF3, (c) OCF3, (d) OH, (e) -oxo, (f) (C1-C6)alkoxy, (g) CN, (h) aryl, (i) heteroaryl, (j) (C3-C10)cycloalkyl, (k) heterocycloalkyl, (l) SRf, (m) S(O)R1, (n) S(O)2Rf, (o) S(O)2NRaRf (p) NRaRf or (q) C(O)NRaRf;
Group VI is (a) halogen, (b) hydroxy, (c) oxo, (d) (C1-C6)alkoxy, (e) aryl, (f) heteroaryl, (g) (C3-C8)cycloalkyl, (h) heterocycloalkyl, (i) CN, or a) OCF3;
provided that when the substituent R4 is (C1Cl2)alkyl substituted with zero to three substituents independently selected from Group V wherein the Group V substituent is oxo, the oxo group is substituted on a carbon atom other than the C1 carbon atom in (C1Cl2)alkyl;
aryl for each occurrence is independently phenyl or naphthyl substituted with zero to four substituents independently selected from (a) halogen, (b) (C1-C6)alkyl, (c) CN, (d) SRf, (e) S(O)RF, (f) S(O)2Rf, (g) (C3-C6)cycloalkyl, (h) S(O)2NRaRf, (i) NRaRg, (j) C(O)NRaRf, (k) ORb, (I) -perfluoro-(C1-C4)alkyl, or (m) COORf;
provided that when the substituent(s) on aryl are SRf, S(O)Rf, S(O)2Rf, S(O)2NRaRf, NRaRg, C(O)NRaRf, ORb, or COORf, the substituents Rb, Rg and Rg are other than aryl or heteroaryl;
heteroaryl for each occurrence is independently a 5-, 6-, 7-, 8-, 9- or 10-membered monocyclic or bicyclic ring having from 1 to 3 heteroatoms selected from O, N or S; wherein in the bicyclic ring, a monocyclic heteroaryl ring is fused to a benzene ring or to another heteroaryl ring; and having zero to three substituents independently selected from (a) halogen, (b) (C1-C4)alkyl, (c) CF3, (d) ORb, (e) NRaRg, or (f) CO2Rf;
provided that when the substituent(s) on heteroaryl are ORb, NRaRg or CO2Rf, the substituents Rb, Rf and Rg are other than aryl or heteroaryl;
heterocycloalkyl for each occurrence is independently a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered monocyclic or bicyclic cycloalkyl ring having from 1 to 3 heteroatoms selected from O, NRe or S; and having zero to four substituents independently selected from (a) (C1-C4)alkyl, (b) ORb, (c) oxo, (d) CN, (e) pheny or (f) NRaRg.
2. A compound of claim 1 wherein W is O; R0 is hydrogen; R1 is located at the 5-position and R2 is located at the 3-position; and R1 and R2 are each independently hydrogen, (C1-C6)alkyl, halogen or CN.
3. A compound of claim 2 wherein R3 is hydrogen, (C1-C4)alkyl or halogen; R4 is (a) (C1-C10)alkyl substituted with zero to three substituents independently selected from F, hydroxy, oxo, aryl, heteroaryl, (C3-C8)cycloalkyl, or heterocycloalkyl, (b) (C3-C8)cycloalkyl, (c) heterocycloalkyl, (d) C(O)Rc, (e) ORb, (f) NRaC(O)Rd, (g) NRaC(O)NRcRd or (h) NRaS(O)2Rd;
or R3 and R4 are taken together along with the carbon atoms to which they are attached to form a carbocyclic ring of formula (CH2)i or a heterocyclic ring of formula (CH2)kQ(CH2)i wherein Q is O, Sor NRe; i is 3, 4, 5 or 6; k is 0, 1, 2, 3, 4 or 5; and I is 0, 1, 2, 3, 4 or 5; and wherein the carbocyclic ring and the heterocyclic ring are each substituted with zero to four substituents independently selected from (a) (C1-C4)alkyl, (b) ORb, (c) oxo, (d) CN, (e) phenyl or (f) NRaRg;
provided that when the substituent R4 is (C1C10)alkyl substituted with zero to three substituents, the oxo group is substituted on a carbon atom other than the C1 carbon atom in (C1-C10)alkyl.
4. A compound of claim 3 wherein R5 is OH, OC(O)Rf or F; Rf is-(C1-C10)alkyl substituted with zero to three substituents independently selected from Group VI; R6 is hydrogen, halogen or-(C1-C4)alkyl; R7 is hydrogen or methyl; and R8 and R9 are each independently hydrogen, (C1-C6)alkyl or halogen.
5. A compound of claim 4 wherein R4 is (C0-C2)alkyl-(C3-C6)cycloalkyl, (C1-C10)alkyl, or (C0-C2)alkyl-aryl; and R10 is C(O)OH, C(O)OCH3 or C(O)OCH2CH3.
6. A compound of claim 5 wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is CH2-phenyl-4-F; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH.
7. A compound of claim 4 wherein R4 is CH(OH)-aryl, CH(OH)-heteroaryl, CH(OH)(COC2)alkyl-(C3-C8)cycloalkyl or CH(OH)(COC2)alkyl-heterocycloalkyl; and R10 is C(O)OH, C(O)OCH3 or-C(O)OCH2CH3.
8. A compound of claim 7 selected from the group consisting of:
a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is CH(OH)-phenyl-4-F; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is CH(OH)-phenyl-4-F; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OCH3; a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is CH(OH)CH2-cyclopentyl; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is CH(OH)CH2-cyclobutyl; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is CH3; R3 is hydrogen; R4 is CH(OH)-phenyl-4-F; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is CH3; R3 is hydrogen; R4 is CH(OH)-cyclopentyl; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH; and
a compound wherein R1 is Cl; R2 is CH3; R3 is hydrogen; R4 is CH(OH)-cyclobutyl; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH.
