STAT6 inhibitors and their uses

Abstract

The present invention provides a compound, a composition, and a method of using the same.

Claims

Claim 1 chemical formula I' Compound of: [Chemical Formula I'] Or as a pharmaceutically acceptable salt thereof, in the formula, ring W and its R w The substituent Igo;X 1 , X 4 , and X 5 Each independently CH, CR w , or N and;X 2 and X 3 Each is independently C or N and;X 1 , X 2 , X 3 , X 4 , and X 5 At most 1 of them is N and;Y 1 , Y 2 , and Y 3 Each independently CH, CR w , CH2, CH(R w ), C(R w )2, NH, NR w , N, O, or S and,Y 2 and Y 3 At least one of them is CH, CR w , CH2, CH(R w ), or C(R w )2 and; each of represents a single or double bond; ring X and its R x The substituent or and; here represents a bond to ring W, represents a bond to the remainder of the molecule; ring Y is a ring selected from phenyl, 3-8 member saturated or partially unsaturated monocyclic carbocliclyl or heterocyclic (having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 5-6 member monocyclic heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and R w is hydrogen, R A , R B , halogen, -CN, -NO2, -OR, -SR, -NR2, -SiR3, -S(O)R, -S(O)2R, -S(O)(NR)R , -S(O)2NR 2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NROR, -OC(O)R, -OC(O)NR2, -P(O)R2, -P(O)(OR)2, -OP(O)R2, -OP(O)(OR)2, -NRC(O)OR, -NRC(O)R, -NRC(O)N(R)2, and -NRS(O)2R is selected from;R x and R y is independently hydrogen, R A , halogen, -CN, -NO2, -OR, -SR, -NR2, -SiR3, -S(O)R, -S(O)2R, -S(O)(NR)R , -S(O)2NR 2, Selected from -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NROR, -OC(O)R, -OC(O)NR2, -P(O)R2, -P(O)(OR)2, -OP(O)R2, -OP(O)(OR)2, -NRC(O)OR, -NRC(O)R, -NRC(O)N(R)2, and -NRS(O)2R; each R A C independently 1-6 An optionally substituted group selected from aliphatic, phenyl, 3- to 7-membered saturated or partially unsaturated carbon-ring or heterocyclic rings (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 5- to 6-membered heteroaryl rings (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and each R B is independently -L B -Cy B1 -H or -L B -Cy B1 -Cy B2 and; each L B is independently a covalent bond or C 1-3 The divalent linear or branched saturated or unsaturated hydrocarbon chain, wherein 1 to 2 methylene units of the chain are independently optionally replaced with -O-, -C(O)-, -C(S)-, -C(NR)R-, -CR2-, -CF2-, -CRF-, -CR(OR)-, -NR-, -S-, -S(O)-, -S(O)2-, -S(O)(NR)-, or -CR=CR-; and each Cy B1 is an optionally substituted ring independently selected from phenylenyl, 3-10 member saturated or partially unsaturated monocyclic or dicyclic carbocyclylenyl or heterocyclylenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), 5-10 member monocyclic or dicyclic arylenyl or heteroarylenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), or 5-15 member saturated or partially saturated monocyclic, dicyclic, or tricyclic carbocyclylenyl, heterocyclylenyl, arylenyl, or heteroarylenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and each Cy B2 is independently an optionally substituted ring selected from phenyl, a 3- to 10-membered saturated or partially unsaturated monocyclic or dicyclic carbon-ring or heterocyclic ring (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 5- to 10-membered monocyclic or dicyclic aryl or heteroaryl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), or a 5- to 15-membered saturated or partially saturated monocyclic, dicyclic, or tricyclic carbocyclyl, heterocyclyl, aryl, or heteroaryl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and each R is independently hydrogen, or C 1-6 An optionally substituted group selected from an aliphatic, phenyl, 4- to 7-membered saturated or partially unsaturated carbon-ring or hetero-ring (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and a 5- to 6-membered heteroaryl ring (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), or two R groups on the same or adjacent atoms optionally form a 3- to 7-membered saturated or partially unsaturated ring (having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur