SUBSTITUTED PHENYLACETIC ACIDSSubstituted phenylacetic acids, phenylethanols and related compounds are provided that are useful in treating or controlling a number of diseases associated with glucose metabolism, lipid metabolism and insulin secretion.A compound having a formula selected from the group consisting of: wherein X is a member selected from the group consisting of O, S, SO, SO2 and NR, wherein R is H, (C, -C8)alkyl, CORa, COORa and CONRaRb wherein Ra and Rb are each independently selected from the group consisting of H and (Cι-C8)alkyl; Y is a member selected from the group consisting of CH2ORc, CO2Rc, CHO, CONRcRm, CH(=NRC), CH(=NORc) and carboxylic acid surrogates, wherein Rc is a member selected from the group consisting of H, (Cι-C8)alkyl, (C3- C8)alkenyl, (C3-C8)alkynyl, (C3-C7)cycloalkyl, (C4-C8)cycloalkyl-alkyl, aryl, aryl(Cι-C8)alkyl and (Cι-C8)alkylene-Z, wherein Z is selected from the group consisting of CORd, COORd, NRdRe, NRdCONReRf, NRdCORe, NRdCOORe and CONRdRe wherein Rd, Re and Rf are each independently selected from the group consisting of H, (CpC8)alkyl and phenyl, or optionally two of Rd, Re and R when attached to the same nitrogen atom are combined to form a five- or six-membered ring; and wherein Rm is selected from the group consisting of H, (Cι-C8)alkyl, aryl, OH and SO2Rn, wherein Rn is selected from the group consisting of (C C8)alkyl, (Cι-C8)haloalkyl, aryl(Cι-C8)alkyl, ( - C8)heteroalkyl, aryl, heteroaryl, (Cι-C8)alkoxy, aryloxy, alkylamino, dialkylamino, arylamino, diarylamino, haloalkylamino and di(haloalkyl)amino, and Rm and Rc are optionally combined with the nitrogen atom to which each is attached to form a five- or six-membered ring; HAr is heteroaryl moiety, optionally substituted with from one to three substituents independently selected from the group consisting of halogen, hydroxy, (C - C8)alkyl, aryl(Cι-C8)alkyl, (C1-C8)alkoxy, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)cycloalkyl, (C4-C8)cycloalkyl-alkyl, (Cι-C8)heteroalkyl, (C2- C5)heterocyclyl, aryl, aryloxy, heterosubstituted(C -C7)cycloalkyl, heteroalkyl substituted (C3-C7)cycloalkyl, (Cι-C8)haloalkyl, O(Cι-C8)haloalkyl, nitro, cyano, CO2Rg, COR8, NRgRh, S(O)qRg, SO2NRgRh, NRsCONRhR', NRgCORh, NRgCOORh and CONRgRh, wherein Rg, Rh and R' are each independently selected from the group consisting of H and (Cι-C8)alkyl, or optionally two of Rg, Rh and R1 when attached to the same nitrogen atom are combined to form a five- or six-membered ring, and the subscript q is an integer of from 0 to 2; each R1 and R3 is a member independently selected from the group consisting of halogen, hydroxy, (Cι-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (Q- C8)alkoxy, (C3-C7)cycloalkyl, (C4-C8)cycloalkyl-alkyl, (Cι-C8)haloalkyl, (Q- C8)heteroalkyl, (C2-C5)heterocyclyl, heterosubstituted(C3-C7)cycloalkyl, heteroalkyl substituted (C3-C7)cycloalkyl, O(Cι-C8)haloalkyl, nitro, cyano, phenyl, O-phenyl, NRJ-phenyl, S(O)r-phenyl, CORJ, COORJ, NRJRk, S(O)rRJ, SO2NRJR , NRJCONRkR', NRJCORk, NRJCOORk and CONRJRk wherein the phenyl ring is optionally substituted and R , Rk and R1 are each independently selected from the group consisting of H, (Cι-C8)alkyl and (Cι-C8)haloalkyl, or optionally two of RJ , Rk and R1 when attached to the same nitrogen atom are combined to form a five- or six-membered ring, and the subscript r is an integer of from 0 to 2; R2 is a member selected from the group consisting of H, (Cι-C8)alkyl, (C- C8)haloalkyl, aryl(Cι-C8)alkyl and (Cι-C4)alkylene-Z, wherein Z is as defined above; the subscript m is an integer of from 0 to 4; the subscript p is an integer of from 0 to 3; and pharmaceutically acceptable salts thereof.