9. A compound of claim 4 wherein R4 is C(O)-aryl, C(O)-heteroaryl, C(O)(C0-C2)alkyl-(C3-C8)cycloalkyl or C(O)(C0-C2)alkyl-heterocycloalkyl; and R10 is C(O)OH, C(O)OCH3 or C(O)OCH2CH3.
10. A compound of claim 9 selected from the group consisting of:
a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is C(O)-phenyl-4-F; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is C(O)-phenyl-4-F; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OCH3;
a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is C(O)CH2-cyclopentyl; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is C(O)CH2-cyclobutyl; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is CH3; R3 is hydrogen; R4 is C(O)-cyclobutyl; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is CH3; R3 is hydrogen; R4 is C(O)-cyclopentyl; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH; and
a compound wherein R1 is Cl; R2 is CH3; R3 is hydrogen; R4 is C(O)-phenyl-4-F; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH.
11. A compound of claim 3 wherein R3 and R4 are taken together along with the carbon atoms to which they are attached to form a carbocyclic ring of formula (CH2)i or a heterocyclic ring of formula (CH2)kQ(CH2)i wherein Q is O, S, or NRe; i is 3, 4, 5or6; k is 0, 1, 2, 3, 4or 5; and I is 0, 1, 2, 3, 4 or 5; and wherein the carbocyclic ring and the heterocyclic ring are each substituted with zero to four substituents independently selected from (a) (C1-C4)alkyl, (b) ORb, (c) oxo, (d) CN, (e) phenyl or (f) NRaRg.
12. A compound of claim 11 wherein R3 and R4 are taken together along with the carbon atoms to which they are attached to form a carbocyclic ring of formula (CH2)i wherein i is 3 and the carbocyclic ring is optionally substituted with zero to three substituents independently selected from the group consisting of oxo and methyl; or a heterocyclic ring of formula (CH2)kQ(CH21 wherein Q is NRa, Ra is hydrogen or-(C1-C6)alkyl; and k is 1; I is 1; and the heterocyclic ring is optionally substituted with one or two substituents independently selected from the group consisting of oxo and methyl.
13. A compound of claim 12 wherein R1 and R2 are each independently CH3 or Cl; R3 is hydrogen; R5 is OH; R6, R7, R8 and R9 are each hydrogen; and R10 is C(O)OH, C(O)OCH3 or C(O)OCH2CH3.
14. A compound of claim 13 selected from the group consisting of:
a compound wherein R1 is CH3, R2 is CH3, R3 and R4 are taken together along with the carbon atoms to which they are attached to form an indanyl, and R10 is C(O)OH;
a compound wherein R1 is Cl, R2 is CH3, R3 and R4 are taken together along with the carbon atoms to which they are attached to form an indanyl, and R10 is C(O)OH;
a compound wherein R1 is Cl, R2 is CH3, R3 and R4 are taken together along with the carbon atoms to which they are attached to form a 2-methyl-1-oxo-2,3-dihydro-1H-isoindolyl, and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is CH3, R3 and R4 are taken together along with the carbon atoms to which they are attached to form a 2-methyl-1-oxo-2,3-dihydro-1H-isoindolyl, and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is CH3, R3 and R4 are taken together along with the carbon atoms to which they are attached to form a 2-methyl-1-oxo-indanyl, and R10 is C(O)OH; and
a compound wherein R1 is CH3, R2 is CH3, R3 and R4 are taken together along with the carbon atoms to which they are attached to form a 2,2-dimethyl-1-oxo-indanyl, and R10 is C(O)OH.
15. A compound of formula A
45
an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug; wherein R1 and R2 are each independently CH3 or Cl; R4 is SO2NH-cyclopropyl, SO2NH-cyclobutyl, SO2NH-cyclopentyl, SO2NH-cyclohexyl, SO2NH-(C1-C8)alkyl or SO2NH-phenyl optionally substituted with fluoro; R8 and R9 are each independently hydrogen or methyl; and R10 is C(O)OH, C(O)OCH3 or C(O)OCH2CH3.
16. A compound of claim 15 selected from the group consisting of:
a compound wherein R1 is Cl; R2 is Cl; R4 is SO2NH-cyclopropyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is SO2NH-cyclobutyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is CH3; R4 is SO2NH-cyclobutyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is CH3, R4 is SO2NH-cyclobutyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is CH3, R4 is SO2NH-cyclopropyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is CH3; R4 is SO2NH-cyclopropyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is SO2NHCH(CH3)2; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is SO2NH-(CH2)3CH3; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is SO2NH-(CH2)6CH3; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is SO2NH-(4-fluoro-phenyl); R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is CH3, R4 is SO2NH-cyclohexyl; R8 and R9 are each hydrogen; and R10 is C(O)OH; and
a compound wherein R1 is Cl, R2 is Cl, R4 is SO2NH-cyclohexyl; R8 and R9 are each hydrogen; and R10 is C(O)OH.
17. A compound of claim 15 selected from the group consisting of:
N-3,5-dichloro-4-(3-cyclopropylsulfamoyl-4-hydroxy-phenoxy)-phenyl-malonamic acid;
N-3,5-dichloro-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid; and
N-4-(3-cyclopropylsulfamoyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid.
18. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of Formula A, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 15.
19. A compound of formula A
46
an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug; wherein R1 and R2 are each independently CH3 or Cl; R4 is C(O)N(CH3)-(C3-C8)cycloalkyl, C(O)NHCH(CH(CH3)2)2, C(O)N(CH3)CH(CH(CH3)2)2, C(O)N(CH3)CH(CH3)2, C(O)NHCH(CH3)-cyclohexyl, C(O)NHCH2-cyclohexyl, C(O)N(CH3)CH2-cyclohexyl, C(O)N(CH3)CH(CH3)-cyclohexyl, or C(O)NH-phenyl optionally substituted with fluoro; R8 and R9 are each independently hydrogen or methyl; and R10 is C(O)OH, C(O)OCH3 or C(O)OCH2CH3.