in addition to the atoms to which they are attached or adjacent atoms); where w, x, y, and z are each independently 0, 1, 2, 3, or 4, and where: (i) ring X and its R x substituent and X 1 This is N and Y 1 This NH, NR w , or if N, Y 2 and Y 3 is NH, NR w , or not N; (ii) ring X and its R x substituent and X 1 , X 4 , and X 5 Each CH or CR w and X 2 and X 3 Each is C and Y 2 and Y 3 CH, CR respectively w , CH2, CH(R w ), or C(R w In the case of )2, Y 1 Silver CH, CR w , CH2, CH(R w ), or C(R w )not 2; (iii) ring X and its R x substituent and X 1 This is N and Y 1 In the case of this S, ring Y is not a phenyl or a 3- to 8-membered saturated or partially unsaturated monocyclic carboclicly or heterocyclly (having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur); (iv) ring X and its R x substituent and X 1 This is N and Y 1 This NH, NR w , or if N, Y 3 is not S; (v) ring X and its R x substituent and X 1 This is N and Y 1 If this is O, Y 2 is NH, NR w , or not N; (vi) ring X and its R x substituent and X 1 This is N and Y 1 This NH, NR w , or N and Y 2 and Y 3 This CH, CR w , CH2, CH(R w ), or C(R w ) In the case of 2, z is not 0 or 1; (vii) ring X and its R x substituent and X 1 , X 4 , and X 5 Each CH or CR w and X 2 and X 3 Each is C and Y 2 Ga CH, CR w , CH2, CH(R w ), or C(R w In the case of )2, Y 2 and Y 3 Only one of them is O; (viii) ring X and its R x substituent and X 1 , X 4 , and X 5 Each CH or CR w and X 2 and X 3 Each is C and Y 1 This O, NH, NR w , or N and Y 2 and Y 3 This CH, CR w , CH2, CH(R w ), or C(R w ) In the case of 2, z is not 0 or 1; (ix) ring X and its R x substituent and X 5 is N and Y 1 This NH, NR w , or if N, Y 2 is NH, NR w , or not N, and the above compounds do not have the structure ABC defined by the combination of building blocks A, B, and C in the table below: . Claim 2 In paragraph 1, the ring W and its R w The substituent , , , , , , , , , , , or Phosphorus, compound. Claim 3 In paragraph 1, the ring W and its R w The substituent , , , , , , , , , , , or Phosphorus, compound. Claim 4 A compound according to any one of claims 1 to 3, wherein ring Y is a 5- to 6-membered monocyclic heteroaryl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur). Claim 5 In paragraph 4, ring Y is , , or Phosphorus, compound. Claim 6 In any one of paragraphs 1 through 5, R w The existence of is -S(O)R, -S(O)2R, -S(O)(NR)R , -S(O)2NR 2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NROR, -OC(O)R, -OC(O)NR2, -P(O)R2, -P(O)(OR)2, -OP(O)R2, -OP(O)(OR)2, -NRC(O)OR, -NRC(O)R, -NRC(O)N(R)2, or -NRS(O)2R, a compound. Claim 7 In any one of paragraphs 1 through 6, R w The existence of is R B Phosphorus, compound. Claim 8 In any one of paragraphs 1 through 7, R w Compounds in which the presence of is a halogen (e.g., fluoro). Claim 9 In any one of claims 1 to 8, the compound is a chemical formula Ia-1b or Ia-2b Compound of: [Chemical Formula Ia-1b] [Chemical Formula Ia-2b] or a pharmaceutically acceptable salt thereof (in the formula, R w ' is hydrogen, R A , R B , halogen, -CN, -NO2, -OR, -SR, -NR2, -SiR3, -S(O)R, -S(O)2R, -S(O)(NR)R , -S(O)2NR 2, A compound that is -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NROR, -OC(O)R, -OC(O)NR2, -P(O)R2, -P(O)(OR)2, -OP(O)R2, -OP(O)(OR)2, -NRC(O)OR, -NRC(O)R, -NRC(O)N(R)2, or -NRS(O)2R. Claim 10 In Paragraph 9, R w A compound that is an optionally substituted ring selected from phenyl, a 3- to 7-membered saturated or partially unsaturated carbon ring or heterocyclic ring (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and a 5- to 6-membered heteroaryl ring (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur). Claim 11 In any one of claims 1 to 10, the compound is a chemical formula Ib-5 , Ib-6, Ic-5, Ic-6 , Id-5, Id-6, Ie-5 , or Ie-6 Compound of: [Chemical Formula Ib-5] [Chemical Formula Ib-6] [Chemical Formula Ic-5] [Chemical Formula Ic-6] [Chemical Formula Id-5] [Chemical Formula Id-6] [Chemical Formula Ie-5] [Chemical Formula Ie-6] or a pharmaceutically acceptable salt