# US 10,370,368 B2 · Aryl acylsulfonamides as BLT1 antagonists > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,370,368 B2 - Document ID: US10370368B2 - Status: Granted - Kind: B2 - Application number: 15/768,097 - Filed: 2016-11-28 - Published: 2018-10-11 - Granted: 2019-08-06 - Earliest claimed: 2015-11-30 - Assignees: Merck Sharp & Dohme Corp. - Applicants: Merck Sharp & Dohme Corp.; Yongxin Han; Satyanarayana Tummanapalli; Phieng Siliphaivanh; Kerrie Spencer - Inventors: Yongxin Han; Satyanarayana Tummanapalli; Phieng Siliphaivanh; Kerrie Spencer - Web page: https://patentgrep.com/patent/US10370368B2 ## CPC - C07D 417/14: containing three or more hetero rings - A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are antagonists of leukotriene B4 receptor 1 (BLT1) and may be useful in the treatment, prevention and suppression of diseases mediated by the leukotriene B4 receptor 1 (BLT1). The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, insulin resistance, hyperglycemia, dyslipidemia, lipid disorders, obesity, hypertension, Non-alcoholic fatty liver disease/nonalcoholic steatohepatitis, metabolic syndrome, atherosclerosis, and cancer. ## Claims ### Claim 1 A compound of structural formula I: or a pharmaceutically acceptable salt thereof; wherein A is selected from the group consisting of: (1) aryl, and (2) heteroaryl, wherein aryl and heteroaryl are unsubstituted or substituted with 1-4 substituents independently selected from C1-6alkyl and halogen; B is selected from the group consisting of: (1) aryl, and (2) heteroaryl, wherein aryl and heteroaryl are unsubstituted or substituted with 1-4 substituents independently selected from C1-6alkyl and halogen; X is selected from the group consisting of: (1) —C(O)NHSO2CF3, (2) —C(O)NHSO2CH2CF3, (3) —C(O)NHSO2CHF2, (4) —C(O)NHSO2C1-6alkyl, (5) —C(O)NHSO2CH2C3-6cycloalkyl, and (6) —C(O)NHSO2C3-6cycloalkyl, wherein alkyl and cycloalkyl are unsubstituted or substituted with 1-3 substituents independently selected from C1-6alkyl; Z is selected from the group consisting of: (1) heteroaryl, (2) C2-6cycloheteroalkyl, and (3) C3-6cycloalkyl, wherein heteroaryl, cycloheteroalkyl and cycloalkyl are unsubstituted or substituted with 1-4 substituents independently selected from C1-6alkyl; Ra is selected from the group consisting of: (1) hydrogen, (2) halogen, and (3) C1-6alkyl; and Rb is selected from the group consisting of: (1) hydrogen, (2) halogen, and (3) C1-6alkyl. ### Claim 2 (depends on 1) The compound according to claim 1 wherein Z is heteroaryl, wherein heteroaryl is unsubstituted or substituted with 1-4 substituents independently selected from C1-6alkyl; or a pharmaceutically acceptable salt thereof. ### Claim 3 (depends on 1) The compound according to claim 1 wherein Z is thiazole, wherein thiazole is unsubstituted or substituted with 1-2 substituents independently selected from C1-6alkyl; or a pharmaceutically acceptable salt thereof. ### Claim 4 (depends on 1) The compound according to claim 1 wherein X is selected from the group consisting of: (1) —C(O)NHSO2C1-6alkyl, and (2) —C(O)NHSO2C3-6cycloalkyl, wherein alkyl and cycloalkyl are unsubstituted or substituted with 1-3 substituents independently selected from C1-6alkyl; or a pharmaceutically acceptable salt thereof. ### Claim 5 (depends on 1) The compound according to claim 1 wherein X is selected from the group consisting of: (1) —C(O)NHSO2C(CH3)3, and (2) —C(O)NHSO2cyclopropyl, wherein alkyl and cyclopropyl are unsubstituted or substituted with 1-3 substituents independently selected from CH3; or a pharmaceutically acceptable salt thereof. ### Claim 6 (depends on 1) The compound according to claim 1 wherein A is heteroaryl, wherein heteroaryl is unsubstituted or substituted with 1-3 substituents independently selected from C1-6alkyl and halogen; or a pharmaceutically acceptable salt thereof. ### Claim 7 (depends on 1) The compound according to claim 1 wherein A is pyridine, wherein pyridine is unsubstituted or substituted with 1-3 substituents independently selected from C1-6alkyl and halogen; or a pharmaceutically acceptable salt thereof. ### Claim 8 (depends on 1) The compound according