Abstract:
This invention provides novel tricyclic diazepine compounds as well as methods and pharmaceutical compositions utilizing these compounds for the treatment and/or prevention and/or suppression of disorders which may be remedied or alleviated by oxytocin antagonist activity, including treatment of preterm labor, dysmenorrhea, endometritis, and for suppressing labor prior to caesarean delivery. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.

Description:
This application claims priority from copending provisional application Ser. No. 60/283,264, filed Apr. 12, 2001, the entire disclosure of which is hereby incorporated by reference 
    
    
     This invention concerns novel tricyclic diazepines which act as competitive oxytocin receptor antagonists, as well as methods of their manufacture, methods of treatment and pharmaceutical compositions utilizing these compounds. The compounds of the present invention are useful therapeutic agents in mammals, particularly in humans. More specifically, they can be used in the prevention and/or suppression of preterm labor, for the suppression of labor at term prior to caesarean delivery, to facilitate antinatal transport to a medical facility, and for the treatment of dysmenorrhea. These compounds also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders. 
     BACKGROUND OF THE INVENTION 
     Premature labor remains the leading cause of perinatal mortality and morbidity. Infant mortality dramatically decreases with increased gestational age. The survival rate of prematurely born infants increases from 20% at 24 weeks to 94% at 30 weeks. Moreover the cost associated with the care of an infant born prematurely is extremely high. While many agents have been developed for the treatment of premature labor in the last 40 years, the incidence of pre-term births and low birth weight infants has remained relatively unchanged. Therefore there remains an unmet need for the development of a safe and effective treatment of preterm labor. 
     Tocolytic (uterine relaxing) agents currently in use include β 2  adrenergic receptor agonists such as Ritodrine which is moderately effective in suppressing preterm labor, but it is associated with maternal hypotension, tachycardia, and metabolic side effects. Several other agents have been used to suppress premature labor, including other β 2  adrenergic agonists (terbutaline, albuterol), magnesium sulfate, NSAIDs (indomethacin), and calcium channel blockers. The consensus is that none of these agents are very effective; there is no clinical evidence showing that these compounds can prolong gestation for more than 7 days (Johnson, Drugs, 45, 684–692 (1993)). Furthermore, their safety profile is not ideal. Adverse effects include respiratory depression and cardiac arrest (magnesium sulfate), hemodynamic effects (calcium channel blockers), premature closure of the  ductus arteriosus  and oligohydramnios (NSAIDs; prostaglandin synthase inhibitors). Therefore, there is an unmet need for safer and more efficacious agents for the treatment of preterm labor with better patient tolerability. Specific requirements with regard to safety include a product with no or low rates of tachycardia, limited anxiety, improved fetal safety, and few, if any, adverse cardiovascular effects. 
     One target of interest is the oxytocin receptor in the uterus, and a selective oxytocin receptor antagonist has been proposed as an ideal tocolytic agent. While the exact role of oxytocin (OT) in parturition has not been clearly defined, there is evidence strongly suggesting that it may play a critical role in the initiation and progression of labor in humans (Fuchs et al.  Science  215, 1396–1398 (1982); Maggi et al.  J. Clin. Endocrinol. Metab.  70, 1142–1154 (1990); Åkerlund,  Reg. Pept.  45, 187–191 (1993); Åkerlund, Int. Congr. Symp. Semin. Ser.,  Progress in Endocrinology  3, 657–660 (1993); Åkerlund et al., in  Oxytocin , Ed. R. Ivell and J. Russel, Plenum Press, New York, pp 595–600 (1995)). Preliminary clinical trials with oxytocin receptor antagonists support the concept that a blockade of OT receptors reduces uterine myometrial activity and delays the onset of labor (Åkerlund et al.,  Br. J. Obst. Gynaecol.  94, 1040–1044, (1987); Andersen et al.,  Am. J. Perinatol.  6, 196–199 (1989); Melin,  Reg. Pept.  45, 285–288 (1993)). Thus, a selective oxytocin antagonist is expected to block the major effects of oxytocin exerted mainly on the uterus at term, and to be more efficacious than current therapies for the treatment of preterm labor. By virtue of its direct action on the receptors in the uterus an oxytocin antagonist is also expected to have fewer side effects and an improved safety profile. 
     The following prior art references describe peptidic oxytocin antagonists: Hruby et al., Structure-Activity Relationships of Neurohypophyseal Peptides, in  The Peptides: Analysis, Synthesis and Biology ; Udenfriend and Meienhofer Eds., Academic Press, New York, Vol. 8, 77–207 (1987); Pettibone et al.,  Endocrinology,  125, 217 (1989); Manning et al., Synthesis and Some Uses of Receptor-Specific Agonists and Antagonists of Vasopressin and Oxytocin,  J. Recept. Res.,  13, 195–214 (1993); Goodwin et al., Dose Ranging Study of the Oxytocin Antagonist Atosiban in the Treatment of Preterm Labor,  Obstet Gynecol.,  88, 331–336 (1996). Peptidic oxytocin antagonists suffer from a lack of oral activity and many of these peptides are non-selective antagonists since they also exhibit vasopressin antagonist activity. Bock et al. [ J. Med. Chem.  33, 2321 (1990)], Pettibone et al. [ J. Pharm. Exp. Ther.  256, 304 (1991)], and Williams et al. [ J. Med. Chem.,  35, 3905 (1992)] have reported on potent hexapeptide oxytocin antagonists which also exhibit weak vasopressin antagonistic activity in binding to V 1  and V 2  receptors. 
     Various non-peptidic oxytocin antagonists and/or oxytocin/vasopressin (AVP) antagonists have recently been reported by Pettibone et al.,  Endocrinology,  125, 217 (1989); Yamamura et al.,  Science,  252, 572–574 (1991); Evans et al.,  J. Med. Chem.,  35, 3919–3927 (1992); Pettibone et al.,  J. Phannacol. Exp. Ther,  264, 308–314 (1992); Ohnishi et al.,  J. Clin. Pharmacol.  33, 230–238, (1993); Evans et al.,  J. Med. Chem.  36, 3993–4006 (1993); Pettibone et al.,  Drug Dev. Res.  30, 129–142 (1993); Freidinger et al., General Strategies in Peptidomimetic Design: Applications to Oxytocin Antagonists, in  Perspect. Med. Chem.  179–193 (1993), Ed. B. Testa, Verlag, Basel, Switzerland; Serradeil-Legal,  J. Clin. Invest,  92, 224–231 (1993); Williams et al.,  J. Med. Chem.  37, 565–571 (1994); Williams et al.,  Bioorg. Med. Chem.  2, 971–985 (1994); Yamamura et al.,  Br. J. Pharmacol.,  105, 546–551 (1995); Pettibone et al.,  Advances in Experimental Medicine and Biology  395, 601–612 (1995); Williams et al.,  J. Med. Chem.  38, 4634–4636 (1995); Hobbs et al.,  Biorg. Med. Chem. Lett.  5, 119 (1995); Williams et al.,  Curr. Pharm. Des.  2, 41–58 (1996); Freidinger et al.,  Medicinal Research Reviews,  17, 1–16 (1997); Pettibone et al.,  Biochem. Soc. Trans.  25 (3), 1051–1057 (1997); Bell et al.,  J. Med. Chem.  41, 2146–2163 (1998); Kuo et al.,  Bioorg. Med. Chem. Lett.  8, 3081–3086 (1998); Williams et al.,  Biorg. Med. Chem. Lett.  9, 1311–1316 (1999). 
     Certain carbostyril derivatives and bicyclic azepines are disclosed as oxytocin and vasopressin antagonists by Ogawa et al. in WO 94/01113 (1994); benzoxazinones are disclosed as oxytocin and vasopressin receptor antagonists by Sparks et al. in WO 97/25992 (1997); Williams et al. disclose piperidine oxytocin and vasopressin receptor antagonists in WO 96/22775 (1996); Bock et al. disclose benzoxazinone and benzopyrimidinone piperidines useful as oxytocin and vasopressin receptor antagonists in U.S. Pat. No. 5,665,719 (1997); piperazines and spiropiperidines useful as oxytocin and vasopressin receptor antagonists are disclosed by Evans et al. in U.S. Pat. No. 5, 670,509 (1997) and by Bock et al. in U.S. Pat. No. 5,756,504 (1998); Bell et al. disclose piperazine oxytocin receptor antagonists in UK Patent Application, GB 2 326 639 A (1998); Bell et al. disclose benzoxazinone and quinolinone oxytocin and vasopressin receptor antagonists in UK Patent Application GB 2 326 410 A (1998); Bell et al. disclose benzoxazinone oxytocin and vasopressin receptor antagonists in U.S. Pat. No. 5,756,497 (1998); Matsuhisa et al. disclose difluoro tetrahydrobenzazepine derivatives as oxytocin antagonists in WO 98/39325 (1998); Ogawa et al. disclose heterocyclic bisamides with vasopressin and oxytocin antagonist activity in U.S. Pat. No. 5,753,644 (1998)); and Ogawa et al. disclose benzazepine derivatives with anti-vasopressin activity, oxytocin antagonistic activity and vasopressin agonist activity, useful as vasopressin antagonists, vasopressin agonists and oxytocin antagonists in WO 97/22591 (1997) and U.S. Pat. No. 6,096,736 (2000). 
     Trybulski et al. disclose 3-carboxamide derivatives of pyrrolobenzodiazepine bisamides with vasopressin antagonist activity in U.S. Pat. No. 5,880,122 (1999); bicyclic thienoazepines with vasopressin and oxytocin receptor antagonist activity are disclosed by Albright et al. in WO 96/22294 (1996) and U.S. Pat. No. 5,654,297 (1997); and tricyclic benzazepines with vasopressin and oxytocin receptor antagonist activity are disclosed by Albright et al. in U.S. Pat. No. 5,849,735 (1998). 
     Albright et al. broadly disclose tricyclic benzazepine vasopressin antagonists in WO 96/22282A1 (1996) which possess antagonistic activity at the V 1  and/or V 2  receptors and exhibit in vivo vasopressin antagonistic activity, as well as antagonistic activity at the oxytocin receptors. 
     Venkatesan et al. broadly disclose tricyclic benzazepines with vasopressin and oxytocin antagonist activity in U.S. Pat. No. 5,521,173 (1996), WO 96/22292 (1996), and in U.S. Pat. No. 5,780,471 (1998) which possess antagonistic activity at the V 1  and/or V 2  receptors and exhibit in vivo vasopressin antagonistic activity, as well as antagonistic activity at the oxytocin receptors. 
     Compounds which behave as potent oxytocin antagonists by binding with high affinity and selectivity to the oxytocin receptors, thus preventing oxytocin from binding to its receptors and exerting its biological and pharmacologic effects in vivo, can be useful for the treatment and/or prevention and/or suppression of preterm labor, for the suppression of term labor prior to a caesarian delivery, and to facilitate antinatal transport to a medical facility. They also can produce contraception in mammals given that oxytocin antagonists have been shown to inhibit the release of oxytocin-stimulated luteneizing hormone (LH) from pituitary cells (Rettori et al.,  Proc. Nat Acad. Sci. U.S.A.  94, 2741–2744 (1997); Evans et al.,  J. Endocrinol.,  122, 107–116 (1989); Robinson et al.,  J. Endocrinol.  125, 425–432 (1990)). 
     Oxytocin antagonists have the ability to relax uterine contractions induced by oxytocin in mammals and thus can be also useful for the treatment of dysmenorrhea, a condition characterized by pain during menstruation (Åkerlund, Int. Congr. Symp. Semin. Ser.,  Progress in Endocrinology  3, 657–660 (1993); Åkerlund,  Reg. Pept.  45, 187–191 (1993); Melin,  Reg. Pept.  45, 285–288 (1993)). Primary dysmenorrhea is associated with ovulatory cycles, and it is the most common complaint of gynecologic patients. Myometrial hypercontractility and decreased blood flow to the uterus are thought to be causative factors for for the symptoms of primary dysmenorrhea (Åkerlund,  Acta Obstet. Gynecol. Scand.  66, 459–461 (1987). In particular, vasoconstriction of small uterine arteries by vasopressin and oxytocin is thought to produce tissue ischemia and pain (Jovanovic et al.,  Br. J. Pharmacol.  12, 1468–1474 (91997); Chen et al.,  Eur. J. Pharmacol.  376, 25–51 (1999)). 
     The administration of oxytocin receptor antagonists to farm animals after fertilization has been found to enhance fertility rates by blocking oxytocin induced luteolysis leading to embryonic loss (Hickey et al., WO 96/09824 A1 (1996), Sparks et al., WO 97/25992 Al (1997); Sparks et al., U.S. Pat. No. 5,726,172 A (1998)). Thus, oxytocin receptor antagonists can be useful in farm animal husbandry to control timing of parturition and delivery of newborns resulting in enhanced survival rates. They can also be useful for the synchronization of estrus by preventing oxytocin induced corpus luteum regression and by delaying estrus (Okano,  J. Reprod. Dev.  42 (Suppl.), 67–70 (1996)). Furthermore oxytocin receptor antagonists have been found to have a powerful effect in inhibiting oxytocin-induced milk ejection in dairy cows (Wellnitz et al.,  Journal of Dairy Research  66, 1–8 (1999)). 
     Oxytocin is also synthesized in the brain and released in the central nervous system. Recent studies have established the importance of central oxytocin in cognitive, affiliative, sexual and reproductive behavior, and in regulating feeding, grooming and response to stress in animals. Oxytocin may also influence normal behavior in humans.Modulators of oxytocin binding to its receptors in the central nervous system may be useful in the prevention and treatment of disfunctions of the oxytocin system, including obsessive compulsive disorder (OCD) and other neuropsychiatric disorders (Kovacs et al.,  Psychoneuroendocrinology  23, 945–962 (1998); McCarthy et al.,  U.K. Mol. Med. Today  3, 269–275 (1997); Bohus,  Peptidergic Neuron, [Int. Symp. Neurosecretion],  12 th  (1996), 267–277, Publ. Birkhauser, Basel, Switz.; Leckman et al.,  Psychoneuroendocrinology  19, 723–749 (1994)). 
     Competitive inhibitors of vasopressin binding to its receptors are useful in the treatment or prevention of state diseases involving vasopressin disorders in mammals, which include vasodilation and aquaresis (free-water diuresis), treating hypertension and inhibiting platelet aggregation. They are also useful in the treatment of congestive heart failure, cirrhosis with ascites, and in the syndrome of inappropriate secretion of antiduretic hormone (SIADH). Furthermore, vasopressin receptor antagonists have been found to be useful in treating disturbances or illnesses of the inner ear, particularly those related to Meniere&#39;s disease (Zenner et al., WO 99/24051-A2 (1999)); and for the prevention and treatment of ocular circulatory disorders, particularly intraocular hypertension or glaucoma and vision disorders such as shortsightedness (Ogawa et al., WO 99/38533-A1 (1999)); Ohtake et al., WO 99/65525 (1999)). 
     SUMMARY OF THE INVENTION 
     This invention comprises compounds of Formula (I): 
     
       
                 
         
             
             
         
      
         
         R 1  and R 2  are, independently, selected from hydrogen, (C 1 –C 6 )lower alkyl, halogen, cyano, trifluoromethyl, hydroxy, amino, (C 1 –C 6 ) lower alkylamino, (C 1 –C 6 ) lower alkoxy, —OCF 3 , (C 1 –C 6 ) lower alkoxy carbonyl, —NHCO[(C 1 –C 6 )lower alkyl], carboxy, —CONH 2 , —CONH[(C 1 –C 6 ) lower alkyl], or —CON[(C 1 –C 6 ) lower alkyl] 2 ; 
         R 3  is a substituent selected from hydrogen, (C 1 –C 6 ) lower alkyl, (C 1 –C 6 ) lower alkoxy, hydroxy, amino, (C 1 –C 6 ) lower alkylamino, —CO lower alkyl (C 1 –C 6 ), or halogen; 
         R 4  consists of the moiety B-C; wherein: 
         B is selected from the group of: 
       
    
                                
wherein:
     A is CH or N;   R 5 , R 6 , R 7 , R 8 , R 9 , R 10  are, independently, selected from hydrogen, (C 1 –C 6 ) lower alkyl, (C 1 –C 6 ) lower alkoxy, (C 1 –C 6 ) lower alkyl carbonyl, (C 3 –C 6 ) lower alkenyl, (C 3 –C 6 ) lower alkynyl, hydroxy (C 1 –C 6 ) lower alkyl, alkoxy (C 1 –C 6 ) lower alkyl, acyloxy (C 1 –C 6 ) lower alkyl, (C 3 –C 8 ) cycloalkyl, formyl, cycloalkylcarbonyl, carboxy, lower alkoxy carbonyl, cycloalkyloxycarbonyl, aryl alkyloxycarbonyl, carbamoyl, —O—CH 2 —CH═CH 2 , halogen, halo lower alkyl, trifluoromethyl, —OCF 3 , —S[(C 1 –C 6 ) lower alkyl], —OC(O)N[(C 1 –C 6 ) lower alkyl] 2 , —CONH[(C 1 –C 6 ) lower alkyl], —CON[(C 1 –C 6 ) lower alkyl] 2 , (C 1 –C 6 ) lower alkylamino, di-[(C 1 –C 8 ) lower alkyl]amino, (C 1 –C 6 ) lower alkyl di-[(C 1 –C 6 ) lower alkyl]amino, hydroxy, cyano, trifluoromethylthio, nitro, amino, (C 1 –C 6 ) lower alkylsulfonyl, aminosulfonyl, (C 1 –C 6 ) lower alkylaminosulfonyl,   
                                
phenyl or naphthyl;
     and R is selected from —OH, NHOR 36 , or any of the following groups:   
                                                          
wherein:
     R 11  and R 12  are, independently, selected from hydrogen, (C 1 –C 6 ) lower alkyl, (C 3 –C 6 ) lower alkenyl, (C 3 –C 8 ) cycloalkyl optionally mono- or di-[(C 1 –C 6 ) loweralkyl] substituted, bicycloalkyl including but not limited to adamantanyl, adamantane lower alkyl, bornyl, norbornyl, or quinuclidyl;   
     
       
                 
         
             
             
         
      
         
         
           
             cycloalkyl lower alkyl, halo lower alkyl, cyano lower alkyl, lower alkyl thiol, alkoxycarbonyl lower alkyl, alkylthio lower alkyl, indolyl lower alkyl; aryl, optionally substituted with 1 to three substituents selected from the group of lower alkyl, hydroxy, (C 1 –C 6 ) lower alkoxy, aryl lower alkoxy, halogen, —CF 3 , —OCF 3 , —OCHF 2 , —OCH 2 F, —OCH 2 CF 3 , —OCF 2 CF 3 , —OCH 2 CHF 2 , alkylamido lower alkyl, dialkylamido lower alkyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl, —SCF 3 , —SO 2 [lower alkyl], sulfonyl cycloalkyl, 
           
         
       
    
                                
or (C 7 –C 12 ) aryl lower alkyl, wherein the aryl moiety is optionally substituted with halogen or alkoxy; with the proviso that R 11  and R 12  can be taken together with the nitrogen to which they are attached to form an unsaturated heteroaromatic ring containing 2 nitrogen atoms;
     R 13  is selected from hydrogen, (C 1 –C 6 ) lower alkyl, (C 7 –C 12 ) lower aralkyl, or—(CH 2 ) p —N(lower alkyl) 2 ;   R 14  and R 15  are, independently, selected from hydrogen, (C 1 –C 6 ) lower alkyl, or (C 7 –C 12 ) aryl lower alkyl, with the proviso that R 14  and R 15  can be taken together with the nitrogen atom to which they are attached to form a 5 to 7 membered saturated heterocycle, optionally containing one additional O or S atom (all of the above rings being optionally substituted with 1 or more alkyl groups); or a 5-membered unsaturated heterocycle containing 1 to 3 nitrogen atoms;   R 16  and R 17  are, independently selected from the group of hydrogen, (C 1 –C 6 ) lower alkyl, [(C 1 –C 6 ) lower alkyl] 2 , (C 7 –C 12 ) aryl lower alkyl, lower alkoxy carbonyl, aryl lower alkoxy carbonyl, —CONH 2 , —CONH [(C 1 –C 6 ) lower alkyl], —CON [(C 1 –C 6 ) lower alkyl] 2 ; cycloalkylamino (C 1 –C 6 ) lower alkyl, [(C 1 –C 6 ) lower alkyl] 2  amino; with the proviso that R 16  and R 17  can be joined to form a 5 to 6 membered saturated ring to provide a bicyclic system, optionally containing one or more alkyl groups including, but not limited to, 1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane;   R 18  is one to three substituents selected independently from the group of hydrogen, or (C 1 –C 6 ) lower alkyl;   R 19  is selcted from the group of hydrogen, (C 1 –C 6 ) lower alkyl, —N[(C 1 –C 6 ) lower alkyl] 2 , or cycloalkylamine when Y′=CH 2 ; or it is selected from the group of hydrogen and (C 1 –C 6 ) lower alkyl when Y′=X′;   R 20  is selected from the group of hydrogen, (C 1 –C 6 ) lower alkyl, (C 3 –C 6 ) lower alkenyl, (C 3 –C 6 ) lower alkynyl, (C 3 –C 8 ) cycloalkyl, —CONH 2 , —CON[lower alkyl] 2 , carbonyl lower alkyl, lower alkyl CONH[lower alkyl], lower alkyl CON[lower alkyl] 2 , cycloalkylamino carbonyl, cycloalkylamino carbonyl lower alkyl, arylamino carbonyl lower alkyl, lower alkoxy carbonyl, lower alkoxy carbonyl lower alkyl, —(CH 2 ) p —N[lower alkyl] 2 , —(CH 2 ) p —N[lower alkenyl] 2 , —CH[aryl] 2  wherein the aryl is optionally substituted by (C 1 –C 6 ) lower alkyl, C 1 –C 6 ) lower alkoxy, or halogen;   
     
       
                 
         
             
             
         
      
         
         
           
             benzodioxolyl, benzodioxolyl lower alkyl, benzodioxanyl, benzodioxanyl lower alkyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, furancarbonyl, —SO 2 [lower alkyl], aryl optionally substituted by one to three substituents selected independently, from the group of hydrogen, halogen, (C 1 –C 6 ) lower alkyl, (C 3 –C 6 ) lower alkenyl, (C 3 –C 6 ) lower alkynyl, lower alkoxy, —CF 3 , —OCF 3 , —OCH 2 CF 3 , —OCHF 2 , —OCH 2 F, —OCF 2 CF 3 , —OCH 2 CHF 2 , —CO lower alkyl, —CN, nitro, —SCH 3 , aryl lower alkoxy, aryl lower alkoxy carbonyl, indolyl, morpholino or thiomorpholino; or (C 7 –C 12 ) lower aralkyl wherein the aryl moiety is optionally substituted with halogen, (C 1 –C 6 ) lower alkyl, or (C 1 –C 6 ) lower alkoxy; 
           
         
         R 21  and R 22  are selected, independently, from the group of hydrogen, (C 1 –C 6 ) lower alkyl, or (C 7 –C 12 ) aryl lower alkyl; 
         R 23  is selected from hydrogen, or (C 1 –C 6 ) lower alkyl; 
         R 24  is selected from the group of (C 1 –C 6 ) lower alkyl, (C 7 –C 12 ) aryl lower alkyl, lower alkoxycarbonyl, or SO 2 [(C 1 –C 6 ) lower alkyl]; 
         R 25  is selected from (C 1 –C 6 ) lower alkyl, (C 7 –C 12 ) aryl lower alkyl, lower alkoxycarbonyl, aryl lower alkoxycarbonyl, —COOH, —CONH 2 , —CONH[(C 1 –C 6 ) lower alkyl], —CONH[(C 7 –C 12 ) aryl lower alkyl], —CON[(C 1 –C 6 ) lower alkyl] 2 , or —CON[(C 7 –C 12 ) aryl lower alkyl] 2 ; 
         R 26  is selected from hydrogen, lower alkoxycarbonyl, fluorenylalkoxycarbonyl, aryl lower alkyl, or aryl lower alkoxycarbonyl; 
         R 27  and R 28  are, independently, selected from the group of hydrogen, lower alkyl, aryl lower alkyl (the aryl moiety being optionally substituted by hydroxy, alkoxy, or halogen), or 
       
    
                                
with the proviso that R 27  and R 28  can be taken together with the carbon to which they are attached to form a 3 to 6-membered saturated ring;
     R 29  and R 30  are, independently, selected from the group of hydrogen, (C 1 –C 6 ) lower alkyl, (C 3 –C 6 ) lower alkenyl, (C 3 –C 6 ) lower alkynyl, cyclo lower alkyl, or aryl [optionally substituted by hydroxy, (C 1 –C 6 ) lower alkoxy, (C 1 –C 6 ) lower alkyl, halo, cyano, —SO 2 [(C 1 –C 6 ) lower alkyl, or —S[(C 1 –C 6 ) lower alkyl];   R 31  is selected from the group of hydroxy, (C 1 –C 6 ) lower alkoxy, aryl lower alkoxy, amino, —NH[(C 1 –C 6 ) lower alkyl], or —N[(C 1 –C 6 ) lower alkyl] 2 ;   R 32  is selected from the group of hydrogen, or (C 1 –C 6 ) lower alkyl;   R 33  is one to three substituents selected from the group of hydrogen, or (C 1 –C 6 ) lower alkyl;   R 34  and R 35  are, independently, selected from the group of hydrogen, (C 1 –C 6 ) lower alkyl, (C 7 –C 12 ) aryl lower alkyl, with the proviso that R 34  and R 35  taken together with the nitrogen atom to which they are attached, may form a 4 to 8 membered saturated heterocycle, optionally containing one additional O, S or N[(C 1 –C 6 ) lower alkyl], all the above rings being optionally substituted with 1 or more alkyl groups; or a 5 membered unsaturated heterocycle containing 2 to 3 nitrogen atoms;   R 36  is selected from the group of hydrogen, or (C 1 –C 6 ) lower alkyl;   X′ is O, S, SO, SO 2 ;   Y′=CH 2  or X′;   K=Y′ or N[(C 1 –C 6 ) lower alkyl];   m is an integer from 1 to 4;   n is an integer from 1 to 4;   p is an integer from 2 to 4;   q is an integer from 1 to 5;   r is an integer from 1 to 2;   s is an integer from 0 to 1;   and the pharmaceutically acceptable salts, or pro-drug forms thereof.   
     Among the preferred compounds of this invention are those of the formula: 
                                
wherein:
 