20. A compound of claim 19 selected from the group consisting of:
a compound wherein R1 is CH3; R2 is CH3; R4 is C(O)N(CH3)-cyclobutyl; R3 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is CH3; R2 is CH3; R4 is C(O)N(CH3)-cyclobutyl; R8 and R9 are each hydrogen; and R10 is C(O)OCH3;
a compound wherein R1 is Cl; R2 is CH3; R4 is C(O)N(CH3)-cyclobutyl; R8 and R9 are each hydrogen; and R1 is C(O)OH;
a compound wherein R1 is Cl; R2 is CH3; R4 is C(O)NHCH(CH(CH3)2)2; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is C(O)NHCH(CH(CH3)2)2; R3 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is C(O)NHCH(CH3)-cyclohexyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is CH3; R2 is CH3; R4is C(O)N(CH3)-cyclopentyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is CH3; R2 is CH3; R4is C(O)N(CH3)CH(CH3)2, R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is C(O)NH-(4-fluoro-phenyl); R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is C(O)NHCH2-cyclohexyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is C(O)N(CH3)CH2-cyclohexyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is C(O)N(CH3)-cyclohexyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is C(O)N(CH3)-cyclopentyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is C(O)N(CH3)-cycloheptyl; R8 and R9 are each hydrogen; and R10 is C(O)OH;
a compound wherein R1 is Cl; R2 is Cl; R4 is C(O)N(CH3)CH(CH(CH3)2)2; R8 and R9 are each hydrogen; and Rt is C(O)OH; and
a compound wherein R1 is Cl; R2 is Cl; R4 is C(O)N(CH3)CH(CH3)-cyclohexyl; R3 and R9 are each hydrogen; and R10 is C(O)OH.
21. A compound of claim 19 selected from the group consisting of:
N-4-3-(cyclobutyl-methyl-carbamoyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-malonamic acid;
N-3-chloro-4-4-hydroxy-3-(1-isopropyl-2-methyl-propylcarbamoyl)-phenoxy-5-methyl-phenyl-malonamic acid; and
N-3,5-dichloro-4-3-((1S)-cyclohexyl-ethylcarbamoyl)-4-hydroxy-phenoxy-phenyl-malonamic acid.
22. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of Formula A, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 19.
23. A compound of formula A
47
an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug; wherein R1 and R2 are each independently CH3 or Cl; R4 is SO2CH2-cyclopropyl, SO2CH2-cyclobutyl, SO2CH2-cyclopentyl, SO2CH2-cyclohexyl, SO2-cyclopentyl or SO2-cyclohexyl; ; R8 and R9 are each independently hydrogen or methyl; and R10 is C(O)OH, C(O)OCH3 or C(O)OCH2CH3.
24. A compound of claim 23 selected from the group consisting of:
a compound wherein R1 is Cl, R2 is CH3, R4 is SO2CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OCH3;
a compound wherein R1 is Cl, R2 is CH3, R4 is SO2CH2-cyclobutyl, R3 is hydrogen, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is Cl, R2 is CH3, R4 is SO2CH2-cyclobutyl, R8 is hydrogen, R9 is methyl and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is Cl, R4 is SO2CH2-cyclobutyl, R3 is hydrogen, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is H, R4 is SO2CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is Cl, R2 is CH3, R4 is SO2CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OCH2CH3;
a compound wherein R1 is Cl, R2 is CH3, R4 is SO2CH2-cyclopropyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is Cl, R2 is Cl, R4 is SO2CH2-cyclopropyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is CH3, R4 is SO2CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OCH2CH3;
a compound wherein R1 is CH3, R2 is CH3, R4 is SO2CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OCH3;
a compound wherein R1 is CH3, R2 is CH3, R4 is SO2CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is CH3, R4 is SO2CH2-cyclobutyl, R8 is hydrogen, R9 is methyl and R10 is C(O)OH;
a compound wherein R1 is Cl, R2 is Cl, R4 is SO2CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is CH3, R4 is SO2CH2-cyclopentyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is CH3, R4 is SO2CH2-cyclobutyl, R8 is methyl, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is Cl, R2 is CH3, R4 is SO2CH2-cyclohexyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is Cl, R2 is CH3, R4 is SO2CH2-cyclobutyl, R8 is methyl, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is Cl, R2 is CH3, R4 is SO2CH2-cyclopentyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is CH3, R4 is SO2CH2-cyclohexyl, R3 is hydrogen, R9 is hydrogen and R10 is C(O)OH;
a compound wherein R1 is CH3, R2 is CH3, R4 is SO2-cyclopentyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OH; and
a compound wherein R1 is Cl, R is CH3, R4 is SO2-cyclopentyl, R8 is hydrogen, R9 is hydrogen and R10 is C(O)OH.
25. A compound of claim 23 selected from the group consisting of:
N-3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclopropylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-3,5-dichloro-4-(3-cyclopropylmethanesulfonyl-4-hydroxy-phenoxy)-phenyl-malonamic acid;
N-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-3,5-dichloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-phenyl-malonamic acid;
N-4-(3-cyclopentylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-2-methyl-malonamic acid;
N-3-chloro-4-(3-cyclohexylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-2-methyl-malonamic acid;
N-3-chloro-4-(3-cyclopentylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-4-(3-cyclohexylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid methyl ester;
N-3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid ethyl ester;
N-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid ethyl ester;
N-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid methyl ester;
N-3-chloro-4-(3-cyclopentanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid; and
N-4-(3-cyclopentanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid.
26. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of Formula A, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 23.
