PATENT CLAIM ANALYSIS

Application Number: 15905461
Application Type: Utility
Filing Date: 2018-02
Publication Date: 2018-07
Patent Classification: ["514", "094000"]

Abstract:
Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I″ and I′″ or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduces the excessive activation of complement.

Claim (Index 1):
A compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein\n A is selected from A1, and A2; \n B is selected from B1, B1\u2032, B2, B3, and B4; \n C is selected from C1, C2, and C3; \n L is selected from L1 and L2; \n L3 is selected from L4 and L5; \n at least one of A, B, C, L, or L3 is selected from A2, B3, C3, L2, or L5; \n A1 is selected from: \n A2 is selected from: B1 is selected from a monocyclic or bicyclic carbocyclic; a monocyclic or bicyclic carbocyclic-oxy group; a monocyclic, bicyclic, or tricyclic heterocyclic group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S and from 4 to 7 ring atoms per ring; C 2 -C 6 alkenyl; C 2 -C 6 alkynyl; \u2014(C 0 -C 4 alkyl)(aryl); \u2014(C 0 -C 4 alkyl)(heteroaryl); or \u2014(C 0 -C 4 alkyl)(biphenyl), each of which B1 is unsubstituted or substituted with one or more substituents independently chosen from R 33  and R 34 , and 0 or 1 substituents chosen from R 35  and R 36 ; B1\u2032 is selected from: B2 is selected from: B3 is selected from:\n (i) a monocyclic or bicyclic carbocyclic; a monocyclic or bicyclic carbocyclic-oxy group; a monocyclic, bicyclic, or tricyclic heterocyclic group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S and from 4 to 7 ring atoms per ring; C 2 -C 6 alkenyl; C 2 -C 6 alkynyl; \u2014(C 0 -C 4 alkyl)(aryl); \u2014(C 0 -C 4 alkyl)(heteroaryl); or \u2014(C 0 -C 4 alkyl)(biphenyl); each of which B3 is substituted with one or more of the following: S(O)\u2550NHR 21 , SF 5 , and JC(R 9 )\u2550NR 21 ; \n (ii) a monocyclic, bicyclic, or tricyclic heterocyclic group that has at least one boron or silicon atom in the ring or a monocyclic, bicyclic, or tricyclic heteroaryl group that has at least one boron in the ring; \n (iii) a 6-membered aryl group fused to a 5-membered saturated cyclic group that optionally contains 1 or 2 heteroatoms independently chosen from N and S wherein one of the CH 2  groups of the 5-membered cyclic group is substituted by oxo, excluding dihydrobenzofuran; and \n (iv) (alkyl)-(cycloalkyl), (alkenyl)-(cycloalkyl), or (alkynyl)-(cycloalkyl); \n wherein B3 can be further substituted one or more times with the substituents independently selected from R 35 , R 36  and R 48 ; B4 is selected from the following:\n (i) a 4-membered carbocyclic fused to a 5- or 6-membered heteroaryl having 1, 2, or 3 heteroatoms independently chosen from N, O, and S; \n (ii) a 4-membered carbocyclic fused to a 6-membered aryl ring; \n (iii) a monocyclic or bicyclic carbocyclic; a monocyclic or bicyclic carbocyclic-oxy group; a monocyclic, bicyclic, or tricyclic heterocyclic group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S and from 4 to 7 ring atoms per ring; C 2 -C 6 alkenyl; C 2 -C 6 alkynyl; \u2014(C 0 -C 4 alkyl)(aryl); \u2014(C 0 -C 4 alkyl)(heteroaryl); or \u2014(C 0 -C 4 alkyl)(biphenyl); each of which B3 is substituted one or more times with S(O) 2 OR 21 ; \n (iv) (cycloalkyl)-(aryl), (cycloalkyl)-(heteroaryl), (cycloalkyl)-(heterocycle), (alkyl)-alkenyl, cycloalkyl-alkenyl; \n (v) alkyl, (alkyl)-(alkenyl), alkyl(alkynyl), or cycloalkyl-; \n (vi) (alkyl)-(cycloalkyl), (alkenyl)-(cycloalkyl), (alkynyl)-(cycloalkyl), or (cycloalkyl)-(cycloalkyl); \n wherein B4 can be substituted 1, 2, 3 or 4 times or more with the substituents independently selected from R 33 , R 34 , R 35  R 36  and R 48 ; C1 is C2 is selected from: wherein q is 0, 1, 2 or 3 and r is 1, 2 or 3; C3 is selected from: L1 is a bond or is chosen from the formulas L2 is selected from: L3 is selected from L4 or L5; L4 is \u2014C(O)\u2014; L5 is \u2014C(S)\u2014, \u2014P(O)OH\u2014, \u2014S(O)\u2014, \u2014S(O) 2 \u2014 or \u2014C(R 52 ) 2 \u2014; Q 1  is N(R 1 ) or C(R 1 R 1\u2032 ); Q 2  is C(R 2 R 2\u2032 ), C(R 2 R 2\u2032 )\u2014C(R 2 R 2\u2032 ), S, O, N(R 2 ) or C(R 2 R 2\u2032 )O; Q 3  is N(R 3 ), S, or C(R 3 R 3\u2032 ); X 1  and X 2  are independently N, CH, or CZ, or X 1  and X 2  together are C\u2550C; Z is F, Cl, NH 2 , CH 3 , CH 2 D, CHD 2 , or CD 3 ; X 11  is N or CR 11 ; X 12  is N or CR 12 ; X 13  is N or CR 13 ; X 14  is N or CR 14 , and wherein no more than 2 of X 11 , X 12 , X 13 , and X 14  are N; X 15  is NH, O, or S; X 16  is CR 12 ; X 17  is N or CR 13 ; X 18  is CR 12 ; X 19  is N or CR 13 ; X 20  is NH or O; R and R\u2032 are independently chosen from H, alkyl, cycloalkyl, cycloalkylalkyl, heterocycle, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl; R 1 , R 1\u2032 , R 2 , R 2\u2032 , R 3 , and R 3\u2032  are independently chosen at each occurrence from hydrogen, halogen, hydroxyl, nitro, cyano, amino, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 2 -C 6 alkynyl, C 2 -C 6 alkanoyl, C 1 -C 6 thioalkyl, hydroxyC 1 -C 6 alkyl, aminoC 1 -C 6 alkyl, \u2014C 0 -C 4 alkylNR 9 R 10 , \u2014C(O)OR 9 , \u2014OC(O)R 9 , \u2014NR 9 C(O)R 10 , \u2014C(O)NR 9 R 10 , \u2014OC(O)NR 9 R 10 , \u2014NR 9 C(O)OR 10 , C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy; or R 1  and R 2  are linked to form a 3- to 6-membered carbocyclic or aryl ring; or R 2  and R 3  are linked to form a 3- to 6-membered carbocyclic ring; or R 1  and R 1\u2032 , or R 2  and R 2\u2032 , or R 3  and R 3\u2032  are linked to form a 3- to 6-membered carbocyclic spiro ring; or R 1  and R 1\u2032 , R 2  and R 2\u2032  or R 3  and R 3\u2032  are linked to form a 3- to 6-membered heterocyclic spiro ring; each of which ring is unsubstituted or substituted with 1 or more substituents independently chosen from halogen, hydroxyl, cyano, \u2014COOH, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 2 -C 4 alkanoyl, hydroxyC 1 -C 4 alkyl, (mono- and di-C 1 -C 4 alkylamino)C 0 -C 4 alkyl, \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), \u2014O\u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy; or R 1  and R 1\u2032  or R 2  and R 2\u2032  are linked to form a carbonyl group; or R 1  and R 2  or R 2  and R 3  can be taken together to form a carbon-carbon double bond; R 4 , R 5 , and R 6  are selected from hydrogen, -JCHO, -JC(O)NH 2 , -JC 2 -C 6 alkanoyl, -JC(O)NH(CH 3 ), -J-COOH, -JP(O)(OR 9 ) 2 , -JOC(O)R 9 , -JC(O)OR 9 , -JC(O)N(CH 2 CH 2 R 9 )(R 10 ), -JNR 9 C(O)R 10 , -JSO 2 NH 2 , -JS(O)NH 2 , -JC(CH 2 ) 2 F, -JCH(CF 3 )NH 2 , -JC(O)C 0 -C 2 alkyl(C 3 -C 7 cycloalkyl), -JNR 9 (C 2 -C 6 alkanoyl), -JNR 9 C(O)NR 9 R 10 , -JSO 2 (C 1 -C 6 alkyl), -JSO 2 (C 1 -C 6 haloalkyl), -JSO 2 NR 7 