     
       
                 
         
             
             
         
      
         
         R 1  and R 2  are, independently, selected from hydrogen, (C 1 –C 6 )lower alkyl, halogen, cyano, trifluoromethyl, hydroxy, amino, (C 1 –C 6 ) lower alkylamino, (C 1 –C 6 ) lower alkoxy, —OCF 3 , (C 1 –C 6 ) lower alkoxy carbonyl, —NHCO[(C 1 –C 6 )lower alkyl], carboxy, —CONH 2 , —CONH[(C 1 –C 6 ) lower alkyl], or —CON[(C 1 –C 6 ) lower alkyl] 2 ; 
         R 3  is a substituent selected from hydrogen, (C 1 –C 6 ) lower alkyl, (C 1 –C 6 ) lower alkoxy, hydroxy, amino, (C 1 –C 6 ) lower alkylamino, —CO lower alkyl (C 1 –C 6 ), or halogen; 
         R 4  consists of the moiety B-C; wherein: 
         B is selected from the group of: 
       
    
                                
and C is selected from the group of:
 
                                
wherein:
     A is CH or N;   R 5 , R 6 , R 7 , R 8 , R 9 , R 10  are independently selected from hydrogen, (C 1 –C 6 ) lower alkyl, (C 1 –C 6 ) lower alkoxy, (C 1 –C 6 ) lower alkyl carbonyl, (C 3 –C 6 ) lower alkenyl, (C 3 –C 6 ) lower alkynyl, hydroxy (C 1 –C 6 ) lower alkyl, alkoxy(C 1 –C 6 ) lower alkyl, acyloxy(C 1 –C 6 ) lower alkyl, (C 3 –C 8 ) cycloalkyl, formyl, cycloalkylcarbonyl, carboxy, lower alkoxy carbonyl, cycloalkyloxycarbonyl, carbamoyl, —O—CH 2 —CH═CH 2 , halogen, halo lower alkyl, trifluoromethyl, —OCF 3 , —S[(C 1 –C 6 ) lower alkyl], —OC(O)N[(C 1 –C 6 ) lower alkyl] 2 , —CONH[(C 1 –C 6 ) lower alkyl], —CON[(C 1 –C 6 ) lower alkyl] 2 , (C 1 –C 6 ) lower alkylamino, di-[(C 1 –C 6 ) lower alkyl]amino, (C 1 –C 6 ) lower alkyl di-[(C 1 –C 6 ) lower alkyl]amino, hydroxy, cyano, trifluoromethylthio, nitro, amino, (C 1 –C 6 ) lower alkylsulfonyl, aminosulfonyl, or (C 1 –C 6 ) lower alkylaminosulfonyl;   R 29  and R 30  are, independently, selected from the group of H, C 1 –C 6  alkyl, (C 3 –C 6 ) lower alkenyl, C 3 –C 6  alkynyl, or cyclo C 3 –C 6  alkyl;   R is selected from lower alkyl, —NHNH 2 , —NHOR 31 ; or —CH═CH—N[R 32 ] 2 ; lower alkoxy; phenyl optionally substituted by from one to three substituents selected from (C 1 –C 6 ) lower alkyl or halogen; or a moiety of the formulae:   
     
       
                 
         
             
             
         
      
       
                 
         
             
             
         
       
         
         R 11  and R 12  are, independently, selected from hydrogen, (C 1 –C 6 ) lower alkyl, (C 3 –C 6 ) lower alkenyl, (C 3 –C 8 ) cycloalkyl optionally mono- or di-[(C 1 –C 6 ) loweralkyl] substituted, cycloalkyl lower alkyl, halo lower alkyl, cyano lower alkyl, lower alkyl thiol, alkoxycarbonyl lower alkyl, or alkylthio lower alkyl; or a moiety of the formulae: 
       
    
     
       
                 
         
             
             
         
      
         
         R 13  is selected from hydrogen, (C 1 –C 6 ) lower alkyl, (C 7 –C 12 ) lower aralkyl, or —(CH 2 ) p —N(lower alkyl) 2 ; 
         R 14  and R 15  are, independently, selected from hydrogen, (C 1 –C 6 ) lower alkyl, with the proviso that R 14  and R 15  can be taken together with the nitrogen atom to which they are attached to form:
       a) a 5 to 7 membered saturated heterocycle, optionally substituted with 1 or more alkyl groups; or   b) a 5-membered unsaturated heterocycle containing 1 to 3 nitrogen atoms;   
     
         R 18  is one to three substituents selected independently from the group of hydrogen, or (C 1 –C 6 ) lower alkyl; 
         R 19  is selcted from the group of hydrogen, (C 1 –C 6 ) lower alkyl, —N[(C 1 –C 6 ) lower alkyl] 2 , or cycloakylamine when Y′=CH 2 ; or it is selected from the group of hydrogen and (C 1 –C 6 ) lower alkyl when Y′=X′; 
         R 20  is selected from the group of hydrogen, (C 1 –C 6 ) lower alkyl, (C 3 –C 6 ) lower alkenyl, (C 3 –C 6 ) lower alkynyl, (C 3 –C 8 ) cycloalkyl, —CONH 2 , —CON[lower alkyl] 2 , carbonyl lower alkyl, lower alkyl CONH[lower alkyl], lower alkyl CON[lower alkyl] 2 , lower alkoxy carbonyl, (CH 2 ) p —N[lower alkyl] 2 , —(CH 2 ) p —N[lower alkenyl] 2 , —CH[phenyl] 2  wherein the phenyl ring is optionally substituted by (C 1 –C 6 ) lower alkyl, C 1 –C 6 ) lower alkoxy, or halogen; or R 20  is a moiety of the formula: 
       
    
     
       
                 
         
             
             
         
      
         
         R 21  and R 22  are selected, independently, from the group of hydrogen, (C 1 –C 6 ) lower alkyl, or (C 7 –C 12 ) aryl lower alkyl; 
         R 23  is selected from hydrogen, cyano or (C 1 –C 6 ) lower alkyl; 
         R 24  is selected from the group of (C 1 –C 6 ) lower alkyl, lower alkoxycarbonyl, or SO 2 [(C 1 –C 6 ) lower alkyl]; 
         R 25  is selected from (C 1 –C 6 ) lower alkyl, lower alkoxycarbonyl, —COOH, —CONH 2 , —CONH[(C 1 –C 6 )lower alkyl)], or —CON[(C 1-C6 )lower alkyl)] 2 ; 
         R 26  is selected from hydrogen, lower alkoxycarbonyl, or fluorenylalkoxycarbonyl; 
         R 27  and R 28  are, independently, selected from the group of hydrogen or lower alkyl; with the proviso that R 27  and R 28  can be taken together with the carbon to which they are attached to form a 3 to 6-membered saturated ring; 
         R 31  is selected from the group of hydroxy, (C 1 –C 6 ) lower alkoxy, amino, —NH[(C 1 –C 6 ) lower alkyl], or —N[(C 1 –C 6 ) lower alkyl] 2 ; 
         R 32  is elected from the group of hydrogen, or (C 1 –C 6 ) lower alkyl; 
         R 33  is one to three substituents selected from the group of hydrogen, or (C 1 –C 6 ) lower alkyl; 
         R 34  and R 35  are, independently, selected from the group of hydrogen, or (C 1 –C 6 ) lower alkyl, with the proviso that R 34  and R 35  taken together with the nitrogen atom to which they are attached, may form a 5 membered unsaturated heterocycle containing 2 to 3 nitrogen atoms; 
         X′ is O; 
         Y′=CH 2  or X′; 
         K=Y′ or N[(C 1 –C 6 ) lower alkyl]; 
         m is an integer from 1 to 4; 
         n is an integer from 1 to 4; 
         p is an integer from 2 to 4; 
         q is an integer from 1 to 5; 
         r is an integer from 1 to 2; 
         s is an integer from 0 to 1; 
         and the pharmaceutically acceptable salts, or pro-drug forms thereof. 
       
    
     Within each of the groups of compounds described herein is a further subset of compounds having the general formula: 
                                
wherein R, R 1 , R 2 , R 3  and R 4  are as defined in the relevant group, or a pharmaceutically acceptable salt form thereof. A further subset of each of these groups includes those compounds wherein R 1 , R 2  and R 3  are each hydrogen and all other variables are as described in the relevant group, or a pharmaceutically acceptable salt thereof.
 
     As used herein the term “lower” in relation to carbon chains, such as alkoxy, alkyl, alkynyl, alkenyl, etc., is understood to refer to those groups having up to 6 carbon atoms. Halogen refers to fluorine, chlorine, bromine or iodine. Cycloalkyl, whether used separately or as a part of a combined moiety, refers to cycloalkyl groups from 3 to 8 carbon atoms, preferably from 3 to 6 carbon atoms. 
     It is understood by those practicing the art that some of the compounds of this invention depending on the definition of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 29 , and R 30  may contain one or more asymmetric centers and may thus give rise to enantiomers and diastereomers. The present invention includes all stereoisomers including individual diastereomers and resolved, enantiomerically pure R and S stereoisomers; as well as racemates, and all other mixtures of the R and S stereoisomers and pharmaceutically acceptable salts thereof, which possess the indicated activity. Optical isomers may be obtained in pure form by standard procedures known to those skilled in the art. It is also understood that this invention encompasses all possible regioisomers, E/Z isomers, endo-exo isomers, and mixtures thereof which possess the indicated activity. Such isomers may be obtained in pure form by standard separation procedures known to those skilled in the art. It is understood also by those practicing the art that some of the compounds of this invention depending on the definition of R 5 , R 6 , R 8 , R 9 , R 10 , R 29  and R 30  may be chiral due to hindered rotation, and give rise to atropisomers which can be resolved and obtained in pure form by standard procedures known to those skilled in the art. Also included in the present invention are all polymorphs and hydrates of the compounds of the present invention. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention comprises the compounds described above, as well as pharmaceutical compositions containing the compounds of this invention in combination or association with one or more pharmaceutically acceptable carriers or excipients. In particular, the present invention provides a pharmaceutical composition which comprises a therapeutically or pharmaceutically effective amount of one or more compounds of this invention and a pharmaceutically acceptable carrier or excipient. 
     This invention also comprises methods for treating conditions in a mammal, preferably a human, which are remedied or alleviated by oxytocin antagonist activity including, but not limited to, treatment or prevention of preterm labor, dysmenorrhea and suppressing labor prior to caesarian delivery whenever desirable in a mammal, preferably in a human. The methods comprise administering to a mammal in need thereof a pharmaceutically or therapeutically effective amount of one or more of the compounds of this invention. 
     The present invention also comprises combinations of the compounds of the present invention with one or more agents useful in the treatment of disorders such as preterm labor, dysmenorrhea, and stopping labor prior to caesarian delivery. More specifically, the compounds of the present invention may be effectively administered in combination with effective amounts of other tocolytic agents used in the treatment or prevention of preterm labor, dysmenorrhea or suppressing labor prior to caesarean delivery including β-adrenergic agonists, calcium channel blockers, prostaglandin synthesis inhibitors, other oxytocin antagonists (e.g. atosiban), magnesium sulfate, ethanol, and other agents useful in the treatment of said disorders. The present invention is to be understood as embracing all simultaneous or alternating treatments of any combination of the compounds of the present invention with other tocolytic agents with any pharmaceutical composition useful for the treatment of preterm labor, dysmenorrhea, and suppressing labor prior to caesarean delivery in mammals. 
     The compositions are preferably adapted for intravenous (both bolus and infusion) and oral administration. However, they may be adapted for other modes of administration including subcutaneous, intraperitoneal, or intramuscular administration to a human or a farm animal in need of a tocolytic agent. 
     The compounds of the present invention can be used in the form of salts derived from non toxic pharmaceutically acceptable acids or bases. These salts include, but are not limited to, the following: salts with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and, as the case may be, such organic acids as acetic acid, oxalic acid, citric acid, tartaric acid, succinic acid, maleic acic, benzoic acid, benzene sulfonic acid, fumaric acid, malic acid, methane sulfonic acid, pamoic acid, and para-toluen sulfonic acid . Other salts include salts with alkali metals or alkaline earth metals, such as sodium, potassium, calcium or magnesium, or with organic bases including quaternary ammonium salts. The compounds can also be used in the form of esters, carbamates and other conventional prodrug forms, which in general, will be functional derivatives of the compounds of this invention which are readily converted to the active moiety in vivo. This is meant to include the treatment of the various conditions described hereinbefore with a compound of this invention or with a compound which is not specifically disclosed but which converts to a compound of this invention in vivo upon administration. Also included are metabolites of the compounds of the present invention defined as active species produced upon introduction of these compounds into a biological system. 
     When the compounds of this invention are employed for the above utilities, they may be combined with one or more pharmaceutically acceptable excipients or carriers, for example, solvents, diluents and the like, and may be administered orally in such forms as tablets, capsules (including time release and sustained release formulations), pills, dispersible powders, granules, or suspensions containing, for example, from 0.05 to 5% of suspending agent, syrups containing, for example, from about 10 to 50% of sugar, and elixirs and the like, or parenterally in the form of sterile injectable solutions, suspensions or emulsions containing from about 0.05 to 5% suspending agent in an isotonic medium. Such pharmaceutical preparations may contain, for example, from about 25 to about 90% of the active ingredient in combination with the carrier, more usually between about 5% and 60% by weight. 
     The effective dosage of active ingredients employed may vary depending on the particular compound or salt employed, the mode of administration, age, weight, sex and medical condition of the patient, and the severity of the condition being treated. An ordinarily skilled physician, veterinarian or clinician can readily determine and prescribe the effective amount of the agent required to prevent, counter or arrest the progress of the condition. However, in general, satisfactory results are obtained when the compounds of the invention are administered at a daily dose of from about 0.5 to about 500 mg/Kg of mammal body weight, preferably given in divided doses two to four times a day, or in a sustained release form. For most large mammals the total daily dosage is from about 0.5 to 100 mg, preferably from 0.5 to 80 mg/Kg. Dosage forms suitable for internal use comprise from about 0.05 to 500 mg of the active compound in intimate admixture with a solid or liquid pharmaceutically acceptable carrier. This dosage re.g.imen may be adjusted to provide the optimal therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation. 
     These active compounds may be administered orally as well as by intravenous, intramuscular, or subcutaneous routes. Solid carriers include starch, lactose, dicalcium phosphate, microcrystalline cellulose, sucrose and kaolin, while liquid carriers include sterile water, polyethylene glycols, glycerol, non-ionic surfactants and edible oils such as corn, peanut and sesame oils, as are appropriate to the nature of the active ingredient and the particular form of administration desired. Adjuvants customarily employed in the preparation of pharmaceutical compositions may be advantageously included, such as flavoring agents, coloring agents, preserving agents, and antioxidants, for example vitamin E, ascorbic acid, BHT and BHA. 
     These active compounds may also be administered parenterally or intraperitoneally. Solutions or suspensions of these active compounds as a free base or pharmacologically acceptable salt can be prepared in water suitably mixed with a surfactant such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols and mixtures thereof in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. 
     The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases, the form must be sterile and must be fluid to the extent that easy injectability exists. It must be stable under conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol (e.g. glycerol, propylene glycol, and liquid polyethylene glycol), suitable mixtures thereof, and vegetable oil. 
     Furthermore, active compounds of the present invention can be administered intranasally using vehicles suitable for intranasal delivery, or transdermally using transdermal skin patches known to those ordinarily skilled in the art. When using a transdermal delivery system, the dosage administration will be continuous rather than in a single or divided daily doses. The compounds of the present invention can also be administered in the form of liposome delivery system wherein the liposomal lipid bilayers are formed from a variety of phospholipids. 
     Compounds of the present invention may also be delivered by the use of carriers such as monoclonal antibodies to which the active compounds are coupled. The compounds of the present invention may also be coupled to soluble polymers as drug carriers or to biode.g.radable polymers useful in achieving controlled release of the active agent. 
     Also according to the present invention there are provided processes for producing the compounds of the present invention. 
     Process of the Invention 
     The compounds of the present invention may be prepared according to one of the general processes outlined below. 
     The compounds of general formula (I) wherein R 4  consists of the moiety B-C, where B is selected from the group (a) or (b) and C is selected from the group of (c), (d), (e) and (f) defined hereinbefore, can be conveniently prepared as shown in Scheme I. 
     
       
                 
         
             
             
         
      
     
     According to the above preferred process, a tricyclic diazepine of formula (1) wherein 
                                
R 3  and R 4  are defined hereinbefore, is reacted with perhaloalkanoyl halide preferably trichloroacetyl chloride in the presence of an organic base such as N,N-diisopropylethyl amine (Hünig&#39;s base) in an aprotic organic solvent such as dichloromethane at temperatures ranging from −10° C. to ambient to provide the desired trichloroacetyl intermediate of formula (2). Subsequent hydrolysis of (2) with aqueous base such as sodium hydroxide in an organic solvent such as tetrahydrofuran or acetone at temperatures ranging from −10° C. to ambient, yields the intermediate acid of formula (3). The required activation of the carboxylic acid (3) for the subsequent coupling with a primary or secondary amine, hydroxylamine or hydrazine of formula (5) can be accomplished in several ways. Thus, (3) can be converted to an acid halide preferably a chloride or bromide of formula (4, J=COCl or COBr) by reaction with thionyl chloride(bromide) or oxalyl chloride(bromide) or similar reagents known in the art, either neat or in the presence of an inorganic base such as potassium carbonate, or in the presence of an organic base such as pyridine, 4-(dimethylamino)pyridine, or a tertiary amine such as triethylamine in an aprotic solvent such as dichloromethane, N,N-dimethylformamide or tetrahydrofuran at temperatures ranging from −5° C. to 50° C. to yield the intermediate acylated derivative (4). Subsequent coupling of the acid chloride(bromide) (4, J=COCl or COBr) with an appropriately substituted primary or secondary amine, hydroxylamine or hydrazine of formula (5) in the presence of a stoichiometric amount of Hünig&#39;s base in an aprotic solvent such as dichloromethane, N,N-dimethylformamide or tetrahydrofuran at temperatures ranging from ambient to the reflux temperature of the solvent provides the desired compounds of formula (I) wherein
 
                                
R, R 3  and R 4  are as defined hereinbefore.
 
     Alternatively, the acylating species can be a mixed anhydride of the corresponding carboxylic acid, such as that prepared by treating said acid of formula (3) with 2,4,6-trichlorobenzoyl chloride in an aprotic organic solvent such as dichloromethane according to the procedure of Inanaga et al.,  Bull. Chem. Soc. Jpn.  52, 1989 (1979). Treatment of said mixed anhydride of formula (4) with an appropriately substituted primary or secondary amine, hydroxylamine or hydrazine of formula (5) in an aprotic solvent such as dichloromethane, at temperatures ranging from ambient to the reflux temperature of the solvent provides the desired compounds of formula (I) wherein 
                                
R, R 3  and R 4  are as defined hereinbefore.
 
     Alternatively, amidation of the carboxylic acids of formula (3) can be effectively carried out by treatment of said acid with triphosgene in an aprotic solvent such as dichloromethane followed by reaction of the activated intermediate with an appropriately substituted primary or secondary amine, hydroxylamine or hydrazine of formula (5) in the presence of an organic base such as Hunig&#39;s base at temperatures ranging from −10° C. to ambient. 
     Another preferred process for the preparation of the compounds of the present invention of formula (I) wherein 
                                
R, R 3  and R 4  are as defined hereinbefore, consists of treating the acid of formula (3) with an activating reagent such as N,N-dicyclohexylcarbodiimide or 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide hydrochloride in the presence of 1-hydroxybenzotriazole followed by reaction of the activated intermediate with an appropriately substituted primary or secondary amine, hydroxylamine or hydrazine of formula (5), preferably in the presence of an organic base such as Hünig&#39;s base and a catalytic amount of 4-(dimethylamino)pyridine, in an aprotic solvent such as dichloromethane, N,N-dimethylformamide or tetrahydrofuran, at temperatures ranging from −10° C. to ambient.
 
     In another preferred process, said acid (3) can be activated by treatment with other activating agents such as N,N′carbonyldiimidazole, in an aprotic solvent such as dichloromethane or tetrahydrofuran, at temperatures ranging from −10° C. to the reflux temperature of the solvent. Subsequent reaction of the intermediate activated imidazolide with an appropriately substituted primary or secondary amine, hydroxylamine or hydrazine of formula (5) provides the desired compounds of formula (I) wherein 
                                
R, R 3  and R 4  are as defined hereinbefore.
 
     Alternatively, the coupling of the appropriately substituted primary or secondary amine of formula (5) with said acid of formula (3) can be effectively carried out by using hydroxybenzotriazole tetramethyluronium hexafluorophosphate as the coupling reagent in the presence of an organic base such as Hünig&#39;s base, and in a solvent such as N,N-dimethylformamide, at temperatures ranging from −10° C. to ambient to provide in good isolated yield and purity the desired compounds of formula (I) wherein 
                                
R, R 3  and R 4  are as defined hereinbefore.
 
     Related coupling reagents such as diphenylphosphoryl azide, diethyl cyano phosphonate, benzotriazol-1-yl-oxy-tris-(dimethylamino) phosphonium hexafluorophosphate and all other reagents known in the literature that have been used in the formation of amide bonds in peptide synthesis can also be used for the preparation of compounds of formula (I) wherein 
                                
R, R 3  and R 4  are as defined hereinbefore.
 
     As an alternative, reaction of the intermediate 3-trihalomethylketone of formula (2) directly with an appropriately substituted primary or secondary amine, hydroxylamine or hydrazine of formula (5) also provides the desired compounds of formula (I) wherein 
                                
R, R 3  and R 4  are as defined hereinbefore.
 
     The method of choice for the preparation of compounds of formula (I) from the intermediate carboxylic acid (3) is ultimately chosen on the basis of its compatibility with the R, R 3  and R 4  groups, and its reactivity with the tricyclic diazepine of formula (1). 
     Another preferred process for the preparation of (I) of Scheme I is shown in Scheme II. A tricyclic diazepine of formula (1) is reacted with diphosgene in an aprotic solvent such as dichloromethane preferably in the presence of an organic base such as triethylamine, followed by reaction of the resulting acylated intermediate with an appropriately substituted primary or secondary amine, hydroxylamine or hydrazine of formula (5) to provide the desired compounds of formula (I) wherein 
                                
R, R 3 and R 4  are as defined hereinbefore.
 
     
       
                 
         
             
             
         
      
     
     The tricyclic diazepines of formula (1) of Scheme (I) wherein R 4  is defined hereinbefore, can be conveniently prepared as shown in Scheme III. 
     
       
                 
         
             
             
         
      
     
     Thus, a tricyclic diazepine of formula (6) is treated with an appropriately substituted acylating agent such as an aroyl halide, preferably an appropriately substituted acyl chloride (or bromide) of formula (7, J=COCl or COBr) wherein R 4  is ultimately chosen on the basis of its compatibility with the present reaction scheme, in the presence of an inorganic base such as potassium carbonate, or in the presence of an organic base such as pyridine, 4-(dimethylamino)pyridine, or a tertiary amine such as triethylamine or N,N-diisopropylethyl amine, in an aprotic solvent such as dichloromethane, N,N-dimethiylformamide or tetrahydrofuran, at temperatures ranging from −5° C. to 50° C. to provide intermediates of general formula (1) wherein R 4  is defined hereinbefore. 
     Alternatively, the acylating species of formula (7) can be a mixed anhydride of the corresponding carboxylic acid, such as that prepared by treating said acid with 2,4,6-trichlorobenzoyl chloride in an aprotic organic solvent such as dichloromethane according to the procedure of Inanaga et al.,  Bull. Chem. Soc. Jpn.,  52, 1989 (1979). Treatment of said mixed anhydride of general formula (7) with a tricyclic diazepine of formula (6) in a solvent such as dichloromethane and in the presence of an organic base such as 4-(dimethylamino)pyridine at temperatures ranging from 0° C. to the reflux temperature of the solvent, yields the intermediate acylated derivative (1) of Scheme III. 
     The acylating intermediate of formula (7) is ultimately chosen on the basis of its compatibility with the R 4  groups, and its reactivity with the tricyclic diazepine of formula (6). 
     The desired intermediates of formula (7) of Scheme III wherein R 4  consists of the moiety B-C wherein B is (a) and C is (c) can be conveniently prepared by a process shown in Scheme IV. Thus, an appropriately substituted aryl(heteroaryl) iodide (bromide, chloride, or trifluoromethane sulfonate) of formula (8, wherein P is a carboxylic acid protecting group, preferably P=alkyl or benzyl, M=I, Br, Cl, OTf), and A, R 5 , R 6  and R 7  are defined hereinbefore, is reacted with an aryl(heteroaryl) tri(alkyl)tin(IV) derivative of formula (9, W=Sn(trialkyl) 3 , preferably Sn(n-Bu) 3 ) wherein A, R 8 , R 9  and R 10  are defined hereinbefore, in the presence of a Pd(0) catalyst in the presence or absence of inorganic salts (e.g. LiCl), to provide the intermediate ester (10). Subsequent unmasking of the carboxylic acid by hydrolysis, hydrogenolysis or similar methods known in the art, followed by activation of the intermediate acid (11) provides the desired intermediates of formula (19) wherein A, R 5 , R 6 , R 7 , R 8 , R 9  and R 10  are hereinbefore defined, suitable for coupling with the tricyclic diazepine of formula (6). 
                                
The desired intermediates of formula (7) of Scheme III wherein R 4  consists of the moiety B-C where B is (a) and C is (d), (e) or (f) or B is (b) and C is either (c), (d), (e) or (f) can be prepared by a process analogous to that exemplified in Scheme IV by replacing intermediates of formula (8 and 9) with appropriately substituted naphthyl, quinolyl, pyrimidinyl or pyrazinyl intermediates.
 