27. A compound selected from the group consisting of:
N-4-3-(cyclobutyl-methyl-carbamoyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-malonamic acid;
N-3-chloro-4-4-hydroxy-3-(1-isopropyl-2-methyl-propylcarbamoyl)-phenoxy-5-methyl-phenyl-malonamic acid;
N-3,5-dichloro-4-3-((1 S)-cyclohexyl-ethylcarbamoyl)-4-hydroxy-phenoxy-phenyl-malonamic acid;
N-3,5-dichloro-4-(3-cyclopropylsulfamoyl-4-hydroxy-phenoxy)-phenyl-malonamic acid;
N-3,5-dichloro-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-4-(3-cyclopropylsulfamoyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclopropylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-3,5-dichloro-4-(3-cyclopropylmethanesulfonyl-4-hydroxy-phenoxy)-phenyl-malonamic acid;
N-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-3,5-dichloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-phenyl-malonamic acid;
N-4-(3-cyclopentylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-2-methyl-malonamic acid;
N-3-chloro-4-(3-cyclohexylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-2-methyl-malonamic acid;
N-3-chloro-4-(3-cyclopentylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-4-(3-cyclohexylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-malonamic acid;
N-3-chloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-5-methyl-phenyl-malonamic acid;
N-4-3-(4-fluoro-benzoyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-malonamic acid;
N-4-(3-cyclopentylacetyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-(4-3-(4-fluoro-phenyl)-hydroxy-methyl-4-hydroxy-phenoxy-3,5-dimethyl-phenyl)-malonamic acid;
N-4-3-(2-cyclopentyl-1-hydroxy-ethyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid methyl ester;
N-3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid ethyl ester;
N-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid ethyl ester;
N-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid methyl ester;
N-3-chloro-4-(3-cyclopentanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-4-(3-cyclopentanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-3-chloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-5-methyl-phenyl-malonamic acid;
N-3-chloro-4-3-(4-fluoro-benzenesulfonyl)4-hydroxy-phenoxy-5-methyl-phenyl-malonamic acid methyl ester;
N-3,5-dichloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-phenyl-malonamic acid methyl ester;
N-3,5-dichloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-phenyl-malonamic acid ethyl ester;
N-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-2-methyl-malonamic acid methyl ester;
N-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-2-methyl-malonamic acid;
N-3-chloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-5-methyl-phenyl-2-methyl-malonamic acid methyl ester;
N-3-chloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-5-methyl-phenyl-2-methyl-malonamic acid;
N-3,5-dichloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-phenyl-2-methyl-malonamic acid methyl ester; and
N-3,5-dichloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-phenyl-2-methyl-malonamic acid; or an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug.
28. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of claim 27, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug.
29. A method of claim 28 wherein the condition is obesity.
30. A method of claim 28 wherein the condition is diabetes.
31. A method of claim 29 which further comprises administering an anorectic agent.
32. A method of claim 31 wherein the anorectic agent is selected from the group consisting of phentermine, sibutramine, fenfluramine, dexfenfluramine and bromocriptine.
33. A method of claim 29 which further comprises administering a lipase inhibitor.
34. A method of claim 33 wherein the lipase inhibitor is selected from the group consisting of lipstatin, tetrahydrolipstatin (orlistat), FL-386, WAY-121898, Bay-N-3176, valilactone, esterastin, ebelactone A, ebelactone B and RHC 80267, stereoisomers thereof, and pharmaceutically acceptable salts of said compounds and stereoisomers.
35. A pharmaceutical composition comprising a compound of claim 27, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug.
36. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of Formula I, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 1.
37. A method of claim 36 wherein the condition is obesity.
38. A method of claim 36 wherein the condition is diabetes.
39. A pharmaceutical composition comprising a compound of Formula I, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 1.
40. A method of treating hair loss in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of
48
an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug; wherein W is (a) O, (b) S, (c) SO, (d) SO2, (e) CH2, (f) CF2, (g) CHF,
49
(h) C(O), (i) CH(OH), (j) NRaor (k)
R0 is (a) hydrogen, (b) (C1-C6)alkyl substituted with zero or one substituent selected from the group consisting of (1) (C3-C6)cycloalkyl, (2) heterocycloalkyl and (3) phenyl substituted with zero or one substituent selected from the group consisting of (i) (C1-C4)alkyl, (ii) halogen, (iii) CF3 and (iv) OCF3; (c) C(O)Rh, (d) S(O)2Rh or (e) halogen;
R1, R2, R3 and R6 are each independently (a) hydrogen, (b) halogen, (c) (C1-C8)alkyl, (d) CF3, (e) OCF3, (f) O(C1-C8)alkyl, or (g) CN;
R4 is (a) hydrogen, (b) (C1-C12)alkyl substituted with zero to three substituents independently selected from Group V, (c) (C2-C12 )alkenyl, (d) (C2Cl2)alkynyl, (e) halogen, (f) CN, (g) ORb, (h) SRc, (i) S(O)Rc, (O)S(O)2R1, (k) aryl, (I) heteroaryl, (m) (C3-C10)cycloalkyl, (n) heterocycloalkyl, (o) S(O)2NRcRd, (p) C(O)NRcRd, (q) C(O)ORc, (r)-NRaC(O)Rd, (s)-NRaC(O)NRcRd, (t)-NRaS(O)2Rd, (u) -NRaRd or (v) C(O)Rc;