R 7 , -JSO\u2550NH(C 1 -C 6 alkyl), -J-nitro, -J-halogen, -J-hydroxyl, -J-phenyl, a 5- to 6-membered heteroaryl, -J-cyano, -J-cyanoimino, -J-amino, -J-imino, \u2014C 1 -C 6 alkyl, \u2014C 0 -C 4 alkyl(C 3 -C 7 heterocycloalkyl), \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), each of which R 4 , R 5  and R 6  other than hydrogen, nitro, halogen, cyano, cyanoimino, or \u2014CHO, is unsubstituted or substituted with one or more of amino, imino, halogen, hydroxyl, cyano, cyanoimino, C 1 -C 2 alkyl, C 1 -C 2 alkoxy, \u2014C 0 -C 2 alkyl(mono- and di-C 1 -C 4 alkylamino), C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;\n R 7  is hydrogen, C 1 -C 6 alkyl, or \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl); \n R 8  and R 8\u2032  are independently chosen from hydrogen, halogen, hydroxyl, C 1 -C 6 alkyl, \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), C 1 -C 6 alkoxy, and (C 1 -C 4 alkylamino)C 0 -C 2 alkyl; or R 8  and R 8\u2032  are taken together to form an oxo group; or R 8  and R 8\u2032  can be taken together with the carbon that they are bonded to form a 3-membered carbocyclic ring; \n R 9  and R 10  are independently chosen at each occurrence from hydrogen, C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 4 alkyl, \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), and \u2014O\u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl); \n R 11 , R 14 , and R 15  are independently chosen at each occurrence from hydrogen, halogen, hydroxyl, nitro, cyano, \u2014O(PO)(OR 9 ) 2 , \u2014(PO)(OR 9 ) 2 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 2 -C 6 alkenyl(aryl), C 2 -C 6 alkenyl(cycloalkyl), C 2 -C 6 alkenyl(heterocycle), C 2 -C 6 alkenyl(heteroaryl), C 2 -C 6 alkynyl, C 2 -C 6 alkynyl(aryl), C 2 -C 6 alkynyl(cycloalkyl), C 2 -C 6 alkynyl(heterocycle), C 2 -C 6 alkynyl(heteroaryl), C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, C 1 -C 6 thioalkyl, \u2014C 0 -C 4 alkyl(mono- and di-C 1 -C 6 alkylamino), \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), \u2014C 0 -C 4 alkoxy(C 3 -C 7 cycloalkyl), C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy; \n one of R 12  and R 13  is chosen from R 31  and the other of R 12  and R 13  is chosen from R 32  or both R 12  and R 13  are each independently selected from a R 32 ; \n R 16  is absent or selected from halogen, hydroxyl, nitro, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, \u2014C 0 -C 4 alkyl(mono- and di-C 1 -C 6 alkylamino), \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy; \n R 17  is hydrogen, C 1 -C 6 alkyl, or \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl); \n R 18  and R 18\u2032  are independently selected from hydrogen, halogen, hydroxymethyl, and methyl; and m is 0, 1, 2, or 3; \n R 19  is hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkanoyl, \u2014SO 2 C 1 -C 6 alkyl, (mono- and di-C 1 -C 6 alkylamino)C 1 -C 4 alkyl, \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), \u2014C 0 -C 4 alkyl(C 3 -C 7 heterocycloalkyl), \u2014C 0 -C 4 alkyl(aryl), C 0 -C 4 alkyl(heteroaryl), and wherein R 19  other than hydrogen is unsubstituted or substituted with one or more substituents independently chosen from halogen, hydroxyl, amino, \u2014COOH, and \u2014C(O)OC 1 -C 4 alkyl; \n R 21  and R 22  are independently chosen at each occurrence from