     Alternatively, the desired intermediates of formula (10) of Scheme IV wherein R 4  consists of the moiety B-C where B is (a) and C is (c) can be prepared by coupling of the iodide(bromide, chloride, trifluoromethanesulfonate) (8, M=I, Br, Cl, or OTf) with an appropriately substituted aryl(heteroaryl) boron derivative of formula (9, preferably W=B(OH) 2 ) in the presence of a palladium catalyst such as palladium(II) acetate or tetrakis(triphenylphosphine) palladium(0) and an organic base such as triethylamine or an inorganic base such as sodium(potassium or cesium) carbonate with or without added tetrabutylammonium bromide(iodide), in a mixture of solvents such as toluene-ethanol-water, acetone-water, water or water-acetonitrile at temperatures ranging from ambient to the reflux temperature of the solvent (Suzuki,  Pure  &amp;  Appl. Chem.  66, 213–222 (1994), Badone et al.,  J. Org. Chem.  62, 7170–7173 (1997); Wolfe et al.  J. Am. Chem. Soc.  121, 9559 (1999); Shen,  Tetr. Letters  38, 5575 (1997)). The exact conditions for the Suzuki coupling of the halide and the boronic acid intermediates are chosen on the basis of the nature of the substrate and the substituents. Alternatively, the coupling of (8, M=I or Br) with (9, A=N) can be carried out by using a dialkylborane, preferably a diethylpyridoborane in the presence of an inorganic base such as potassium hydroxide and tetrabutylammonium bromide(iodide) in an aprotic solvent such as tetrahydrofuran, according to the method of Ishikura et al.,  Synthesis  936–938 (1984). The desired intermediates of formula (10) of Scheme IV can be similarly prepared from the bromide (8, M=Br) and the boronic acid (9) in a solvent such as dioxane, in the presence of potassium phosphate and a Pd(0) catalyst. 
     Alternatively, a cross coupling reaction of an iodide (bromide, or trifluoromethanesulfonate) of formula (9, W=Br, I, OTf) with a bis(pinacolato)diboron [boronic acid, or trialkyl tin(IV)] derivative of formula (8, M= 
                                
B(OH) 2 , or SnBu 3 ) yields the desired intermediate of formula (10) which is converted to (I) in the manner of Scheme IV.
 
     The desired intermediates of formula (10) of Scheme IV wherein R 4  consists of the moiety B-C wherein B is (a) and C is (d), (e) or (f), or B is (b) and C is either (c), (d), (e) or (f), can be prepared in analogous fashion by replacing intermediates of formulas (8 and 9) with appropriately substituted naphthyl, quinolyl, pyrimidinyl or pyrazinyl intermediates. 
     The required appropriately substituted aryl(heteroaryl) halides of formula (8, M=Br or I) of Scheme IV are either available commercially, or are known in the art or can be readily accessed in quantitative yields and high purity by diazotization of the corresponding substituted anilines (8, P=H, alkyl or benzyl, M=NH 2 ) followed by reaction of the intermediate diazonium salt with iodine and potassium iodide in aqueous acidic medium essentially according to the procedures of Street et al,.  J. Med. Chem.  36, 1529 (1993) and Coffen et al.,  J. Org. Chem.  49, 296 (1984) or with copper(I) bromide, respectively (March,  Advanced Organic Chemistry,  3 rd  Edn., p. 647–648, John Wiley &amp; Sons, New York (1985)). 
     Alternatively, the desired intermediates of formula (11, A=CH) of Scheme IV wherein R 4  consists of the moiety B-C wherein B is (a, A=CH) and C is (c, A=CH) can be conveniently prepared as shown in Scheme V by cross-coupling reaction of an appropriately substituted pinacolato borane of formula (13, A=CH) wherein R 8 , R 9  and R 10  are hereinbefore defined, with an aryl triflate of formula (14, Y=OTf) or an aryl halide (14, Y=Br, I) wherein R 5 , R 6  and R 7  are defined hereinbefore, according to the general procedures of Ishiyama et al.,  Tetr. Lett.  38, 3447–3450 (1997) and Giroux et al.  Tetr. Lett.  38, 3841–3844 (1997), followed by basic or acidic hydrolysis of the intermediate nitrile of formula (15) (cf. March,  Advanced Organic Chemistry,  3rd Edn., John Wiley &amp; Sons, New York, p. 788 (1985)). 
     
       
                 
         
             
             
         
      
     
     Alternatively, reaction of an iodide (bromide, chloride, or trifluoromethanesulfonate) of formula (12, X=Br, Cl, I, or OTf) with a bis(pinacolato)diboron [boronic acid or trialkyltin(IV)] derivative of formula (14, Y= 
                                
B(OH) 2 , or SnBu 3 ) yields the desired intermediate of formula (15) which is converted to (11) in the manner of Scheme V.
 
     The desired intermediates of formula (11) of Scheme IV can be prepared in analogous fashion by replacing intermediates of formulas (13 and 14) with appropriately substituted naphthyl intermediates. 
     The desired phenyl boronic esters of formula (13) of Scheme V can be conveniently prepared by the palladium-catalyzed cross-coupling reaction of the pinacol ester of diboronic acid (16) with an appropriately substituted aryl halide preferably a bromide or iodide (12, X=Br, I) or aryl triflate (12, X=OTf) according to the described procedures of Ishiyama et al.,  J. Org. Chem.  60, 7508–7510 (1995) and Giroux et al.,  Tetr. Lett.  38, 3841–3844 (1997). 
     The desired compounds of formula (1) of Scheme IV wherein R 4  consists of the moiety B-C wherein B is (a) and C is (c) can be alternatively prepared by a process shown in Scheme VI. 
     
       
                 
         
             
             
         
      
     
     Thus, a tricyclic diazepine of formula (6) is treated with an appropriately substituted acylating agent such as a halo aroyl(heteroaroyl)halide, preferably an iodo(bromo) aroyl(heteroaroyl) chloride(bromide) of formula (17, J=COCl or COBr; X=I, Br) wherein A, R 5 , R 6  and R 7  are hereinbefore defined using any of the procedures hereinbefore described, to provide the acylated intermediate of general formula (18) of Scheme VI. 
     Alternatively, the acylating species of formula (17) can be a mixed anhydride of the corresponding carboxylic acid. Treatment of said mixed anhydride of general formula (17) with a tricyclic diazepine of formula (6) according to the procedure described hereinbefore yields the intermediate acylated derivative (18). 
     The acylating intermediate of formula (17) is ultimately chosen on the basis of its compatibility with A and the R 5 , R 6  and R 7  groups, and its reactivity with the tricyclic diazepine of formula (6). 
     A Stille coupling reaction of (18, X=I) with an appropriately substituted organotin reagent such as a trialkyltin(IV) derivative, preferably a tri-n-butyltin(IV) derivative of formula (9, W=SnBu 3 ) where A, R 8 , R 9  and R 10  are hereinbefore defined, in the presence of a catalyst such as tetrakis (triphenylphosphine) palladium (0) in an aprotic organic solvent such as toluene and N,N-dimethylformamide, at temperatures ranging from ambient to 150° C. (cf. Farina et al.,  J. Org. Chem,  59, 5905 (1994) and references cited therein) affords the desired compounds of formula (1) wherein 
                                
A, R 3 , R 5 , R 6 , R 7 , R 8 , R 9  and R 10  are as defined hereinbefore.
 
     Alternatively, the reaction of a compound of formula (18, X=Cl, Br or I) with an appropriately substituted aryl(heteroaryl) boronic acid of formula (9, W=B(OH) 2 ) wherein A, R 5 , R 6 , R 7 , R 8 , R 9  and R 10  are hereinbefore defined, in a mixture of solvents such as toluene-ethanol-water, and in the presence of a Pd(0) catalyst and a base such as sodium carbonate, at temperatures ranging from ambient to the reflux temperature of the solvent, yields the desired compounds of formula (1) wherein 
                                
A, R 3 , R 5 , R 6 , R 7 , R 8 , R 9  and R 10  are as defined hereinbefore.
 
     The preferred substituted aroyl(heteroaroyl) chlorides(bromides) of formula (17) of Scheme VI (X=I, Br; J=COCl or COBr) wherein A, R 5 , R 6  and R 7  are as defined hereinbefore, are either available commercially, or are known in the art, or can be readily prepared by procedures analogous to those in the literature for the known compounds. 
     The intermediates of formula (9, W=Sn(alkyl) 3 , alkyl=n-butyl) of Scheme VI are either commercially available, or can be conveniently prepared as shown in Scheme VII from the corresponding bromo starting materials of formula (20) wherein A, R 8 , R 9 , and R 10  are hereinbefore defined, by first reacting them with n-butyl lithium followed by reaction of the intermediate lithiated species with a trialkyl (preferably trimethyl or tri-n-butyl)tin(IV) chloride. 
     
       
                 
         
             
             
         
      
     
     The preferred substituted aryl(heteroaryl) boronic acids of formula (9, W=B(OH) 2 ) are either available commercially, or are known in the art, or can be readily prepared by procedures analogous to those in the literature for the known compounds. 
     The desired compounds of formula (1) of Scheme VI wherein R 4  consists of the moiety B-C wherein B is (a) and C is (d), (e) or (f), or B is (b) and C is either (c), (d), (e) or (f) can be prepared in analogous fashion by replacing intermediates of formulas (17 and 9) with appropriately substituted naphthyl, quinolyl, pyrimidinyl or pyrazinyl intermediates. 
     Alternatively, as shown in Scheme Vil, the appropriately substituted aroyl(heteroaroyl) halides, preferably aroyl(heteroaroyl) chlorides of formula (21, J=COCl) where A, R 5 , R 6  and R 7  are hereinbefore defined, are reacted with a tricyclic diazepine of formula (6) to provide the intermediate bromides of formula (22). Subsequent reaction of (22) with an hexa alkyl-di-tin (preferably hexa-n-butyl-di-tin(IV)) in the presence of a Pd(0) catalyst such as tetrakis(tri-phenylphosphine)palladium(0) and lithium chloride, provides the stannane intermediate of formula (23). Further reaction of the tri-n-butyl tin(IV) derivative (23) with the appropriately substituted aryl(heteroaryl) halide of formula (24, M=bromo or iodo) wherein A, R 8 , R 9 , and R 10  are hereinbefore defined, in the presence of a Pd(0) catalyst such as tetrakis(triphenylphosphine) palladium(0), yields the desired compounds of formula (1) wherein R 4  consists of the moiety B-C wherein B is (a) and C is (c), and 
                                
A, R 5 , R 6 , R 7 , R 8 , R 9  and R 10  are defined hereinbefore.
 
     
       
                 
         
             
             
         
      
     
     The desired compounds of formula (1) of Scheme VII wherein R 4  consists of the moiety B-C wherein B is (a) or (b) and C is (d), (e) or (f) can be prepared in analogous fashion by replacing intermediates of formulas (21 and 24) with appropriately substituted naphthyl, quinolyl, pyrimidinyl or pyrazinyl intermediates. 
     Alternatively, the desired compounds of formula (1) of Scheme VIII wherein R 4  consists of the moiety B-C wherein B is (a, A=CH), and C is (c, A=CH) can be prepared as shown in Scheme IX. 
     
       
                 
         
             
             
         
      
     
     Thus, an appropriately substituted biphenyl of formula (43) wherein R 5 , R 6 , R 7 , R 8 , R 9  and R 10  are defined hereinbefore, is treated with carbon monoxide in the presence of a tricyclic diazepine of formula (6), a palladium(0) catalyst preferably PdBr 2 (Ph 3 P) 2  and a tertiary amine preferably n-tributylamine, in a solvent such as anisole or dioxane at temperatures ranging from ambient to the reflux temperature of the solvent (cf. Schoenberg et al.,  J. Org. Chem.  39, 3327 (1974)) to provide the desired compounds of formula (1) wherein A is CH, and 
                                
, R 3 , R 5 , R 6 , R 7 , R 8 , R 9  and R 10  are defined hereinbefore.
 
     In analogous fashion one can prepare compounds of formula (1) of Scheme IX wherein R 4  consists of the moiety B-C wherein B is (b) and C is (c, A=CH) or (d, A=CH) provided that the intermediates of formula (43) are replaced by the appropriately substituted phenyl or naphthyl intermediates. 
     A preferred process for the preparation of the compounds of formula (1) of Scheme I wherein 
                                
, A, R 3 , R 5 , R 6  and R 7  are defined hereinbefore, R 4  consists of the moiety B-C wherein B is (a) and C is (g) defined hereinbefore, is shown in Scheme X.
 
     
       
                 
         
             
             
         
      
     
     Thus, an appropriately substituted aroyl(heteroaroyl) halide preferably an aroyl(heteroaroyl) chloride, of formula (25, J=COCl) is reacted with a tricyclic diazepine of formula (6) in the presence of a base such as pyridine, or a tertiary amine such as triethylamine or N,N-diisopropylethyl amine, in an aprotic organic solvent such as dichloromethane or tetrahydrofuran, at temperatures from −40° C. to 50° C. to provide the acylated intermediate of formula (26). Alternatively, the acylating species can be a mixed anhydride under the reaction conditions described hereinbefore. Subsequent reduction of (26) is preferably effected under conditions of catalytic reduction (i.e. hydrogen, Pd on charcoal), transfer hydrogenation (i.e. hydrazine/ethanol/Pd on charcoal) or under chemical reduction conditions (i.e. with tin(II)chloride dihydrate in a protic organic solvent such as ethanol, or zinc in acetic acid) or related reduction conditions known in the art, to yield the desired aniline of formula (27). The exact conditions for the conversion of the nitro to amino group are chosen on the basis of compatibility with the preservation of other functional groups in the molecule. Condensation of (27) with a 1,4-diketone of formula (28) in an aprotic organic solvent such as benzene or toluene in the presence of acetic acid or a catalytic amount of p-toluene sulfonic acid with concomitant removal of water at temperatures ranging from ambient to reflux temperature of the solvent according to the general procedure of Bruekelman et al.,  J. Chem. Soc. Perkin Trans. I,  2801–2807 (1984), provides the desired compounds of formula (1) wherein R consists of the moiety B-C wherein B is (a) and C is (9), and 
                                
, A, R 3 , R 5 , R 6 , R 7 , R 29  and R 30  are defined hereinbefore.
 
     The desired compounds of formula (1) of Scheme X wherein R 4  consists of the moiety B-C wherein B is (b) and C is (g) can be prepared in analogous fashion by replacing the intermediate of formula (25) with an appropriately substituted naphthyl. 
     Alternatively, the desired compounds of formula (1) of Scheme X can be prepared as shown in Scheme XI. 
     
       
                 
         
             
             
         
      
     
     According to this process an aryl(heteroaryl) nitrile of formula (29) is condensed with a 1,4-diketone of formula (28) in an aprotic organic solvent such as benzene or toluene, in the presence of acetic acid or a catalytic amount of p-toluenesulfonic acid with concomitant removal of water, at temperatures ranging from ambient to reflux temperature of the solvent according to the general procedure of Bruekelman et al.,  J. Chem. Soc. Perkin Trans. I,  2801–2807 (1984), to yield the intermediate pyrrole of formula (30). Subsequent hydrolysis of the nitrile (30) to the carboxylic acid of formula (31) is efficiently accomplished by treatment of (30) with aqueous base (cf. March,  Advanced Organic Chemistry,  3 rd  Edn., John Wiley &amp; Sons, New York, p. 788 (1985)). Subsequent conversion of the acid (31) into an acylating species, preferably an acid chloride(bromide) of formula (32, J=COCl or COBr) or a mixed anhydride is accomplished by procedures analogous to those described hereinbefore. The acylating agent (32) is used to acylate a tricyclic diazepine of formula (6) to provide the desired compounds of formula (1) wherein 
                                
A and R 3  are defined hereinbefore, and R 4  consists of the moiety B-C wherein B is (a) and C is the moiety (g) defined hereinbefore.
 
     The compounds of formula (1) of Scheme XI wherein R 4  consists of the moiety B-C wherein B is (b) and C is (g) defined hereinbefore can be prepared in analogous fashion by replacing the intermediates of formula (29) with an appropriately substituted naphthyl. 
     A preferred process for the preparation of the desired compounds of general formula (I) of Scheme I wherein R 4  consists of the moiety B-C, where B is selected from the group (a) and C is selected from the group (9) defined hereinbefore is shown in Scheme XII. 
     
       
                 
         
             
             
         
      
     
     Thus, a tricyclic diazepine of formula (33) wherein 
                                
and R 3  are defined hereinbefore, carrying a protecting group such as a fluorenylalkoxycarbonyl group, preferably a fluorenylmethyloxycarbonyl (P=Fmoc) group, or an alkoxycarbonyl protecting group preferably a tert-butyloxycarbonyl (P=Boc) group is reacted with a perhaloalkanoyl halide preferably trichloroacetyl chloride in the presence of an organic base such as N,N-diisopropylethyl amine (Hünig&#39;s base) or a tertiary amine such as triethylamine, optionally in the presence of catalytic amounts of 4-(dimethylamino)pyridine, in an aprotic organic solvent such as dichloromethane, at temperatures ranging from −10° C. to ambient to provide the desired trichloroacetyl intermediate of formula (34). Subsequent hydrolysis of the trichloroacetyl group with aqueous base such as sodium hydroxide in an organic solvent such as acetone at temperatures ranging from −10° C. to ambient, is accompanied by simultaneous removal of the protecting group and yields the intermediate acid of formula (35). The required amidation of the carboxylic acid (35) can be effectively accomplished by treating (35) with an activating reagent such as N,N-dicyclohexylcarbodiimide or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in the presence of 1-hydroxybenzotriazole, followed by reaction of the activated intermediate with an appropriately substituted primary or secondary amine of formula (5) preferably in the presence of Hünig&#39;s base or a catalytic amount of 4-(dimethylamino)pyridine, in an aprotic solvent such as dichloromethane, N,N-dimethylformamide or tetrahydrofuran, at temperatures ranging from −10° C. to ambient.
 
     Other coupling reagents known in the literature that have been used in the formation of amide bonds in peptide synthesis can also be used for the preparation of compounds of formula (36) wherein 
                                
R and R 3  are as defined hereinbefore. The method of choice for the preparation of compounds of formula (36) from the intermediate carboxylic acid (35) is ultimately chosen on the basis of its compatibility with the various substituents, and its reactivity with the tricyclic diazepine of formula (6). Subsequent reaction of a tricyclic diazepine amide (36) with an acylating agent of formula (32) of Scheme XI provides the desired compounds of formula (I) wherein
 
                                
A and R 3  are defined hereinbefore, R 4  consists of the moiety B-C wherein B is (a) and C is the moiety (g) defined hereinbefore.
 
     The preferred compounds of formula (I) of Scheme I wherein R 4  consists of the moiety B-C wherein B is (b) and C is the moiety (g) defined hereinbefore, can be prepared in analogous fashion by replacing the intermediate of formula (32) of Scheme XII with an appropriately substituted naphthyl intermediate. 
     Preferred processes for the preparation of compounds of formula (I) of Scheme I wherein R 4  consists of the moiety B-C wherein B is (a) or (b) and C is (d), (e) or (f) and 
                                
A, R, R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  are defined hereinbefore, also utilize acylation of the amide intermediate (36) of Scheme XII with an acylating agent of formula (19) of Scheme IV.
 
     An alternate preferred process for the preparation of the compounds of formula (I) of Scheme I wherein R 4  consists of the moiety B-C wherein B is (a) and C is (g) defined hereinbefore, is shown in Scheme XIII. 
     
       
                 
         
             
             
         
      
       
                 
         
             
             
         
       
     
     According to the above process a substituted tricyclic diazepine of formula (37) wherein 
                                
A, R 3 , R 5 , R 6  and R 7  and are defined hereinbefore, carrying a protecting group such as a fluorenylalkoxycarbonyl group, preferably a fluorenylmethyloxycarbonyl (P=Fmoc) group is reacted with a perhaloalkanoyl halide preferably trichloroacetyl chloride in the presence of an organic base such as N,N-diisopropylethyl amine (Hünig&#39;s base) or a tertiary amine such as triethylamine in an aprotic organic solvent such as dichloromethane at temperatures ranging from −10° C. to ambient, to provide the desired trichloroacetyl intermediate of formula (38). Subsequent deprotection of (38) is carried out by treatment with a solution of an organic base preferably piperidine, in an organic solvent such as N,N-dimethylformamide, at ambient temperature to provide the desired aniline (44). Condensation of (44) with a 1,4-diketone of formula (28) either neat or in an aprotic organic solvent such as benzene or toluene, in the presence of a catalytic amount of a carboxylic acid preferably p-toluene sulfonic acid or acetic acid , with concomitant removal of water, at temperatures ranging from ambient to 100° C. or to the reflux temperature of the solvent according to the general procedure of Bruekelman et al.,  J. Chem. Soc. Perkin Trans. I,  2801–2807 (1984), provides the desired intermediate of formula (45). Subsequent hydrolysis of the trichloroacetyl group with aqueous base such as sodium hydroxide, in an organic solvent such as acetone or tetrahydrofuran, at temperatures ranging from −10° C. to the reflux temperature of the solvent, yields the intermediate carboxylic acid of formula (46). Subsequent amidation provides the desired compounds of formula (I) wherein R 4  consists of the moiety B-C wherein B is (a) and C is (g), and
 
                                
A, R 3 , R 5 , R 6 , R 7 , R 29  and R 30  are defined hereinbefore,
 
     The required amidation of (46) can be effectively accomplished by treating said carboxylic acid with an activating reagent such as N,N-dicyclohexylcarbodiimide or 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide hydrochloride in the presence of 1-hydroxybenzotriazole, followed by reaction of the activated intermediate with an appropriately substituted primary or secondary amine of formula (5) preferably in the presence of Hünig&#39;s base or a catalytic amount of 4-(dimethylamino)pyridine, in an aprotic solvent such as dichloromethane, N,N-dimethylformamide or tetrahydrofuran, at temperatures ranging from −10° C. to ambient. Other coupling reagents known in the literature that have been used in the formation of amide bonds in peptide synthesis can also be used for the preparation of compounds of formula (I) wherein R 4  consists of the moiety B-C wherein B is (a) and C is (g), and 
                                
A, R 3 , R 5 , R 6 , R 7 , R 29  and R 30  are defined hereinbefore. The method of choice for the preparation of compounds of formula (I) from the intermediate carboxylic acid (46) is ultimately chosen on the basis of its compatibility with the
 
                                
and R 3  groups, and its reactivity with the tricyclic diazepine of formula (6).
 
     The desired compounds of formula (I) of Scheme XII wherein R 4  consists of the moiety B-C wherein B is (b) and C is (g) can be prepared in analogous fashion by replacing the intermediate of formula (27) with an appropriately substituted naphthyl intermediate. 
     Alternatively, the intermediate acids of formula (35) of Scheme XII wherein 
                                
and R 3  are defined hereinbefore, can be obtained by reacting a tricyclic diazepine of formula (6) with an excess of acylating agent preferably trifluoroacetic anhydride or trichloroacetyl chloride in the presence of an inorganic base such as potassium carbonate or an organic base such as N,N-diisopropylethyl amine, in an aprotic solvent such as N,N-dimethylformamide, followed by basic hydrolysis of the intermediate bis-trifluoroacetyl (trichloroacetyl) intermediate of formula (39 X=F or Cl), preferably with aqueous sodium hydroxide in a protic organic solvent such as ethanol, at temperatures ranging from ambient to the reflux temperature of the solvent as exemplified in Scheme XIV.
 
     
       
                 
         
             
             
         
      
     
     Preferred processes for the preparation of compounds of formula (I) of Scheme I wherein R 4  consists of the moiety B-C wherein B is (a) or (b) and C is (d), (e) or (f) and 
                                
A, R, R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  are defined hereinbefore, also utilize acylation of the amide intermediate (36) of Scheme XII with an acylating agent of formula (17) of Scheme IV, as shown in Scheme XV.
 
     
       
                 
         
             
             
         
      
     
     Alternatively, the preferred compounds of formula (I) of Scheme I wherein R 4  consists of the moiety B-C wherein B is (a) and C is (c) and 
                                
A, R, R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  are defined hereinbefore, can be prepared by acylation of the amide intermediate (36) of Scheme XII with an acylating agent of formula (21) of Scheme VIII, as shown in Scheme XVI.
 
     
       
                 
         
             
             
         
      
     
     Alternatively, the preferred compounds of formula (I) of Scheme (I) wherein R 4  consists of the moiety B-C wherein B is (a) and C is (c) and 
                                
A, R, R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  are defined hereinbefore, can be prepared by acylation of the amide intermediate (36) of Scheme XII with an acylating agent of formula (19) of Scheme IV, wherein J is hereinbefore defined, as shown in Scheme XVII.
 
     
       
                 
         
             
             
         
      
     
     The subject compounds of the present invention were tested for biological activity according to the following procedures. 
     Vasopressin Binding in Chinese Hamster Ovary Cell Membranes Expressing Human Vasopressin V 1a  Subtype Receptors 
     Receptor Source: 
     Chinese hamster ovary cells (CHO cells) stably transfected with the human vasopressin V 1a  subtype receptors were either obtained from BioSignal Inc., 1744 rue Williams, Montreal, Quebec, Canada or obtained from M. Thibonnier, Case Western Reserve University School of Medicine, Cleveland, Ohio.
 
A. Passaging and Amplification of Cells:
 
CHO cells transfected with the human vasopressin V 1a  subtype receptors obtained from M. Thibonnier (pZeoSV vector) are allowed to grow to confluency (approx. &gt;90%) in T-150 flasks under sterile conditions, in a cell culture medium of F-12 Nutrient Mixture (HAM) with L-glutamine (Gibco Cat. # 11765-054) containing 15 mM HEPES (Gibco Cat. # 15630-080), 1% antibiotic/antimycotic (add 5 mL 100×, Gibco Cat. # 15240-062 per 500 mL F-12), 250 μg/mL Zeocin (add 1.25 mL of 100 mg/mL Invitrogen R-250-01 per 500 mL F-12) and 10% Fetal Bovine Serum (Qualified, heat inactivated, Gibco Cat. # 16140-063). The medium is removed by aspiration and the cells are washed with 10 mL of Hank&#39;s Balanced Salt solution (Gibco Cat. # 14175-095). The salt solution is removed by aspiration and the cells are trypsinized with 5 mL of trypsin-EDTA (0.05% trypsin, 0.53 mM EDTA-4Na, Gibco Cat. # 25300-070) for 1 min. The trypsin is removed by aspiration and the cells dislodged by tapping. Cell Culture medium (e.g. 30 mL for 1:30 split) is immediately added and mixed well to inactivate trypsin. 1 mL of detached cells is added to new culture flasks containing fresh cell culture medium (e.g., into 25 mL per T-150 flask), and mixed gently. The cells are incubated at 37° C. in 5% CO 2 . The medium is changed at 3 to 4 days interval (or as appropriate). The cells grow to confluency (approx. &gt;75%–95%) within 7–8 days. All steps are done under sterile conditions.
 
