Carbazole-containing sulfonamides as cryptochrome modulators
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07D-405/12
C07D-405/14
C07D-403/12
C07D-401/12
C07D-413/12
C07D-417/12
C07D-493/08
C07D-209/86
C07D-209/88
A61K-031/403
A61K-031/541
A61K-031/549
A61P-003/00
A61K-031/4155
A61K-031/427
A61K-045/06
C07D-417/06
C07D-401/06
C07D-403/06
C07D-409/12
출원번호
US-0891407
(2013-05-10)
등록번호
US-9265772
(2016-02-23)
발명자
/ 주소
Bersot, Ross
Humphries, Paul
출원인 / 주소
RESET THERAPEUTICS, INC.
대리인 / 주소
Cooley LLP
인용정보
피인용 횟수 :
4인용 특허 :
79
초록▼
The subject matter herein is directed to carbazole-containing sulfonamide derivatives and pharmaceutically acceptable salts or hydrates thereof of structural formula I wherein the variable R1, R2, R3, R4, R5, R6, R7, A, B, C, D, E, F, G, H, a, and b are accordingly described. Also provided are pharm
The subject matter herein is directed to carbazole-containing sulfonamide derivatives and pharmaceutically acceptable salts or hydrates thereof of structural formula I wherein the variable R1, R2, R3, R4, R5, R6, R7, A, B, C, D, E, F, G, H, a, and b are accordingly described. Also provided are pharmaceutical compositions comprising the compounds of formula I to treat a Cry-mediated disease or disorder, such as diabetes, obesity, metabolic syndrome, Cushing's syndrome, and glaucoma.
대표청구항▼
1. A compound of formula I or a pharmaceutically acceptable salt or hydrate thereof, whereineach of A, B, C′, D, E, F, G, and H′ is independently C;each of R1 and R2, is independently selected from the group consisting of H, halo, cyano, nitro, —CF3, —CHF2, —CH2F, trifluoromethoxy, azido, hydroxyl,
1. A compound of formula I or a pharmaceutically acceptable salt or hydrate thereof, whereineach of A, B, C′, D, E, F, G, and H′ is independently C;each of R1 and R2, is independently selected from the group consisting of H, halo, cyano, nitro, —CF3, —CHF2, —CH2F, trifluoromethoxy, azido, hydroxyl, (C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C═O)—R8, —(C═O)—O—R8, —O—(C═O)—R8, —NR8(C═O)—R10, —(C═O)—NR8R9, —NR8R9, —NR8OR9, —S(O)cNR8R9, —S(O)d(C1-C8)alkyl, —O—SO2—R8, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(C6-C10)aryl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)f(C═O)(CR8R9)e(C6-C10)aryl, —(CR8R9)f(C═O)(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —(CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, and —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl;each of R3 and each of R5 is independently selected from the group consisting of H, cyano, —CF3, —CHF2, —CH2F, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C═O)—R8, —(C═O)—O—R8, —(C═O)—NR8R9, —S(O)cNR8R9, —S(O)d(C1-C8)alkyl, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(C6-C10)aryl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)f(C═O)(CR8R9)e(C6-C10)aryl, —(CR8R9)f(C═O)(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —(CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, and —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl;wherein each of the R3 groups are optionally linked to each other as a 4-12 membered mono- or bicyclic ring;wherein each of the R5 groups are optionally linked to each other as a 4-12 membered mono- or bicyclic ring;R4 is selected from the group consisting of H, —CF3, —CHF2, —CH2F, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C═O)—R8, —(C═O)—O—R8, —(C═O)—NR8R9, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(C6-C10)aryl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)f(C═O)(CR8R9)e(C6-C10)aryl, —(CR8R9)f(C═O)(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, and —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl;R6 is selected from the group consisting of H, —CF3, —CHF2, —CH2F, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C═O)—R8, —(C═O)—O—R8, —(C═O)—NR8R9, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(C6-C10)aryl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)f(C═O)(CR8R9)e(C6-C10)aryl, —(CR8R9)f(C═O)(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —(CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, and —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl;wherein one R5 group and R6 are optionally linked to each other as a 4-12 membered mono- or bicyclic ring;R7 is selected from the group consisting of —CF3, —CHF2, —CH2F, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C═O)—R8, —(C═O)—O—R8, —NR8(C═O)—R10, —(C═O)—NR8R9, —NR8R9, —NR8OR9, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)f(C═O)(CR8R9)e(C6-C10)aryl, —(CR8R9)f(C═O)(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —(CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, and —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl;R6 and R7 can be linked to each other as a 4-12 membered mono- or bicyclic ring;each of R8, R9 and R10 are independently selected from the group consisting of H, (C1-C6)alkyl, —(CR11R12)e(3-10)-membered cycloalkyl, —(CR11R12)g(C6-C10)aryl, and —(CR11R12)g(4-10)-membered heterocyclyl;any carbon atoms of the (C1-C6)alkyl, the (3-10)-membered cycloalkyl, the (C6-C10)aryl and the (4-10)-membered heterocyclyl of the foregoing R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R15, and R16 are independently optionally substituted with 1 to 3 R14 substituents each independently selected from the group consisting of halo, cyano, nitro, —CF3, —CHF2, —CH2F, trifluoromethoxy, azido, hydroxyl, —O—R15, (C1-C6)alkoxy, —(CR8R9)e(C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C═O)—R11, —(C═O)—R15, —(C═O)—O—R11, —(C═O)—O—R15, —O—(C═O)—R11, —O—(C═O)—R15, —NR11(C═O)—R13, —(C═O)—NR11R12, —(C═O)—NR11R15, —NR11R12, —NR11R15, —NR11OR12, —NR11OR15, —S(O)cNR11R12, —S(O)cNR11R15, —S(O)d(C1-C6)alkyl, —S(O)dR15, —O—SO2—R11, —O—SO2—R15, —(CR11R12)e(3-10)-membered cycloalkyl, —(CR11R12)e(C6-C10)aryl, —(CR11R12)e(4-10)-membered heterocyclyl, —(CR11R12)f(C═O)(CR11R12)e(C6-C10)aryl, —(CR11R12)f(C═O)(CR11R12)e(4-10)-membered heterocyclyl, —(CR11R12)eO(CR11R12)f(C6-C10)aryl, —(CR11R12)eO(CR11R12)f(4-10)-membered heterocyclyl, —(CR11R12)fS(O)d(CR11R12)e(C6-C10)aryl, and —(CR11R12)fS(O)d(CR11R12)e(4-10)-membered heterocyclyl;any carbon atoms of the (C1-C6)alkyl, the (3-10)-membered cycloalkyl, the (C6-C10)aryl and the (4-10)-membered heterocyclyl of the foregoing R14 are independently optionally substituted with 1 to 3 R16 substituents each independently selected from the group consisting of halo, cyano, nitro, —CF3, —CHF2, —CH2F, trifluoromethoxy, azido, (CH2)eOH, (C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C═O)—R11, —(C═O)—R15, —(C═O)—O—R11, —(C═O)—O—R15, —O—(C═O)—R11, —O—(C═O)—R15, —NR11(C═O)—R13, —(C═O)—NR11R12, —NR11R12, and —NR11R15;any nitrogen atoms of the (4-10)-membered heterocyclyl of the foregoing R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R14, and R15 are independently optionally substituted with (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C═O)—R11, —(C═O)—O—R11, —(C═O)—NR11R12, —(CR11R12)e(3-10)- membered cycloalkyl, —(CR11R12)e(C6-C10)aryl, —(CR11R12)e(4-10)-membered heterocyclyl, —(CR11R12)f(C═O)(CR11R12)e(C6-C10)aryl, or —(CR11R12)f(C═O)(CR11R12)e(4-10)-membered heterocyclyl;each R11, R12, and R13 are independently H or (C1-C6)alkyl;R15 is —(CR11R12)e(3-10)-membered cycloalkyl, —(CR11R12)e(C6-C10)aryl, or —(CR11R12)e(4-10)-membered heterocyclyl;a and b are each independently 1, 2, 3, or 4;c is 1 or 2;d is 0, 1, or 2; ande, f, and g are each independently 0, 1, 2, 3, 4, or 5,and wherein when R7 is (C1-C6)alkyl, R6 is selected from the group consisting of —CF3, —CHF2, —CH2F, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C═O)—R8, —(C═O)—O—R8, —(C═O)—NR8R9, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(4-10)-membered non-aromatic heterocyclyl, —(CR8R9)f(C═O)(CR8R9)e(C6-C10)aryl, —(CR8R9)f(C═O)(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —(CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, and —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl. 2. The compound according to claim 1, wherein each of R1 and R2 is independently selected from H or halo; R4 is H or (C1-C6)alkyl; R3 and R5 are H; R6 is —CF3, —CHF2, —CH2F, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(C6-C10)aryl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —(CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, or —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl; R7 is —CF3, —CHF2, —CH2F, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —(CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, or —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl. 3. The compound according to claim 1, wherein each of R1 and R2 is independently selected from H or halo; R4 is H or (C1-C6)alkyl; R3 and R5 are H; R6 and R7 are linked to each other as a 4-12 membered mono- or bicyclic ring. 4. The compound according to claim 1, wherein each of R1 and R2 is independently selected from H or halo; R4 is H or (C1-C6)alkyl; R3 and one R5 are H; one R5 and R6 are linked to each other as a 4-12 membered mono- or bicyclic ring; R7 is —CF3, —CHF2, —CH2F, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —(CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, or —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl. 5. The compound according to claim 1, wherein the compound is the single enantiomer bearing an (S)-configuration at C-3; each of R1 and R2 is independently selected from H or halo; R4 is H or (C1-C6)alkyl, R3 and R5 are H; R6 is —CF3, —CHF2, —CH2F, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(C6-C10)aryl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —(CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, or —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl; R7 is —CF3, —CHF2, —CH2F, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —(CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, or —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl. 6. The compound according to claim 1, wherein the compound is the single enantiomer bearing an (S)-configuration at C-3; each of R1 and R2 is independently selected from H or halo; R4 is H or (C1-C6)alkyl; R3 and R5 are H; R6 and R7 are linked to each other as a 4-12 membered mono- or bicyclic ring. 7. A compound selected from the group consisting of: (S)—N-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)-1,2-thiazinane-1,1-dioxide;N-(3-(3,6-Difluoro-9H-carbazol-9-yl)-2-hydroxypropyl)-isothiazolidine-1,1-dioxide;(S)—N-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)isothiazolidine-1,1-dioxide;2-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)-5-fluoro-isothiazolidine-1,1-dioxide;2-(3-(3,6-Difluoro-9H-carbazol-9-yl)-2-hydroxypropyl)-1,2,6-thiadiazinane-1,1-dioxide;N-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)-N-(1-methylcyclopentyl)methanesulfonamide;N-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)isothiazolidine-1,1-dioxide;N-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)-2,3-dihydrobenzo[d]isothiazole-1,1-dioxide;N-(3-(2,6-Difluoro-9H-carbazol-9-yl)-2-hydroxypropyl)-1,2-thiazinane-1,1-dioxide; and2-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)-1,2,6-thiadiazinane-1,1-dioxide; or a pharmaceutically acceptable salt or hydrate thereof. 8. The compound according to claim 7 which is (S)—N-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)-1,2-thiazinane-1,1-dioxide; or a pharmaceutically acceptable salt thereof. 9. The compound according to claim 7 which is N-(3-(3,6-Difluoro-9H-carbazol-9-yl)-2-hydroxypropyl)-isothiazolidine-1,1-dioxide; or a pharmaceutically acceptable salt or hydrate thereof. 10. The compound according to claim 7 which is (S)—N-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)isothiazolidine-1,1-dioxide; or a pharmaceutically acceptable salt or hydrate thereof. 11. The compound according to claim 7 which is 2-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)-5-fluoro-isothiazolidine-1,1-dioxide; or a pharmaceutically acceptable salt or hydrate thereof. 12. The compound according to claim 7 which is 2-(3-(3,6-Difluoro-9H-carbazol-9-yl)-2-hydroxypropyl)-1,2,6-thiadiazinane-1,1-dioxide; or a pharmaceutically acceptable salt or hydrate thereof. 13. The compound according to claim 7 which is N-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)-N-(1-methylcyclopentyl)methanesulfonamide; or a pharmaceutically acceptable salt or hydrate thereof. 