or R3 and R4 are taken together along with the carbon atoms to which they are attached to form a carbocyclic ring of formula (CH2)i or a heterocyclic ring of formula (CH2)kQ(CH21 wherein Q is O, Sor NRe; i is 3, 4, 5 or 6; k is 0, 1, 2, 3, 4 or 5; and I is 0, 1, 2, 3, 4 or 5; and wherein the carbocyclic ring and the heterocyclic ring are each substituted with zero to four substituents independently selected from (a) (C1-C4)alkyl, (b) ORb, (c) oxo, (d) CN, (e) phenyl or (f) NRaRg;
R5 is (a) OH, (b) O(C1-C6)alkyl, (c) OC(O)Rf, (d) F, or (e) C(O)ORc;
or R4 and R5 are taken together along with the carbon atoms to which they are attached to form a heterocyclic ring selected from the group consisting of CRcCRaNH, NCRaNH, CR1CRaO, CRcCRaS, CRcNNH and CRaCRaCRaN;
R7 is (a) hydrogen or (b) (C1-C6)alkyl;
R8 and R9 are each independently (a) hydrogen, (b) (C1-C6)alkyl, (c) aryl, or (d) halogen;
R10 is (a) (C0-C1)alkyl-C(O)OH, (b) (C0-C1)alkyl-C(O)ORf, (c) (C0-C1)alkyl-C(O)NRcRd, or (d) (C0-C1)alkyl-OH;
Ra for each occurrence is independently (a) hydrogen or (b) (C1-C6)alkyl substituted with zero or one (C3-C6)cycloalkyl or methoxy;
Rb for each occurrence is independently (a) hydrogen, (b) (C1-C12)alkyl substituted with zero to three substituents independently selected from Group V, (c) aryl, (d) heteroaryl, (e) (C3-C10)cycloalkyl, (f) heterocycloalkyl, (g) C(O)NRcRd, or (h) C(O)R1;
Rc and Rd for each occurrence are each independently (a) hydrogen, (b) (C1-C12)alkyl substituted with zero to three substituents independently selected from Group VI, (c) (C2-C12)alkenyl, (d) (C2-C12)alkynyl, (e) aryl, (f) heteroaryl, (g) (C3-C10)cycloalkyl or (h) heterocycloalkyl;
provided that when R4 is the moiety SRc, S(O)Rc or S(O)2Rc, Rc is other than hydrogen;
or Rc and Rd are taken together along with the atom(s) to which they are attached to form a 3-10 membered heterocyclic ring which may optionally contain a second heterogroup selected from O, NRe or S; and wherein the heterocyclic ring is substituted with zero to four substituents independently selected from (a) (C1-C4)alkyl, (b) ORb, (c) oxo, (d) CN, (e) phenyl or (f) NRaR9;
Re for each occurrence is (a) hydrogen, (b) CN, (c) (C1-C10)alkyl substituted with zero to three substitutents independently selected from Group V, (d) (C2-C10)alkenyl, (e) (C2-C10)alkoxy, (f) (C3-C10)cycloalkyl, (g) aryl, (h) heteroaryl, (i) C(O)Rf, (j) C(O)ORf, (k) C(O)NRaRf or (I) S(O)2Rf;
Rf for each occurrence is independently (a) (C1-C10)alkyl substituted with zero to three substituents independently selected from the Group VI, (b) (C2-C10)alkenyl, (C) (C2-C10)alkynyl, (d) (C3-C10)cycloalkyl, (e) aryl, (f) heteroaryl or (g) heterocycloalkyl;
R9 for each occurrence is independently (a) hydrogen, (b) (C1-C6)alkyl, (c) (C2-C6)alkenyl, (d) aryl, (e) C(O)Rf, (f) C(O)ORf, (g) C(O)NRaRf, (h) S(O)2Rf or (i) (C3-C8)cycloalkyl;
Rh is (a) (C1-C6)alkyl substituted with zero or one substituent selected from the group consisting of (1) (C3-C6)cycloalkyl, (2) heterocycloalkyl and (3) phenyl substituted with zero or one substituent selected from the group consisting of (i) (C1-C4)alkyl, (ii) halogen, (iii) CF3 and (iv) OCF3; (b) phenyl substituted with zero to two substituents independently selected from the group consisting of (1) (C1-C4)alkyl, (2) halogen, (3) CF3 and (4) OCF3; (c) (C3-C6)cycloalkyl or (d) heterocycloalkyl;
Group V is (a) halogen, (b) CF3, (c) OCF3, (d) OH, (e) -oxo, (f) (C1-C6)alkoxy, (g) CN, (h) aryl, (i) heteroaryl, (j) (C3-C10)cycloalkyl, (k) heterocycloalkyl, (I) SRf, (m) S(O)Rf, (n) S(O)2Rf, (o) S(O)2NRaRf (p) NRaRg or (q) C(O)NRaRf;
Group VI is (a) halogen, (b) hydroxy, (c) oxo, (d) (C1-C6)alkoxy, (e) aryl, (f) heteroaryl, (g) (C3-C8)cycloalkyl, (h) heterocycloalkyl, (i) CN, or (j) OCF3;
provided that when the substituent R4 is (C1-C12)alkyl substituted with zero to three substituents independently selected from Group V wherein the Group V substituent is oxo, the oxo group is substituted on a carbon atom other than the C1 carbon atom in (C1-C12)alkyl;
aryl for each occurrence is independently phenyl or naphthyl substituted with zero to four substituents independently selected from (a) halogen, (b) (C1-C6)alkyl, (c) CN, (d) SRf, (e) S(O)Rf, (f) S(O)2Rf, (g) (C3-C6)cycloalkyl, (h) S(O)2NRaRf, (i) NRaRg, (j) C(O)NRaRf, (k) ORb, (I) -perfluoro-(C1-C4)alkyl, or (m) COOR1;
provided that when the substituent(s) on aryl are SRf, S(O)Rf, S(O)2Rf, S(O)2NRaRg, NR1Rg, C(O)NRaW, OR , or COORf, the substituents Rb, Rf and Rg are other than aryl or heteroaryl;
heteroaryl for each occurrence is independently a 5-, 6-, 7-, 8-, 9- or 10-membered monocyclic or bicyclic ring having from 1 to 3 heteroatoms selected from O, N or S; wherein in the bicyclic ring, a monocyclic heteroaryl ring is fused to a benzene ring or to another heteroaryl ring; and having zero to three substituents independently selected from (a) halogen, (b) (C1-C4)alkyl, (c) CF3, (d) ORb, (e) NRAR1, or (f) CO2Rf;
provided that when the substituent(s) on heteroaryl are ORb, NRaRg or CO2Rf, the substituents Rb, Rf and R9 are other than aryl or heteroaryl;
heterocycloalkyl for each occurrence is independently a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered monocyclic or bicyclic cycloalkyl ring having from 1 to 3 heteroatoms selected from O, NRe or S; and having zero to four substituents independently selected from (a) (C1-C4)alkyl, (b) ORb, (c) oxo, (d) CN, (e) phenyl or (f) NRaR9.