thereof (in the formula, R w ' is hydrogen, R A , R B , halogen, -CN, -NO2, -OR, -SR, -NR2, -SiR3, -S(O)R, -S(O)2R, -S(O)(NR)R , -S(O)2NR 2, A compound that is -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NROR, -OC(O)R, -OC(O)NR2, -P(O)R2, -P(O)(OR)2, -OP(O)R2, -OP(O)(OR)2, -NRC(O)OR, -NRC(O)R, -NRC(O)N(R)2, or -NRS(O)2R. Claim 12 In any one of paragraphs 1 through 11, R B is -L B -Cy B1 -H, compound. Claim 13 In any one of paragraphs 1 through 11, R B is -L B -Cy B1 -Cy B2 Phosphorus, compound. Claim 14 In any one of paragraphs 1 through 13, Cy B1 A compound that is an 8- to 10-membered saturated or partially unsaturated dicyclic heterocyclylenyl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur). Claim 15 In any one of paragraphs 1 through 13, Cy B1 A compound that is an arbitrarily substituted 3 to 7-membered saturated or partially unsaturated heterocyclylenyl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur). Claim 16 In any one of paragraphs 1 through 11, R B Is or Phosphorus, compound. Claim 17 In any one of paragraphs 1 through 16, Cy B2 A compound that is an arbitrarily substituted 5-6 member monocyclic heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur). Claim 18 In paragraph 1, (i) ring W and its R w The substituent or and; ring Y is a 5–6-membered monocyclic heteroaryl (having 1–4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); z is 2; and each L B is independently a covalent bond or C 1-3 The divalent linear or branched saturated or unsaturated hydrocarbon chain, wherein 1 to 2 methylene units of the chain are independently optionally replaced with -O-, -C(O)-, -C(S)-, -CR2-, -CF2-, -CRF-, -CR(OR)-, -NR-, -S-, -S(O)-, -S(O)2-, -S(O)(NR)-, or -CR=CR-; and each Cy B1 is an optionally substituted ring independently selected from phenylenyl, 3-7 member saturated or partially unsaturated carbocyclyllenyl or heterocyclyllenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 5-10 member monocyclic or dicyclic arylenyl or heteroarylenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and each Cy B2 is an optionally substituted ring selected independently from phenyl, a 3- to 7-membered saturated or partially unsaturated carbon ring or heterocyclic ring (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and a 5- to 10-membered monocyclic or dicyclic aryl or heteroaryl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); or (ii) ring W and its R w The substituent and; ring Y is a 5–6-membered monocyclic heteroaryl (having 1–4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); z is 2; and each L B is independently a covalent bond or C 1-3 The divalent linear or branched saturated or unsaturated hydrocarbon chain, wherein 1 to 2 methylene units of the chain are independently optionally replaced with -O-, -C(O)-, -C(S)-, -CR2-, -CF2-, -CRF-, -CR(OR)-, -NR-, -S-, -S(O)-, -S(O)2-, -S(O)(NR)-, or -CR=CR-; and each Cy B1 is an optionally substituted ring independently selected from phenylenyl, 3-7 member saturated or partially unsaturated carbocyclyllenyl or heterocyclyllenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 5-10 member monocyclic or dicyclic arylenyl or heteroarylenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and each Cy B2 is an optionally substituted ring selected independently from phenyl, a 3- to 7-membered saturated or partially unsaturated carbon ring or heterocyclic ring (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and a 5- to 10-membered monocyclic or dicyclic aryl or heteroaryl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); or (iii) ring W and its R w The substituent and; ring Y is a 5–6-membered monocyclic heteroaryl (having 1–4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); z is 2; and each L B is independently a covalent bond or C 1-3 The divalent linear or branched saturated or unsaturated hydrocarbon chain, wherein 1 to 2 methylene units of the chain are independently optionally replaced with -O-, -C(O)-, -C(S)-, -CR2-, -CF2-, -CRF-, -CR(OR)-, -NR-, -S-, -S(O)-, -S(O)2-, -S(O)(NR)-, or -CR=CR-; and each Cy B1 is an optionally substituted ring independently selected from phenylenyl, 3-7 member saturated or partially unsaturated carbocyclyllenyl or heterocyclyllenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 5-10 member monocyclic or dicyclic arylenyl or heteroarylenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and each Cy B2 A compound which is an optionally substituted ring selected independently from phenyl, a 3- to 7-membered saturated or partially unsaturated carbon ring or heterocyclic ring (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and a 5- to 10-membered monocyclic or dicyclic aryl or heteroaryl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur). Claim 19 In any one of claims 1 to 18, the compound is Table B A compound that is not a compound selected from. Claim 20 In paragraph 1, the above compound is Table 1B A compound selected from, or a pharmaceutically acceptable salt thereof. Claim 21 Table 2B A compound selected from, or a pharmaceutically acceptable salt thereof. Claim 22 A pharmaceutical composition comprising a compound of any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. Claim 23 A method for inhibiting STAT6, comprising the step of contacting STAT6 with a compound of any one of claims 1 to 21, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. Claim 24 In paragraph 23, the above contact occurs in a patient or biological sample. Claim 25 As a method to inhibit STAT6, STAT6 chemical formula I Compound of: [Chemical Formula I] or a method comprising the step of contacting with a pharmaceutically acceptable salt thereof [wherein, ring W and its R w The substituent or Igo;X 1 , X 4 , X 5 , and X 6 Each independently CH, CR w , or N and;X 2 and X 3 Each is independently C or N and;X 1 , X 2 , X 3 , X 4 , X 5 , and X 6 At most 1 of them is N and;Y 1 , Y 2 , and Y 3 Each independently CH, CR w , CH2, CH(R w ), C(R w )2, NH, NR w , N, O, or S and,Y 2 and Y 3 At least one of them is CH, CR w , CH2, CH(R w ), or C(R w )2 and; each of represents a single or double bond; ring X and its R x The substituent or and; here represents a bond to ring W, is L x Representing a bond for; ring Y is a ring selected from phenyl, naphthyl, 3-11 member saturated or partially unsaturated monocyclic, dicyclic, cross-linked dicyclic, or spirocyclic carbocyclil or heterocyclil (having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 5-10 member monocyclic or dicyclic heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); L x Is , , , , , , , , , , , , , , or and, here represents the bond for ring Y; R w is hydrogen, R A , R B , halogen, -CN, -NO2, -OR, -SR, -NR2, -SiR3, -S(O)R, -S(O)2R, -S(O)(NR)R , -S(O)2NR 2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NROR, -OC(O)R, -OC(O)NR2, -P(O)R2, -P(O)(OR)2, -OP(O)R2, -OP(O)(OR)2, -NRC(O)OR, -NRC(O)R, -NRC(O)N(R)2, and -NRS(O)2R is selected from;R x and R y is independently hydrogen, R A , halogen, -CN, -NO2, -OR, -SR, NR2, -SiR3, -S(O)R, -S(O)2R, -S(O)(NR)R , -S(O)2NR 2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NROR, -OC(O)R, -OC(O)NR2, -P(O)R2, -P(O)(OR)2, -OP(O)R2, -OP(O)(OR)2, -NRC(O)OR, -NRC(O)R, -NRC(O)N(R)2, and -NRS(O)2R is selected from;R Z is R A , -OR, or NR2 and; each R A C independently 1-6 An optionally substituted group selected from aliphatic, phenyl, 3- to 7-membered saturated or partially unsaturated carbon-ring or heterocyclic rings (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 5- to 6-membered heteroaryl rings (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and each R B is independently -L B -Cy B1 -H or -L B -Cy B1 -Cy B2 and; each L B is independently a covalent bond or C 1-3 The divalent linear or branched saturated or unsaturated hydrocarbon chain, wherein 1 to 2 methylene units of the chain are independently optionally replaced with -O-, -C(O)-, -C(S)-, -C(NR)R-, -CR2-, -CF2-, -CRF-, -CR(OR)-, -NR-, -S-, -S(O)-, -S(O)2-, -S(O)(NR)-, or -CR=CR-; and each Cy B1 is an optionally substituted ring independently