hydrogen, hydroxyl, cyano, amino, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, (C 3 -C 7 cycloalkyl)C 0 -C 4 alkyl, (phenyl)C 0 -C 4 alkyl, \u2014C 1 -C 4 alkylOC(O)OC 1 -C 6 alkyl, \u2014C 1 -C 4 alkylOC(O)C 1 -C 6 alkyl, \u2014C 1 -C 4 alkylC(O)OC 1 -C 6 alkyl, (4- to 7-membered heterocycloalkyl)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently chosen from N, O, and S, and (5- or 6-membered unsaturated or aromatic heterocycle)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently chosen from N, O, and S; \n R 23  is independently chosen at each occurrence from C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, (aryl)C 0 -C 4 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 4 alkyl, (phenyl)C 0 -C 4 alkyl, (4- to 7-membered heterocycloalkyl)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently chosen from N, O, and S, and (5- or 6-membered unsaturated or aromatic heterocycle)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently chosen from N, O, and S; \n R 24  and R 25  are taken together with the nitrogen to which they are attached to form a 4- to 7-membered monocyclic heterocycloalkyl group, or a 6- to 10-membered bicyclic heterocyclic group having fused, spiro, or bridged rings; \n R 31  is chosen from hydrogen, halogen, hydroxyl, nitro, cyano, amino, \u2014COOH, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 6 alkyl, \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), C 2 -C 6 alkenyl, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyloxy, \u2014C(O)OR 9 , C 1 -C 6 thioalkyl, \u2014C 0 -C 4 alkylNR 9 R 10 , \u2014C(O)NR 9 R 10 , \u2014SO 2 R 9 , \u2014SO 2 NR 9 R 10 , \u2014OC(O)R 9 , and \u2014C(NR 9 )NR 9 R 10 , each of which R 31  other than hydrogen, halogen, hydroxyl, nitro, cyano, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy is unsubstituted or substituted with one or more substituents independently selected from halogen, hydroxyl, nitro, cyano, amino, \u2014COOH, \u2014CONH 2  C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy, and each of which R 31  is also optionally substituted with one substituent chosen from phenyl and 4- to 7-membered heterocycle containing 1, 2, or 3 heteroatoms independently chosen from N, O, and S; which phenyl or 4- to 7-membered heterocycle is unsubstituted or substituted with one or more substituents independently chosen from halogen, hydroxyl, nitro, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, (mono- and di-C 1 -C 6 alkylamino)C 0 -C 4 alkyl, C 1 -C 6 alkylester, \u2014C 0 -C 4 alkyl)(C 3 -C 7 cycloalkyl), C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy; \n R 32  is selected from C(O)NR 21 R 71 , \u2014C(O)NR 24 R 25 , \u2014C(O)NR 9 R 71 , \u2014C(O)NR 21 SO 2 R 22 , NR 9 C(O)OR 10 , \u2014NR 9 C(O)OR 23 , \u2014NR 9 C(O)R 21 , \u2014NR 9 C(O)NR 9 R 10 , \u2014NR 9 C(O)NR 10 R 23  NR 9 C(O)NR 24 R 25 , each of which is optionally substituted with one or more groups independently selected from halogen, hydroxyl, amino, cyano, \u2014CHO, \u2014COOH, \u2014CONH 2 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, \u2014C 1 -C 6 alkoxy, C 2 -C 6 alkanoyl, C 1 -C 6 alkylester, (mono- and di-C 1 -C 6 alkylamino)C 0 -C 2 alkyl, C 1 -C 2 haloalkyl, hydoxyC 1 -C 6 alkyl, ester, carbamate, urea, sulfonamide, \u2014C 1 -C 6 alkyl(heterocyclo), C 1 -C 6 alkyl(heteroaryl), \u2014C 1 -C 6 alkyl(C 