41. A method of claim 40 which comprises administering a compound of Formula I wherein W is O; R0 is hydrogen; R1 is located at the 5-position and R2 is located at the 3-position; and R1 and R2 are each independently hydrogen, (C1-C6)alkyl, halogen or CN.
42. A method of claim 41 which comprises administering a compound of Formula I wherein R3 is hydrogen, (C1-C4)alkyl or halogen; R4 is (a) (C1-C10)alkyl substituted with zero to three substituents independently selected from F, hydroxy, oxo, aryl, heteroaryl, (C3-C8)cycloalkyl, or heterocycloalkyl, (b) S(O)2NRcRd, (c) C(O)NRcRd, (d) S(O)2Rc, (e) (C3-C8)cycloalkyl, (f) heterocycloalkyl, (g) C(O)Rc, (h) ORb, (i) SRr, (j) S(O)Rc, (k) NRaC(O)Rd, (I) NRaC(O)NRcRd or (m) NRaS(O)2Rd;
or R3 and R4 are taken together along with the carbon atoms to which they are attached to form a carbocyclic ring of formula (CH2)i or a heterocyclic ring of formula (CH2)kQ(CH21 wherein Q is O, Sor NRe; i is 3, 4, 5 or 6; k is 0, 1, 2, 3, 4 or 5; and I is 0, 1, 2, 3, 4 or 5; and wherein the carbocyclic ring and the heterocyclic ring are each substituted with zero to four substituents independently selected from (a) (C1-C4)alkyl, (b) ORb, (c) oxo, (d) CN, (e) phenyl or (f) NRaRg;
provided that when the substituent R4 is (C1C10)alkyl substituted with zero to three substituents, the oxo group is substituted on a carbon atom other than the C1 carbon atom in (C1-C10)alkyl.
43. A method of claim 42 which comprises administering a compound of Formula I wherein R5 is OH, OC(O)Rf or F; and Rf is (C1-C10)alkyl substituted with zero to three substituents independently selected from Group VI; R6 is hydrogen, halogen or (C1-C4)alkyl; R7 is hydrogen or methyl; and R8 and R9 are each independently hydrogen, (C1-C6)alkyl or halogen.
44. A method of claim 43 which comprises administering a compound of Formula I wherein R4 is (a) (C1-C10)alkyl substituted with zero to three substituents independently selected from F, hydroxy, oxo, aryl, heteroaryl, (C3-C8)cycloalkyl, or heterocycloalkyl, (b) S(O)2NRcRd, (c) C(O)NRcRd, (d)S(O)2Rc, (e) (C3-C8)cycloalkyl, (f) heterocycloalkyl or (g) C(O)Rc; and R10 is C(O)OH, C(O)OCH3 or C(O)OCH2CH3 or a pharmaceutically acceptable salt or prodrug thereof.
45. A method of claim 44 which comprises administering a compound selected from the group consisting of:
N-4-3-(cyclobutyl-methyl-carbamoyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-malonamic acid;
N-3-chloro-4-4-hydroxy-3-( 1-isopropyl-2-methyl-propylcarbamoyl)-phenoxy-5-methyl-phenyl-malonamic acid;
N-3,5-dichloro-4-3-((1 S)-cyclohexyl-ethylcarbamoyl)-4-hydroxy-phenoxy-phenyl-malonamic acid;
N-3,5-dichloro-4-(3-cyclopropylsulfamoyl-4-hydroxy-phenoxy)-phenyl-malonamic acid;
N-3,5-dichloro-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-4-(3-cyclopropylsulfamoyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclopropylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-3,5-dichloro-4-(3-cyclopropylmethanesulfonyl-4-hydroxy-phenoxy)-phenyl-malonamic acid;
N-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-3,5-dichloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-phenyl-malonamic acid;
N-4-(3-cyclopentylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-2-methyl-malonamic acid;
N-3-chloro-4-(3-cyclohexylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-2-methyl-malonamic acid;
N-3-chloro-4-(3-cyclopentylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-4-(3-cyclohexylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-malonamic acid;
N-3-chloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-5-methyl-phenyl-malonamic acid;
N-4-3-(4-fluoro-benzoyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-malonamic acid;
N-4-(3-cyclopentylacetyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-(4-3-(4-fluoro-phenyl)-hydroxy-methyl-4-hydroxy-phenoxy-3,5-dimethyl-phenyl)-malonamic acid;
N-4-3-(2-cyclopentyl-1-hydroxy-ethyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-malonamic acid;
N-3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid methyl ester;
N-3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid ethyl ester;
N-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid ethyl ester;
N-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid methyl ester;
N-3-chloro-4-(3-cyclopentanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl-malonamic acid;
N-4-(3-cyclopentanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl-malonamic acid;
N-3-chloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-5-methyl-phenyl-malonamic acid;
N-3-chloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-5-methyl-phenyl-malonamic acid methyl ester;
N-3,5-dichloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-phenyl-malonamic acid methyl ester;
N-3,5-dichloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-phenyl-malonamic acid ethyl ester;
N-4-3-(4-fluoro-benzenesulfonyl)4-hydroxy-phenoxy-3,5-dimethyl-phenyl-2-methyl-malonamic acid methyl ester;
N-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-2-methyl-malonamic acid;
N-3-chloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-5-methyl-phenyl-2-methyl-malonamic acid methyl ester;
N-3-chloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-5-methyl-phenyl-2-methyl-malonamic acid;
N-3,5-dichloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-phenyl-2-methyl-malonamic acid methyl ester; and
N-3,5-dichloro-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-phenyl-2-methyl-malonamic acid;
N-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-malonamic acid; and
N-4-3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy-3,5-dimethyl-phenyl-malonamic acid methyl ester; or an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug.
46. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, comprising:
administering to a patient having or at risk of having a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, a therapeutically effective amount of
1) a compound of Formula I, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 1; and
2) an additional compound useful for treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss.
47. A method of claim 46 wherein the condition is obesity.
48. A method of claim 47 wherein the additional compound is a lipase inhibitor.
49. A method of claim 48 wherein the lipase inhibitor is selected from the group consisting of lipstatin, tetrahydrolipstatin (orlistat), FL-386, WAY-121898, Bay-N-3176, valilactone, esterastin, ebelactone A, ebelactone B and RHC 80267, stereoisomers thereof, and pharmaceutically acceptable salts of said compounds and stereoisomers.
50. A method of claim 47 wherein the additional compound is an anorectic agent.
51. A method of claim 50 wherein the anorectic agent is selected from the group consisting of phentermine, sibutramine, fenfluramine, dexfenfluramine and bromocriptine.
52. A kit for treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, the kit comprising:
a) a first pharmaceutical composition comprising a compound of Formula I, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 1;
b) a second pharmaceutical composition comprising an additional compound useful for treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss; and
c) a container.
53. A pharmaceutical composition comprising a compound of Formula I, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 1; and an additional compound useful to treat a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss.
54. A composition of claim 53 wherein the condition is obesity.
55. A composition of claim 54 wherein the additional compound is a lipase inhibitor.
56. A composition of claim 55 wherein the lipase inhibitor is selected from the group consisting of lipstatin, tetrahydrolipstatin (orlistat), FL-386, WAY-121898, Bay-N-3176, valilactone, esterastin, ebelactone A, ebelactone B and RHC 80267, stereoisomers thereof, and pharmaceutically acceptable salts of said compounds and stereoisomers.
57. A composition of claim 54 wherein the additional compound is an anorectic agent.
58. A composition of claim 57 wherein the anorectic agent is selected from the group consisting of phentermine, sibutramine, fenfluramine, dexfenfluramine and bromocriptine.
59. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, comprising:
administering to a patient having or at risk of having a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, a therapeutically effective amount of
1) a compound of claim 27, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug; and
2) an additional compound useful for treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss.
60. A method of claim 59 wherein the condition is obesity.
61. A method of claim 60 wherein the additional compound is a lipase inhibitor.
62. A method of claim 61 wherein the lipase inhibitor is selected from the group consisting of lipstatin, tetrahydrolipstatin (orlistat), FL-386, WAY-121898, Bay-N-3176, valilactone, esterastin, ebelactone A, ebelactone B and RHC 80267, stereoisomers thereof, and pharmaceutically acceptable salts of said compounds and stereoisomers.
63. A method of claim 60 wherein the additional compound is an anorectic agent.
64. A method of claim 63 wherein the anorectic agent is selected from the group consisting of phentermine, sibutramine, fenfluramine, dexfenfluramine and bromocriptine.
65. A kit for treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, the kit comprising:
a) a first pharmaceutical composition comprising a compound of claim 27, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug;
b) a second pharmaceutical composition comprising an additional compound useful for treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss; and
c) a container.
66. A pharmaceutical composition comprising a compound of claim 27, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug; and an additional compound useful to treat a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss.
67. A composition of claim 66 wherein the condition is obesity.
68. A composition of claim 67 wherein the additional compound is a lipase inhibitor.
69. A composition of claim 68 wherein the lipase inhibitor is selected from the group consisting of lipstatin, tetrahydrolipstatin (orlistat), FL-386, WAY-121898, Bay-N-3176, valilactone, esterastin, ebelactone A, ebelactone B and RHC 80267, stereoisomers thereof, and pharmaceutically acceptable salts of said compounds and stereoisomers.
70. A composition of claim 67 wherein the additional compound is an anorectic agent.
71. A composition of claim 68 wherein the anorectic agent is selected from the group consisting of phentermine, sibutramine, fenfluramine, dexfenfluramine and bromocriptine.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A programmable dynamic range receiver, comprising:
a jammer detector for detecting the presence of jamming in an RF signal; and
a state machine controlling the receiver based on the results of the jammer detector detecting the presence of jamming in the RF signal, the state machine operative to transition the receiver between a plurality of states, said states including at least one state corresponding to a high linearity receiving mode and at least one state corresponding to a low linearity receiving mode,
wherein the state machine is operative to enter a state corresponding to the high linearity receiving mode faster than entering a state corresponding to the low linearity receiving mode and operative to leave a state corresponding to the high linearity receiving mode slower than leaving a state corresponding to the low linearity receiving mode.
2. The programmable dynamic range receiver of claim 1, further comprising:
an amplifier being coupled or integral to the jammer detector.
3. The programmable dynamic range receiver of claim 1, further comprising:
an RF bandpass filter electronically connected to the output of the LNA;
a mixer coupled to the output of the RF bandpass filter;
an oscillator coupled to the mixer;
a low pass filter coupled to the mixer; and
the jammer detector coupled to the output of the mixer before the input of the low pass filter.