selected from phenylenyl, 3-10 member saturated or partially unsaturated monocyclic or dicyclic carbocyclylenyl or heterocyclylenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), 5-10 member monocyclic or dicyclic arylenyl or heteroarylenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), or 5-15 member saturated or partially saturated monocyclic, dicyclic, or tricyclic carbocyclylenyl, heterocyclylenyl, arylenyl, or heteroarylenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and each Cy B2 is independently an optionally substituted ring selected from phenyl, a 3- to 10-membered saturated or partially unsaturated monocyclic or dicyclic carbon-ring or heterocyclic ring (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 5- to 10-membered monocyclic or dicyclic aryl or heteroaryl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), or a 5- to 15-membered saturated or partially saturated monocyclic, dicyclic, or tricyclic carbocyclyl, heterocyclyl, aryl, or heteroaryl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and each R is independently hydrogen, or C 1-6 [A unilaterally substituted group selected from an aliphatic, phenyl, 4- to 7-membered saturated or partially unsaturated carbon ring or heterocyclic ring (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and a 5- to 6-membered heteroaryl ring (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), or two R groups on the same or adjacent atoms optionally form a 3- to 7-membered saturated or partially unsaturated ring (having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur in addition to the atoms or adjacent atoms to which they are attached); and w, x, y, and z are each independently 0, 1, 2, 3, or 4]. Claim 26 In paragraph 25, the above compound is a chemical formula I' Compound of: [Chemical Formula I'] or a pharmaceutically acceptable salt thereof [in the formula, ring W and its R w The substituent [and; ring Y is a ring selected from phenyl, 3-8 member saturated or partially unsaturated monocyclic carbocyclil or heterocyclil (having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 5-6 member monocyclic heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur)], method. Claim 27 In paragraph 25, the above compound is a chemical formula II Compound of: [Chemical Formula II] or a pharmaceutically acceptable salt thereof [in the formula, ring W and its R w The substituent [and; ring Y is a ring selected from naphthyl, 5-10-membered saturated or partially unsaturated dicyclic or cross-linked dicyclic carbocyclyl or heterocyclyl (having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 8-10-membered dicyclic heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur)], method. Claim 28 In paragraph 25, the above compound is a chemical formula III Compound of: [Chemical Formula III] or a pharmaceutically acceptable salt thereof [in the formula, ring W and its R w The substituent and; ring Y is a ring selected from phenyl, 3-8 member saturated or partially unsaturated monocyclic carbocyclyl or heterocyclyl (having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur), 5-6 member monocyclic heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), naphthyl, 5-10 member saturated or partially unsaturated dicyclic or cross-linked dicyclic carbocyclyl or heterocyclyl (having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 8-10 member dicyclic heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and L x Is , , , , , , , , , , , , , or and, here [represents the bond for ring Y], method. Claim 29 In any one of paragraphs 25 through 28, the ring W and its R w The substituent , , , , , , , , , , , or Person, method. Claim 30 In any one of paragraphs 25 through 28, the ring W and its R w The substituent , , , , , , , , , , , or Person, method. Claim 31 In paragraph 25, the above compound is a chemical formula IV Compound of: [Chemical Formula IV] or a pharmaceutically acceptable salt thereof [in the formula, ring W and its R w The substituent [and; ring Y is a ring selected from phenyl, 