B. Membrane Preparation:
 
The cells are washed twice gently with Hank&#39;s Balanced Salt solution (e.g,. use 10 mL per T-150 flask). The excess is removed and the cells are bathed for 15–30 min. in an enzyme-free Cell Dissociation Buffer (e.g. use 8 mL Hank&#39;s Based, Gibco Cat. # 13150-016 per T-150 flask) until the cells are loosened. The contents are transferred to centrifuge tubes (50 mL) kept in an ice bath. All subsequent steps are done at 4° C. The tubes are centrifuged at 300×g for 15 min (1380 rpm on SORVAL, Model RT6000D, using the rotor for 50 mL tubes). The supernatant is discarded and the cells suspended in homogenizing buffer(10 mM Tris-HCl containing 0.25 M sucrose and 1 mM EDTA, pH 7.4) ensuring that the volume of the buffer is about ten times the volume of the cell pellet. The cells are pooled into a centrifuge tube (50 mL) and homogenized with a Polytron at setting 6 for 10 sec. The homogenate is transferred into a Potter-Elvjehm homogenizer and homogenized with 3 strokes. The homogenate is centrifuged at 1500×g for 10 min at 4° C. (3100 rpm using SORVAL, model RT6000D, using the rotor for 50 mL tubes). The pellet is discarded. The supernatant is centrifuged at 100,000×g for 60 min. at 4° C. (Beckman L8-80M ultracentrifuge; spin at 37,500 rpm with rotor type 70 Ti for 50 mL tubes; 38,000 rpm with type 80Ti for 15 mL tubes; or 35,800 rpm with rotor type 45Ti). The supernantant is discarded and the pellet suspended in 3 to 4 mL of Tris buffer (50 mM TRIS-HCl, pH 7.4). The protein content is estimated by the Bradford or Lowry method. The volume of the membrane suspension is adjusted with the membrane buffer (50 mM Tris-HCl containing 0.1% BSA and 0.1 mM PMSF) to give 3.0 mg/mL (or as appropriate) of protein. The membranes are aliquoted and stored at −70° C.
 
C. Radioligand Binding Assay:
 
In wells of a 96-well format microtiter plate, is added 90, 110 or 130 μL (to make up a final volume of 200 μL) of assay buffer containing 50 mM of Tris-HCl (pH 7.4), BSA (heat inactivated, protease-free), 0.1% of 5 mM MgCl 2 , 1 mg % aprotinin, 1 mg % leupeptin, 2 mg % 1,10-phenanthroline, 10 mg % trypsin inhibitor, and 0.1 mM PMSF. The inhibitors are added on the day of the experiment. The components are mixed at room temperature, and then kept in ice bath following adjustment of the pH to 7.4.
 
To each well is added 20 μL of unlabeled Manning ligand (to give a final concentration of 0.1 to 10 nM for standard curve and 1000 nM for non specific binding) or test compounds in 50% DMSO (e.g. for final concentrations of 0.1 to 1000 nM or as appropriate) or 50% DMSO as vehicle control. 20 μL of 50% DMSO is added for Manning and other peptide ligands and the assay buffer volume is adjusted accordingly.
 
To each well is added 50 μL of frozen membrane suspension thawed immediately prior to use and diluted in the assay buffer to the required concentration (equivalent to 25 to 50 μg of protein/well as needed). 20 μL of 8 nM [ 3 H]Manning ligand in the assay buffer, prepared just before use, is added, and incubated at room temperature for 60 min. shaking the plate on a mechanical shaker for the first 15 min. The incubation is stopped by rapid filtration of the the plate contents followed by wash with ice-cold buffer (50 mM Tris-HCl, pH 7.4) using a cell harvester (Tomtek and Printed filtermat-B filter paper). The filter paper is thoroughly dried (7–12 min. in a microwave oven) and impregnated with MeltiLex B/H melt-on scintillation wax sheets and the radioactivity counted in a betaplate scintillation counter.
 
     Vasopressin Binding in Chinese Hamster Ovary Cell Membranes Expressing Human Vasopressin V 2  Subtype Receptors 
     Receptor Source: 
     Chinese Hamster Ovary (CHO) cells stably transfected with the human V 2  subtype receptors were obtained from M. Thibonnier, Case Western Reserve University School of Medicine, Cleveland, Ohio. 
     A. Passaging and Amplification of Cells: 
     CHO cells transfected with the human vasopressin V 2  subtype receptors obtained from M. Thibonnier (pZeoSV vector) are allowed to grow to confluency (approx. &gt;90%) in T-150 flasks under sterile conditions, in a cell culture medium of F-12 Nutrient Mixture (HAM) with L-glutamine (Gibco Cat. # 11765-054) containing 15 mM HEPES (Gibco Cat. # 15630-080), 1% antibiotic/antimycotic (add 5 mL 100×, Gibco Cat. # 15240-062 per 500 mL F-12), 250 μg/mL Zeocin (add 1.25 mL of 100 mg/mL Invitrogen R-250-01 per 500 mL F-12) and 10% Fetal Bovine Serum (Qualified, heat inactivated, Gibco Cat. # 16140-063). The medium is removed by aspiration and the cells washed with 10 mL of Hank&#39;s Balanced Salt solution (Gibco Cat. # 14175-095). The salt solution is removed by aspiration and the cells trypsinized with 5 mL of trypsin-EDTA (0.05% trypsin, 0.53 mM EDTA-4Na, Gibco Cat. # 25300-070) for 1 min. The trypsin is removed by aspiration and the cells dislodged by tapping. Cell Culture medium (e.g. 30 mL for 1:30 split) is immediately added and mixed well to inactivate trypsin. 1 mL of detached cells is added to new culture flasks containing fresh Cell Culture medium (e.g. into 25 mL per T-150 flask), and mixed gently. The cells are incubated at 37° C. in 5% CO 2 . The medium is changed at 3 to 4 day interval (or as appropriate). The cells grow to confluency (approx. &gt;75%–95%) within 7–8 days. All steps are done under sterile conditions.
 
B. Membrane Preparation:
 
The cells are washed twice gently with Hank&#39;s Balanced Salt solution (e.g. use 10 mL per T-150 flask). The excess solution is removed and the cells bathed for 15–30 min. in an enzyme-free Cell Dissociation Buffer (e.g. use 8 mL Hank&#39;s Based, Gibco Cat. # 13150-016 per T-150 flask) until cells are loosened. The contents are transferred to centrifuge tubes (50 mL) kept in ice bath. All subsequent steps are done at 4° C. The tubes are centrifuged at 300×g for 15 min (1380 rpm on SORVAL, Model RT6000D, using the rotor for 50 mL tubes). The supernatant is discarded and the cells suspended in homogenizing buffer (10 mM Tris-HCl containing 0.25 M sucrose and 1 mM EDTA, pH 7.4) ensuring that the volume of the buffer is about ten times the volume of the cell pellet. The cells are pooled into a centrifuge tube (50 mL) and homogenized with a Polytron at setting 6 for 10 sec. The homogenate is transferred into a Potter-Elvjehm homogenizer and homogenized with 3 strokes. The homogenate is centrifuged at 1500×g for 60 min at 4° C. (3100 rpm using SORVAL, model RT6000D, using the rotor for 50 mL tubes). The pellet is discarded. The supernatant is centrifuged at 100,000×g for 60 min. at 4° C. (Beckman L8-80M ultracentrifuge; spin at 37,500 rpm with rotor type 70 Ti for 50 mL tubes; 38,000 rpm with type 80Ti for 15 mL tubes; or 35,800 rpm with rotor type 45Ti). The supernantant is discarded and the pellet suspended in 3 to 4 mL of Tris buffer (50 mM TRIS-HCl, pH 7.4). The protein content is estimated by the Bradford or Lowry method. The volume of the membrane suspension is adjusted with the membrane buffer (50 mM Tris-HCl containing 0.1% BSA and 0.1 mM PMSF) to give 3.0 mg/mL (or as appropriate) of protein. The membranes are aliquoted and stored at −70° C.
 
C. Radioligand Binding Assay:
 
In wells of a 96-well format microtiter plate, is added 90, 110 or 130 μL (to make up a final volume of 200 μL) of assay buffer containing 50 mM of Tris-HCl (pH 7.4), BSA (heat inactivated, protease-free), 5 mM of 0.1% MgCl 2 , 1 mg % aprotinin, 1 mg % leupeptin, 2 mg % 1,10-phenanthroline, 10 mg % trypsin inhibitor, and 0.1 mM PMSF. The inhibitors are added on the day of the experiment. The components are mixed at room temperature, and then kept in ice bath following adjustment of the pH to 7.4.
 
To each well is added 20 μL of unlabeled arginine vasopressin (AVP) (to give a final concentration of 0.1 to 10 nM for standard curve and 1000 nM for non specific binding) or test compounds in 50% DMSO (e.g. for final concentrations of 0.1 to 1000 nM or as appropriate) or 50% DMSO as vehicle control. For vasopressin and other peptide ligands 20 μL of 50% DMSO is added and the assay buffer volume is adjusted accordingly.
 
To each well is added 50 μL of frozen membrane suspension thawed immediately prior to use and diluted in assay buffer to the required concentration (equivalent to 25 to 50 μg of protein/well as needed). 20 μL of 8 nM [ 3 H]arginine vasopressin ligand in the assay buffer, prepared just before use is added and incubated at room temperature for 60 min. shaking the plate on a mechanical shaker for the first 15 min. The incubation is stopped by rapid filtration of the plate contents followed by wash with ice-cold buffer (50 mM Tris-HCl, pH 7.4) using a cell harvester (Tomtek and Printed filtermat-B filter paper). The filter paper is thoroughly dried (7–12 min. in a microwave oven) and impregnated with MeltiLex B/H melt-on scintillation wax sheets and the radioactivity counted in a betaplate scintillation counter.
 
     Oxytocin Binding in Chinese Hamster Ovary Cell Membranes Expressing Human Oxytocin Receptors 
     Receptor Source: 
     Chinese Hamster Ovary (CHO) cells stably transfected with the human oxytocin receptor (cf. Tanizawa et al., U.S. Pat. No. 5,466,584 (1995) to Rohto Pharmaceutical Co. Ltd., Osaka, Japan) were obtained from M. Thibonnier, Case Western Reserve University School of Medicine, Cleveland, Ohio.
 
A. Passaging and Amplification of Cells:
 
CHO cells transfected with the human oxytocin receptors obtained from M. Thibonnier (pcDNA3.1 vector) are allowed to grow to confluency (approx. &gt;90%) in T-150 flasks under sterile conditions, in a cell culture medium of F-12 Nutrient Mixture (HAM) with L-glutamine (Gibco Cat. # 11765-054) containing 15 mM HEPES (Gibco Cat. # 15630-080), 1% antibiotic/antimycotic (add 5 mL 100×, Gibco Cat. # 15240-062 per 500 mL F-12), 400 μg/mL of Geneticin (add 4 mL of 50 mg/mL per 500 mL F-12) and 10% Fetal Bovine Serum (Qualified, heat inactivated, Gibco Cat. # 16140-063). The medium is removed by aspiration and the cells are washed with 10 mL of Hank&#39;s Balanced Salt solution (Gibco Cat. # 14175-095). The salt solution is removed by aspiration and the cells trypsinized with 5 mL of trypsin-EDTA (0.05% trypsin, 0.53 mM EDTA-4Na, Gibco Cat. # 25300-070) for 1 min. The trypsin is removed by aspiration and the cells dislodged by tapping. Cell Culture medium (e.g. 30 mL for 1:30 split) is immediately added and mixed well to inactivate trypsin. 1 mL of detached cells is added to new culture flasks containing fresh Cell Culture medium (e.g. into 25 mL per T-150 flask), and mixed gently. The cells are incubated at 37° C. in 5% CO 2 . The medium is changed at 3 to 4 days interval (or as appropriate). The cells grow to confluency (approx. &gt;75%–95%) within 7–8 days. All steps are done under sterile conditions.
 
B. Membrane Preparation:
 
The cells are washed twice gently with Hank&#39;s Balanced Salt solution (e.g., use 10 mL per T-150 flask). The excess solution is removed and the cells bathed for 15–30 min. in an enzyme-free Cell Dissociation Buffer (e.g., use 8 mL Hank&#39;s Based, Gibco Cat. # 13150-016 per T-150 flask) until cells are loosened. The contents are transferred to centrifuge tubes (50 mL size) kept in ice bath. All subsequent steps are done at 4° C. The tubes are centrifuged at 300×g for 15 min (1380 rpm on SORVAL, Model RT6000D, using rotor for 50 mL tubes). The supernatant is discarded and the cells suspended in homogenizing buffer (10 mM Tris-HCl containing 0.25 M sucrose and 1 mM EDTA, pH 7.4) ensuring that the volume of the buffer is about ten times the volume of the cell pellet. The cells are pooled into a centrifuge tube (50 mL) and homogenized with a Polytron at setting 6 for 10 sec. The homogenate is transferred into a Potter-Elvjehm homogenizer and homogenized with 3 strokes. The homogenate is centrifuged at 1500×g for 10 min at 4° C. (3100 rpm using SORVAL, model RT6000D, using rotor for 50 mL tubes). The pellet is discarded. The supernatant is centrifuged at 100,000×g for 60 min. at 4° C. (Beckman L8-80M ultracentrifuge; spin at 37,500 rpm with rotor type 70 Ti for 50 mL tubes; 38,000 rpm with type 80Ti for 15 mL tubes; or 35,800 rpm with rotor type 45Ti). The supernantant is discarded and the pellet suspended in 3 to 4 mL of Tris buffer (50 mM TRIS-HCl, pH 7.4). The protein content is estimated by the Bradford or Lowry method. The volume of the membrane suspension is adjusted with the membrane buffer (50 mM Tris-HCl containing 0.1% BSA and 0.1 mM PMSF) to give 3.0 mg/mL (or as appropriate) of protein. The membranes are aliquoted and stored at −70° C.
 
C. Radioligand Binding Assay:
 
In wells of a 96-well format microtiter plate, is added 90, 110 or 130 μL (to make up a final volume of 200 μL) of assay buffer containing 50 mM of Tris-HCl (pH 7.4), BSA (heat inactivated, protease-free), 5 mM of 0.1% MgCl 2 , 1 mg % aprotinin, 1 mg % leupeptin, 2 mg % 1,10-phenanthroline, 10 mg % trypsin inhibitor, and 0.1 mM PMSF. The inhibitors are added on the day of the experiment. The components are mixed at room temperature, and then kept in ice bath following adjustment of the pH to 7.4.
 
To each well is added 20 μL of unlabeled oxytocin (to give a final concentration of 0.1 to 10 nM for standard curve and 1000 nM for non specific binding) or test compounds in 50% DMSO (e.g. for final concentrations of 0.1 to 1000 nM or as appropriate) or 50% DMSO as vehicle control. For oxytocin and other peptide ligands, 20 μL of 50% DMSO is added and the assay buffer volume is adjusted accordingly.
 
To each well is added 50 μL of frozen membrane suspension thawed immediately prior to use and diluted in assay buffer to the required concentration (equivalent to 25 to 50 μg of protein/well as needed). 20 μL of 8 nM [ 3 H]oxytocin in the assay buffer, prepared just before use is added and incubated at room temperature for 60 min. shaking the plate on a mechanical shaker for the first 15 min. The incubation is stopped by rapid filtration of the plate contents followed by washing with ice-cold buffer (50 mM Tris-HCl, pH 7.4) using a cell harvester (Tomtek and Printed filtermat-B filter paper). The filter paper is thoroughly dried (7–12 min. in a microwave oven) and impregnated with MeltiLex B/H melt-on scintillation wax sheets and the radioactivity counted in a betaplate scintillation counter.
 
     Binding data is either reported as percent inhibition at a certain concentration or if an IC 50  was calculated, as a nanomolar concentration. 
     The results of these tests on representative compounds of this invention are shown in Table I. 
                                       TABLE 1                   Binding to membranes of Chinese Hamster Ovary (CHO) cell line       stably transfected with human vasopressin V 1a  receptor subtype, human       vasopressin V 2  receptor subtype and human oxytocin receptor                OT                   %   V 1a     V 2         Exam-   inhibition @ 100%   % inhibition @ 100   % inhibition @ 100       ple   nM (IC 50 , nM)*   nM (IC 50,  nM)*   nM (IC 50 , nM)*                2   (12.46)   (2718.5)   (1759.2)        3   37   −8   22        4   (8.89)   14   24        5   24   −6   3        6   56   2   13        7   (11.4)   (2481.3)   (2459.18)        8   (6.37)   (1370)   (1475)        9   32   10   42        11   (3.44)   (70.41)   (1351)        12   21   −10   −1        13   33   4   −4        14   9   −16   −3        15   −4   −8   27        17   28   −11   32        18B   (14.5)   (386)   (189)        19D   97   51   84        20   (1.81)   (717)   (4355)        21   (1.7)   (378)   (1163)        22   (1.74)   (225)   (1428)        24   (8.0)   (22.5)   (4.7)        25   (55.8)   (130.6)   (11.3)        26   17   −3   3        27   (18.1)   (45.6)   (148.9)        28   (29.51)   (66.56)   (58.82)        29   51   74   24        30   48   8   3        31   69   30   31        32   (185)   (&gt;3000)   (605)        33   101   68   11        43   (1.66)   (312)   (409)        47   (6.61)   (1004)   (722)        48   (6.7)   (484)   (700)        49   92   5   27        50   95   40   15        51   81   14   17        52   86   54   17        53   89   38   23        54   78   −4   7        55   67   4   30        56   68   2   27        57   76   15   11        58   24   5   18        59   (16.45)   (1886)   (2307)        60   (5.39)   (681)   (1203)        61   (4.5)   (316.4)   (744.6)        62   91   10   27        63   98   57   9        64   74   13   19        65   68   40   6        66   87   52   20        67   79   −4   4        68   64   9   29        69   71   8   22        70   75   19   11        71   25   4   13        72   74   8   26        73   85   46   21        74   45   12   14        75   66   27   14        76   65   58   17        77   65   44   28        78   62   −3   14        79   35   0   7        80   44   16   43        81   43   4   21        82   50   37   10        83   10   8   18        84   48   1   11        85   (3.02)   (788)   (3126)        86   (2.31)   (172)   (1698)        87   (4.63)   (349)   (2176)        88   98   44   30        89   97   50   13        90   100   63   19        91   97   90   17        92   99   78   20        93   90   29   36        94   94   28   26        95   97   68   13        96   54   10   24        97   (7.14)   (1092)   (2004)        98   (2.48)   (238)   (1026)        99   (2.04)   (311)   (1333)       100   98   27   26       101   100   75   7       102   95   45   18       103   98   43   11       104   96   85   20       105   97   74   18       106   88   22   34       107   87   15   19       108   96   52   8       109   49   9   14       110   (7.93)   (661)   (788)       111   (6.7)   (458.7)   (772.3)       112   89   8   32       113   97   45   9       114   76   11   22       115   25   11   12       116   84   42   22       117   70   −3   14       118   54   14   39       119   58   9   15       120   69   20   6       121   0   0   13       122   77   8   8       123   47   9   15       124   60   16   21       125   36   10   8       126   43   9   18       127   29   16   3       128   43   18   17       129   52   6   5       130   46   4   5       131   26   8   13       132   31   2   16       133   46   20   8       134   15   5   16       135   24   2   1       136   (7.19)   (538)   (597)       137   88   4   −4       138   95   47   29       139   76   9   12       140   87   24   29       141   −6   −3   8       142   83   46   −5       143   69   −3   7       144   53   −1   3       145   53   −4   −5       146   78   37   12       147   33   3   20       148   78   −9   1       149   75   17   20       150   75   42   18       151   47   17   6       152   63   23   10       153   60   50   11       154   54   39   9       155   56   0   15       156   30   2   12       157   38   5   23       158   50   16   19       159   50   44   16       160   20   6   24       161   53   8   4       162   71   18   20       163   82   43   13       164   54   23   16       165   64   24   25       166   27   29   3       167   60   50   20       168   52   8   10       169   36   9   5       170   47   21   27       171   40   14   14       172   47   43   11       173   21   0   17       174   59   8   7       175   98   28   17       176   88   27   18       177   98   42   18       178   93   79   15       179   93   73   23       180   98   26   14       181   100   23   12       182   70   14   35       183   97   26   18       184   83   0   9       185   95   37   27       186   97   53   8       187   100   81   31       188   96   89   10       189   99   83   22       190   99   40   9       191   100   41   17       192   91   31   28       193   96   41   16       194   96   23   0       195   (3.84)   (367)   (298)       196   (11.63)   (1243)   (855)       197   (5.39)   (524)   (497)       198   94   50   19       199   84   23   6       200   87   64   10       201   86   43   19       202   73   2   8       203   62   4   28       204   72   16   6       205   24   −6   18       206   (3.66)   (317)   (190)       207   (9.5)   (488)   (601.1)       208   81   20   12       209   81   64   10       210   82   39   17       211   87   45   23       212   95   35   43       213   70   12   33       214   64   8   11       215   26   5   22       216   82   10   0       217   98   21   34       218   98   45   23       219   (12.07)   (1807)   (1324)       220   (7.2)   (387)   (1816)       221   (11.1)   (818)   (832.7)       222   84   15   1       223   71   12   13       224   −3   1   7       225   87   35   −4       226   71   3   10       227   69   2   2       228   77   22   20       229   19   8   27       230   67   3   4       231   63   7   −5       232   81   13   4       233   86   31   23       234   82   26   22       235   64   9   17       236   46   6   5       237   79   39   −3       238   79   3   27       239   61   2   16       240   62   1   9       241   51   −4   −17       242   69   33   25       243   17   5   21       244   68   44   9       245   (16.91)   (933)   (423)       246   (17.8)   (373)   (508.2)       247   97   62   21       248   77   17   7       249   18   12   9       250   87   53   −10       251   87   6   24       252   72   8   21       253   71   16   −10       254   66   7   −4       255   80   53   27       256   33   7   40       257   85   10   16       258   (2.85)   (913)   (5679)       259   97   21   −3       260   102   55   20       261   52   13   18       262   76   8   4       263   (2.31)   (202)   (4124)       264   94   67   12       265   100   31   10       266   97   49   −17       267   93   12   24       268   90   6   34       269   88   −1   −19       270   95   40   25       271   (6.29)   (983)   (1915)       272   (2.61)   (301)   (1302)       273   (4.26)   (481.07)   (811.98)       274   103   90   32       275   89   9   21       276   74   4   −3       277   41   8   19       278   (7.87)   (303)   (1679)       279   100   39   17       280   95   77   6       281   93   58   −9       282   84   1   −17       283   91   40   29       284   87   0   12       285   93   38   32       286   86   8   27       287   88   0   26       288   95   24   32       289   45   6   7       290   78   47   −6       291   32   2   5       292   69   6   −7       293   53   2   3       294   54   −3   −2       295   79   6   22       296   88   31   24       297   73   −2   13       298   94   20   29       299   86   14   22       300   72   −2   19       301   82   1   9       302   64   −15   17       303   66   −4   14       304   74   −7   19       306   34   0   0       307   30   −7   8       308   7   −12   1       309   72   11   7       310   58   4   12       311   16   −5   7       312   16   7   3       313   32   2   2       314   19   6   7       315   10   7   −4       316   24   0   −2       317   32   10   15       318   32   5   17       319   22   9   13       320   34   4   21       321   62   5   23       322   66   12   24       323F   33   2   5               Binding in Chinese Hamster Ovary cell membranes expressing human vasopressin V 1a  and V 2  subtype receptors, and human oxytocin receptors            
The following Examples are presented to illustrate rather than limit the scope of this invention.
 
