PATENT CLAIM ANALYSIS

Application Number: 16027988
Application Type: Utility
Filing Date: 2018-07
Publication Date: 2019-01
Patent Classification: ["514", "315000"]

Abstract:
To provide a pharmaceutical, in particular a compound which can be used as a therapeutic agent for irritable bowel syndrome (IBS). It was found that a tetrahydroisoquinolin-1-one derivative having an amide group at the 4-position or a pharmaceutically acceptable salt thereof has an excellent bombesin 2 (BB2) receptor antagonistic action. It is also found that the tetrahydroisoquinolin-1-one derivative is highly effective on bowel movement disorders. From the above, the tetrahydroisoquinolin-1-one derivative of the present invention is useful as a therapeutic agent for diseases associated with a BB2 receptor, in particular IBS.

Claim (Index 8):
A pharmaceutical composition comprising a compound of formula (I) a pharmaceutically acceptable salt, solvate, or hydrate thereof and a pharmaceutically acceptable excipient, wherein formula (I) is represented by: in which groups R 1 -R 5  and m are as follows R 1 : lower alkylene-OH, lower alkylene-N(R 0 )(R 6 ), lower alkylene-CO 2 R 0 , cycloalkyl, cycloalkenyl, aryl, heterocyclic group, -(lower alkylene substituted with \u2014OR 0 )-aryl or lower alkylene-heterocyclic group, wherein the lower alkylene, cycloalkyl, cycloalkenyl, aryl and heterocyclic group in R 1  may each be substituted, R 0 : the same as or different from each other, each representing \u2014H or lower alkyl, R 6 : R 0 , \u2014C(O)\u2014R 0 , \u2014CO 2 -lower alkyl or \u2014S(O) 2 -lower alkyl, R 2 : lower alkyl, lower alkylene-OR 0 , lower alkylene-aryl, lower alkylene-heterocyclic group, lower alkylene-N(R 0 )CO-aryl, lower alkylene-O-lower alkylene-aryl, \u2014CO 2 R 0 , \u2014C(O)N(R 0 ) 2 , \u2014C(O)N(R 0 )-aryl, \u2014C(O)N(R 0 )-lower alkylene-aryl, or aryl, wherein the aryl and heterocyclic group in R 2  may each be substituted, R 3 : \u2014H or lower alkyl, or R 2  and R 3  may be combined to form C 2-6  alkylene, R 4 : \u2014N(R 7 )(R 8 ), \u2014N(R 0 )\u2014OH, \u2014N(R 10 )\u2014OR 7 , \u2014N(R 0 )\u2014N(R 0 )(R 7 ), \u2014N(R 0 )\u2014S(O) 2 -aryl, or \u2014N(R 0 )\u2014S(O) 2 \u2014R 7 , wherein the aryl in R 4  may be substituted, R 7 : lower alkyl, halogeno-lower alkyl, lower alkylene-CN, lower alkylene-OR 0 , lower alkylene-CO 2 R 0 , lower alkylene-C(O)N(R 0 ) 2 , lower alkylene-C(O)N(R 0 )N(R 0 ) 2 , lower alkylene-C(\u2550NH)NH 2 , lower alkylene-C(\u2550NOH)NH 2 , heteroaryl, lower alkylene-X-aryl, or lower alkylene-X-heterocyclic group, wherein the lower alkylene, aryl, heteroaryl, and heterocyclic group in R 7  may each be substituted, X: single bond, \u2014O\u2014, \u2014C(O)\u2014, \u2014N(R 0 ), \u2014S(O p \u2014, or *-C(O)N(R 0 )\u2014, wherein * in X represents a bond to lower alkylene, m: an integer of 0 to 3, p: an integer of 0 to 2, R 8 : \u2014H or lower alkyl, or R 7  and R 8  may be combined to form lower alkylene-N(R 9 )-lower alkylene, lower alkylene-CH(R 9 )-lower alkylene, lower alkylene-arylene-lower alkylene, or lower alkylene-arylene-C(O)\u2014, R 9 : aryl and heteroaryl which may each be substituted, R 10 : \u2014H, lower alkyl, or \u2014C(O)R 0 , R 5 : lower alkyl, halogeno-lower alkyl, halogen, nitro, \u2014OR 0 , \u2014O-halogeno-lower alkyl, \u2014N(R 0 ) 2 , \u2014O-lower alkylene-CO 2 R 0 , or \u2014O-lower alkylene-aryl, wherein the aryl in R 5  may be substituted, provided that, when R 4  is \u2014N(R 7 )(R 8 ), (1) a compound wherein R 1  is unsubstituted cyclopentyl and R 2  is unsubstituted 2-thienyl; (2) a compound wherein R 1  is unsubstituted cyclohexyl and R 2  is 4-methoxyphenyl; (3) a compound wherein R 1  is 4-methoxyphenyl and R 2  is 4-methoxyphenyl; and (4) a compound wherein R 1  is (morpholin-4-yl)ethyl and R 2  is 4-ethoxyphenyl are excluded, and further provided that, 2,3-bis(4-chlorophenyl)-N-(2-methoxyethyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide, 3-(4-chlorobenzyl)-2-(4-chlorophenyl)-N-(2-methoxyethyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide, 3-[3,5-bis(trifluoromethyl)phenyl]-2-cyclopropyl-N-(2-furylmethyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide, 3-[3,5-bis(trifluoromethyl)phenyl]-2-cyclopropyl-N-(2-methoxyethyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide, ethyl 3-{3-[3,5-bis(trifluoromethyl)phenyl]-4-{[2-(4-methoxyphenyl)ethyl]carbamoyl}-1-oxo-3,4-dihydroisoquinolin-2(1H)-yl}propanoate, N-benzyl-3-[3,5-bis(trifluoromethyl)phenyl]-1-oxo-2-(tetrahydrofuran-2-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxamide, 3-[3,5-bis(trifluoromethyl)phenyl]-N-(2-methoxyethyl)-2-(2-morpholin-4-ylethyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide, 3-[3,5-bis(trifluoromethyl)phenyl]-2-(2-furylmethyl)-N-(2-methoxyethyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide, 3-[3,5-bis(trifluoromethyl)phenyl]-N-(2-furylmethyl)-2-(2-morpholin-4-ylethyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide, and (4-chlorophenyl)[3-(4-chlorophenyl)-4-[(2-methoxyethyl)carbamoyl]-1-oxo-3-,4-dihydroisoquinolin-2(1H)-yl]acetic acid are excluded.

Metadata:
- Claim Count in Document: 10.0
- Percentile: 95.0
- Lexical Diversity: 1.56923
- Patent Class: 514.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: True
- Related Applications: ['13942158', '15350427', '12600894', '14836228', '12693597']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7794514705925999
- 35 USC 102 Novelty (BERT): 0.6149071747347135
- Combined Prediction Score: 0.7629970410068113
- Mean Citation Score: 450.04597200000006
- Max Citation Score: 550.0178
- Similarity Product: 501.6763917968749

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