SUBSTITUTED 2-BENZYLIDENE-2H-BENZO[b][1,4]THIAZIN-3(4H)-ONES, DERIVATIVES THEREOF, AND THERAPEUTIC USES THEREOFThe present invention relates to compounds according to Formula I and salts thereof, wherein R1, R2, R3, R4, Ar, and n are as defined herein. Methods for preparing compounds of Formula I are also provided. The present invention further includes methods of treating cellular proliferative disorders, such as cancer, with the compounds of Formula I.A compound of Formula I or a salt thereof:Formula Iwhereinn is 0, 1 , or 2;R1 is selected from the group consisting of -H, -(Ci-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aryl-(Ci-C6)alkyl, optionally substituted heteroaryl-(C]-C6)alkyl, -C(=0)(Ci- C6)alkyl, -C(=0)(C2-C6)alkenyl, -C(=0)-optionally substituted aryl,-C(=0)(CH2)m-optionally substituted aryl, and -C(=0)(CH2)p-optionally substituted heteroaryl;R2, R3, and R4 are independently selected from the group consisting of -H, halogen,-CN, -NR10Rn , -OH, -OR13, -(CrC6)alkoxy, -N02, -(C,-C6)alkyl, -(Ci-C6)perfluoroalkyl, -(C,-C6)perfluoroalkoxy, -C(=0)R15, -C(=0)OR15, -OC(=0)R12, -OC(=0)OR12,-C(=0)NR, 7R18, -SH, -S(C,-C6)alkyl, -SR13, -S(=0)R13, -S(=0)2R13, -OS(=0)2R13, -S(=0)qR15, -OS(=0)qR15, -S(=0)2NR17R18, -S(=0)NR17R18, optionally substituted aryl, optionally substituted aryl-(Ci-C6)alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-(Ci-C6)alkyl, optionally substituted (C2-C9)heterocyclyl, optionally substituted (C2-C9)heterocyclyl-(Ci-C6)alkyl, -NH(CH2)mC(=0)OR14, -C(=NR14)NR142, -C(=N-OR14)NR142, -P(=0)(OR14)2, and -OP(=0)(OR14)2; Ar is optionally substituted heteroaryl, optionally substituted (Ci0-Ci4)aryl, or whereinR5, R6, R7, R8, and R9 are independently selected from the group consisting of -H, -OH, -OR13, -NO2, halogen, -CN, -NR10Rn, -(CH2)mNR10Rn, -O(CH2)mNR10Rn, -(Cr C6)alkyl, -(CH2)mO(C,-C6)alkyl, -(C,-C6)alkoxy, -(d-C^perfluoroalkyl, -(CrC6)perfluoroalkoxy, -SH, -S(C,-C6)alkyl, -SR13, -S(=0)R15, -S(=0)2R15, -C(=0)R15, -C(=0)OR15, -C(=0)NR17R18, -OC(=0)R16, -0C(O)0R12, -OC(=0)NR17R18,heterocyclyl, optionally substituted heteroaryl, -NH(CH2)mC(=0)0R14, -0S(=0)2R16, - C(=NR,4)NR, 42, -C(=N-OR,4)NR142, -P(=0)(OR14)2, and -OP(=0)(OR14)2;each R10 and R1 1 is independently selected from the group consisting