SG11201408529VA - Piperazino[1,2-a]indol-1-ones and [1,4]diazepino[1,2-a]indol-1-one - Google Patents

Abstract

(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 13 February 2014 (13.02.2014) WIPOIPCT (10) International Publication Number WO 2014/023674 A1 (51) International Patent Classification: C07D 487/04 (2006.01) A61P 25/00 (2006.01) (21) International Application Number: (22) International Filing Date: (25) Filing Language: (26) Publication Language: PCT/EP2013/066344 5 August 2013 (05.08.2013) English English (30) Priority Data: 12179381.4 6 August 2012 (06.08.2012) EP (71) Applicant (for all designated States except US): F. HOFF­ MANN-LA ROCHE AG [CH/CH]; Grenzacherstrasse 124, CH-4070 Basel (CH). (71) Applicant (for US only): HOFFMANN-LA ROCHE INC. [US/US]; 340 Kingsland Street, Nutley, New Jersey 07110 (US). (72) Inventors: CECCARELLI, Simona M.; Unterer Rhein- weg 62, CH-4057 Basel (CH). JAGASIA, Ravi; Tuellinger StraBe 25 b, 79541 Loerrach (DE). JAKOB- ROETNE, Roland; Oberer Baselblick 37, 79594 Inzlingen — (DE). WICHMANN, Juergen; Birkenweg 25, 79585 Steinen (DE). (74) Agent: POPPE, Regina; Grenzacherstrasse 124, CH-4070 Basel (CH). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17 : of inventorship (Rule 4.17(ivf) Published: — with international search report (Art. 21(3)) (54) Title: PTPF.R A7.TNO[l ,2-AjTNDOL-l -ONES AND [l,4]DIAZEPINO[l,2-A]INDOL-l-ONE (I) •t l> m CJ o o CJ o & (57) Abstract: The present invention relates to compounds of general formula (I), wherein R 1 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkoxy substituted by halogen or cyano; R 2 is hydrogen, lower alkyl or lower alkyl substituted by halogen; R 3 is phenyl, benzo[l,3]dioxolyl, 2,3-dihydro-benzofuran-5-yl or a 5- and 6-membered heteroaryl, wherein phenyl and the 5- and 6- membered heteroaryl groups may be substituted by one or more substituents, selected from cyano, nitro, amino and lower di-al- kylamino, lower alkyl sulfonyl, lower alkoxy, lower alkoxy substituted by halogen, halogen, lower alkyl, lower alkyl substituted by halogen or lower alkyl substituted by hydroxyl; X is -CH(lower alkyl)-, -CH -, 2 -CH CH - 2 2 or -CH(lower alkyl)CH -; 2 R is hydrogen or lower alkyl; n is 1 or 2; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enan- tiomer and/or optical isomers thereof. The compounds may be used for the treatment of schizophrenia, obsessive-compulsive person­ ality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down syndrome, autism spectrum disorders, hearing loss, tin­ nitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine and cocaine.