     EXAMPLE 1 
     10-[(2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     Step A. 4-Bromo-3-methylbenzoic acid methyl ester 
     To a suspension of 4-bromo-3-methylbenzoic acid (10.0 g, 46.5 mmol) in methanol (125 mL) was added concentrated sulfuric acid (1 mL). The reaction was heated at reflux overnight with a homogeneous solution obtained after several minutes of heating. After cooling, the methanol was removed in vacuo and the residue was dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 10.2 g of title compound as a brown solid, m.p. 41–43° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 2.39 (s, 3H), 3.85 (s, 3H), 7.64–7.72 (m, 2H), 7.88–7.89 (m, 1H). MS [EI, m/z]: 228 [M] + . Anal. Calcd. for C 9 H 9 BrO 2 : C, 47.19; H, 3.90. Found: C, 47.22; H, 3.80. 
     Step B. (2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carboxylic acid methyl ester 
     A mixture of 4-bromo-3-methylbenzoic acid methyl ester of Step A (2.0 g, 8.7 mmol), 2-trifluoromethyl-phenyl boronic acid (1.65 g, 8.7 mmol) and sodium carbonate (4.1 g, 38.7 mmol) in toluene:ethanol:water (50 mL:25 mL:25 mL) was purged with nitrogen for 1 hour. After addition of the tetrakis(triphenylphosphine) palladium(0) catalyst (0.50 g, 0.43 mmol) the reaction was heated at 100° C. overnight. The cooled reaction mixture was filtered through Celite and the cake washed with ethyl acetate. The organic layer was washed with water, dried over anhydrous. sodium sulfate, filtered and concentrated in vacuo to give a brown oil. Purification by flash chromatography with a solvent gradient of 25% to 50% dichloromethane in hexane provided 2.0 g of the title compound as a colorless oil. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 2.03 (s, 3H), 3.88 (s, 3H), 7.26 (d, 1H), 7.34 (d, 1H), 7.66 (t, 1H), 7.75 (t, 1H), 7.81–7.83 (m, 1H), 7.86–7.88 (m, 1H), 7.90–7.91 (m, 1H). MS [(+)ESI, m/z]: 312 [M+NH 4 ] + . Anal. Calcd. for C 16 H 13 F 3 O 2 : C, 65.31; H, 4.45. Found: C, 64.92; H, 4.54. 
     Step C. (2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carboxylic acid 
     To a solution of (2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carboxylic acid methyl ester of Step B (1.9 g, 6.5 mmol) in tetrahydrofuran (30 mL) was added 1 N sodium hydroxide (13 mL, 13 mmol). The reaction mixture was heated at reflux overnight, then cooled and acidified with 2 N hydrochloric acid. The aqueous layer was extracted with ethyl acetate and the combined extracts were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 1.65 g of the title compound as a white solid, m.p. 171–174° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 2.02 (s, 3H), 7.23 (d, 1H), 7.34 (d, 1H), 7.65 (t, 1H), 7.75 (t, 1H), 7.79–7.81 (m, 1H), 7.86–7.89 (m, 2H), 13.00 (br s, 1H). MS [(−)ESI, m/z]: 279 [M−H] − . Anal. Calcd. for C 15 H 11 F 3 O 2 : C, 64.29; H, 3.96. Found: C, 64.26; H, 3.80. 
     Step D. (10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]methanone 
     A suspension of (2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carboxylic acid of Step C (0.50 g, 1.78 mmol) in thionyl chloride (3 mL) was heated at reflux for 90 minutes. After cooling, the thionyl chloride was removed in vacuo and the residue dissolved in toluene. The solution was concentrated in vacuo to yield the crude acid chloride as a brown oil. The acid chloride was dissolved in dichloromethane (5 mL) and slowly added to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.49 g, 2.66 mmol) and N,N-diisopropylethyl amine (0.68 mL, 3.90 mmol) in dichloromethane (15 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was sequentially washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification by flash chromatography on silica gel using a solvent gradient of 15 to 25% ethyl acetate in hexane gave a white foam which was crystallized upon sonication in ethanol/hexane to provide the title compound (0.55 g) as a white solid, m.p. 127–130° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.86 (s, 3H), 4.80–5.40 (br, 4H), 5.93–5.98 (m, 2H), 6.85 (t, 1H), 6.91–6.96 (m, 2H), 7.03–7.05 (m, 1H), 7.10–7.14 (m, 1H), 7.19–7.24 (m, 2H), 7.29 (s, 1H), 7.47–7.49 (m, 1H), 7.61 (t, 1H), 7.70 (t, 1H), 7.81 (d, 1H). MS [EI, m/z]: 446 [M] + . Anal. Calcd. for C 27 H 21 F 3 N 2 O: C, 72.64; H, 4.74; N, 6.27. Found: C, 72.48; H, 4.57; N, 6.16. 
     Step E. 2,2,2-Trichloro-1-(10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)ethanone 
     To a solution of (10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]-[(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]methanone of Step D (1.87 g, 4.19 mmol) in dichloromethane (20 mL) was added N,N-diisopropylethyl amine (1.46 mL, 8.38 mmol) followed by the slow addition of trichloroacetyl chloride (1.45 mL, 13.0 mmol). The reaction mixture was stirred overnight at room temperature, and then quenched with water. The organic phase was washed with 0.1 N hydrochloric acid followed by water, then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a green oil. Purification by flash chromatography on silica gel using a solvent system of 20% ethyl acetate in hexane provided 2.2 g of title product as a pale, yellow foam. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.84 (s, 3H), 5.25 (br, 2H), 5.97 (br, 2H), 6.37 (d, 1H), 6.89–6.92 (m, 2H), 7.02–7.04 (m, 1H), 7.06–7.10 (m, 1H), 7.15–7.22 (m, 2H), 7.28 (s, 1H), 7.41–7.46 (m, 2H), 7.58 (t, 1H), 7.67 (t, 1H), 7.79 (d, 1H). MS [(+)APCI, m/z]: 591 [M+H] + . Anal. Calcd. for C 29 H 20 Cl 3 F 3 N 2 O 2 +0.20 C 4 H 8 O 2 +0.80 H 2 O: C, 57.37; H, 3.75; N, 4.49. Found: C, 57.06; H, 3.39; N, 4.50. 
     Step F. 10-[(2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     To a solution of 2,2,2-trichloro-1-(10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)ethanone of Step E (2.3 g, 3.9 mmol) in acetone (20 mL) was added 2.5 N sodium hydroxide (3.1 mL, 7.8 mmol). After stirring overnight, the reaction mixture was acidified with 2 N hydrochloric acid (4.3 mL, 8.6 mmol) and then concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a brown solid. Trituration with diethyl ether/hexane provided the title compound (1.32 g) as a white solid, m.p. 233–235° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.84 (s, 3H), 5.17 (br, 2H), 5.94 (br, 2H), 6.10–6.11 (m, 1H), 6.76 (d, 1H), 6.85–6.91 (m, 2H), 7.00–7.06 (m, 2H), 7.12–7.16 (m, 1H), 7.21 (d, 1H), 7.25 (s, 1H), 7.32–7.34 (m, 1H), 7.59 (t, 1H), 7.68 (t, 1H), 7.79 (d, 1H), 12.33 (br, 1H). MS [(+)ESI, m/z]: 491 [M+H] + . Anal. Calcd. for C 28 H 21 F 3 N 2 O 3 : C, 68.57; H, 4.32; N, 5.71. Found: C, 68.39; H, 4.25; N, 5.64. 
     EXAMPLE 2 
     (4-Methyl-piperazin-1-yl)-[10-(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)-carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl-methanone 
     A suspension of 10-[(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)-carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 1, Step F (1.65 g, 3.36 mmol) in dichloromethane (15 mL) containing a few drops of N,N-dimethylformamide was treated dropwise under nitrogen with oxalyl chloride (0.38 mL, 4.36 mmol). After the gas evolution subsided, the reaction mixture was refluxed for an additional 15 min. The cooled solution was evaporated to dryness to give the crude acid chloride as a brown solid. The acid chloride was then dissolved in dichloromethane (10 mL) and slowly added to a solution of 1-methylpiperazine (1.5 mL, 13.5 mmol) and N,N-diisopropylethyl amine (3.5 mL, 20.1 mmol) in dichloromethane (25 mL). After stirring overnight, the reaction was quenched with water. The organic layer was sequentially washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a brown oil. Purification by flash chromatography on silica gel using a solvent system of 10% methanol in ethyl acetate gave a pale yellow foam which was crystallized from diethyl ether to provide the desired title compound (1.17 g) as a white solid. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.83 (s, 3H), 2.20 (s, 3H), 2.31–2.33 (m, 4H), 3.61–3.63 (m, 4H), 5.15 (br, 2H), 5.40 (s, 2H), 6.06 (d, 1H), 6.23 (d, 1H), 6.85–6.90 (m, 2H), 6.99–7.06 (m, 2H), 7.12–7.16 (m, 1H), 7.20 (d, 1H), 7.25 (s, 1H), 7.37–7.39 (m, 1H), 7.58 (t, 1H), 7.67 (t, 1H), 7.79 (d, 1H). MS [(+)ESI, m/z]: 573 [M+H] + . Anal. Calcd. for C 33 H 31 F 3 N 4 O 2 : C, 69.22; H, 5.46; N, 9.78. Found: C, 68.79; H, 5.45; N, 9.72. 
     EXAMPLE 3 
     10-[(2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)-carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid bis-(3-dimethylamino-propyl)-amide 
     A suspension of 10-[(2-methyl-2′-trifluoromethyl-[1,1 l′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 1, Step F (0.50 g, 1.02 mmol) in dichloromethane (5 mL) containing a few drops of N,N-dimethylformamide was treated dropwise under nitrogen with oxalyl chloride (0.12 mL, 1.38 mmol). After gas evolution subsided, the reaction mixture was refluxed for an additional 15 minutes. The cooled solution was evaporated to dryness to give the crude acid chloride as a brown solid. The acid chloride was then dissolved in dichloromethane (5 mL) and slowly added to a solution of bis-(3-dimethylamino-propyl)-amine (0.90 mL, 4.04 mmol) and N,N-diisopropylethyl amine (1.1 mL, 6.31 mmol) in dichloromethane (5 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was sequentially washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a brown oil. Purification was achieved by preparative HPLC on a Primesphere S C18 column (0.21×15 cm) using a solvent gradient from 60:40:0.1 to 80:20:0.1 acetonitrile-water-trifluoroacetic acid. After removal of the acetonitrile in vacuo, the aqueous solution was basified with 2.5 N sodium hydroxide then extracted with dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give the title compound (0.24 g) as a white foam, m.p. 55–64 ° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.68 (br, 4H), 1.83 (s, 3H), 2.00–2.23 (br, 16H), 3.43 (t, 4H), 5.10 (br, 2H), 5.34 (s, 2H), 6.04 (d, 1H), 6.21 (d, 1H), 6.87–6.90 (m, 2H), 6.99–7.04 (m, 2H), 7.13 (t, 1H), 7.21 (d, 1H), 7.24 (s, 1H), 7.31–7.33 (m, 1H), 7.58 (t, 1H), 7.67 (t, 1H), 7.79 (d, 1H). MS [(+)ESI, m/z]: 660 [M+H] + . Anal. Calcd. for C 38 H 44 F 3 N 5 O 2 : C, 69.18; H, 6.72; N, 10.61. Found: C, 68.26; H, 6.68; N, 10.43. 
     EXAMPLE 4 
     [4-(3-Dimethylaminopropyl)-piperazin-1-yl]-[10-(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carbonyl]-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl]-methanone 
     10-[(2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 1, Step F (0.50 g, 1.02 mmol), 1-[3-(dimethylamino)propyl]piperazine (0.21 mL, 1.23 mmol) and 1-hydroxybenzotriazole monohydrate (0.15 g, 1.11 mmol) were dissolved in N,N-dimethylformamide (4 mL). 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.22 g, 1.15 mmol) was then added followed by N,N-diisopropylethyl amine (0.27 mL, 1.55 mmol). The reaction mixture was stirred overnight, diluted with ethyl acetate and washed with water and saturated aqueous sodium bicarbonate. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow oil. Purification by flash chromatography on silica gel using a solvent system of 10% methanol in chloroform provided the title compound (0.19 g) as a white foam, m.p. 85–95° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.52–1.60 (m, 2H), 1.83 (s, 3H), 2.13 (s, 6H), 2.25 (t, 2H), 2.31 (t, 2H), 2.37 (br, 4H), 3.61 (br, 4H), 5.15 (br, 2H), 5.40 (s, 2H), 6.05 (d, 1H), 6.22 (d, 1H), 6.84–6.90 (m, 2H), 6.98–7.06 (m, 2H), 7.14 (t, 1H), 7.21 (d, 1H), 7.25 (s, 1H), 7.37–7.39 (m, 1H), 7.58 (t, 1H), 7.68 (t, 1H), 7.79 (d, 1H). MS [(+)ESI, m/z]: 644 [M+H] + . Anal. Calcd. for C 37 H 40 F 3 N 5 O 2 +0.40 H 2 O: C, 68.26; H, 6.32; N, 10.76. Found: C, 67.94; H, 6.37; N, 10.46. 
     EXAMPLE 5 
     [3-Methyl-4-(3-methyl-phenyl)-piperazin-1-yl]-[10-(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl-methanone 
     10-[(2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 1, Step F (0.50 g, 1.02 mmol), 2-methyl-1-(3-methylphenyl)piperazine (0.24 mL, 1.26 mmol) and 1-hydroxybenzotriazole monohydrate (0.15 g, 1.11 mmol) were dissolved in N,N-dimethylformamide (5 mL). 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.22 g, 1.15 mmol) was then added followed by N,N-diisopropylethyl amine (0.27 mL, 1.55 mmol). The reaction mixture was stirred overnight, diluted with ethyl acetate and washed with water and saturated aqueous bicarbonate. The organic phase was then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a brown oil. Purification by flash chromatography on silica gel using a solvent system of 40% ethyl acetate in hexane provided a white foam which was redissolved in dichloromethane and evaporated to dryness in vacuo prior to use in the next step. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 0.91 (d, 3H), 1.83 (s, 3H), 2.24 (s, 3H), 3.00–3.05 (m, 1H), 3.28–3.32 (m, 2H), 3.46–3.49 (m, 1H), 3.99–4.07 (m, 2H), 4.22–4.25 (m, 1H), 5.15 (br, 2H), 5.40–5.49 (m, 2H), 6.09 (d, 1H), 6.31 (d, 1H), 6.59 (d, 1H), 6.70–6.73 (m, 2H), 6.85–6.90 (m, 2H), 6.99–7.15 (m, 4H), 7.20 (d, 1H), 7.26 (s, 1H), 7.36 (d, 1H), 7.58 (t, 1H), 7.67 (t, 1H), 7.79 (d, 1H). MS [(+)ESI, m/z]: 663 [M+H] + . Anal. Calcd. for C 40 H 37 F 3 N 4 O 2 +O0.13 CH 2 Cl 2 +0.17 C 4 H 8 O 2 : C, 71.17; H, 5.65; N, 8.13. Found: C, 70.85; H, 5.50; N, 8.01. 
     EXAMPLE 6 
     4-[[10,11-Dihydro-10-[[2-methyl-2′-trifluoromethyl[1,1′-biphenyl]-4-yl]carbonyl]-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl]carbonyl]-1-piperazine-carboxylic acid, tert-butyl ester 
     10-[(2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 1, Step F (1.0 g, 2.04 mmol), 1-(tert-butoxycarbonyl)piperazine (0.46 g, 2.47 mmol) and 1-hydroxybenzotriazole monohydrate (0.30 g, 2.22 mmol) were dissolved in N,N-dimethylformamide (8 mL). 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.43 g, 2.24 mmol) was then added followed by N,N-diisopropylethyl amine (0.55 mL, 3.09 mmol). The reaction mixture was stirred overnight, diluted with ethyl acetate and washed with water and saturated aqueous sodium bicarbonate. The organic phase was then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a brown oil. Purification by flash chromatography using a solvent gradient from 30% to 50% ethyl acetate in hexane provided the desired title compound as a white foam, which was redissolved in dichloromethane and evaporated to dryness in vacuo prior to use in the next step. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.41 (s, 9H), 1.83 (s, 3H), 3.38 (br, 4H), 3.59–3.61 (m, 4H), 5.15 (br, 2H), 5.41 (s, 2H), 6.07 (d, 1H), 6.28 (d, 1H), 6.85–6.90 (m, 2H), 6.99–7.06 (m, 2H), 7.12–7.16 (m, 1H), 7.21 (d, 1H), 7.25 (s, 1H), 7.40–7.42 (m, 1H), 7.58 (t, 1H), 7.67 (t, 1H), 7.79 (d, 1H). MS [(+)APCI, m/z]: 659[M+H] + . Anal. Calcd. for C 37 H 37 F 3 N 4 O 4 +0.09CH 2 Cl 2 +0.18C 4 H 8 O 2 : C, 66.56; H, 5.71; N, 8.21. Found; C, 66.27; H, 5.40; N, 8.00. 
     EXAMPLE 7 
     10,11-Dihydro-10-[[2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl]-3-(1-piperazinylcarbonyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine hydrochloride salt 
     The 4-[[10,11-dihydro-10-[[2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl]-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl]carbonyl]-1-piperazine-carboxylic acid, tert-butyl ester of Example 6 (0.85 g, 1.29 mmol) was added in one portion to stirred ethyl acetate (10 mL) saturated with hydrogen chloride gas at 0° C. A precipitate formed after several minutes. The reaction mixture was stirred for 90 minutes under anhydrous conditions. The reaction was then warmed to room temperature and diluted with diethyl ether. The precipitated product was collected by filtration and dried under high vacuum to provide the desired title compound hydrochloride salt (0.65 g) as an off-white foam. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.84 (s, 3H), 3.16 (br, 4H), 3.83–3.85 (m, 4H), 5.15 (br, 2H), 5.43 (s, 2H), 6.09 (d, 1H), 6.38 (d, 1H), 6.87–6.91 (m, 2H), 6.99–7.01 (m, 1H), 7.06 (t, 1H), 7.13–7.17 (m, 1H), 7.21 (d, 1H), 7.26 (s, 1H), 7.44–7.46 (m, 1H), 7.59 (t, 1H), 7.68 (t, 1H), 7.79 (d, 1H), 9.28 (br, 2H). MS [(+)APCI, m/z]: 559[M+H] + . Anal. Calcd. for C 32 H 29 F 3 N 4 O 2 +1.0HCl+1.00H 2 O+0.06C 4 H 10 O: C, 62.70; H, 5.32; N, 9.07. Found: C, 62.42; H, 5.22; N, 8.94. 
     EXAMPLE 8 
     N-[(10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)carbonyl]guanidine 
     10-[(2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]4-yl)-carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 1, Step F (0.50 g, 1.02 mmol) and 1,1′-carbonyldiimidazole (0.17 g, 1.05 mmol) were dissolved in anhydrous N,N-dimethylformamide (5 mL). After stirring for 30 minutes, guanidine carbonate (0.19 g, 1.05 mmol) was added, and the reaction was heated to 100° C. for 4 hours. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give an orange oil. Purification was achieved by preparative HPLC on a Primesphere 5 C18 (0.2×15 cm) column using a solvent gradient from 55:45:0.1 to 90:10:0.1 acetonitrile-water-trifluoroacetic acid. After removal of the acetonitrile in vacuo, the aqueous solution was neutralized with saturated aqueous sodium bicarbonate, and then extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 0.25 g of the title compound as a white solid. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.85 (s, 3H), 5.15 (br, 2H), 6.00 (d, 1H), 6.20 (br, 2H), 6.65 (d, 1H), 6.80 (d, 1H), 6.97 (d, 1H), 6.96–7.01 (m, 2H), 7.11 (t, 1H), 7.22–7.25 (m, 2H), 7.36–7.38 (m, 1H), 7.60 (t, 1H), 7.69 (t, 1H), 7.80 (d, 1H). MS [(+)APCI, m/z]: 532[M+H] + . Anal. Calcd. for C 29 H 24 F 3 N 5 O 2 +0.15C 4 H 8 O 2 : C, 65.26; H, 4.66; N, 12.86. Found: C, 64.53; H, 4.45; N, 12.77. 
     EXAMPLE 9 
     10-[(2′-Methoxy-2-methyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     Step A. (2-Methyl-2′-methoxy-[1,1′-biphenyl]-4-yl)carboxylic acid methyl ester 
     A mixture of 3-methyl-4-bromobenzoic acid methyl ester (2.0 g, 8.7 mmol), 2-methoxyphenyl boronic acid (1.32 g, 8.7 mmol) and sodium carbonate (4.1 g, 38.7 mmol) in toluene:ethanol:water (50 mL:25 mL:25 mL) was purged with nitrogen for 1 hour. After addition of the tetrakis(triphenylphosphine) palladium(0) catalyst (0.50 g, 0.43 mmol), the reaction mixture was heated at 100° C. overnight. After cooling, the reaction was filtered through Celite and the cake washed with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a brown oil. Purification by flash chromatography on silica gel with a solvent gradient from 20% to 50% dichloromethane in hexane gave 2.0 g of product as a colorless oil. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 2.09 (s, 3H), 3.70 (s, 3H), 3.85 (s, 3H), 7.00–7.04 (m, 1H), 7.08–7.11 (m, 2H), 7.23 (d, 1H), 7.37–7.41 (m, 1H), 7.77–7.79 (m, 1H), 7.83–7.84 (m, 1H). MS [(+)APCI, m/z]: 257[M+H] + . Anal. Calcd. for C 16 H 16 O 3 : C, 74.98; H, 6.29. Found: C, 74.06; H, 6.17. 
     Step B. (2-Methyl-2′-methoxy-[1,1′-biphenyl]-4-yl)carboxylic acid 
     The (2-methyl-2′-methoxy-[1,1′-biphenyl]-4yl)carboxylic acid methyl ester of Step A (1.9 g, 7.4 mmol) was dissolved in tetrahydrofuran (30 mL) and 1 N sodium hydroxide (15 mL, 15 mmol) was added. The reaction mixture was heated at reflux overnight, then cooled and acidified with 2 N hydrochloric acid. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 1.6 g of product as a white solid, m.p. 160–162° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 2.09 (s, 3H), 3.70 (s, 3H), 7.00–7.03 (m, 1H), 7.08–7.10 (m, 2H), 7.20 (d, 1H), 7.36–7.40 (m, 1H), 7.75–7.78 (m, 1H), 7.82 (s, 1H), 12.85 (br, 1H). MS [(−) APCI, m/z]: 241[M−H] − . Anal. Calcd. for C 15 H 14 O 3 : C, 74.36; H, 5.82. Found: C, 73.93; H, 5.71. 
     Step C. (10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(2′-methoxy-2-methyl-[1,1′-biphenyl]-4-yl)-methanone 
     The (2-methyl-2′-methoxy-[1,1′-biphenyl]4-yl)carboxylic acid of Step B (0.50 g, 2.06 mmol) was suspended in thionyl chloride (3 mL) and the mixture heated at reflux for 30 minutes. After cooling, the thionyl chloride was removed in vacuo. The residue was dissolved in toluene and concentrated in vacuo to give the crude acid chloride as a brown oil. The acid chloride was then dissolved in dichloromethane (5 mL) and slowly added to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.57 g, 3.10 mmol) and N,N-diisopropylethyl amine (0.79 mL, 4.53 mmol) in dichloromethane (15 mL). After stirring for 1 hour, the reaction was quenched with water. The organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification by flash chromatography using a solvent gradient of 5 to 15% ethyl acetate in hexane yielded a white foam which crystallized upon sonication in ethanol/hexane to give 0.42 g of the desired title product as a white solid, m.p. 133–135° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.93 (s, 3H), 3.65 (s, 3H), 4.80–5:40 (br, 4H), 5.92–5.96 (m, 2H), 6.81–6.82 (m, 1H), 6.89–6.91 (m, 1H), 6.95–7.05 (m, 5H), 7.16–7.25 (m, 3H), 7.31–7.35 (m, 1H), 7.47–7.49 (m, 1H). MS [(+)ESI, m/z]: 409[M+H] + . Anal. Calcd. for C 27 H 24 N 2 O 2 : C, 79.39; H, 5.92; N, 6.86. Found: C, 79.16; H, 5.87; N, 6.90. 
     Step D. 2,2,2-Trichloro-1-{10-[(2′-methoxy-2-methyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone 
     To a solution of (10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(2′-methoxy-2-methyl-[1,1′-biphenyl]-4-yl)-methanone of Step C (1.5 g, 3.67 mmol) in dichloromethane (20 mL) was added N,N-diisopropylethyl amine (1.28 mL, 7.35 mmol) followed by slow addition of trichloroacetyl chloride (1.23 mL, 11.0 mmol). The reaction mixture was stirred overnight at room temperature then quenched with water. The organic phase was washed with 0.1 N hydrochloric acid followed by water, then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a green oil. Purification by flash chromatography on silica gel using a solvent system of 20% ethyl acetate in hexane provided 2.1 g of title compound. The material was redissolved in dichloromethane and evaporated to dryness to provide a yellow foam, which was used in the next step. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.94 (s, 3H), 3.65 (s, 3H), 5.25 (br, 2H), 5.97 (br, 2H), 6.36–6.37 (m, 1H), 6.90–6.92 (m, 1H), 6.96–7.06 (m, 5H), 7.15–7.23 (m, 2H), 7.26 (s, 1H), 7.32–7.36 (m, 1H), 7.44–7.47 (m, 2H). MS [(+)APCI, m/z]: 553[M+H] + . Anal. Calcd. for C 29 H 23 Cl 3 N 2 O 3 +0.13C 4 H 8 O 2 +0.13CH 2 Cl 2 : C, 61.79; H, 4.25; N, 4.86. Found: C, 60.43; H, 4.50; N, 4.80. 
     Step E. 10-[(2′-Methoxy-2-methyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     To a solution of 2,2,2-richloro-1-{10-[(2′-methoxy-2-methyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone of Step D (2.0 g, 3.6 mmol) in acetone (20 mL) was added 2.5 N sodium hydroxide (2.9 mL, 7.25 mmol). After stirring overnight, the reaction mixture was acidified with 2 N hydrochloric acid (4.0 mL, 8.0 mmol) then concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a brown solid. Trituration with diethyl ether-hexane provided 1.4 g of the desired product as a white solid, m.p.174–184° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.93 (s, 3H), 3.65 (s, 3H), 5.17 (br, 2H), 5.94 (br, 2H), 6.09–6.10 (m, 1H), 6.77 (d, 1H), 6.89–7.06 (m, 6H), 7.10–7.19 (m, 2H), 7.23 (s, 1H), 7.31–7.38 (m, 2H), 12.31 (br, 1H). MS [(−)APCI, m/z]: 451[M−H] − . Anal. Calcd. for C 28 H 24 N 2 O 4 +0.10C 4 H 10 O: C, 74.17; H, 5.48; N, 6.09. Found: C, 73.63; H, 5.68; N, 5.94. 
     EXAMPLE 10 
     10-[(3-Methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     Step A. 4-Iodo-2-methoxybenzoic acid methyl ester 