of-H, -(C,-C6)alkyl, -(Ci-C6)alkoxy, -C(=0)R12, -C(=0)NR17R18, -C(=0)OR12, -C(=0)OR12, -C(=NR, )NR17R18, R13, optionally substituted aryl, optionally substituted heteroaryl, and -C(=NR14)R15; or R10 and Ru, together with the nitrogen to which they are bound, form an optionally substituted (C2-C5)heterocycle;each R12 is independently selected from the group consisting of -(Ci-C6)alkyl, and optionally substituted aryl;each R13 is independently selected from the group consisting of optionally substituted aryl and -(CH2)mR16;each R14 is independently selected from the group consisting of-H and -(d- C6)alkyl; or two occurrences of R14 bound to the same nitrogen form a (C2-C6)heterocycle, together with the nitrogen atom to which they are bound;each R15 is independently selected from the group consisting of-H, -(Cj-C6)alkyl, optionally substituted aryl, and NR 14 each R16 is independently selected from the group consisting of -(Ci-C6)alkyl, -NRI 42, and Ar' ;each R17 and R18 is independently selected from the group consisting of-H, -(Ci-C6)alkyl, -(Ci-C6)alkoxy, R13, optionally substituted aryl, and optionally substituted heteroaryl; or R17 and R18, together with the nitrogen to which they are bound, form an optionally substituted (C2-C5)heterocycle;m is independently at each occurrence 1, 2, 3, 4, or 5;p is independently at each occurrence 0, 1 , 2, or 3;q is independently at each occurrence 0, 1, or 2;each optionally substituted aryl, optionally substituted (Cio-Ci4)aryl, optionally substituted heteroaryl, optionally substituted aryl-(C]-C6)alkyl, optionally substituted heteroaryl-(Ci -C6)alkyl, optionally substituted (C2-C ))heterocyclyl, optionally substituted (C2-Cg)heterocyclyl-(Ci-C6)alkyl, and optionally substituted (C2-C5)heterocycle is optionally substituted with one or more substituents independently selected from the group consisting of halogen, -CN, -NR142, -(CH2)mNR,42, -0(CH2)mNR142, C6)alkyl, -NR,4C(=0)0(C,-C6)alkyl, -NR14C(=0)NR142, -NR14C(=NR14)NR142,-NH(CH2)mC(=0)OR14, -OH, -N02, -(Q-C^alkyl, -(CH2)mO(Ci-C6)alkyl, -(C]-C6)alkoxy, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -SR14, -S(=0)R15, -S(=0)2R15, -NR14S(=0)2R15, -(C C6)perfluoroalkyl, -(C]-C6)perfluoroalkoxy, -C(=0)R14, -C(=0)OR14, -C(=0)NR142, -OC(=0)R14, -OC(=0)NR142, -OC(=0)0(CrC6)alkyl, -P(=0)(OR14)2, -OP(=0)(OR14)2, heterocyclyl, and