to claim 1 wherein B is aryl, wherein aryl is unsubstituted or substituted with 1-4 substituents independently selected from C1-6alkyl and halogen; or a pharmaceutically acceptable salt thereof. ### Claim 9 (depends on 1) The compound according to claim 1 wherein B is phenyl, wherein phenyl is unsubstituted or substituted with 1-4 substituents independently selected from C1-6alkyl and halogen; or a pharmaceutically acceptable salt thereof. ### Claim 10 (depends on 1) The compound according to claim 1 wherein Ra and Rb are each independently selected from the group consisting of: hydrogen, and C1-6alkyl; or a pharmaceutically acceptable salt thereof. ### Claim 11 (depends on 1) The compound according to claim 1 wherein Ra and Rb are each hydrogen; or a pharmaceutically acceptable salt thereof. ### Claim 12 (depends on 1) The compound according to claim 1 wherein A is heteroaryl, wherein heteroaryl is unsubstituted or substituted with 1-3 substituents independently selected from C1-6alkyl and halogen; B is aryl, wherein aryl is unsubstituted or substituted with 1-4 substituents independently selected from C1-6alkyl and halogen; X is selected from the group consisting of: (1) —C(O)NHSO2C1-6alkyl, and (2) —C(O)NHSO2C3-6cycloalkyl, wherein alkyl and cycloalkyl are unsubstituted or substituted with 1-3 substituents independently selected from C1-6alkyl; Z is heteroaryl, wherein heteroaryl is unsubstituted or substituted with 1-4 substituents independently selected from C1-6alkyl; and Ra and Rb are each independently selected from the group consisting of: hydrogen, and C1-6alkyl; or a pharmaceutically acceptable salt thereof. ### Claim 13 (depends on 1) The compound according to claim 1 wherein A is pyridine, wherein pyridine is unsubstituted or substituted with 1-3 substituents independently selected from C1-6alkyl and halogen; B is phenyl, wherein phenyl is unsubstituted or substituted with 1-4 substituents independently selected from C1-6alkyl and halogen; X is selected from the group consisting of: (1) —C(O)NHSO2C(CH3)3, and (2) —C(O)NHSO2cyclopropyl, wherein alkyl and cyclopropyl are unsubstituted or substituted with 1-3 substituents independently selected from CH3; Z is thiazole, wherein thiazole is unsubstituted or substituted with 1-2 substituents independently selected from C1-6alkyl; and Ra and Rb are each hydrogen; or a pharmaceutically acceptable salt thereof. ### Claim 14 (depends on 1) The compound according to claim 1 selected from: (1) 2-((Rac-trans)-4-Hydroxy-3-((5-(thiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)benzamide; (2) 2-((3S, 4R)-4-Hydroxy-3-((5-(thiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)benzamide; (3) 2-((3R, 4S)-4-Hydroxy-3-((5-(thiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)benzamide; (4) N-(tert-Butylsulfonyl)-2-((rac-trans)-4-hydroxy-3-((5-(thiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)benzamide; (5) N-(tert-Butylsulfonyl)-2-((3S, 4R)-4-hydroxy-3-((5-(thiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)benzamide; (6) N-(tert-Butylsulfonyl)-2-((3R, 4S)-4-hydroxy-3-((5-(thiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)benzamide; (7) N-(tert-Butylsulfonyl)-2-((rac-trans)-4-hydroxy-3-((5-(2-methylthiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)benzamide; (8) N-(Cyclopropylsulfonyl)-2-((rac-trans)-4-hydroxy-3-((5-(thiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)benzamide; (9) N-(Cyclopropylsulfonyl)-2-((rac-trans)-4-hydroxy-3-((5-(2-methylthiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)benzamide; (10) N-(Cyclopropylsulfonyl)-2-((3S,4R)-4-hydroxy-3-((5-(2-methylthiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)benzamide; and (11) N-(Cyclopropylsulfonyl)-2-((3R,4S)-4-hydroxy-3-((5-(2-methylthiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)benzamide; or a pharmaceutically acceptable salt thereof. ### Claim 15 (depends on 1) A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. ### Claim 16 (depends on 1) A method of treating type 2 diabetes mellitus in a patient in need of treatment comprising the administration to the patient of a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.