     4-Amino-2-methoxybenzoic acid methyl ester (3.0 g, 16.6 mmol) was suspended in water (40 mL) and concentrated sulfuric acid (10 mL) was added. The suspension was cooled in an ice/salt water bath, and an aqueous solution (10 mL) of sodium nitrite (1.26 g, 18.3 mmol) was added dropwise so that the temperature remained close to 0° C. After the addition, a homogeneous, yellow-green solution was obtained. An aqueous solution (60 mL) of potassium iodide (3.02 g, 18.2 mmol) and iodine (2.31 g, 9.1 mmol) was then added dropwise, and the reaction stirred for an additional 1 hour. The reaction mixture was then extracted with ethyl acetate, the organic extracts were combined and washed with 1 N sodium thiosulfate, 1 N sodium hydroxide and brine. After drying over anhydrous sodium sulfate the solution was filtered and concentrated in vacuo to give 2.7 g of the title product as an orange oil which was used in the next step. 
       1 H NMR (DMSO-d6, 400 MHz): δ 2.76 (s, 3H), 3.82 (s, 3H), 7.39 (s, 2H), 7.48 (s, 1H). MS [EI, m/z]: 292[M] + . 
     Step B. 4-Iodo-2-methoxybenzoic acid 
     The 4-iodo-2-methoxybenzoic acid methyl ester of Step A (2.7 g, 9.24 mmol) was dissolved in tetrahydrofuran (40 mL) and 1 N sodium hydroxide (20 mL, 20 mmol) was added. The reaction mixture was heated at reflux for 3 hours, then cooled and concentrated in vacuo to give an orange oil that was partitioned between ethyl acetate and 2 N hydrochloric acid. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 2.5 g of title product as a yellow-orange solid, m.p. 144–146° C. 
       1 H NMR (DMSO-d 6,  400 MHz): δ 3.81 (s, 3H), 7.37 (s, 2H), 7.44 (s, 1H), 12.72 (br, 1H). MS [EI, m/z]: 278[M] + . Anal. Calcd. for C 8 H 7 IO 3+ 0.10C 4 H 8 O 2 : C, 35.17; H, 2.74. Found: C, 35.37; H, 2.49. 
     Step C. 10-(4-Iodo-2-methoxybenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine 
     A suspension of 4-iodo-2-methoxybenzoic acid of Step B (2.5 g, 9.0 mmol) in thionyl chloride (10 mL) was heated at reflux for 1 hour. After cooling, the thionyl chloride was removed in vacuo. The residue was dissolved in toluene and concentrated in vacuo to give the crude acid chloride as a brown solid. The acid chloride was then dissolved in dichloromethane (10 mL) and slowly added to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.75 g, 9.5 mmol) and N,N-diisopropylethyl amine (3.4 mL, 19.5 mmol) in dichloromethane (20 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification by flash chromatography on silica gel using a solvent gradient of 15 to 25% ethyl acetate in hexane provided 3.6 g of title product as a white foam, which was redissolved in dichloromethane and evaporated to dryness prior to use in the next step. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 3.55 (br, 3H), 4.80–5.32 (br, 4H), 5.88–5.90 (m, 1H), 5.94 (s, 1H), 6.79 (s, 1H), 6.94 (s, 1H), 7.03 (t, 1H), 7.09–7.13 (m, 3H), 7.20–7.22 (m, 1H), 7.36–7.38 (m, 1H). MS [(+)ESI, m/z]: 445[M+H] + . Anal. Calcd. for C 20 H 17 IN 2 O 2 +0.10C 4 H 8 O 2 +0.13CH 2 Cl 2 : C, 53.13; H, 3.92; N, 6.04. Found: C, 53.03; H, 3.65; N, 6.03. 
     Step D. (10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[3-methoxy-2′-methyl-[1,1′-biphenyl]-4-yl]-methanone 
     A mixture of 10-(4-iodo-2-methoxybenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step C (1.8 g, 4.1 mmol), 2-methylphenyl boronic acid (0.55 g, 4.1 mmol) and sodium carbonate (1.9 g, 17.9 mmol) in toluene:ethanol: water (20 mL:10 mL:10 mL) was purged with nitrogen for 1 hour. After addition of the tetrakis(triphenylphosphine) palladium(0) catalyst (0.24 g, 0.21 mmol), the reaction mixture was heated at 100° C. overnight. After cooling, the reaction was filtered through Celite and the cake washed with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a brown oil. Purification by flash chromatography on silica gel using a solvent system of 20% ethyl acetate in hexane provided 1.5 g of title product as a white foam, which was redissolved in dichloromethane and evaporated to dryness in vacuo prior to use in the next step. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 2.08 (s, 3H), 3.54 (s, 3H), 4.80–5.30 (br, 4H), 5.89–5.91 (m, 1H), 5.97 (s, 1H), 6.66 (s, 1H), 6.77–6.80 (m, 2H), 6.93–7.01 (m, 2H), 7.09–7.10 (m, 2H), 7.19–7.24 (m, 3H), 7.36–7.38 (m, 2H). MS [(+)ESI, m/z]: 409[M+H] + . Anal. Calcd. for C 27 H 24 N 2 O 2 +0.10CH 2 Cl 2 : C, 78.05; H, 5.84; N, 6.72. Found: C, 78.12; H, 5.13; N, 6.69. 
     Step E. 2,2,2-Trichloro-1-{10-[(3-methoxy-2′-methyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone 
     To a solution of (10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[3-methoxy-2′-methyl-[1,1′-biphenyl]-4-yl]-methanone of Step D (1.36 g, 3.33 mmol) in dichloromethane (15 mL) was added N,N-diisopropylethyl amine (1.2 mL, 6.89 mmol) followed by slow addition of trichloroacetyl chloride (1.1 mL, 9.85 mmol). The reaction mixture was stirred overnight at room temperature then was quenched with water. The organic phase was washed with 0.1 N hyrochloric acid followed by water, then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a green oil. Purification by flash chromatography on silica gel using a solvent system of 20% ethyl acetate in hexane gave 1.7 g of title product as a yellow foam. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 2.09 (s, 3H), 3.50 (s, 3H), 5.30 (br, 2H), 5.87 (br, 2H), 6.37–6.38 (m, 1H), 6.64 (s, 1H), 6.82–6.83 (m, 1H), 6.90–6.92 (m, 1H), 6.97–6.99 (m, 1H), 7.10–7.12 (m, 2H), 7.20–7.25 (m, 4H), 7.35–7.37 (m, 1H), 7.44–7.46 (m, 1H). MS [(+)APCI, m/z]: 553[M+H] + . Anal. Calcd. for C 29 H 23 Cl 3 N 2 O 3 +0.20C 4 H 8 O 2 +0.40H 2 O: C, 61.85; H, 4.42; N, 4.84. Found: C, 61.50; H, 4.07; N, 4.72. 
     Step F. 10-[(3-Methoxy-2′-methyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     To a solution of 2,2,2-trichloro-1-{10-[(3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone of Step E (1.6 g, 2.9 mmol) in acetone (20 mL) was added 2.5 N sodium hydroxide (2.3 mL, 5.8 mmol). After stirring overnight, the reaction was acidified with 2 N hydrochloric acid (3.2 mL, 6.4 mmol) then concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The layers were separated, and the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a brown solid. Trituration with diethyl ether/hexane provided 1.2 g of desired product as an off-white solid, m.p. 201–204° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 2.09 (s, 3H), 3.48 (s, 3H), 5.20 (br, 2H), 5.85 (br, 2H), 6.12 (s, 1H), 6.62 (s, 1H), 6.73 (d, 1H), 6.79–6.87 (m, 2H), 6.91–6.95 (m, 1H), 6.99–7.03 (m, 1H), 7.06–7.12 (m, 1H), 7.18–7.25 (m, 4H), 7.39 (br, 1H), 12.31 (br, 1H). MS [(+) ESI, m/z]: 453[M+Na] + . Anal. Calcd. for C 28 H 24 N 2 O 4 +0.10C 4 H 10 O+0.15C 4 H 8 O 2 : C, 73.61; H, 5.58; N, 5.92. Found: C, 73.23; H, 5.49; N, 6.06. 
     EXAMPLE 11 
     N-Methyl-N-[3-(dimethylamino)propyl]-10-[(3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     To a solution of 10-[(3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 10, Step F (0.40 g, 0.88 mmol), 3-(dimethylaminopropyl)-1-methyl amine (0.16 mL, 1.09 mmol) and 1-hydroxybenzotriazole (0.135 g, 0.96 mmol) in N,N-dimethylformamide (4 mL) was added 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.19 g, 1.09 mmol) followed by N,N-diisopropylethyl amine (0.24 mL, 1.35 mmol). The reaction mixture was stirred overnight, then diluted with ethyl acetate and washed with water and saturated aqueous sodium bicarbonate. The organic phase was then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification by flash chromatography on silica gel using a solvent system of 5% methanol in dichloromethane afforded 0.36 g of title compound as a white foam. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.67–1.73 (m, 2H), 2.08–2.25 (m, 10H), 3.03 (s, 3H), 3.45–3.50 (m, 6H), 4.60–5.40 (br m, 4H), 6.05–6.06 (m, 1H), 6.25–6.26 (m, 1H), 6.62 (s, 1H), 6.79–6.81 (m, 1H), 6.85–6.87 (m, 1H), 6.91–6.95 (m, 1H), 7.03–7.06 (m, 1H), 7.09–7.11 (m, 1H), 7.19–7.30 (m, 4H), 7.38 (br, 1H). MS [(+)ESI, m/z]: 551[M+H] + . Anal. Calcd. for C 34 H 38 N 4 O 3 +0.20H 2 O: C, 73.67; H, 6.98; N, 10.11. Found: C, 73.50; H, 7.08; N, 9.96. 
     EXAMPLE 12 
     7,8-Dimethoxy-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl][2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]methanone 
     Step A. 1-[(4,5-Dimethoxy-2-nitrophenyl)methyl]-1H-pyrrole-2-carboxaldehyde 
     To a suspension of sodium hydride (0.724 g, 60% suspension in oil) in N,N-dimethyl formamide (50 mL) was added pyrrole 2-carboxaldehyde (1.7 g, 18.1 mmol) and the reaction mixture was stirred for 30 minutes. It was then cooled to 0° C. and 4,5-dimethoxy-2-nitrobenzyl bromide (5.0 g, 1 equiv) was added dropwise over 20 minutes. After the addition, the reaction mixture was stirred at room temperature for 3 hours. It was then diluted with ethyl acetate (450 mL), washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The crude product was triturated with water, filtered and washed with water. This material was dried over anhydrous potassium carbonate in vacuo to provide the title compound as a yellow crystalline solid (4.97 g), m.p. 109–112° C., which was used in the next step. 
     Step B. 7,8-Dimethoxy-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine 
     A mixture of the 1-[(4,5-dimethoxy-2-nitrophenyl)methyl]-1H-pyrrole-2-carboxaldehyde of Step A (4.97 g), acetic acid (0.5 mL), magnesium sulfate (0.5 g) and 10% palladium on charcoal (0.5 g) in ethyl acetate (50 mL) was hydrogenated overnight at atmospheric pressure. The reaction was then filtered through Celite and the solvent removed in vacuo to give the crude title compound as an amber foam (3.2 g) which was used in the next step without further purification. 
     Step C. 7,8-Dimethoxy-(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(4-bromo-3-methyl-phenyl)-methanone 
     To a solution of 7,8-dimethoxy-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step B (3.20 g) in dichloromethane (20 mL) was added 3-methylbenzoyl chloride (3.4 g, 1.1 equiv) and triethylamine (2.0 9, 1.5 equiv) and the mixture was stirred at room temperature overnight. The solvent was then removed in vacuo and the residue chromatographed on silica gel eluting with a solvent gradient from 5 to 50% of ethyl acetate in petroleum ether to provide the title compounds as a yellow crystalline solid (3.5 g), m.p. 165–168° C. 
       1 H NMR (CDCl 3 , 200 MHz): δ 2.30 (s, 3H), 3.55 (br, 3H), 3.85 (s, 3H), 5.1 (br, 4H), 6.05 (br, 1H), 6.1 (t, 1H), 6.3 (br, 1H), 6.65 (t, 1H), 6.8 (s, 2H), 7.3 (s, 2H). MS [(+)ESI, m/z]: 442[M +H] + . 
     Step D. 7,8-Dimethoxy-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl][2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]methanone 
     The 7,8-dimethoxy-(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(4-bromo-3-methyl-phenyl)-methanone of Step C (1.0 g) was reacted with 2-trifluoromethylphenyl boronic acid (0.645 g, 1.5 equiv.), potassium phosphate (0.964 g, 2.0 equiv.) and a catalytic amount (0.050 g) of tetrakis(triphenylphosphine) palladium(0) in refluxing dioxane (10 mL) under nitrogen for 24 hours. The reaction was then cooled to room temperature, filtered through Celite, and the solvent removed in vacuo. The residue was dissolved in dichloromethane and the solution was washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The crude product so obtained was purified by chromatography on silica gel eluting with 5% ethyl acetate/dichloromethane to provide the title product (1.0 g) as a white crystalline solid, m.p. 187–188° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.85 (s, 3H), 3.40 (s, 3H), 3.70 (s, 3H), 5.20 (br, 4H), 5.92 (t, 1H), 5.96 (s, 1H), 6.56 (s, 1H), 6.77 (t, 1H), 6.90 (m, 1H), 7.05 (m, 2H), 7.20 (d, 1H), 7.30 (s, 1H), 7.58 (t, 1H), 7.68 (t, 1H), 7.80 (d, 1H). MS [(+)APCI, m/z]: 507[M+H] + . Anal. Calcd. for C 29 H 25 F 3 N 2 O 3 : C, 68.77; H, 4.97; N, 5.53. Found: C, 68.85; H, 5.05; N, 5.43. 
     EXAMPLE 13 
     N-Methyl-[N-(3-dimethylamino)propyl]-7,8-dimethoxy-10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide hydrochloride salt 
     A solution of the 7,8-dimethoxy-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl][2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]methanone of Example 12, Step D (0.31 mmol), diphosgene (1.1 equiv.) and triethylamine (1.5 equiv.) in dichloromethane (5 mL) was stirred at room temperature overnight. The solvent was removed in vacuo and the residue was dissolved in dichloromethane (5 mL). To the solution was added triethylamine (1.5 equiv.) and 3-(dimethylaminopropyl)-1-methyl amine (1.5 equiv.). The reaction mixture was then washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was first chromatographed on silica gel eluting with a solvent gradient from 2 to 5% of methanol in dichloromethane and then chromatographed again with solvent gradient from 2 to 5% of methanol in ethyl acetate to provide the title compound (0.100 g) as a colorless foam. Treatment of a solution of the free base in ethanol with anhydrous hydrogen chloride in dioxane followed by removal of the solvent provided the hydrochloride salt as a brown solid, m.p. 118° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.85 (s, 3H), 2.00 (m, 2H), 3.05 (t, 2H), 2.75 (s, 6H), 3.10 (s, 3H), 3.40 (s, 3H), 3.55 (t, 2H), 3.70 (s, 3H), 5.30 (s, 4H), 6.05 (s, 1H), 6.35 (d, 1H), 6.50 (s, 1H), 6.90 (s, 1H), 6.95 (s, 2H), 7.20 (d, 1H), 7.30 (s, 1H), 7.60 (t, 1H), 7.70 (t, 1H), 7.80 (d, 1H), 10.25 (br, 1H). MS [(+)ESI, m/z]: 649[M+H] + . Anal. Calcd. For C 36 H 39 F 3 N 4 O 4 +HCl+2H 2 O: C, 59.95; H, 6.15; N, 7.77. Found: C, 59.40; H, 6.63; N, 7.86. 
     EXAMPLE 14 
     7,8-Dimethoxy-10-{[2-methyl-2′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl]carbonyl}-[(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)carbonyl]-4-piperidinone 
     A solution of the 7,8-dimethoxy-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl][2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]methanone of Example 12, Step D (0.31 mmol), diphosgene (1.1 equiv.) and triethylamine (1.5 equiv.) in dichloromethane (5 mL) was stirred at room temperature overnight. The solvent was removed in vacuo, the residue was dissolved in dichloromethane (5 mL), and then triethylamine (1.5 equiv.) and 4-piperidone (1.5 equiv.) were added. The reaction mixture was stirred overnight, washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was first chromatographed on silica gel eluting with 2% methanol in dichloromethane and then chromatographed again with 2% methanol in ethyl acetate to provide the title compound as a yellow solid, m.p. 132–134° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.85 (s, 3H), 2.45 (m, 4H), 3.40 (s, 3H), 3.65 (s, 3H), 3.90 (t, 4H), 5.20 (br, 2H), 5.35 (s, 2H), 6.10 (s, 1H), 6.40 (d, 1H), 6.50 (s, 1H), 6.90 (s, 1H), 7.00 (s, 1H), 7.05 (s, 1H), 7.20 (d, 1H), 7.30 (s, 1H), 7.60 (t, 1H), 7.65 (t, 1H), 7.80 (d, 1H). MS [(+)APCI, m/z]: 632[M+H] + . Anal. Calcd. for C 35 H 32 F 3 N 3 O 5 +H 2 O: C, 64.71; H, 5.38; N, 6.47. Found: C, 65.20; H, 5.12; N, 6.41. 
     EXAMPLE 15 
     10-{[6-Chloro-3-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     Step A. 4-Iodo-5-chloro-2-methoxy benzoic acid 
     A stirred solution of 4-amino-5-chloro-2-methoxy benzoic acid (12.25 g , 60.8 mmol) in water (136 mL ) and concentrated sulfuric acid (34 mL) was cooled to 0° C. in a flask fitted with an overhead stirrer. A solution of sodium nitrite (4.62 g , 66.9 mmol) in water (26 mL) was added dropwise while keeping the internal temperature around 0° C. Potassium iodide (11.11 g , 66.9 mmol) and iodine (4.246 g , 33.5 mmol) were dissolved in water (130 mL) and added dropwise to the stirred reaction mixture. After 2 hours the reaction was extracted with ethyl acetate. The organic extracts were then washed with 10% sodium thiosulfate and brine, then dried over magnesium sulfate, filtered and evaporated to dryness to yield 11.32 g of the title compound, m.p. 150–151° C. This material was used in the next step without further purification. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 13.03 (br, 1H), 7.70 (s, 1H), 7.63 (s, 1H), 3.82 (s, 3H). MS [(−)-APCI, m/z]: 311[M−H] − . Anal. Calcd. for C 8 H 6 CIIO 3 : C, 30.75; H, 1.94. Found: C, 31.28; H, 1.78. 
     Step B. 2-Chloro-2′-trifluoromethyl-5-methoxy[1,1′-biphenyl]-4-carboxylic acid. 
     To a stirred solution of 4-iodo-5-chloro-2-methoxy benzoic acid of Step A (3.12 g, 10 mmol) in N,N-dimethylformamide (100 mL) was added 2-trifluoromethyl phenyl boronic acid (5.70 g, 30 mmol) and potassium carbonate (12.73 g, 92 mmol). This mixture was purged with nitrogen and then treated with tetrakis(triphenylphosphine) palladium(0) (0.58 g, 0.5 mmol). The reaction was heated to reflux overnight, cooled, acidified with 2 N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated to provide a nearly quantitative amount of the title acid which was used in the next step without further purification. 
     Step C. 10-{[6-Chloro-3-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine 
     A stirred solution of the 2-chloro-2′-trifluoromethyl-5-methoxy[1,1′-biphenyl]-4-carboxylic acid of Step B (3.46 g, 10.46 mmol) in tetrahydrofuran (20 mL) containing a catalytic amount of N,N-dimethylformamide was treated dropwise with thionyl chloride (1.36 g, 11.51 mmol). The reaction mixture was stirred for 2 hours, and then added dropwise to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.92 g 10.46 mmol) in tetrahydrofuran (20 mL) containing triethylamine (2.32 g, 23 mmol). The reaction mixture was stirred for 2 hours, diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. Trituration of the residue with acetone gave the title compound (3.14 g). Recrystallization from acetone/hexanes provided white crystals, m.p. 208–210° C.; 
       1 H NMR (DMSO-d 6 , 400 MHz) δ 3.46 (s, 3H), 5.16–5.20 (br d, 3H), 5.89 (t, 1H), 5.97 (s, 1H), 6.70 (s, 1H), 6.80 (t, 1H), 7.80–7.00 (m, 10H); MS [(+) ESI, m/z]: 497[M+H] + . Anal. Calcd. for C 27 H 20 CIF 3 N 2 O 2 +0.5H 2 O: C, 64.10; H, 4.18; N, 5.54. Found: C, 64.40; H, 3.97; N, 5.54. 
     Step D. 10-{[6-Chloro-3-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     A solution of the 10-{[6-chloro-3-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step C (2.29 g, 4.6 mmol) in dichloromethane (30 mL) was treated with N,N-diisopropylethyl amine (0.62 g, 4.84 mmol) and stirred for 10 minutes. Trichloroacetyl chloride (0.92 g, 5.07 mmol) was then added dropwise. The reaction mixture was stirred overnight, diluted with dichloromethane, washed with 0.1 N hydrochloric acid, saturated aqueous sodium bicarbonate, and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered, and evaporated to yield the crude trichloroketone intermediate which without further purification, was dissolved in acetone and treated with an excess of 1N sodium hydroxide. The mixture was stirred overnight, and then diluted with isopropyl acetate and acidified with 1 N hydrochloric acid. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. The solid residue was triturated with methanol to provide the title compound (1.23 g ) as a white solid, m.p. 220–222° C. (dec). 
       1 H NMR (DMSO-d 6 , 400 MHz) δ 3.40 (s, 3H), 6.12 (d, 1H), 6.68 (s, 1H), 6.72 (d, 1H), 6.94 (s, 2H), 7.07 (t, 1H), 7.25 (d, 2H), 7.62 (t, 2H), 7.70 (t, 1H), 7.78 (d, 1H), 12.31 (br, 1H). MS [(+)APCI, m/z]: 541[M+H] + . Anal. Calcd. for C 28 H 20 CIF 3 N 2 O 4 +0.25H 2 O: C, 61.66; H, 3.79; N, 5.14. Found: C, 61.47; H, 3.64; N, 5.06. 
     EXAMPLE 16 
     10{[2′-Chloro-6-chloro-3-methoxy-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     Step A. 2′-Chloro-2-chloro-5-methoxy-[1,1′-biphenyl]-4-carboxylic acid. 
     To a stirred solution of 4-iodo-5-chloro-2-methoxy benzoic acid (3.12 g, 10 mmol) in N,N-dimethylformamide (100 mL) was added 2-chloro phenyl boronic acid (5.07 g, 32.4 mmol) and potassium carbonate (12.73 g, 92 mmol). This mixture was purged with nitrogen and then treated with tetrakis(triphenylphosphine) palladium(0) (0.58 g, 0.5 mmol). The reaction was heated to reflux overnight, cooled, acidified with 2 N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated to provide a nearly quantitative amount of the title acid which was used in the next step without further purification. 
     Step B. 10-{[2′-Chloro-6-chloro-3-methoxy-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine 
     A stirred solution of the 2′-chloro-2-chloro-5-methoxy-[1,1′-biphenyl]-4-carboxylic acid of Step A (3.09 g, 10.46 mmol) in tetrahydrofuran (20 mL) containing a catalytic amount of N,N-dimethylformamide was treated dropwise with thionyl chloride (1.36 g, 11.51 mmol). The reaction mixture was stirred for 2 hours, and then added dropwise to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.92 g 10.46 mmol) in tetrahydrofuran (20 mL) containing triethylamine (2.32 g, 23 mmol). The reaction mixture was stirred for 2 hours, diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. Trituration of the residue with ethyl acetate gave the title compound (1.93 g) which was recrystallized from ethyl acetate/hexanes as white crystals, m.p. 209–211° C.; 
       1 H NMR (DMSO-d 6 , 400 MHz) δ 3.55 (s, 3H), 5.16–5.20 (br m, 3H), 5.89 (t, 1H), 5.97 (s, 1H), 6.71 (s, 1H), 6.80 (s, 1H), 7.04–7.60 (m, 1OH). MS [(+) APCI, m/z]: 463[M+H] + . Anal. Calcd. for C 26 H 20 C 12 N 2 O 2 +0.25 C 4 H 8 O 2 : C, 66.81, H, 4.57, N, 5.77. Found: C 66.76, H, 4.24, N, 5.93. 
     Step C. 10-{[2′-Chloro-6-chloro-3-methoxy-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     A solution of 10-{[2′-chloro-6-chloro-3-methoxy-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step B (2.1 g, 4.6 mmol) in dichloromethane (30 mL) was treated with N,N-diisopropylethyl amine (0.62 g, 4.84 mmol) and stirred for 10 minutes. Trichloroacetyl chloride (0.92 g, 5.07 mmol) was then added dropwise. The reaction mixture was stirred overnight, diluted with dichloromethane, washed with 0.1 N hydrochloric acid, saturated aqueous sodium bicarbonate, and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered, and evaporated to yield the crude trichloroketone intermediate which without further purification, was dissolved in acetone and treated with an excess of 1N sodium hydroxide. The mixture was stirred overnight, diluted with isopropyl acetate and acidified with 1 N hydrochloric acid. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. The solid residue was triturated with methanol to provide the title compound as a white solid, which was used without further purification. 
     EXAMPLE 17 
     10-{[6-Chloro-3-methoxy-2′-ethoxy[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine 
     Step A. 2-Chloro-2′-ethoxy-5-methoxy[1,1′-biphenyl]-4-carboxylic acid 
     To a stirred solution of 4-iodo-5-chloro-2-methoxy benzoic acid of Example 15, Step A (0.500 g, 1.6 mmol) in N,N-dimethylformamide (30 mL) was added 2-ethoxy phenyl boronic acid (0.8 g, 4.8 mmol) and potassium carbonate (2.04 g, 14.7 mmol). This mixture was purged with nitrogen and then treated with a catalytic amount of tetrakis (triphenylphosphine) palladium(0) (0.093 g, 0.08 mmol). The reaction was heated to reflux overnight, cooled, acidified with 2 N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated to yield the title acid which was used in the next step without further purification. 
     Step B. 10-{[6-Chloro-3-methoxy-2′-ethoxy-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine 