heteroaryl;Ar1 is a radical according to Formula II:Formula II wherein R19, R20, R21, R22, and R23 are independently selected from the group consisting of -H, -OH, -N02, halogen, -CN, -NR10Rn, -(CH2)mNR10Rn,-O(CH2)mNR10R', -(C,-C6)alkyl, -(CH2)mO(Ci-C6)alkyl, -(d-C6)alkoxy, -(C- C6)perfluoroalkyl, -(C,-C6)perfluoroalkoxy, -SH, -SR12, -S(=0)R15, -S(=0)2R15,-C(=0)R15, -C(=0)OR15, -C(=0)NR17R18, -OC(=0)R16, -OC(=0)OR12, -OC(=0)NR17R18, heterocyclyl, optionally substituted heteroaryl, -NH(CH2)mC(=0)OR14, -OS(=0)2R16, - C(=NRI4)NRI42, -C(=N-ORI4)NRI 42, -P(=0)(ORI4)2, and -OP(=0)(OR14)2;provided that:i) at least one of R2, R3, or R4 is other than hydrogen;ii) when none of R2, R3, and R4 are -OR13, -NHR13, -SR13, -S(=0)R13, or - S(=0)2R13, and...
치환된 2-벤질리덴-2H-벤조[b][1,4]티아진-3(4H)-온, 이의 유도체, 및 이의 치료적 용도본 발명은 화학식 I의 화합물 및 이의 염에 관한 것이며, 여기서, R1, R2, R3, R4, Ar 및 n은 본원에서 정의된 바와 같다. 화학식 I의 화합물의 제조 방법이 또한 제공된다. 나아가, 본 발명은 세포 증식성 질환, 예컨대 암을 화학식 I의 화합물로 치료하는 방법을 포함한다.  I화학식 I의 화합물, 또는 이의 염.(식에서,n은 0, 1, 또는 2이며;R1은 -H, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, 임의로 치환된 아릴, 임의로 치환된 헤테로아릴, 임의로 치환된 아릴-(C1-C6)알킬, 임의로 치환된 헤테로아릴-(C1-C6)알킬, -C(=O)(C1-C6)알킬, -C(=O)(C2-C6)알케닐, -C(=O)-임의로 치환된 아릴, -C(=O)(CH2)m-임의로 치환된 아릴, 및 -C(=O)(CH2)p-임의로 치환된 헤테로아릴로 구성되는 그룹으로부터 선택되며;R2, R3, 및 R4는 -H, 할로겐, -CN, -NR10R11, -OH, -OR13, -(C1-C6)알콕시, -NO2, -(C1-C6)알킬, -(C1-C6)퍼플루오로알킬, -(C1-C6)퍼플루오로알콕시, -C(=O)R15, -C(=O)OR15, -OC(=O)R12, -OC(=O)OR12, -C(=O)NR17R18, -SH, -S(C1-C6)알킬, -SR13, -S(=O)R13, -S(=O)2R13, -OS(=O)2R13, -S(=O)qR15, -OS(=O)qR15, -S(=O)2NR17R18, -S(=O)NR17R18, 임의로 치환된 아릴, 임의로 치환된 아릴-(C1-C6)알킬, 임의로 치환된 헤테로아릴, 임의로 치환된 헤테로아릴-(C1-C6)알킬, 임의로 치환된 (C2-C9)헤테로사이클릴, 임의로 치환된 (C2-C9)헤테로사이클릴-(C1-C6)알킬, -NH(CH2)mC(=O)OR14, -C(=NR14)NR142, -C(=N-OR14)NR142, -P(=O)(OR14)2, 및 -OP(=O)(OR14)2로 구성되는 그룹으로부터 독립적으로 선택되며;Ar은 임의로 치환된 헤테로아릴, 임의로 치환된 (C10-C14)아릴, 또는 이며;식에서,R5, R6, R7, R8, 및 R9는 -H, -OH, -OR13, -NO2, 할로겐, -CN, -NR10R11, -(CH2)mNR10R11, -O(CH2)mNR10R11, -(C1-C6)알킬, -(CH2)mO(C1-C6)알킬, -(C1-C6)알콕시, -(C1-C6)퍼플루오로알킬, -(C1-C6)퍼플루오로알콕시, -SH, -S(C1-C6)알킬, -SR13, -S(=O)R15, -S(=O)2R15, -C(=O)R15, -C(=O)OR15, -C(=O)NR17R18, -OC(=O)R16, -OC(=O)OR12, -OC(=O)NR17R18, 헤테로사이클릴(heterocyclyl), 임의로 치환된 헤테로아릴, -NH(CH2)mC(=O)OR14, -OS(=O)2R16, -C(=NR14)NR142, -C(=N-OR14)NR142, -P(=O)(OR14)2, 및 -OP(=O)(OR14)2로 