14. The compound according to claim 7 which is N-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)isothiazolidine-1,1-dioxide; or a pharmaceutically acceptable salt or hydrate thereof. 15. The compound according to claim 7 which is N-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)-2,3-dihydrobenzo[d]isothiazole-1,1-dioxide; or a pharmaceutically acceptable salt or hydrate thereof. 16. The compound according to claim 7 which is N-(3-(2,6-Difluoro-9H-carbazol-9-yl)-2-hydroxypropyl)-1,2-thiazinane-1,1-dioxide; or a pharmaceutically acceptable salt or hydrate thereof. 17. The compound according to claim 7 which is 2-(3-(9H-Carbazol-9-yl)-2-hydroxypropyl)-1,2,6-thiadiazinane-1,1-dioxide; or a pharmaceutically acceptable salt or hydrate thereof. 18. The compound according to claim 1, wherein said compound modulates Cry1 or Cry2. 19. The compound according to claim 18, wherein said modulation comprises any one of the following: (i) binding to Cry1 or Cry2;(ii) inhibiting modification of Cry1 or Cry2;(iii) altering Cry1 or Cry2 localization;(iv) increasing or decreasing Cry1 or Cry2 stabilization;(v) increasing or decreasing the binding between Cry1 or Cry2 to a target;(vi) increasing or decreasing Cry1 or Cry2 activity; and(vii) increasing or decreasing activity of a Cry1 or Cry2 target. 20. The compound according to claim 19, wherein said target is Per1, Per2, glucocorticoid receptor (GR), CLOCK, BMAL1, or a CLOCK-BMAL1 promoter sequence. 21. A pharmaceutical composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt or hydrate thereof, and a pharmaceutically acceptable carrier, adjuvant, or diluent. 22. The pharmaceutical composition according to claim 21, further comprising one or more additional therapeutic agents.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (79)
Black Cameron (Pointe Claire CAX) Leger Serge (Dollard des Ormeaux CAX) Prasit Petpiboon (Kirkland CAX) Wang Zhaoyin (Pierrefonds CAX) Hamel Pierre (Laval CAX) Han Yongxin (Kirkland CAX) Hughes Grego, 3,4-diaryl-2-hydroxy-2,5-dihydrofurans as prodrugs to COX-2 inhibitors.
Harris Elbert E. (Westfield NJ) Patchett Arthur A. (Westfield NJ) Tristram Edward W. (Watchung NJ) Wyvratt Matthew J. (Mountainside NJ), Aminoacid derivatives as antihypertensives.
Lifer Sherryl L. (Indianapolis IN) Marshall Winston S. (Bargersville IN) Mohamadi Fariborz (Indianapolis IN) Reel Jon K. (Indianapolis IN) Simon Richard L. (Greenwood IN) Steinberg Mitchell I. (India, Angiotensin II antagonist 1,3-imidazoles and use thereas.
Chakravarty Prasun K. (Edison NJ) Greenlee William J. (Teaneck NJ) Mantlo Nathan B. (Westfield NJ) Patchett Arthur A. (Westfield NJ) Schoen William (Edison NJ) Walsh Thomas F. (Westfield NJ), Angiotensin II antagonists.
Hoffman William F. (Wilmington Lansdale PA) Smith Robert L. (Wilmington Lansdale PA) Willard Alvin K. (Wilmington DE), Antihypercholesterolemic compounds.
Gauthier Jacques Y. (Laval CAX) Lau Cheuk K. (Ile Bizard CAX) LeBlanc Yves (Kirkland CAX) Li Chun-Sing (Dollard des Ormeaux CAX) Roy Patrick (Dollard des Ormeaux CAX) Therien Michel (Laval CAX) Wang , Aryl substituted 5,5 fused aromatic nitrogen compounds as anti-inflammatory agents.
Prasit Petpiboon (Kirkland CAX) Guay Daniel (Iie Perrot CAX) Wang Zhaoyin (Pierrefonds CAX) Leger Serge (Dollar des Ormeaux CAX) Therien Michel (Laval CAX), Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2.
Black Cameron (Point Claire CAX) Grimm Erich (Baie D\Urfe CAX) Wang Zhaoyin (Pierrefonds CAX) Leger Serge (Dollard des Ormeaux CAX), Diaryl-5-oxygenated-2-(5H) -furanones as COX-2 inhibitors.
Rger Wolfgang (Kelkheim DEX) Urbach Hansjrg (Kronberg/Taunus DEX) Ruppert Dieter (Kronberg/Taunus DEX) Schlkens Bernward (Kelkheim DEX), Enzyme-inhibiting urea derivatives of dipeptides, a process for the preparation thereof, agents containing these, and th.
Monaghan Richard L. (Somerset NJ) Alberts Alfred W. (Short Hills NJ) Hoffman Carl H. (Scotch Plains NJ) Albers-Schonberg George (Princeton NJ), Hypocholesteremic fermentation products and process of preparation.