     To a stirred solution of the 2-chloro-2′-ethoxy-5-methoxy[1,1′-biphenyl]-4-carboxylic acid of Step A (0.491 g) in tetrahydrofuran (5 mL) containing a catalytic amount of N,N-dimethyl formamide was added dropwise thionyl chloride (0.210 g, 1.76 mmol). The reaction mixture was stirred for 2 hours, and then added dropwise to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.294 g, 1.60 mmol) in tetrahydrofuran (5 mL) containing triethylamine (0.357 g, 3.52 mmol). The reaction mixture was stirred for 2 hours, diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. Trituration of the residue with methanol provided the title compound as an off-white solid, 99.24% pure by analytical HPLC [Primesphere C-18 column (2.0×150 mm); mobile phase 70/30 acetonitrile/water containing 0.1% phosphoric acid], m.p. 213–215° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.11, (t, 3H), 3.51 (s, 3H), 3.92 (q, 2H), 5.17–5.20 (br, m, 3H), 5.89 (t, 1H), 5.97 (s, 1H), 6.67–7.55 (m, 10H). MS [(+)APCI, m/z]: 473[M+H] + . Anal. Calcd. for C 28 H 25 CIN 2 O 3 : C, 71.11; H, 5.33; N, 5.92. Found: C, 70.31; H, 5.27; N, 5.79. 
     EXAMPLE 18 
     10-{[6-Chloro-3-methoxy-2′-fluoro-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     Step A. 2-Chloro-2′-fluoro-5-methoxy[1,1′-biphenyl]-4-carboxylic acid 
     To a stirred solution of 4-iodo-5-chloro-2-methoxy benzoic acid of Example 15, Step A (3.72 g, 19.1 mmol) in N,N-dimethylformamide (20 mL) was added 2-fluoro phenyl boronic acid (5.0 g, 35.7 mmol) and potassium carbonate (14.8 g, 107 mmol). This mixture was purged with nitrogen and then treated with a catalytic amount of tetrakis (triphenylphosphine) palladium(0) (0.688 g, 0.59 mmol). The reaction was heated to reflux overnight, cooled, acidified with 2 N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. The residue was flash chromatographed on acid washed silica using a 10 to 50% gradient of diethyl ether in hexane to provide the desired title compound (3.8 g) as a white solid. 
       1 H NMR (DMSO-d 6 1,400 MHz) δ 3.83 (s, 3H), 7.15 (s, 1H), 7.30–7.35 (m, 2H), 7.42 (m, 1H), 7.48–7.54 (m, 1H), 7.74 (s, 1H). MS [(+)ESI, m/z]: 298[M+NH 4 ] + . Anal. Calcd. for C 14 H 10 CIFO 3 : C, 59.91; H, 3.59. Found: C, 59.79; H, 3.35. 
     Step B. 10-{[6-Chloro-3-methoxy-2′-fluoro-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine 
     To a stirred solution of 2-chloro-2′-fluoro-5-methoxy[1,1′-biphenyl]-4-carboxylic acid of Step A (3.80 g, 13.5 mmol) in tetrahydrofuran (20 mL) containing a catalytic amount of N,N-dimethylformamide was added dropwise thionyl chloride (1.77 g, 14.9 mmol). The reaction mixture was stirred for 2 hours, and then added dropwise to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (2.49 g, 13.5 mmol) in tetrahydrofuran (20 mL) containing triethylamine (3.0 g, 29.8 mmol). The reaction mixture was stirred for 2 hours, diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. Recrystallization of the residue from ethyl acetate/heptane provided the title compound as a pale yellow solid, m.p. 192–194° C., found to be 99.99% pure by analytical HPLC [Primesphere C-18 column (2.0×150 mm); mobile phase: gradientfrom 10 to 100% of acetonitrile/water containing 0.1% phosphoric acid, 7 minute gradient]. 
       1 H NMR (DMSO-d 6 , 400 MHz) δ 3.55 (s, 3H), 5.19 (br m, 2H), 5.90 (t, 1H), 5.96 (s, 1H), 6.80 (s, 2H), 7.07–7.63 (m, 10H). MS [(+)ESI, m/z]: 447[M+H] + . Anal. Calcd. for C 26 H 20 CIFN 2 O 2 +H 2 O: C, 69.60; H, 4.54; N, 6.24. Found: C, 69.39; H, 4.41; N, 6.20. 
     Step C. 10-{[6-Chloro-3-methoxy-2′-fluoro-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     A solution of the 10-{[6-chloro-3-methoxy-2′-fluoro-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step B (3.02 g, 6.76 mmol) in dichloromethane (35 mL) was treated with N,N-diisopropylethyl amine (0.960 g, 7.43 mmol) and stirred for 10 minutes. Trichloroacetyl chloride (1.47 g, 8.10 mmol) was then added dropwise. The reaction mixture was stirred overnight, diluted with dichloromethane, washed with 0.1 N hydrochloric acid, saturated aqueous sodium bicarbonate, and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered, and evaporated to yield the crude trichloroketone intermediate which without further purification, was dissolved in acetone and treated with an excess of 1 N sodium hydroxide The mixture was stirred overnight, and then diluted with isopropyl acetate and acidified with 1 N hydrochloric acid. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. The solid residue was triturated with methanol to provide the title compound (2.95 g) as a beige solid, m.p. 207–208° C. 
       1 H NMR (DMSO-d 6 , 400 MHz) δ 3.49 (br, 3H), 6.12 (d, 1H), 6.72 (d, 1H), 6.77 (s, 1H), 7.01 (d, 2H), 7.09 (m, 1H), 7.26 (m, 4H), 7.45 (m, 2H), 7.61 (br, 1H), 12.35 (br, 1H). MS [(+)APCI, m/z]: 491[M+H] + . Anal. Calcd for C 27 H 20 CIFN 2 O 4 : C, 66.06; H, 4.11; N, 5.71. Found: C, 65.68; H, 4.24; N, 5.48. 
     EXAMPLE 19 
     10-{[2-Methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     Step A. Trifluoromethanesulfonic acid 4-formyl-2-methoxy-phenyl ester 
     To a solution of vanillin (6.08 g, 40.0 mmol) and triethylamine (6.70 mL, 48.0 mmol) in dichloromethane (300 mL) was added dropwise a solution of trifluoromethane sulfonic anhydride (12.4 g, 44.0 mmol) in dichloromethane (100 mL) at 0° C. After stirring for 2 hours, the solution was concentrated, and the residue washed with water and extracted twice with ethyl acetate. Upon drying and concentrating, the residual dark oil was subjected to flash chromatography on silica gel eluting with 20% ethyl acetate in hexane providing the title product (8.91 g) as a light yellow oil, which was used in the next step without further purification. 
     Step B. 2-Methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-carboxaldehyde 
     A stirred solution of trifluoromethanesulfonic acid 4-formyl-2-methoxy-phenyl ester of Step A (6.9 g, 22.1 mmol), 2-trifluoromethyl phenyl boronic acid (5.4 g, 28.6 mmol) and potassium phosphate (13.2 g, 62.2 mmol) in N,N-dimethylformamide (120 mL) was degassed with nitrogen, whereupon a catalytic amount (0.285 g) of [1,4-bis-(diphenylphosphine)butane]palladium (II) dichloride was added. The solution was heated to 120° C. for 5 hours, poured into water and extracted with ethyl acetate. The combined extracts were washed with water, dried over anhydrous magnesium sulfate and filtered through a plug of silica gel. Removal of the solvent provided the crude title compound (4.54 g) as an oil, which was used as such in the next step. 
       1 H NMR (200 MHz, CDCl 3 ): δ 10.03 (s, 1H), 8.14 (d, 1H), 7.31–7.56 (m, 6H), 3.91 (s, 3H). 
     Step C. 2-Methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-carboxylic acid 
     The 2-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-carboxaldehyde of Step B (0.95 9, 3.41 mmol) and sulfamic acid (0.43 g, 4.43 mmol) were dissolved in a mixture of tetrahydrofuran and water (1:1, v/v, 30 mL). Sodium chlorite (0.31 g, 4.43 mmol) was added under stirring, and the solution turned yellow. After 30 minutes, additional sodium chlorite and sulfamic acid were added, and the solution stirred an additional hour. The solution was then concentrated, and the residue partitioned between ethyl acetate and water. The ethyl acetate layer was dried and concentrated to yield an oil, which solidified upon trituration with hexane to provide the title compound (0.84 g) as a yellow solid, which was used in the next step. 
     Step D. (10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(2-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)-methanone 
     The 2-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-carboxylic acid of step C (1.6 g, 5.40 mmol) was added to a flask containing toluene (30 mL), thionyl chloride (1.4 mL) and one drop of N,N-dimethylformamide. The solution was stirred at 70° C. for 1 hour and then concentrated in vacuo. The residue was diluted with dichloromethane (40 mL) and to this solution was added 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.94 9, 5.16 mmol). After the solution became homogeneous, N,N-diisopropylethyl amine (1.07 mL, 6.19 mmol) was added in one portion at 0° C. After 30 minutes the solution was concentrated, and the residue partitioned between water and ethyl acetate. The ethyl acetate was dried and concentrated to give a crude oil, which was chromatographed on silica gel eluting with 30% ethyl acetate in hexane to yield 1.2 g of product. The solid was recrystallized from ethyl acetate/hexane to provide the desired title product (0.87 g) as colorless crystals, m.p. 146–148° C. 
       1 H NMR (400 MHz, DMSO-d 6 ) δ 7.72 (d, 1H), 7.62 (t, 1H ), 7.53 (t, 1H), 7.46 (d, 1H), 7.19 (m, 2H), 7.11 (t, 1H), 6.92–7.01 (m, 4H), 6.83 (s, 1H), 5.95 (bs, 1H), 5.91 (s, 1H), 5.31 (br, 4H), 3.45 (s, 3H). MS [(+)ESI, m/z]: 463[M+H] + . Anal. Calcd. for C 27 H 21 F 3 N 2 O 2 : C, 70.12; H, 4.58; N, 6.06. Found: C, 70.53; H, 4.72; N, 5.89. 
     Step E. 10-{[2-Methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     To a stirred solution of the (10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(2-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)-methanone of Step D (2.34 g, 5.0 mmol) and N,N-diisopropylethyl amine (1.04 mL, 6.0 mmol) in dichloromethane (100 mL) was added dropwise a solution of trichloroacetyl chloride (1.09 g, 6.0 mmol) in dichloromethane (20 mL) kept at 0° C. After the addition was complete, the solution was stirred overnight at room temperature, then washed with 10% aqueous potassium carbonate. The organic phase was dried and concentrated to yield a black residue. The residue was purified by filtration through a plug of silica gel, eluting with 20% ethyl acetate in hexane. The resulting tan colored product was dissolved in acetone and 1 N sodium hydroxide (2:1, v/v) and the mixture was stirred for 30 minutes. The solution was then concentrated and extracted with ethyl acetate. The combined organic phases were dried and concentrated to yield a yellow oil. The oil was triturated with hexane, and the resulting solid was removed by filtration to yield the title compound (1.86 g) as an off white solid, which was used without further purification. 
     EXAMPLE 20 
     {[10-(2-Methoxy)-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-[(2S)-[(2-pyrrolidin-1-yl)methyl]pyrrolidin-1-yl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl-methanone 
     To a stirred solution of the 10-{[2-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 19 (0.230 g, 0.5 mmol) in N,N-dimethylformamide (15 mL), was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.120 g, 0.625 mmol) and 1-hydroxybenzotriazole (0.087 g, 0.625 mmol). After the solution became homogeneous, (S)-(+)-1-[(2-pyrrolidin-1-yl)methyl]-pyrrolidine (0.100 g, 0.625 mmol) was added, and the mixture was stirred at room temperature overnight. The solution was then poured into water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried over anhydrous sodium sulfate and concentrated to dryness. The residue was subjected to silica chromatography eluting with 5% methanol in chloroform. The pure fractions were concentrated and the residue triturated several times with hexane to provide the title product (0.120 g) as a white solid, m.p. 125–128° C. 
       1 H NMR (400 MHz, DMSO-d 6 ): δ 7.74 (d, 1H), 7.62 (t, 1H ), 7.56 (t, 1H), 7.38 (m, 1H), 7.19 (d, 1H), 7.11 (t, 1H), 7.04 (t, 1H), 6.85–6.973 (m, 4H), 6.40 (s, 1H), 6.06 (s, 1H), 5.62 (br, 1H), 5.46 (br, 1H), 4.35 (br, 1H), 3.57 (m, 2H), 1.4–1.98 (m, 8H). MS [EI, m/z]: 642[M] + . Anal. Calcd. for C 37 H 37 F 3 N 4 O 3 +0.5H 2 O: C, 68.19; H, 5.88; N, 8.60. Found: C, 68.38; H, 6.15; N, 8.20. 
     EXAMPLE 21 
     N-Methyl-[N-(3-dimethylamino)propyl]-10-{[2-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-carboxamide 
     The title compound (white solid, m.p. 140–142° C.) was prepared by coupling the 10-{[2-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 19, with 3-(dimethylamino)propyl-1-methylamine (1.25 equiv), in the manner of Example 20. 
       1 H NMR (400 MHz, DMSO-d 6 ): δ 1.65 (m, 2H), 2.05–2.21 (m, 8H), 3.06 (s, 3H), 3.42 (s, 3H), 3.44 (t, 2H), 5.20 (br, 2H), 5.44 ( br, 2H), 6.06 (s, 1H), 6.23 (s, 1H), 6.85–6.97 (m, 4H), 7.04 (t, 1H), 7.11 (t, 1H), 7.19 (d, 1H), 7.38 (d, 1H), 7.56 (t, 1H), 7.62 (t, 1H), 7.74 (d, 1H). MS [EI, m/z]: 604[M] + . Anal. Calcd. for C 34 H 35 F 3 N 4 O 3 : C, 67.54; H, 5.83; N, 9.27. Found: C, 67.15; H, 5.82; N, 9.20. 
     EXAMPLE 22 
     N-Methyl-[N-(2-dimethylamino)ethyl]-10-{[2-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     The title compound (white solid, 0.149 g, m.p. 187–190° C.) was prepared by coupling the 10-{[2-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 19, with 3-(dimethylamino)ethyl-1-methyl amine (1.25 equiv), in the manner of Example 20. 
       1 H NMR (400 MHz, DMSO-d 6 ): δ 3.06 (s, 3H), 3.42 (m, 5H), 3.84 (t, 2H), 5.54 (br, 2H), 6.06 (s, 1H), 6.42 (s, 1H), 6.85–6.97 (m, 4H), 7.04 (t, 1H), 7.11 (t, 1H), 7.19 (m, 2H), 7.38 (d, 1H), 7.56 (t, 1H), 7.62 (t, 1H), 7.74 (d, 1H). MS [EI, m/z]: 590[M+. Anal. Calcd. for C 33 H 33 F 3 N 4 O 3 : C, 63.21; H, 5.46; N, 8.93. Found: C, 62.15; H, 5.59; N, 8.28. 
     EXAMPLE 23 
     [4-(Naphtalen-1-yl)phenyl][10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     Step A. 4-Naphthalen-1-yl-benzoic acid methyl ester 
     Methyl 4-bromobenzoate (0.96 g, 4.46 mmol) was added to a mixture of 1-naphthaleneboronic acid (0.73 g, 4.25 mmol) and sodium carbonate (0.075 g, 7.08 mmol) in toluene (30 mL), ethanol (6 mL) and water (12 mL). The resultant solution was purged with nitrogen for 10 minutes before tetrakis(triphenylphosphine)palladium(0) (0.10 g, 0.09 mmol) was added. The reaction mixture was heated to reflux for 65 hours. The solution was cooled to ambient temperature, then filtered through a pad of Celite, which was subsequently rinsed with ethyl acetate. The combined filtrate was diluted to 100 mL with water/ethyl acetate (1:1). The aqueous layer was extracted with ethyl acetate, and the combined extracts were dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness to yield the title compound as a gold oil (1.09 g). This material was used without further purification in the next step. 
       1 H NMR (300 MHz, DMSO-d 6 ): δ 3.92 (s, 3H), 7.57 (m, 6H), 7.75 (d, 1H), 8.02 (t, 2H), 8.10 (d, 2H). 
     Step B. 4-Naphthalen-1-yl-benzoic acid 
     To a stirred solution of the 4-naphthalen-1-yl-benzoic acid methyl ester of Step A (1.09 g, 4.15 mmol) in methanol (18 mL) and water (6 mL), cooled to 5° C., was added lithium hydroxide monohydrate (0.42 g, 10.0 mmol). The solution was allowed to warm to ambient temperature as stirring was continued for 20 hours. The reaction mixture was poured into water, acidified to pH, 4 with acetic acid, and the resultant precipitate was isolated by vacuum filtration to afford the title compound as an off-white solid (0.92 g), m.p. 221–224° C. 
       1 H NMR (400MHz, DMSO-d6): δ 6.40–7.60 (m, 6H), 7.56 (d, 1H), 7.98 (d, 1H), 8.01 (d, 1H), 8.07 (d, 2H). MS [EI, m/z]: 248[M] + . Anal. Calc&#39;d. for C 17 H 12 O 2 : C, 82.24; H, 4.87. Found: C, 81.90; H, 4.63. 
     Step C. [4-(Naphtalen-1-yl)phenyl][10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     N,N-Dimethylformamide (2 drops) was added to a solution of the 4-naphthalen-1-yl-benzoic acid of Step B (0.60 g, 2.40 mmol), in anhydrous tetrahydrofuran (15 mL) followed by oxalyl chloride (0.34 g, 2.64 mmol) and the mixture was warmed to reflux. The resultant solution was cooled to ambient temperature before being evaporated to dryness to give the crude acid chloride as a gold solid, which was used without further purification. To a mixture of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.37 g, 2.00 mmol) and triethylamine (0.24 g, 2.40 mmol) in dichloromethane (5 mL), cooled in an ice bath, was added dropwise a solution of the crude acid chloride in dichloromethane (5 mL). The cooling bath was removed and after stirring for 48 hours, the reaction mixture was washed sequentially with water, saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride and 1 N sodium hydroxide. The dichloromethane solution was dried with anhydrous magnesium sulfate, filtered, then evaporated to dryness to yield a brown foam. Purification by flash chromatography on silica gel eluting with hexane-ethyl acetate (4:1) resulted in a white foam (0.47 g). Treatment of the white foam with diethyl ether and sonication resulted in a white solid (0.37g), m.p. 169.5–171° C. 
       1 H NMR (400 MHz, DMSO-d 6 ): δ 5.32 (br, 4H), 5.93 (m, 1H), 5.97 (s, 1H), 6.83 (m, 1H), 7.01 (d, 1H), 7.18 (m, 2H), 7.32 (t, 2H), 7.41, (d, 1H), 6.45–7.60 (m, 5H), 7.93 (d, 1H), 7.97 (d, 1H). MS [EI, m/z]: 414[M] + . Anal. Calcd. for C 29 H 22  N 2 O+0.4H 2 O: C, 82.60; H, 5.45; N, 6.64. Found: C, 82.71; H, 5.44; N, 6.54. 
     EXAMPLE 24 
     [2-Chloro-4-(naphthalen-1-yl)phenyl][10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     Step A. (4-Bromo-2-chloro-benzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4] 
     N,N-Dimethylformamide (1 drop) was added to a solution of 4-bromo-2-chiorobenzoic acid (2.20 g, 9.35 mmol) in anhydrous tetrahydrofuran (20 mL). Oxalyl chloride (1.46 g, 11.46 mmol) was added and the mixture was warmed to reflux. The resultant solution was cooled to ambient temperature before being evaporated to dryness to give the crude acid chloride as a gold viscous liquid, which was used without further purification. To a mixture of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.44 g, 7.79 mmol) and triethylamine (0.95 g, 9.35 mmol) in dichloromethane (40 mL) cooled in an ice bath, was added dropwise a solution of the acid chloride in dichloromethane (20 mL). The cooling bath was removed and after stirring for 22 hours, the reaction mixture was washed sequentially with water, saturated aqueous sodium bicarbonate, 0.5 N hydrochloric acid and water. The dichloromethane solution was dried over anhydrous sodium sulfate, filtered, then evaporated to dryness to yield an off-white foam. Purification by flash chromatography on silica gel eluting with hexane-ethyl acetate (2:1) resulted in a white foam (3.02 g), m.p. 77–80° C. This material was used as is in the next step. 
       1 H NMR (400 MHz, DMSO-d6): δ 5.45 (br, 4H), 7.02 (t, 1H), 7.07 (td, 1H), 7.14 (td, 1H), 7.32 (br, 1H), 7.38 (d, 2H), 7.68 (br , 1H). MS [EI, m/z]: 400[M] + . Anal. Calcd. for C 19 H 14 BrClO: C, 56.81; H, 3.51; N, 6.97. Found: C, 56.30; H, 3.32; N, 6.75. 
     Step B. [2-Chloro-4-(naphthalen-1-yl)-phenyl]-(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone 
     1-Naphthaleneboronic acid (0.52 g, 3.00 mmol) was added to a mixture (4-bromo-2-chloro-benzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step A (1.27 g, 3.15 mmol) and sodium carbonate (0.53 g, 4.98 mmol) in toluene (22.5 mL), ethanol (4.5 mL) and water (9 mL). The resultant solution was purged with nitrogen for 10 minutes, then tetrakis(triphenylphosphine)palladium (0.18 g, 0.06 mmol) was added. The reaction mixture was heated to reflux for 76 hours. The solution was cooled to ambient temperature, then filtered through a pad of Celite, which was subsequently rinsed with ethyl acetate. The combined filtrate was diluted to 100 mL water/ethyl acetate (1:1). The aqueous layerwas extractedwith ethyl acetate, and the combined organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness to yield a brown oil. Purification by flash chromatography on silica gel eluting with hexane-ethyl acetate (5:1) resulted in a white solid which was dried under vacuum (0.62 g), m.p. 115–117.5° C. 
       1 H NMR (400 MHz, DMSO-d 6 ): δ 5.91 (t, 1H), 6.02 (br, 1H), 6.84 (br, 1H), 7.14 (m, 2H), 7.24 (d, 1H), 7.34, (d, 1H), 7.95 (d, 1H), 7.98 (d, 1H). MS [(+)ESI, m/z]: 449[M+H] + . Anal. Calcd. for C 29 H 21 ClN 2 O+0.25H 2 O: C, 76.72; H, 4.79; N, 6.17. Found C, 76.72; H, 4.53; N, 5.95. 
     EXAMPLE 25 
     [4-(4-Methyl-naphthalen-1-yl)phenyl][10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     Step A. 4-(4-Methyl)-napthalen-1-yl-benzoic acid 
     To a mixture of 1-bromo-4-methyl napthalene (1.11 g, 5.00 mmol) and 4-carboxyphenyl boronic acid (1.00 g, 6.00 mmol) in ethylene glycol dimethyl ether (20 mL) was added a solution of sodium carbonate (2.37 g, 22.38 mmol) in water (18.75 mL). The resultant mixture was purged with nitrogen for 20 minutes before tetrakis(triphenylphosphine) palladium(0) (0.03 g, 0.02 mmol) was added. The reaction mixture was heated to reflux for 68 hours. After the solution cooled to ambient temperature, the solvent was removed in vacuo and the residue was acidified with 5 N hydrochloric acid to produce an orange-brown solid that was isolated by vacuum filtration. This material was used without further purification in the next step. 
       1 H NMR (300 MHz, DMSO-d 6 ): δ 2.70 (s, 3H), 7.57 (d, 2H), 8.07 (d, 2H). 
     Step B. [4-(4-Methyl-naphthalen-1-yl)phenyl][10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     N,N-Dimethylformamide (2 drops) was added to a solution of 4-(4-methyl)-napthalen-1-yl-benzoic acid of Step A (0.90 g, 3.43 mmol) in anhydrous tetrahydrofuran (10 mL). Oxalyl chloride (0.52 g, 4.12 mmol) was added and the mixture was warmed to reflux. The resultant solution was cooled to ambient temperature before being evaporated to dryness to give the crude acid chloride as a brown residue, which was used without further purification. To a mixture of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.53 g, 2.86 mmol) and triethylamine (0.35 g, 3.43 mmol) in dichloromethane (10 mL) cooled in an ice bath was added dropwise a solution of the crude acid chloride in dichloromethane (10 mL). The cooling bath was removed and after stirring for 137 hours, the reaction mixture was washed sequentially with water, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride. The dichloromethane solution was dried over anhydrous magnesium sulfate, filtered, then evaporated to dryness to yield an amber oil. Purification by flash chromatography on silica gel eluting with hexane-ethyl acetate (4:1) resulted in a tan foam (0.49 g). Treatment of this material with diethyl ether and sonication resulted in an off-white solid (0.37 g), m.p. 160–162° C. 
       1 H NMR (400 MHz, DMSO-d 6 ): δ 2.66 (s, 3H), 5.32 (br, 4H), 5.93 (t, 1H), 5.97(br, 1H), 6.83 (t, 1H), 7.01 (d, 1H), 7.22 (d, 2 H), 7.28 ( d, 2H), 7.39 (t, 3H), 7.45 (m, 2H), 7.57 (m, 2H), 8.06 (d, 1H). MS [(+)ESI, m/z]: 429[M+H] + . Anal. Calcd. for C 30 H 24 N 2 O+0.13H 2 O: C, 83.63; H, 5.67; N, 6.50. Found: C, 83.63; H, 5.64; N, 6.43. 
     EXAMPLE 26 
     Methyl 10-{[2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1.4]benzodiazepine-8-carboxylate 
     Step A. [4-(2-Formyl-1H-pyrrole-1-yl)methyl]-3-nitro]-benzoic acid methyl ester 
     To a suspension of sodium hydride (8.1 g, 60% suspension in oil) in N,N-dimethylformamide (25 mL) was added dropwise over 15 minutes a solution of pyrrole 2-carboxaldehyde (9.1 g, 1 equiv.) in N,N-dimethylformamide (25 mL). After the addition, the reaction mixture was stirred for 30 minutes and then cooled to 0° C. A solution of 4-bromomethyl-2-nitrobenzoic acid (25.0 g, 1 equiv.) in N,N-dimethyl formamide (50 mL) was added dropwise over 20 minutes. After the addition, the reaction mixture was stirred at room temperature for 1 hour and then iodomethane (1.2 eq.) was added. The reaction mixture was stirred at room temperature overnight and diluted with water (200 mL). The solid was filtered, washed with water and dried over anhydrous potassium carbonate in vacuo at 50° C. to provide the crude title compound as a brown solid (26 g).which was used as such in the next step. 
     Step B. 10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-8-carboxylic acid methyl ester 
