PATENT CLAIM ANALYSIS

Application Number: 16173914
Application Type: Utility
Filing Date: 2018-10
Publication Date: 2019-05
Patent Classification: ["514", "507000"]

Abstract:
Compounds are provided to modulate the C5a receptor. The compounds have the following Formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R 1 , R 2  and R 3  are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Claim (Index 1):
A compound of Formula (I) or a pharmaceutically acceptable salt thereof, or a prodrug or bioisostere thereof, wherein: each of R 1a , R 1b , R 1c  and R 1d  is independently selected from the group consisting of H, halogen, CF 3 , CN, C 1-4  alkyl and \u2014O\u2014C 1-4  alkyl, wherein the C 1-4  alkyl and \u2014O\u2014C 1-4  alkyl are optionally further substituted with halogen, hydroxyl, methoxy or ethoxy; L is a linking group selected from the group consisting of: wherein each of the subscripts q is independently 1, 2, 3 or 4, and L is optionally further substituted with one or two members selected from the group consisting of halogen, hydroxy, C 1-3  alkyl, \u2014O\u2014C 1-3  alkyl, C 1-3  hydroxyalkyl, C 1-3  haloalkyl and \u2014CO 2 H; Z is selected from the group consisting of azetidinyl, pyrollidinyl, piperidinyl, piperazinyl, morpholinyl, pyridyl, pyrimidinyl, imidazolyl, guanidinyl, quinuclidine, 2-azaspiro[3.3]heptane and 8-azabicyclo[3.2.1]octane, each of which is optionally substituted with from 1 to 4 groups independently selected from halogen, CN, hydroxy, oxo, C 1-4  alkyl, \u2014NH 2 , \u2014NHC 1-3 alkyl, \u2014N(C 1-3 alkyl) 2 , \u2014O\u2014C 1-3  alkyl, C 1-3  hydroxyalkyl, C 1-3  haloalkyl, \u2014OC(O)(C 1-4  alkyl), \u2014CO 2 (C 1-4  alkyl) and \u2014CO 2 H; or Z is selected from the group consisting of \u2014CO 2 R a  and \u2014NR a R b ; wherein R a  is selected from the group consisting of H, C 1-8  alkyl, C 1-8  haloalkyl and C 1-8  hydroxyalkyl; and R b  is selected from H, \u2014C 1-8  alkyl, C 1-8  haloalkyl, C 1-8  alkyl-COOH, C 1-8  alkyl-OH, C 1-8  alkyl-CONH 2 , C 1-8  alkyl-SO 2 NH 2 , C 1-8  alkyl-PO 3 H 2 , C 1-8  alkyl-C(O)NHOH, \u2014C(O)\u2014C 1-8 alkyl-OH, \u2014C(O)\u2014C 1-8 alkyl-COOH, C 3-10  cycloalkyl, \u2014C 3-10  cycloalkyl-COOH, \u2014C 3-10  cycloalkyl-OH, C 4-8  heterocyclyl, \u2014C 4-8  heterocyclyl-COOH, \u2014C 4-8  heterocyclyl-OH, \u2014C 1-8  alkyl-C 4-8  heterocyclyl, \u2014C 1-8  alkyl-C 3-10  cycloalkyl, C 3-10  heteroaryl and \u2014C 1-8 alkyl-C 5-10  heteroaryl; each R 2a , R 2b  and R 2  is independently selected from the group consisting of H, halogen, \u2014CN, \u2014R d , \u2014CO 2 R e , \u2014CONR e R f , \u2014OC(O)NR e R f , \u2014NR f C(O)R e , \u2014NR f C(O) 2 R d , \u2014NR e \u2014C(O)NR e R f , \u2014NR e R f , \u2014OR e , \u2014X 2 \u2014OR c , \u2014X 2 \u2014NR e R f , \u2014X 2 \u2014CO 2 R e , \u2014SF 5 , and \u2014S(O) 2 NR e R f , wherein each X 2  is a C 1-4  alkylene; each R e  and R f  is independently selected from hydrogen, C 1-8  alkyl, and C 1-8  haloalkyl, or when attached to the same nitrogen atom can be combined with the nitrogen atom to form a five or six-membered ring having from 0 to 2 additional heteroatoms as ring members