3 -C 7 cycloalkyl), O\u2014C 1 -C 6 alkyl(C 3 -C 7 cycloalkyl), B(OH) 2 , phosphate, phosphonate, and C 1 -C 2 haloalkoxy; \n R 71  is chosen at each occurrence from hydroxyl, C 1 -C 6 alkoxy, (C 3 -C 7 cycloalkyl)C 0 -C 4 alkyl, (phenyl)C 0 -C 4 alkyl, \u2014C 1 -C 4 alkylOC(O)OC 1 -C 6 alkyl, \u2014C 1 -C 4 alkylOC(O)C 1 -C 6 alkyl, \u2014C 1 -C 4 alkylC(O)OC 1 -C 6 alkyl, (4- to 7-membered heterocycloalkyl)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently chosen from N, O, and S, and (5- or 6-membered unsaturated or aromatic heterocycle)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently chosen from N, O, and S; \n R 33  is independently chosen from halogen, hydroxyl, \u2014COOH, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, \u2014C 0 -C 4 alkylNR 9 R 10 , \u2014SO 2 R 9 , C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy; \n R 34  is independently chosen from nitro, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 thioalkyl, -JC 3 -C 7 cycloalkyl, \u2014B(OH) 2 , -JC(O)NR 9 R 23 , -JOSO 2 OR 21 , \u2014C(O)(CH 2 ) 1-4 S(O)R 21 , \u2014O(CH 2 ) 1-4 S(O)NR 21 R 22 , -JOP(O)(OR 21 )(OR 22 ), -JP(O)(OR 21 )(OR 22 ), -JOP(O)(OR 21) R 22 , -JP(O)(OR 21 )R 22 , -JOP(O)R 21 R 22 , -JP(O)R 21 R 22 , -JSP(O)(OR 21 )(OR 22 ), -JSP(O)(OR 21 )(R 22 ), -JSP(O)(R 21 )(R 22 ), -JNR 9 P(O)(NHR 21 )(NHR 22 ), -JNR 9 P(O)(OR 21 )(NHR 22 ), -JNR 9 P(O)(OR 21 )(OR 22 ), -JC(S)R 21 , -JNR 21 SO 2 R 22 , -JNR 9 S(O)NR 10 R 22 , -JNR 9 SO 2 NR 10 R 22 , -JSO 2 NR 9 COR 22 , -JSO 2 NR 9 CONR 21 R 22 , -JNR 21 SO 2 R 22 , -JC(O)NR 21 SO 2 R 22 , -JC(NH 2 )\u2550NR 22 , -JCH(NH 2 )NR 9 S(O) 2 R 22 , -JOC(O)NR 21 R 22 , -JNR 21 C(O)OR 22 , -JNR 21 OC(O)R 22 , \u2014(CH 2 ) 1-4 C(O)NR 21 R 22 , -JC(O)R 24 R 25 , -JNR 9 C(O)R 21 , -JC(O)R 21 , -JNR 9 C(O)NR 10 R 22 , \u2014CCR 21 , \u2014(CH 2 ) 1-4 OC(O)R 21 , and -JC(O)OR 23 ; each of which R 34  may be unsubstituted or substituted with one or more substituents independently chosen from halogen, hydroxyl, nitro, cyano, amino, oxo, \u2014B(OH) 2 , \u2014Si(CH 3 ) 3 , \u2014COOH, \u2014CONH 2 , \u2014P(O)(OH) 2 , C 1 -C 6 alkyl, \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), C 1 -C 6 alkoxy, \u2014C 0 -C 2 alkyl(mono- and di-C 1 -C 4 alkylamino), C 1 -C 6 alkylester, C 1 -C 4 alkylamino, C 1 -C 4 hydroxylalkyl, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy; \n R 35  is independently chosen from naphthyl, naphthyloxy, indanyl, (4- to 7-membered heterocycloalkyl)C 0 -C 4 alkyl containing 1 or 2 heteroatoms chosen from N, O, and S, and bicyclic heterocycle containing 1, 2, or 3 heteroatoms independently chosen from N, O, and S, and containing 4- to 7-ring atoms in each ring; each of which R 35  is unsubstituted or substituted with one or more substituents independently chosen from halogen, hydroxyl, nitro, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, (mono- and di-C 1 -C 6 alkylamino)C 0 -C 4 alkyl, C 1 -C 6 alkylester, \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), \u2014SO 2 R 9 , C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy; \n R 36  is independently chosen from tetrazolyl, (phenyl)C 0 -C 2 alkyl, (phenyl)C 1 -C 2 alkoxy, phenoxy, and 5- or 6-membered heteroaryl containing 1, 2, or 3 heteroatoms independently chosen from N, O, B, and S, each of which R 36  is unsubstituted or substituted with one or