Glazer Howard I. (225 E. 64th St. ; Ste. 202A New York NY 10021), Method to treat smoking withdrawal symptoms by potentiated central noradrenergic blocking.
Skold Carl (Mountain View CA) Gould Dennis R. (San Gregorio CA) Ullman Edwin F. (Atherton CA), Methods for modulating ligand-receptor interactions and their application.
Lau Cheuk Kun (Ile Bizard CAX) Black Cameron (Pointe Claire CAX) Guay Daniel (Ile Perrot CAX) Gauthier Jacques-Yves (Laval CAX) LeBlanc Yves (Kirkland CAX) Roy Patrick (Dollard des Ormeaux CAX) Ducha, N-benzyl indol-3-yl butanoic acid derivatives as cyclooxygenase inhibitors.
Lau Cheuk K. (Ile Bizard CAX) Black Cameron (Pointe Claire CAX) Guay Daniel (Ile Perrot CAX) Gauthier Jacques Y. (Laval CAX) LeBlanc Yves (Kirkland CAX) Roy Patrick (Dollard des Ormeaux CAX) Ducharme, N-benzylindol-3-yl propanoic acid derivatives as cyclooxygenase inhibitors.
Heusser Christoph (Bottmingen CHX) Andreatta Rudolf H. (Allschwil CHX) Alkan Sefik (Riehen CHX) Wood Jeanette (Biel-Benken CHX), Novel monoclonal antibodies to human renin and hybridoma cells, processes for their preparation and their applications.
TenBrink Ruth E. (Kalamazoo MI), Novel renin inhibiting polypeptide analogs containing S-aryl-D- or L- or DL-cysteinyl, 3-(arylthio)lactic acid or 3-(ary.
Luly Jay R. (1021 Mayfair Libertyville IL 60048) Plattner Jacob J. (1120 Garfield Ave. Libertyville IL 60048) Kempf Dale J. (36151 N. Grand Oaks Ct. Gurnee ; IL 60031), Peptidylaminodiols.
Attwood Michael R. (Hitchin GB2) Hassall Cedric H. (Harpenden GB2) Lambert Robert W. (Welwyn GB2) Lawton Geoffrey (Hitchin GB2) Redshaw Sally (Hitchin GB2), Pyridazo[1,2-a][1,2]diazepines.
Albright Jay D. (Nanuet NY) Frederick Charles (Upper Saddle River NJ) Levin Jeremy I. (Spring Valley NY) Sum Fuk-Wah (Pomona NY) Reich Marvin F. (Suffern NY), Renin inhibitors.
Doherty Annette M. (Ann Arbor MI) Hamilton Harriet W. (Chelsea MI) Hodges John C. (Ann Arbor MI) Repine Joseph T. (Ann Arbor MI) Sircar Ila (Ann Arbor MI), Renin inhibitors, method for using them, and compositions containing them.
Huang Leeyuan (Watchung NJ) Dunn ; Jr. Joseph (Parlin NJ) Koupal Lawrence (Colonia NJ) Liesch Jerrold (Princeton Junction NJ) Hensens Otto (Red Bank NJ) Woodruff H. Boyd (Watchung NJ), Renin-inhibitory pepstatin phenyl derivatives.
Carini David J. (Wilmington DE) Duncia John Jonas V. (Newark DE) Wells Gregory J. (Wilmington DE), Substituted 1,2,3-triazole angiotensin II antagonists.
Blankley C. John (Ann Arbor MI) Hodges John C. (Ann Arbor MI) Kiely John S. (Ann Arbor MI) Klutchko Sylvester R. (Ann Arbor MI), Substituted diimidazo [1,5-a: 4′,5′-d]pyridines having antihypertensive activity.
Vincent Michel (Bagneux FRX) Remond Georges (Versailles FRX) Laubie Michel (Vaucresson FRX), Substituted iminodiacids, their preparation and pharmaceutical compositions containing them.
Talley John J. (Brentwood MO) Sikorski James A. (Des Peres MO) Norman Bryan H. (Indianapolis IN) Rogers ; deceased Roland S. (late of Richmond Heights MO by Kathy L. Rogers ; legal representative ) D, Substituted sulfonylphenylheterocycles as cyclooxygenase-2 and 5-lipoxygenase inhibitors.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.