selected from N, O and S, and optionally substituted with oxo; each R d  is independently selected from the group consisting of C 1-8  alkyl, C 2-8  alkenyl, and C 1-8  haloalkyl; R 3  is selected from the group consisting of \u2014NR g R h  and C 4-12  heterocyclyl, wherein the C 4-12  heterocyclyl is optionally substituted with 1 to 6 R 3a ; each R 3a  is independently selected from the group consisting of halogen, \u2014CN, oxo, \u2014R i , \u2014CO 2 R j , \u2014CONR j R k , \u2014CONHC 1-6  alkyl-OH, \u2014C(O)R j , \u2014OC(O)NR j R k , \u2014NR j C(O)R k , \u2014NRC(O) 2 R k , \u2014CONHOH, \u2014PO 3 H 2 , \u2014NR j \u2014X 3 \u2014C(O) 2 R k , \u2014NR j C(O)NR j R k , \u2014NR j R k , \u2014OR j , \u2014S(O) 2 NR j R k , \u2014O\u2014X 3 \u2014OR j , \u2014O\u2014X 3 \u2014NR j R k , \u2014O\u2014X 3 \u2014CO 2 R j , \u2014O\u2014X 3 \u2014CONR j R k , \u2014X 3 \u2014OR j , \u2014X 3 \u2014NR j R k , \u2014X 3 \u2014CO 2 R j , \u2014X 3 \u2014CONR j R k , \u2014X 3 \u2014CONHSO 2 R j  and SF 5 ; wherein X 3  is C 1-6  alkylene and is optionally further substituted with OH, SO 2 NH 2 , CONH 2 , C(O)NHOH, PO 3 H 2 , COO\u2014C 1-8 alkyl or CO 2 H, wherein each R j  and R k  is independently selected from hydrogen, C 1-8  alkyl optionally substituted with 1 to 2 substituents selected from OH, SO 2 NH 2 , CONH 2 , C(O)NHOH, PO 3 H 2 , COO\u2014C 1-8 alkyl or CO 2 H, and C 1-8  haloalkyl optionally substituted with 1 to 2 substituents selected from OH, SO 2 NH 2 , CONH 2 , C(O)NHOH, PO 3 H 2 , COO\u2014C 1-8 alkyl or CO 2 H, or when attached to the same nitrogen atom R j  and R k  can be combined with the nitrogen atom to form a five or six-membered ring having from 0 to 2 additional heteroatoms as ring members selected from N, O or S, and optionally substituted with oxo; each R 1  is independently selected from the group consisting of \u2014OH, C 1-8  alkyl, C 2-8  alkenyl, and C 1-8  haloalkyl each of which may be optionally substituted with OH, SO 2 NH 2 , CONH 2 , C(O)NHOH, PO 3 H 2 , COO\u2014C 1-8 alkyl or CO 2 H; R g  is selected from the group consisting of H, C 1-8  haloalkyl and C 1-8  alkyl; R h  is selected from \u2014C 1-8  alkyl, C 1-8  haloalkyl, C 1-8  hydroxyalkyl, C 1-8 alkyl-CO 2 R j , C 1-8 alkyl-CONR j R k , and C 1-8 alkyl-CONHSO 2 R j , C 1-8  alkyl-SO 2 NR j R k , C 1-8  alkyl-SO 3 R j , C 1-8  alkyl-B(OH) 2 , C 1-8  alkyl-PO 3 H 2 , C 1-8  alkyl-C(O)NHOH, C 1-8  alkyl-NR h1 R h2 , \u2014C(O)R j , C 3-10  cycloalkyl, \u2014C 3-10  cycloalkyl-COOR j , \u2014C 3-10  cycloalkyl-OR j , C 4-8  heterocyclyl, \u2014C 4-8  heterocyclyl-COOR j , \u2014C 4-8  heterocyclyl-OR j , \u2014C 1-8  alkyl-C 4-8  heterocyclyl, \u2014C(\u2550O)OC 1-8  alkyl-C 4-8  heterocyclyl, \u2014C 1-8  alkyl-C 3-10  cycloalkyl, C 5-10  heteroaryl, \u2014C 1-8 alkyl-C 5-10  heteroaryl, \u2014C 1-8  alkyl-C 6-10  aryl, \u2014C 1-8  alkyl-(C\u2550O)\u2014C 6-10  aryl, \u2014CO 2 \u2014C 1-8  alkyl-O 2 C\u2014C 1-8  alkyl, \u2014C 1-8  alkyl-NH(C\u2550O)\u2014C 2-8  alkenyl, \u2014C 1-8  alkyl-NH(C\u2550O)\u2014C 1-8  alkyl, \u2014C 1-8  alkyl-NH(C\u2550O)\u2014C 2-8  alkynyl, \u2014C 1-8  alkyl-(C\u2550O)\u2014NH\u2014C 1-8  alkyl-COOR j , and \u2014C 1-8  alkyl-(C\u2550O)\u2014NH\u2014C 1-8  alkyl-OR optionally substituted with CO 2 H; or\n R h  combined with the N to which it is attached is a mono-, di- or tri-peptide comprising 1-3 natural amino acids and 0-2 non-natural amino acids, wherein \n the non-natural aminoacids have an alpha carbon substituent selected from the group consisting of C 2-4  hydroxyalkyl, C 1-3  alkyl-guanidinyl, and C 1-4  alkyl-heteroaryl, \n the alpha carbon of each natural or non-natural amino acids are optionally further substituted with a methyl group, and \n the terminal moiety of the mono-, di-, or tri-peptide is selected from the group consisting of C(O)OH, C(O)O\u2014C 1-6  alkyl, and PO 3 H 2 , wherein \n R h1  and R h2  are each independently selected from the group consisting of H, C 1-6  alkyl, and C 1-4  hydroxyalkyl; \n the C 1-8  alkyl portions of R h  are optionally further substituted with from 1 to 3 substituents independently selected from OH, COOH, SO 2 NH 2 , CONH 2 , C(O)NHOH, COO\u2014C 1-8  alkyl, PO 3 H 2  and C 5-6  heteroaryl optionally substituted with 1 to 2 C 1-3  alkyl substituents, \n the C 5-10  heteroaryl and the C 6-10  aryl portions of R h  are optionally substituted with 1 to 3 substituents independently selected from OH, B(OH) 2 , COOH, SO 2 NH 2 , CONH 2 , C(O)NHOH, PO 3 H 2 , COO\u2014C 1-8 alkyl, C 1-4 alkyl, C 1-4 alkyl-OH, C 1-4 alkyl-SO 2 NH 2 , C 1-4 alkyl CONH 2 , C 1-4 alkyl-C(O)NHOH, C 1-4 alkyl-PO 3 H 2 , C 1-4 alkyl-COOH, and phenyl and the C 4-8  heterocyclyl and C 3-10  cycloalkyl portions of R h  are optionally substituted with 1 to 4 R w  substituents; \n each R w  substituent is independently selected from C 1-4  alkyl, C 1-4  alkyl-OH, C 1-4  alkyl-COOH, C 1-4  alkyl-SO 2 NH 2 , C 1-4  alkyl CONH 2 , C 1-4  alkyl-C(O)NHOH, C 1-4  alkyl-PO 3 H, OH, COO\u2014C 1-8  alkyl, COOH, SO 2 NH 2 , CONH 2 , C(O)NHOH, PO 3 H 2  and oxo; R 4  is selected from the group consisting of O\u2014C 1-8  alkyl, O\u2014C 1-8  haloalkyl, C 6-10  aryl, C 5-10  heteroaryl, \u2014O\u2014C 1-4  alkyl-C 4-7  heterocycloalkyl, \u2014O\u2014C 1-4  alkyl-C 6-10  aryl and \u2014O\u2014C 1-4  alkyl-C 5-10  heteroaryl, each of which is optionally substituted with 1 to 5 R 4a ; each R 4a  is independently selected from the group consisting of halogen, \u2014CN, \u2014R m , \u2014CO 2 R n , \u2014CONR n R p , \u2014C(O)R n , \u2014OC(O)NR n R p , \u2014NR n C(O)R p , \u2014NR n C(O) 2 R m , \u2014NR n \u2014C(O)NR n R p , \u2014NR n R p , \u2014OR n , \u2014O\u2014X 4 \u2014OR n , \u2014O\u2014X 4 \u2014NR n R p , \u2014O\u2014X 4 \u2014CO 2 R n , \u2014O\u2014X 4 \u2014CONR n R p , \u2014X 4 \u2014OR n , \u2014X 4 \u2014NR n R p , \u2014X 4 \u2014CO 2 R n , \u2014X 4 \u2014CONR n R p , \u2014SF 5 , \u2014S(O) 2 R n R p , \u2014S(O) 2 NR n R p , C 3-7  cycloalkyl and C 4-7  heterocycloalkyl, wherein the cycloalkyl and heterocycloalkyl rings are optionally substituted with 1 to 5 R t , wherein each R 1  is independently selected from the group consisting of C 1-8  alkyl, C 1-8 haloalkyl, \u2014CO 2 R n , \u2014CONR n R p , \u2014C(O)R n , \u2014OC(O)NR n R p , \u2014NR n C(O)R p , \u2014NR n C(O) 2 R m , \u2014NR n \u2014C(O)NR n R p , \u2014NR n R P , \u2014OR n , \u2014O\u2014X 4 \u2014OR n , \u2014O\u2014X 4 \u2014NR n R p , \u2014O\u2014X 4 \u2014CO 2 R o , \u2014O\u2014X 4 \u2014CONR n R p , \u2014X 4 \u2014OR o , \u2014X 4 \u2014NR n R p , \u2014X 4 \u2014CO 2 R n , \u2014X 4 \u2014CONR n R p , \u2014SF 5 , and \u2014S(O) 2 NR n R p ; wherein each X 4  is a C 1-6  alkylene; each R n  and R P  is independently selected from hydrogen, C 1-8  alkyl, and C 1-8  haloalkyl, or when attached to the same nitrogen atom can be combined with the nitrogen atom to form a five or six-membered ring having from 0 to 2 additional heteroatoms as ring members selected from N, O or S, and optionally substituted with oxo; each R m  is independently selected from the group consisting of C 1-8  alkyl, C 2-8  alkenyl, and C 1-8  haloalkyl; and optionally when two R 4a  substituents are on adjacent atoms, they are combined to form a fused five or six-membered carbocyclic or heterocyclic ring optionally substituted with oxo; n is 0, 1, 2 or 3; each R 5  is independently selected from the group consisting of halogen, \u2014CN, \u2014R 4 , \u2014CO 2 R r , \u2014CONR r R s , \u2014C(O)R r , \u2014OC(O)NR r R s , \u2014NR r C(O)R s , \u2014NR r C(O) 2 R q , \u2014NR r \u2014C(O)NR r R s , \u2014NR r R s , \u2014OR r , \u2014O\u2014X 5 \u2014OR r , \u2014O\u2014X 5 \u2014NR r R s , \u2014O\u2014X 5 \u2014CO 2 R r , \u2014O\u2014X 5 \u2014CONR r R s , \u2014X 5 \u2014OR r , \u2014X 5 \u2014NR r R s , \u2014X 5 \u2014CO 2 R r , \u2014X 5 \u2014CONR r R s , \u2014SF 5 , \u2014S(O) 2 NR r R s , wherein each X 5  is a C 1-4  alkylene; each R r  and R s  is independently selected from hydrogen, C 1-8  alkyl, and C 1-8  haloalkyl, or when attached to the same nitrogen atom can be combined with the nitrogen atom to form a five or six-membered ring having from 0 to 2 additional heteroatoms as ring members selected from N, O or S, and optionally substituted with oxo; each R 4  is independently selected from the group consisting of C 1-8  alkyl, and C 1-8  haloalkyl; R 6  is selected from the group consisting of H, C 1-4  alkyl and C 1-4  haloalkyl; m is 0, 1, 2, 3 or 4; each R 6b  is independently selected from the group consisting of F, C 1-4  alkyl, O\u2014R u , C 1-4  haloalkyl, NR u R v , wherein each R u  and R v  is independently selected from hydrogen, C 1-8  alkyl, and C 1-8  haloalkyl, or when attached to the same nitrogen atom can be combined with the nitrogen atom to form a five or six-membered ring having from 0 to 2 additional heteroatoms as ring members selected from N, O or S, and optionally substituted with oxo.

Metadata:
- Claim Count in Document: 47.0
- Percentile: 97.0
- Lexical Diversity: 1.3617
- Patent Class: 514.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['13806339', '12643229', '16030729', '15991703', '15991747']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8007160437442804
- 35 USC 102 Novelty (BERT): 0.5476705829271737
- Combined Prediction Score: 0.7754114976625697
- Mean Citation Score: 366.085984
- Max Citation Score: 395.54996
- Similarity Product: 322.1512190514445

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

Dataset: test