치환된 페닐아세트산본 발명은 글루코오스 대사, 지질 대사 및 인슐린 분비와 관련된 다수의 질병을 치료하거나 통제하는 데에 유용한 치환된 페닐아세트산, 페닐에탄올 및 관련 화합물에 관한 것이다.하기 화학식으로 구성된 군으로부터 선택된 화학식을 지닌 화합물 또는 이의약제학적으로 허용되는 염:  상기 식에서, X는 0, S, SO, SO2 및 NR로 구성된 군으로부터 선택되며, 여기에서 R은 H, (C1-C8)알킬, CORa , COORa 및 CONRaRb 이고, 여기에서 Ra 및 Rb 은 각각 독립적으로 H 및 (C1-C8)알킬로 구성된 군으로부터 선택되고; Y는 CH2ORc, CO2Rc, CHO, CONRcRm, CH(=NR c), CH(=NORc) 및 카르복실산 대용물로 구성된 군으로부터 선택되고, 여기에서, Rc는 H, (C1-C8)알킬, (C 3-C8)알케닐, (C3-C8)알키닐, (C3-C7)시클로알킬, (C4-C 8)시클로알킬-알킬, 아릴, 아릴(C1-C8)알킬 및 (C1-C8)알킬렌-Z로 구성된 군으로부터 선택되고, 여기에서 Z는 CORd , COORd, NRdRe, NRdCONReRf, NRdCORe , NRdCOORe 및 CONRdRe 로 구성된 군으로부터 선택되고, Rd, Re 및 Rf는 각각 독립적으로 H, (C1-C8)알킬 및 페닐로 구성된 군으로부터 선택되거나, 임의로, 동일한 질소 원자에 부착되는 경우에 Rd, Re 및 Rf 중 두개는 결합하여 5원 또는 6원 고리를 형성하고; Rm은 H, (C1-C8)알킬, 아릴, OH 및 SO 2Rn으로 구성된 군으로부터 선택되고, 여기에서 Rn은 (C1-C8)알킬, (C1-C 8)할로알킬, 아릴(C1-C8)알킬, (C1-C8)헤테로알킬, 아릴, 헤테로아릴, (C1-C8)알콕시, 아릴옥시, 알킬아미노, 디알킬아미노, 아릴아미노, 디아릴아미노, 할로알킬아미노 및 디(할로알킬)아미노로 구성된 군으로부터 선택되고, Rm 및 Rc는 임의로 이들 각각이 결합되어 있는 질소 원자와 결합하여 5원 또는 6원 고리를 형성하고; HAr은 할로겐, 히드록시, (C1-C8)알킬, 아릴(C1-C8)알킬, (C 1-C8)알콕시, (C2-C8)알케닐, (C2-C8)알키닐, (C3-C7)시클로알킬, (C4-C8)시클로알킬-알킬, (C1-C8)헤테로알킬, (C2-C5)헤테로시클릴, 아릴, 아릴옥시, 헤테로 치환된 (C 3-C7)시클로알킬, 헤테로알킬 치환된 (C3-C7)시클로알킬, (C1-C8)할로알킬, O(C 1-C8)할로알킬, 니트로, 시아노, CO2Rg, CORg, NRgRh, S(O)q Rg, SO2NRgRh, NRgCONRhR i, NRgCORh, NRgCOORh 및 CONRgRh(여기에서, Rg, Rh 및 Ri는 각각 독립적으로 H 및 (C1-C8)알킬로부터 선택되거나, 임의로, 동일한 질소 원자에 부착되는 경우에 Rg, Rh 및 Ri 중 두개는 결합하여 5원 또는 6원 고리를 형성하고, 아래 첨자 q는 0 내지 2의 정수이다)로 구성된 군으로부터 독립적으로 선택된 1개 내지 3개의 치환기로 치환되거나 치환되지 않은, 헤테로아릴 부분이고; 각각의 R1 및 R3는 할로겐, 히드록시, (C1-C8)알킬, (C 2-C8)알케닐, (C2-C8)알키닐, (C1-C8)알콕시, (C3-C7)시클로알킬, (C4-C 8)시클로알킬-알킬, (C1-C8)할로알킬, (C1-C8)헤테로알킬, (C2-C5)헤테로시클릴, 헤테로 치환된(C 3-C7)시클로알킬, 헤테로알킬 치환된 (C3-C7)시클로알킬, O(C1-C8)할로알킬, 니트로, 시아노, 페닐, 0-페닐, NRj-페닐, S(O)r-페닐, CORj, COORj, NRjR k, S(O)rRj, SO2NRjRk, NRj CONRkRl, NRjCORk, NRjCOORk 및 CONRjRk (여기에서, 페닐 고리는 치환되거나 치환되지 않으며, Rj, Rk 및 Rl은 각각 독립적으로 H, (C1-C8)알킬 및 (C1-C8 )할로알킬로부터 선택되거나, 임의로, 동일한 질소 원자에 부착되는 경우에 Rj, Rk 및 Rl 중 두개는 결합하여 5원 또는 6원 고리를 형성하고, 아래 첨자 r은 0 내지 2의 정수이다)로 구성된 군으로부터 독립적으로 선택되고; R2는 H, (C1-C8)알킬, (C1-C8)할로알킬, 아릴(C 1-C8)알킬 및 (C1-C4)알킬렌-Z로 구성된 군으로부터 선택되며, 여기에서 Z는 상기 정의한 바와 같고; 아래 첨자 m은 0 내 4의 정수이고; 아래 첨자 p는 0 내지 3의 정수이다.