3-8 member saturated or partially unsaturated monocyclic carbocyclil or heterocyclil (having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 5-6 member monocyclic heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur)], method. Claim 32 In paragraph 25 or 31, the ring W and its R w The substituent , , , , , , or Person, method. Claim 33 In paragraph 25 or 31, the ring W and its R w The substituent , , , , , , , , , , or Person, method. Claim 34 A method according to any one of claims 25, 26, or 28 through 33, wherein ring Y is a 5-6 member monocyclic heteroaryl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur). Claim 35 In Paragraph 34, ring Y is , , or Person, method. Claim 36 In any one of paragraphs 25 through 35, R w The existence of is -S(O)R, -S(O)2R, -S(O)(NR)R , -S(O)2NR 2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NROR, -OC(O)R, -OC(O)NR2, -P(O)R2, -P(O)(OR)2, -OP(O)R2, -OP(O)(OR)2, -NRC(O)OR, -NRC(O)R, -NRC(O)N(R)2, and -NRS(O)2R method. Claim 37 In any one of paragraphs 25 through 36, R w The existence of is R B Person, method. Claim 38 In any one of paragraphs 25 through 37, R w The presence of is a halogen (e.g., fluoro), a method. Claim 39 In any one of claims 25 to 38, the compound is a chemical formula Ia-1b , Ia-2a, Ia-1b , or Ia-2b Compound of: [Chemical Formula Ia-1a] [Chemical Formula Ia-2a] [Chemical Formula Ia-1b] [Chemical Formula Ia-2b] or a pharmaceutically acceptable salt thereof [in the formula, R w ' is hydrogen, R A , R B , halogen, -CN, -NO2, -OR, -SR, -NR2, -SiR3, -S(O)R, -S(O)2R, -S(O)(NR)R , -S(O)2NR 2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NROR, -OC(O)R, -OC(O)NR2, -P(O)R2, -P(O)(OR)2, -OP(O)R2, -OP(O)(OR)2, -NRC(O)OR, -NRC(O)R, -NRC(O)N(R)2, and -NRS(O)2R] method. Claim 40 In Paragraph 39, R w A method in which 'is an optionally substituted ring selected from phenyl, a 3- to 7-membered saturated or partially unsaturated carbon ring or heterocyclic ring (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and a 5- to 6-membered heteroaryl ring (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur). Claim 41 In any one of claims 25 to 40, the compound is a chemical formula Ib-1 inside Ib-6, Ic-1 inside Ic-6 , chemical formula Id-1 inside Id-6, or chemical formula Ie-1 inside Ie-6 Compound of: [Chemical Formula Ib-1] [Chemical Formula Ib-2] [Chemical Formula Ib-3] [Chemical Formula Ib-4] [Chemical Formula Ib-5] [Chemical Formula Ib-6] [Chemical Formula Ic-1] [Chemical Formula Ic-2] [Chemical Formula Ic-3] [Chemical Formula Ic-4] [Chemical Formula Ic-5] [Chemical Formula Ic-6] [Chemical Formula Id-1] [Chemical Formula Id-2] [Chemical Formula Id-3] [Chemical Formula Id-4] [Chemical Formula Id-5] [Chemical Formula Id-6] [Chemical Formula Ie-1] [Chemical Formula Ie-2] [Chemical Formula Ie-3] [Chemical Formula Ie-4] [Chemical Formula Ie-5] [Chemical Formula Ie-6] or a pharmaceutically acceptable salt thereof [in the formula, R w ' is hydrogen, R A , R B , halogen, -CN, -NO2, -OR, -SR, -NR2, -SiR3, -S(O)R, -S(O)2R, -S(O)(NR)R , -S(O)2NR 2, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NROR, -OC(O)R, -OC(O)NR2, -P(O)R2, -P(O)(OR)2, -OP(O)R2, -OP(O)(OR)2, -NRC(O)OR, -NRC(O)R, -NRC(O)N(R)2, and -NRS(O)2R임]인, method. Claim 42 In any one of paragraphs 25 through 41, R B is -L B -Cy B1 -H person, method. Claim 43 In any one of paragraphs 25 through 41, R B is -L B -Cy B1 -Cy B2 Person, method. Claim 44 In any one of paragraphs 25 through 43, Cy B1 A method in which is an arbitrarily substituted 8- to 10-membered saturated or partially unsaturated dicyclic heterocyclylenyl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur). Claim 45 In any one of paragraphs 25 through 43, Cy B1 A method in which is an arbitrarily substituted 3 to 7-membered saturated or partially unsaturated heterocyclylenyl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur). Claim 46 In any one of paragraphs 25 through 41, R B Is or Person, method. Claim 47 In any one of paragraphs 25 through 46, Cy B2 A method in which is an arbitrarily