4. The programmable dynamic range receiver of claim 1, further comprising:
a comparator coupled to the jammer detector for detecting the level of jamming in the RF signal.
5. The programmable dynamic range receiver of claim 1, further comprising:
a multi-bit Analog-to-Digital converter (ADC) coupled to the jammer detector for detecting the level of jamming in the RF signal.
6. The programmable dynamic range receiver of claim 1, further comprising:
an attenuator coupled to the input of the jammer detector to prevent leaking of the interference back to the signal path.
7. The programmable dynamic range receiver of claim 1, further comprising:
means for interfacing the state machine with the jammer detector.
8. The programmable dynamic range receiver of claim 1, wherein the state machine utilizes a FFT calculation to determine jamming in an RF signal.
9. The programmable dynamic range receiver of claim 1, further comprising:
a power control, including an up bit counter to adjust the gain in the receiver, the up bit counter results being reported to the state machine for controlling the receiver based on an avenge of up bits.
10. The programmable dynamic range receiver of claim 9, further comprising:
a timer for providing temporal hysteresis between high and low power consumption modes based on a combination of average number of up bits counted in a period of time or the presence of jamming in the RF signal.
11. The programmable dynamic range receiver of claim 1, further comprising:
an analog to digital converter being coupled the output of a mixer, wherein an analog to digital converter goes to fewer number of effective bits if the total interference in the channel is less than a predetermined threshold.
12. The programmable dynamic range receiver of claim 1, wherein the state machine comprises logic circuitry.
13. The programmable dynamic range receiver of claim 1, wherein the state machine controls the receiver by software, hardware, or a combination of software and hardware.
14. The programmable dynamic range receiver of claim 1, wherein the state machine controls the receiver by adjusting, switching, parsing, biasing, turning on or off, or otherwise manipulating components of the receiver or system.
15. A programmable dynamic range receiver, comprising:
a power control component, including an up bit counter to adjust the gain in the receiver, the up bit counter results being reported to a state machine for controlling the receiver based on an average of up bits, the state machine operative to transition the receiver between a plurality of states, said states including at least one state corresponding to a high linearity receiving mode and at least one state corresponding to a low linearity receiving mode,
wherein the state machine is operative to enter a state corresponding to the high linearity receiving mode faster than entering a state corresponding to the low linearity receiving mode and operative to leave a state corresponding to the high linearity receiving mode slower than leaving a state corresponding to the low linearity receiving mode.
16. A method of providing programmable linearity in a receiver, comprising:
detecting the presence of jamming in the RF signal; and
controlling the receiver based on the results of the detecting step indicating the presence of jamming in the RF signal, said controlling performed by a state machine operative to transition the receiver between a plurality of states, said states including at least one state corresponding to a high linearity receiving mode and at least one state corresponding to a low linearity receiving mode,
wherein the state machine is operative to enter a state corresponding to the high linearity receiving mode faster than entering a state corresponding to the low linearity receiving mode and operative to leave a state corresponding to the high linearity receiving mode slower than leaving a state corresponding to the low linearity receiving mode.
17. The method of claim 16, further comprising:
providing the results of the detecting step indicating the presence of the jamming in the RF signal step to a component in the receiver.
18. The method of claim 16, further comprising:
providing a filter to reject band jammers.
19. The method of claim 16, wherein the state machine controls the low-noise amplifier based on the results of detecting the presence of jamming in the RF signal so as to lower the power consumption of the programmable receiver when jamming is not present in the RF signal.
20. The method of claim 16, further comprising:
after detecting the presence of jamming in the RF signal, measuring the amount of jamming in the RF signal;
comparing the amount of jamming in the RF signal versus a threshold amount; and
providing the results of the measured amount of jamming in the RF signal step to the receiver.
21. The method of claim 16, further comprising:
providing temporal hysteresis to the receiver depending upon the results of the step of detecting the presence of jamming in the RF signal.
22. The method of claim 16, further comprising the step of:
providing means for determining a carrier-to-noise ratio for detecting the presence of jamming in the RF signal.
23. The method of claim 22, further comprising the step of:
utilizing the means for determining the carrier-to-noise ratio to count the number of up bits in a time period to detect the presence of jamming in the RF signal.
24. The method of claim 16, further comprising the step of:
providing an analog to digital converter being coupled to the output of a mixer, wherein the analog to digital converter goes to fewer bits if the total interference in the channel is less than a predetermined threshold.
25. An integrated chip (IC) for providing programmable linearity in a receiver, comprising:
a jammer detector for detecting the presence of jamming in an RF signal; and
a state machine controlling the receiver based on the results of the jammer detector detecting the presence of jamming in the RF signal, the state machine operative to transition the receiver between a plurality of states, said states including at least one state corresponding to a high linearity receiving mode and at least one state corresponding to a low linearity receiving mode,
wherein the state machine is operative to enter a state corresponding to the high linearity receiving mode faster than entering a state corresponding to the low linearity receiving mode and operative to leave a state corresponding to the high linearity receiving mode slower than leaving a state corresponding to the low linearity receiving mode.
26. The integrated chip of claim 25, wherein the integrated chip is an RF chip.
27. An integrated chip (IC) for providing programmable linearity in a receiver, comprising:
means for detecting the presence of jamming in the RF signal; and
state machine means for controlling the receiver based on the results received from the means for detecting indicating the presence of jamming in the RF signal, the state machine means operative to transition the receiver between a plurality of states, said states including at least one state corresponding to a high linearity receiving mode and at least one state corresponding to a low linearity receiving mode,
wherein the state machine means is operative to enter a state corresponding to the high linearity receiving mode faster than entering a state corresponding to the low linearity receiving mode and operative to leave a state corresponding to the high linearity receiving mode slower than leaving a state corresponding to the low linearity receiving mode.
28. The integrated chip of claim 27, wherein the integrated chip is an RF chip.