more substituents independently chosen from halogen, hydroxyl, nitro, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, (mono- and di-C 1 -C 6 alkylamino)C 0 -C 4 alkyl, C 1 -C 6 alkylester, \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), \u2014SO 2 R 9 , \u2014OSi(CH 3 ) 2 C(CH 3 ) 3 , \u2014Si(CH 3 ) 2 C(CH 3 ) 3 , C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy; \n R 44 , R 44\u2032 , R 45 , R 45\u2032  are independently hydrogen, hydroxyl, amino, cyano, halogen, alkyl, cycloalkyl, cycloalkylalkyl, heterocycle, heterocycloalkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl; \n R 48  is independently chosen from hydrogen, halogen, hydroxyl, nitro, cyano, amino, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 thioalkyl, C 1 -C 6 alkoxy, -JC 3 -C 7 cycloalkyl, \u2014B(OH) 2 , -JC(O)NR 9 R 23 , -JOSO 2 OR 21 , \u2014C(O)(CH 2 ) 1-4 S(O)R 21 , \u2014O(CH 2 ) 1-4 S(O)NR 21 R 22 , -JOP(O)(OR 21 )(OR 22 ), -JP(O)(OR 21 )(OR 22 ), -JOP(O)(OR 21 )R 22 , -JP(O)(OR 21 )R 22 , -JOP(O)R 21 R 22 , -JP(O)R 21 R 22 , -JSP(O)(OR 21 )(OR 22 ), -JSP(O)(OR 21 )(R 22 ), -JSP(O)(R 21 )(R 22 ), -JNR 9 P(O)(NHR 21 )(NHR 22 ), -JNR 9 P(O)(OR 21 )(NHR 22 ), -JNR 9 P(O)(OR 21 )(OR 22 ), -JC(S)R 21 , -JNR 21 SO 2 R 22 , -JNR 9 S(O)NR 10 R 22 , -JNR 9 SO 2 NR 10 R 22 , -JSO 2 NR 9 COR 22 , -JSO 2 NR 9 CONR 21 R 22 , -JNR 21 SO 2 R 22 , -JC(O)NR 21 SO 2 R 22 , -JC(NH 2 )\u2550NR 22 , -JCH(NH 2 )NR 9 S(O) 2 R 22 , -JOC(O)NR 21 R 22 , -JNR 21 C(O)OR 22 , -JNR 21 OC(O)R 22 , \u2014(CH 2 ) 1-4 C(O)NR 21 R 22 , -JC(O)R 24 R 25 , -JNR 9 C(O)R 21 , -JC(O)R 21 , -JNR 9 C(O)NR 10 R 22 , \u2014CCR 21 , \u2014(CH 2 ) 1-4 OC(O)R 21 , -JC(O)OR 23 ; SC 1 -C 6 alkyl(O)\u2550NH; each of which R 48  may be unsubstituted or substituted with one or more substituents independently chosen from halogen, hydroxyl, nitro, cyano, amino, oxo, \u2014B(OH) 2 , \u2014Si(CH 3 ) 3 , \u2014COOH, \u2014CONH 2 , \u2014P(O)(OH) 2 , C 1 -C 6 alkyl, \u2014C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), C 1 -C 6 alkoxy, \u2014C 0 -C 4 alkyl(mono- and di-C 1 -C 4 alkylNR 9 R 10 ), C 1 -C 6 alkylester, C 1 -C 4 alkylamino, C 1 -C 4 hydroxylalkyl, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, \u2014OC(O)R 9 , \u2014NR 9 C(O)R 10 , \u2014C(O)NR 9 R 10 , \u2014OC(O)NR 9 R 10 , \u2014NR 9 C(O)OR 10 , C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy; \n R 51  is CH 3 , CH 2 F, CHF 2  or CF 3 ; \n R 52  is independently selected from halo, hydrogen, or C 1 -C 6 alkyl; and \n J is independently chosen at each occurrence from a covalent bond, C 1 -C 4 alkylene, \u2014OC 1 -C 4 alkylene, C 2 -C 4 alkenylene, and C 2 -C 4 alkynylene.

Metadata:
- Claim Count in Document: 19.0
- Percentile: 88.0
- Lexical Diversity: 1.58974
- Patent Class: 514.0
- Transitional Phrase Type: none
- Component Type: 0
- Foreign Priority: False
- Related Applications: ['15905524', '15247440', '15247429', '15905427', '15247424']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7933630175019275
- 35 USC 102 Novelty (BERT): 0.5666141435387753
- Combined Prediction Score: 0.7706881301056123
- Mean Citation Score: 414.3301540000001
- Max Citation Score: 443.95505
- Similarity Product: 354.61985872390267

Labels:
- Claim Label 101: 1
- Claim Label 102: 1
- Claim Label 103: 1
- Claim Label 112: 0
- Combined Label: 1
- Label 101 Adjusted: 1

Dataset: test