substituted 5-6-membered monocyclic heteroaryl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur). Claim 48 In paragraph 26, (i) ring W and its R w The substituent or and; ring Y is a 5–6-membered monocyclic heteroaryl (having 1–4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); z is 2; and each L B is independently a covalent bond or C 1-3 The divalent linear or branched saturated or unsaturated hydrocarbon chain, wherein 1 to 2 methylene units of the chain are independently optionally replaced with -O-, -C(O)-, -C(S)-, -CR2-, -CF2-, -CRF-, -CR(OR)-, -NR-, -S-, -S(O)-, -S(O)2-, -S(O)(NR)-, or -CR=CR-; and each Cy B1 is an optionally substituted ring independently selected from phenylenyl, 3-7 member saturated or partially unsaturated carbocyclyllenyl or heterocyclyllenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 5-10 member monocyclic or dicyclic arylenyl or heteroarylenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and each Cy B2 is an optionally substituted ring selected independently from phenyl, a 3- to 7-membered saturated or partially unsaturated carbon ring or heterocyclic ring (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and a 5- to 10-membered monocyclic or dicyclic aryl or heteroaryl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); or (ii) ring W and its R w The substituent and; ring Y is a 5–6-membered monocyclic heteroaryl (having 1–4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); z is 2; and each L B is independently a covalent bond or C 1-3 The divalent linear or branched saturated or unsaturated hydrocarbon chain, wherein 1 to 2 methylene units of the chain are independently optionally replaced with -O-, -C(O)-, -C(S)-, -CR2-, -CF2-, -CRF-, -CR(OR)-, -NR-, -S-, -S(O)-, -S(O)2-, -S(O)(NR)-, or -CR=CR-; and each Cy B1 is an optionally substituted ring independently selected from phenylenyl, 3-7 member saturated or partially unsaturated carbocyclyllenyl or heterocyclyllenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 5-10 member monocyclic or dicyclic arylenyl or heteroarylenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and each Cy B2 is an optionally substituted ring selected independently from phenyl, a 3- to 7-membered saturated or partially unsaturated carbon ring or heterocyclic ring (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and a 5- to 10-membered monocyclic or dicyclic aryl or heteroaryl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); or (iii) ring W and its R w The substituent and; ring Y is a 5–6-membered monocyclic heteroaryl (having 1–4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); z is 2; and each L B is independently a covalent bond or C 1-3 The divalent linear or branched saturated or unsaturated hydrocarbon chain, wherein 1 to 2 methylene units of the chain are independently optionally replaced with -O-, -C(O)-, -C(S)-, -CR2-, -CF2-, -CRF-, -CR(OR)-, -NR-, -S-, -S(O)-, -S(O)2-, -S(O)(NR)-, or -CR=CR-; and each Cy B1 is an optionally substituted ring independently selected from phenylenyl, 3-7 member saturated or partially unsaturated carbocyclyllenyl or heterocyclyllenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and 5-10 member monocyclic or dicyclic arylenyl or heteroarylenyl (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); and each Cy B2 A method in which is an optionally substituted ring selected independently from phenyl, a 3- to 7-membered saturated or partially unsaturated carbon ring or heterocyclic ring (having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and a 5- to 10-membered monocyclic or dicyclic aryl or heteroaryl (having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur). Claim 49 In paragraph 25, the above compound is Table 1A or Table 1B A method comprising a compound selected from, or a pharmaceutically acceptable salt thereof. Claim 50 A method according to any one of paragraphs 25 through 49, wherein the contact occurs in a patient or biological sample.

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