구성되는 그룹으로부터 독립적으로 선택되며;R10 및 R11각각은 -H, -(C1-C6)알킬, -(C1-C6)알콕시, -C(=O)R12, -C(=O)NR17R18, -C(=O)OR12, -C(=O)OR12, -C(=NR14)NR17R18, R13, 임의로 치환된 아릴, 임의로 치환된 헤테로아릴, 및 -C(=NR14)R15로 구성되는 그룹으로부터 독립적으로 선택되거나; 또는 R10과 R11은 이들이 결합된 질소와 함께 임의로 치환된 (C2-C5)헤테로고리를 형성하며;각각의 R12는 -(C1-C6)알킬, 및 임의로 치환된 아릴로 구성되는 그룹으로부터 독립적으로 선택되며; 각각의 R13은 임의로 치환된 아릴 및 -(CH2)mR16으로 구성되는 그룹으로부터 독립적으로 선택되며; 각각의 R14는 -H 및 -(C1-C6)알킬로 구성되는 그룹으로부터 독립적으로 선택되거나; 또는 동일한 질소에 결합된 두 개의 R14는 이들이 결합된 질소 원자와 함께 (C2-C6)헤테로고리를 형성하며;각각의 R15는 -H, -(C1-C6)알킬, 임의로 치환된 아릴, 및 NR142로 구성되는 그룹으로부터 독립적으로 선택되며;각각의 R16은 -(C1-C6)알킬, -NR142, 및 Ar1로 구성되는 그룹으로부터 독립적으로 선택되며; R17 및 R18각각은 -H, -(C1-C6)알킬, -(C1-C6)알콕시, R13, 임의로 치환된 아릴, 및 임의로 치환된 헤테로아릴로 구성되는 그룹으로부터 독립적으로 선택되거나; 또는 R17 및 R18은 이들이 결합된 질소와 함께 임의로 치환된 (C2-C5)헤테로고리를 형성하며;m은 각각의 경우에 독립적으로 1, 2, 3, 4, 또는 5이며;p는 각각의 경우에 독립적으로 0, 1, 2, 또는 3이며;q는 각각의 경우에 독립적으로 0, 1, 또는 2이며; 각각 임의로 치환된 아릴, 임의로 치환된 (C10-C14)아릴, 임의로 치환된 헤테로아릴, 임의로 치환된 아릴-(C1-C6)알킬, 임의로 치환된 헤테로아릴-(C1-C6)알킬, 임의로 치환된 (C2-C9)헤테로사이클릴, 임의로 치환된 (C2-C9)헤테로사이클릴-(C1-C6)알킬, 및 임의로 치환된 (C2-C5)헤테로고리는 할로겐, -CN, -NR142, -(CH2)mNR142, -O(CH2)mNR142, -NR14C(=O)(C1-C6)알킬, -NR14C(=O)O(C1-C6)알킬, -NR14C(=O)NR142, -NR14C(=NR14)NR142, -NH(CH2)mC(=O)OR14, -OH, -NO2, -(C1-C6)알킬, -(CH2)mO(C1-C6)알킬, -(C1-C6)알콕시, -(C2-C6)알케닐, -(C2-C6)알키닐, -SR14, -S(=O)R15, -S(=O)2R15, -NR14S(=O)2R15, -(C1-C6)퍼플루오로알킬, -(C1-C6)퍼플루오로알콕시, -C(=O)R14, -C(=O)OR14, -C(=O)NR142, -OC(=O)R14, -OC(=O)NR142, -OC(=O)O(C1-C6)알킬, -P(=O)(OR14)2, -OP(=O)(OR14)2, 헤테로사이클릴, 및 헤테로아릴로 구성되는 그룹으로부터 독립적으로 선택된 하나 이상의 치환체로 임의로 치환되며; Ar1은 화학식 II의 라디칼이며:식에서, R19, R20, R21, R22, 및 R23은 -H, -OH, -NO2, 할로겐, -CN, -NR10R11, -(CH2)mNR10R11, -O(CH2)mNR10R11, -(C1-C6)알킬, -(CH2)mO(C1-C6)알킬, -(C1-C6)알콕시, -(C1-C6)퍼플루오로알킬, -(C1-C6)퍼플루오로알콕시, -SH, -SR12, -S(=O)R15, -S(=O)2R15, -C(=O)R15, -C(=O)OR15, -C(=O)NR17R18, -OC(=O)R16, -OC(=O)OR12, -OC(=O)NR17R18, 헤테로사이클릴, 임의로 치환된 헤테로아릴, -NH(CH2)mC(=O)OR14, -OS(=O)2R16, -C(=NR14)NR142, -C(=N-OR14)NR142, -P(=O)(OR14)2, 및 -OP(=O)(OR14)2로 구성되는 그룹으로부터 독립적으로 선택되며;다만, i) R2, R3, 또는 R4중 적어도 하나는 수소 이외의 것이며;ii) R2, R3, 및 R4중 어느 것도 -OR13, -NHR13, -SR13, -S(=O)R13, 또는 -S(=O)2R13이 아니고 Ar은 인 경우에, R6 및 R8 중 적어도 하나는 -NO2이며, 적어도 R7은 수소 또는 할로겐 이외의 것이며; 그리고iii) Ar이 임의로 치환된 헤테로아릴이고 R2, R3, 또는 R4 중 어느 것도 -OR13, -NHR13, -SR13, -S(=O)R13, 또는 -S(=O)2R13이 아닌 경우에, R1은 수소 이외의 것이다)