     To a stirred solution of tin(II) chloride dihydrate (23 g, 3.5 eq) in 2 N hydrochloric acid (106 mL) was added the [4-(2-formyl-1H-pyrrole-1-yl)methyl]-3-nitro]-benzoic acid methyl ester of Step A (8 g). Methanol (200 mL) was then added to this solution and the reaction mixture was stirred at 40° C. for 2 hours. The reaction was then cooled to room temperature, quenched by the addition of saturated aqueous sodium carbonate (20 mL) and filtered through Celite. The filter pad was washed with methanol and hot ethyl acetate. The filtrate and washings were combined, concentrated in vacuo to a volume of 300 mL and extracted with ethyl acetate. The combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to a volume of 200 mL. Acetic acid (1 g) and 10% palladium on charcoal (1.5 g) were added and the mixture was hydrogenated overnight at atmospheric pressure. The reaction was then filtered through Celite and the solvent removed in vacuo to give a dark brown crystalline solid (16.4 g). This was dissolved in dichloromethane and filtered through a silica pad eluting with dichloromethane to provide the title compound as a yellow crystalline solid (11.7 g). Recrystallization from 1,2-dichloroethane yielded a yellow crystalline solid (5.7 g), m.p. 198–200° C. 
       1 H NMR (CDCl 3 , 200 MHz): δ 3.95 (s, 3H), 4.50 (s, 2H), 5.20 (s, 2H), 6.05 (t, 2H), 6.70 (t, 1H), 7.05 (d, 1H), 7.15 (s, 1H), 7.20 (d, 1H), 7.30 (s, 1H). 
     Step C. Methyl 10-{[2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1.4]benzodiazepine-8-carboxylate 
     To a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-8-carboxylic acid methyl ester of Step B (1.64 g) in 1,2-dichloroethane (25 mL) was added 4-(2-trifluoromethylphenyl)-3-methylbenzoyl chloride (2.0 g, 1.1 eq) prepared in the manner of Example 1, Step D and triethylamine (1.0 g) and the mixture was stirred at room temperature overnight. The solvent was then removed in vacuo and the residue chromatographed on silica gel eluting with 10% ethyl acetate in petroleum ether to provide the title compound as a white crystalline solid, m.p. 180–182° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.80 (s, 3H), 3.70 (s, 3H), 5.0–5.5 (br, 4H), 5.80 (t, 1H), 6.00 (s, 1H), 6.85 (t, 1H), 6.90 (s, 1H), 7.00 (br, 1H), 7.20 (d, 1H), 7.35 (s, 1H), 7.60 (t, 2H), 7.70 (t, 2H), 7.75 (d, 1H), 7.80 (d, 1H). MS [(+)ESI, m/z]: 505[M+H] + . Anal. Calcd. for C 29 H 23 F 3 N 2 O 3 : C, 69.04; H, 4.60; N, 5.55. Found: C, 67.76; H, 4.30; N, 5.40 . 
     EXAMPLE 27 
     [4-(2,5-Dimethyl-1-H-pyrrol-1-yl)-3-methoxy-phenyl][10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     A solution of (4-amino-3-methoxy-phenyl)[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone prepared in the manner of Albright et al., E.P.636625-A2 (0.675g, 2 mmol) and acetonyl acetone (0.3 mL, 2.5 mmol) in benzene (100 mL) was treated with a crystal of para-toluenesulfonic acid. The stirred solution was warmed to reflux for 46 hrs using a Dean Stark trap. The reaction was cooled to room temperature, diluted with dichloromethane (100 mL), washed with saturated aqueous sodium bicarbonate then water. The residue (oil, 0.900 g) was flash chromatography on silica gel eluting with 20% ethyl acetate in hexane to yield 0.610 g of the title compound as a white foam. Recrystallization of a sample of this material yielded yellow crystals, m.p. 141–144° C. 
       1 H NMR (400 MHz, DMSO-d 6 ): δ 1.72 (s, 6H), 3.52 (s, 3H), 5.33 (br, 4H), 5.69 (s, 3H), 5.93 (t, 1H), 5.97 (br, 1H), 6.82(t, 1H), 6.96 (q, 3H), 7.06 (t, 1H), 7.17 (t, 1H), 7.45 (d, 1H), MS [(+)ESI m/z]: 412[M+H] + . Anal. Calcd. for C 26 H 25 N 3 O 2 : C, 75.89; H, 6.12; N, 10.12. Found: C, 75.89; H, 5.95; N, 10.15. 
     EXAMPLE 28 
     [6-(Naphthalen-1-yl)-pyridin-3-yl]-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     Step A. (6-Chloro-pyridin-3-yl)-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     A solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (100 mmol) and N,N-diisopropylethyl amine (130 mmol) in dichloromethane (500 mL) was cooled to 0° C. 6-Chloronicotinoyl chloride (130 mmol) was added dropwise under nitrogen. The solution was stirred for one hour as it returned to room temperature. The reaction mixture was filtered through a sica gel pad, washed with 0.5 N sodium hydroxide and water, dried over anhydrous magnesium sulfate. The solution was again filtered through a silica gel pad and evaporated to dryness in vacuo. The residual oil crystallized from diethyl ether to provide the title compound as a colorless crystalline solid, m.p. 165–167° C. 
       1 HNMR 9400 Mhz, DMSO-d 6 ): δ 5.35 (br, 4H), 5.91 (t, 1H), 5.97 (s, 1H), 6.83 (t, 1H), 7.0 (br d, 1H), 7.18 (t, 1H), 7.19 (t, 1H), 7.39 (d, 1H), 7.46 (dd, 1H), 7.71 (d, 1H), 8.26 (s, 1H). MS [EI, m/z]: 323[M] + . Anal. Calcd. for C 18 H 14 ClN 3 O: C, 66.77; H, 4.36; N, 12.98. Found: C, 65.91; H, 4.18; N, 12.69. 
     Step B. [6-(Naphthalen-1-yl)-pyridin-3-yl]-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     A suspension of (6-chloro-pyridin-3-yl)-[10,11-dihydro-5H-pyrrolo{2,1-c][1,4]benzodiazepin-10-yl]methanone of Step A (0.645 g, 1.9 mmol) and naphthalene boronic acid (0.372 g, 2.1 mmol) in a mixture of toluene (1.2 mL), ethanol (2 mL) and 1M aqueous sodium carbonate (0.4 mL) was sparged with nitrogen for 10 minutes. To this was added palladium(I) acetate (0.026 g, 0.1 mmol). The mixture was heated at reflux under a static pressure of nitrogen for 48 hrs. The reaction was diluted with ethyl acetate and water. The organic layer was washed with saturated aqueous sodium bicarbonate then water. The sample was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to a brown oil. Flash chromatography of the residue on silica gel eluting with 20–50% ethyl acetate in hexane, yielded 0.180 g of a solid which was recrystallized from chloroform to provide the title compound as off white crystals, m.p. 155–158° C. 
       1 H NMR (400MHz, DMSO-d 6 ): δ 5.40 (br, 4H), 5.93(m, 1H), 5.99 (s, 1H), 6.84 (s, 1H), 7.08(br d, 1H), 7.16 (t, 1H), 7.23 (t, 1H), 7.52 (m, 6H), 7.84(d, 2H), 7.98 (dd, 2H), 8.55 (s, 1H). MS [(+)ESI, m/z]: 416[M+H] + . Anal. Calcd. for C 28 H 21 N 3 O+0.5H 2 O: C, 79.22; H, 5.23; N, 9.90. Found: C, 79.08; H, 4.94; N, 9.73. 
     EXAMPLE 29 
     (6-Phenyl-pyridin-3-yl)-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     The title compound was prepared in the manner of Example 28 using phenylboronic acid (0.269 g), (6-chloro-pyridin-3-yl-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone of Example 28, Step A (0.645 g) and palladium(I) acetate (0.01 7g), in a mixture of toluene (1 2 mL), 1 M aqueous sodium carbonate (4 mL) and ethanol (2 mL). The initially obtained foam (0.387 g) was purified by HPLC (Primesphere C18, 5×25 cm column eluting with 55% acetonitrile in water containing 0.1% formic acid) to yield the title product (0.200 g) as a yellow solid. Recrystallization of a sample from acetone/hexane yielded yellow needles, m.p. 171–174° C. 
       1 H NMR (400 MHz, DMSO-d 6 ): δ 5.37 (br, 4H), 5.92 (t, 1H), 5.97 (s, 1H), 6.83 (t, 1H), 7.03 (d, 1H), 7.10 (t, 1H), 7.18 (t, 1H), 7.46 (m, 4H), 7.73(d, 1H), 7.85 (d, 1H), 8.03 (dd, 2H), 8.44 (s, 1H). MS [(+)ESI, m/z]: 366[M+H] + . Anal. Calcd. for C 24 H 19 N 3 O+0.25H 2 O: C, 77.92; H, 5.31; N, 11.36. Found: C, 77.70; H, 5.23; N, 11.39. 
     EXAMPLE 30 
     [4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3,5-dimethyl-phenyl][10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     Step A. Methyl 4-(2,5-dimethyl-1H-pyrrol-1-yl)-3,5-dimethylbenzoate 
     Methyl 4-amino-3,5-dimethylbenzoate [prepared in the manner of Chang et al., WO Patent 9631492 A1] (1.24 g, 6.9 mmol), was converted into the title compound (1.55 g) in the manner of Example 27. Recrystallization from aqueous methanol yielded a white solid, m.p. 104–106° C. 
       1 H NMR (300 MHz, CDCl 3 ): δ 1.95 (s, 6H), 2.00 (s, 6H), 3.95 (s, 3H), 5.95 (br, 2H), 7.85 (s, 2H). 
     Step B. 4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3,5-dimethylbenzoic acid 
     Methyl 4-(2,5-dimethyl-1H-pyrrol-1-yl)-3,5-dimethylbenzoate of Step A (1.55 g, 6 mmol) was dissolved in ethanol (100 mL) and treated with 1M sodium hydroxide (9 mL). The solution was refluxed overnight, cooled to room temperature, acidified with 1N hydrochloric acid, and diluted into water and ethyl acetate. The organic layer was washed with water until neutral, dried with anhydrous sodium sulfate, filtered and evaporated in vacuo to yield the title compound as a a cream colored solid (1.36 g). 
       1 H NMR (300 MHz, CDCl 3 ): δ 1.87 (s, 6H), 2.00 (s, 6H), 5.95 (s, 2H), 7.90 (s, 2H). 
     Step C. [4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3,5-dimethyl-phenyl][10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     A solution of 4-(2,5-dimethyl-1H-pyrrol-1-yl)-3,5-dimethylbenzoic acid of Step B (0.495 g, 2 mmol) was dissolved in tetrahydrofuran (10 mL) and treated with N,N-dimethylformamide (10 μL) followed by oxalyl chloride (250 μL, 2.85 mmol) added dropwise to control gas evolution. When the gas evolution subsided, the solution was warmed to reflux for 5 minutes. The solution was then concentrated in vacuo, the residue was dissolved in tetrahydrofuran and evaporated to dryness. The residue was redissolved in dichloromethane and the solution added dropwise to a cold solution (0° C.) of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.372mg, 2 mmol) and Hünig&#39;s base (0.5 mL) in dichloromethane. The solution was stirred overnight at room temperature, washed successively with 1N hydrochloric acid, saturated aqueous bicarbonate, and brine. The sample was then dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to a yellow foam (0.75 g). Flash chromatography of this material on silica gel eluting with a solvent gradient of 10 to 20% of ethyl acetate in hexane, provided a white solid (0.130 g). Recrystallization of this material from ethyl acetate/hexane provided the title compound (0.120 g) as flat crystals, m.p. 197–199° C. 
       1 H NMR (400 MHz, CDCl 3 ): δ 1.75 (s, 3H), 1.77 (s, 3H), 5.18 (br, 4H), 5.89 (s, 2H), 6.05 (br, 1H), 6.08 (t, 1H), 6.69 (t, 1H), 6.85 (br, 1H), 7.03 (br, 3H), 7.16 (t, 1H), 7.35 (d, 1H). MS [(+)APCI, m/z]: 410[M+H] + . Anal. Calcd. for C 27 H 27 N 3 O+0.25H 2 O: C, 78.33; H, 6.69; N, 10.15. Found: C, 78.04; H, 6.53; N, 10.08. 
     EXAMPLE 31 
     [3-Methyl-4-(4-pyridinyl)phenyl]-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     Step A. (4-Bromo-3-methylphenyl)[10,11-dihydro-5H-pyrrolo[2,1 c][1,4]benzodiazepin-10-yl]methanone 
     A solution of 4-bromo-3-methyl benzoic acid (4.3 g, 2 mmol) in dry tetrahydrofuran (100 mL) was cooled to 0° C. under nitrogen. To this was added N,N-dimethylformamide (50 μL) followed by oxalyl chloride (2.2 mL, 25 mmol) dropwise to control the gas evolution. When the gas evolution ceased, the mixture was warmed to reflux for 5 minutes then cooled to room temperature and concentrated in vacuo. The sample was treated with tetrahydrofuran and evaporated to dryness (twice) to yield the crude acid chloride as an orange oil. A solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (3.60 g, 20 mmol) and Hunig&#39;s base (4.35 mL, 25 mmol) in dichloromethane was cooled to 0° C., and a solution of the crude acid chloride in dichloromethane (25 mL) was added dropwise. The mixture was stirred overnight at room temperature, washed with 1 N hydrochloric acid, saturated aqueous sodium bicarbonate and brine. The solution was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to yield a solid (8.01 g) which was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane to provide the title compound (6.03 g) as a white solid. 
       1 H NMR (300 MHz, CDCl 3 ): δ 2.30 (s, 3H), 5.20 (br, 4H), 6.05 (d, 2H), 6.70 (s, 1H), 6.85 (br, 2H), 7.17 (m, 2H), 7.30 (m, 2H), 7.37 (d, 1H). 
     Step B. [3-Methyl-4-(pyridin-4-yl)phenyl]-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone 
     A suspension of (4-bromo-3-methylphenyl)[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone of Step A (1.14g, 2.9 mmol), pyridine-4-boronic acid (0.368 mg, 2.9 mmol) and sodium carbonate (0.760 g, 7.2 mmol) in a mixture of toluene (30 mL), water (10 mL), and ethanol (5 mL) was sparged with nitrogen for 15 minutes. To this was added tetrakis(triphenylphosphine)palladium(0) (0.027 g) and the mixture was heated to reflux under a static pressure of nitrogen. After 24 hours additional boronic acid (0.128 mg, 1 mmol) and sodium carbonate (0.116 g) were added and the heating was continued for 24 hours. Additional catalyst (0.012 g) was added and heating was continued for another 24 hours. The mixture was partitioned between ethyl acetate and hexane. The water layer was washed twice with ethyl acetate and the combined organic layers were dried over anhydrous magnesium sulfate and stripped to a solid. Flash chromatography of the residue on silica gel eluting with 30% ethyl acetate in hexane provided a solid which was recrystallized from ethyl acetate/hexane to provide the title compound (0.254 g) as tan plates m.p. 208–210° C. 
       1 H NMR (400 MHz, DMSO-d 6 ): δ 1.75 (s, 3H), 1.77 (s, 3H), 5.18 (br, 4H), 5.89 (s, 2H), 6.05 (br, 1H), 6.08 (t, 1H), 6.69 (t, 1H), 6.85 (br, 1H), 7.03 (br, 3H), 7.16 (t, 1H), 7.35 (d, 1H). MS [EI, m/z]: 379 [M] + . Anal. Calcd. for C 25 H 21 N 3 O+0.5H 2 O: C, 77.30; H, 5.71; N, 10.82. Found: C, 77.01; H, 5.37; N, 10.68. 
     EXAMPLE 32 
     10-{[3,6-Dimethoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine 
     Step A. 2,5-Dimethoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-carboxylic acid 
     A suspension of 4-bromo-2,5-dimethoxybenzoic acid [prepared in the manner of Bortnik et al.,  Zh. Org. Khim.  8, 340 (1972)] (2.43g, 9 mmol), 2-trifluoromethylphenyl boronic acid (5.3 g, 28 mmol), and potassium carbonate (6.21 g, 60 mmol) in dioxane (40 mL) was sparged with nitrogen and treated with tetrakis(triphenylphosphine)palladium(0) (0.328 g, 0.2 mmol). The mixture was heated to reflux for 48 hours, cooled, acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extracts were dried over anhydrous magnesium sulfate, filtered and stripped to a solid which was used as such in the next step. 
       1 H NMR (300 MHz, CDCl 3 ): δ 3.90 (s, 3H), 4.05 (s, 3H), 7.30 (d, 1H), 7.70 (s, 1H). 
     Step B. 10-{[3,6-Dimethoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine 
     The title compound was prepared in the manner of Example 31, Step A using 2,5-dimethoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-carboxylic acid of Step A (1.63 g, 5 mmol), oxalyl chloride (700 μL, 8 mmol), N,N-dimethylformamide (10 μL), 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.93 g, 5 mmol) and Hünig&#39;s base (1.78 ml, 10 mmol). Flash chromatography over silica gel using a solvent gradient from 30% ethyl acetate in hexane to 100% ethyl acetate provided the title compound (0.900 g) as a solid. Recrystallization from acetonelhexane yielded white needles, m.p. 210–213° C. 
       1  H NMR (400 MHz, DMSO-d 6 : δ 3.41 (s, 3H), 3.56 (s, 3H), 5.21 (br, 4H), 5.90 (t, 1H), 5.96 (s, 1H), 6.50 (s, 1H), 6.80 (s, 1H), 7.00 (s, 2H), 7.07 (s, 1H), 7.10 (t, 1H), 7.18 (d, 1H), 7.37 (d, 1H), 7.53 (t, 1H), 7.62 (t, 1H), 7.73 (d, 1H). MS [(+)ESI, m/z]: 493[M+H] + . Anal. Calcd. for C 28 H 23 F 3 N 2 O 3 : C, 68.29; H, 4.71; N, 5.69. Found: C, 67.98; H, 4.66; N, 5.61. 
     EXAMPLE 33 
     {[10-(2-Methoxy)-2′-chloro-[1,1′-biphenyl]-4-yl]carbonyl}-[(2S)-[(2-pyrrolidin-1-yl)methyl]pyrrolidin-1-yl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl-methanone 
     10-{[2-methoxy-2′-chloro[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid (0.230 g, 0.54 mmol) [prepared from trifluoromethanesulfonic acid 4-formyl-2-methoxy-phenyl ester of Example 19, Step A and 2-chlorophenyl boronic acid, in the manner of Example 19, Steps B-E], 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.120 g, 0.625 mmol) and 1-hydroxybenzotriazole (0.087 g, 0.625 mmol) were added to a flask containing N,N-dimethylformamide (15 mL). To the homogeneous solution was added (S)-(+)-1-[(2-pyrrolidin-1-yl)methyl]-pyrrolidine (0.100 g, 0.625 mmol) and stirring continued at room temperature overnight. At the end of this time the solution was poured into water and extracted with ethyl acetate. The combined extracts were washed with water, dried and concentrated and the residue was chromatographed on silica gel, eluting with 95:5 chloroform:methanol. The pure fractions were concentrated, and the residue azeotroped and triturated several times with hexane to yield the title product, m.p. 109° C. 
       1 H NMR (400 MHz, DMSO-d 6 ): δ 1.4–1.98 (m, 8H), 3.57 (m, 2H), 4.35 (br, 1H), 5.46 (br, 1H), 5.62 ( br, 1H), 6.06 (s, 1H), 6.40 (s, 1H), 6.84–7.49 (m 7H). MS [(+)APCI, m/z]: 609[M+H] + . 
     EXAMPLE 34 
     10-[(6-Chloro-3-methoxy-2′-ethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methylpiperidin-4-yl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     Step A. 10-{[6-Chloro-3-methoxy-2′-ethoxy[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     Prepared by treatment of 10-{[6-chloro-3-methoxy-2′-ethoxy-1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Example 17 with trichloroacetyl chloride, followed by basic hydrolysis of the intermediate trichloroacetate ester in the manner of Example 15, Step D. 
     Step B. 10-[(6-Chloro-3-methoxy-2′-ethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methylpiperidin-4-yl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide Prepared by coupling the 10-{[6-chloro-3-methoxy-2′-ethoxy[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Step A with 1-methyl-4-(methylamino)piperidine (1.25 equiv.) in the manner of Example 16. 
     EXAMPLE 35 
     N-[3-(Dimethylamino)propyl]-N-methyl-10-[(6-chloro-3-methoxy-2′-fluoro[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     Prepared by coupling of the [(6-chloro-3-methoxy-2′-fluoro-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 18, with 3-(dimethylaminopropyl)-1-methyl amine (1.25 equiv.), in the manner of Example 11. 
     EXAMPLE 36 
     [4-(3-Dimethylaminopropyl)-piperazin-1-yl]-{10-[4-(naphthalen-1-yl)-phenyl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl-methanone 
     Step A. 10-[4-(Naphthalen-1-yl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     Prepared by treatment of [4-(naphthalen-1-yl)phenyl][10,11-dihydro-5H-pyrrolo [2,1c][1,4]benzodiazepin-10-yi]-methanone of Example 23 with trichloroacetyl chloride, followed by basic hydrolysis of the intermediate trichloroacetate ester in the manner of Example 15, Step D. 
     Step B. [4-(3-Dimethylaminopropyl)-piperazin-1-yl]-{10-[4-(naphthalen-1-yl)-phenyl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl-methanone 
     The title compound was prepared by coupling the 10-[4-(naphthalen-1-yl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Step A, with 1-(3-dimethylamino-propyl)-piperazine (1.25 equiv) in the manner of Example 4. 
     EXAMPLE 37 
     (4-Methyl-piperazin-1-yl)-{10-[2-chloro-[4-(naphthalen-1-yl)]phenyli]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl-methanone 
     Step A. 10-{[2-Chloro-4-(naphthalen-1-yl)phenyl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     Prepared by treatment of [2-chloro-4-(naphthalen-1-yl)-phenyl]-(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone of Example 24 with trichloroacetyl chloride, followed by basic hydrolysis of the intermediate trichloroacetate ester in the manner of Example 15, Step D. 
     Step B. (4-Methyl-piperazin-1-yl)-{10-[2-chloro-[4-(naphthalen-1-yl)]phenyl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl-methanone 
     The title compound was prepared by the coupling the 10-[2-chloro-4-(naphthalen-1-yl)phenyl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Step A, with 1-methyl-piperazine (1.25 equiv) in the manner of Example 2. 
     EXAMPLE 38 
     10-{[2-Methyl-2′-trifluoromethyl-[I, 1′-biphenyl]-4-yl]carbonyl}-8-(piperidine-1-carbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid-methyl-(1-methyl-piperidin-4-yl)-amide hydrochloride salt 
     Step A. 10-{[2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-8-carboxylic acid sodium salt 
     To a stirred solution of methyl 10-{[2-methyl-2′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1.4]benzodiazepine-8-carboxylate of Example 26 (0.200 g) in ethanol (5 mL) was added 2.5 N sodium hydroxide (4 mL). The reaction mixture was then stirred overnight at room temperature and the solvent removed in vacuo. The residue was acidified with 2 N hydrochloric acid and extracted with diethyl ether. The combined extracts were dried over anhydrous magnesium sulfate and filtered, and the the filtrate evaporated to dryness. The residue was dissolved in anhydrous ethanol and treated with 2.5 N sodium hydroxide (1.0 equiv.). After stirring for 30 minutes at room temperature, the solvent was removed in vacuo to provide the title compound sodium salt as a white solid, m.p. 210° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.85 (s, 3H), 5.20 (br, 3H), 5.90 (s, 2H), 6,80 (t, 1H), 6.90–7.80 (m, 11H). MS [(+)APCI, m/z]: 491[M+H] + . Anal. Calcd. for C 28 H 21 F 3 N 2 O 3 Na+H 2 O: C, 63.27; H, 4.36; N, 5.27. Found: C, 63.04; H, 4.21; N, 4.99. 
     Step B. 8-[(Piperidin-1-yl)carbonyl]-{[2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine 
     Prepared by coupling of 10-{[2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-8-carboxylic acid of Step A with piperidine, in the manner of Example 2. 
     Step C. 10-{[2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-8-(piperidine-1-carbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid-methyl-(1-methyl-piperidin-4-yl)-amide hydrochloride salt 
     Prepared by treatment of 8-[(piperidin-1-yl)carbonyl]-{[2-methyl-2′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step B with diphosgene (1.1 equiv.) and triethylamine (1.5 equiv.) followed by 1-methyl-4-(methylamino)piperidine (1.5 equiv.) in the manner of Example 13. 
     EXAMPLE 39 
     [3-Methyl-4-(pyridin-4-yl)-phenyl]-{[(2S)-3-[(2-pyrrolidin-1-yl)methyl]pyrrolidin-1-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-yl-methanone 
     Step A. 10-[3-Methyl-4-(4-pyridinyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1 c][1,4]benzodiazepine-3-carboxylic acid 
     To a stirred solution of [3-methyl-4-(pyridin-4-yl)phenyl][10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone of Example 31, Step B (5 mmol) and N,N-diisopropylethyl amine (12 mmol) in dichloromethane (200 mL) cooled to 0° C. was added dropwise a solution of trichloroacetyl chloride (12 mmol) in dichloromethane. The temperature was maintained at 0° C. until the addition was complete. The reaction was stirred overnight as it warmed to room temperature. The solution was then washed with 10% aqueous sodium bicarbonate and the organic layer was dried, concentrated and filtered through a pad of silica gel with 1:1 ethyl acetate/hexane containing 0.1% acetic acid. The filtrate was concentrated in vacuo and the residue was dissolved in acetone and 1 N sodium hydroxide (2:1,v/v) and stirred at room temperature for 1 hour and then the pH was adjusted to pH, 4 with glacial acetic acid. The solution was concentrated to one half the volume in vacuo and the residue extracted with ethyl acetate. The combined organic layers were dried and evaporated to an oil which was triturated with hexane to yield a solid (0.98 g). 
     Step B. [3-Methyl-4-(pyridin-4-yl)-phenyl]-{[(2S)-3-[(2-pyrrolidin-1-yl)methyl]pyrrolidin-1-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-yl-methanone 
     The title compound was obtained from the carboxylic acid of Step A and (S)-(+)-1-[(2-pyrrolidinyl)methyl]-pyrrolidine ((1.2 equiv.), in the manner of Example 20. 
     EXAMPLE 40 
     10-[(6-Phenyl-pyridin-3-yl)carbonyl]-N-methyl-N-(1-methyl-piperidin-4-yl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     Step A. 10-(Methoxycarbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     A solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (5 mmol) and N,N-diisopropylethyl amine (12 mmol) in dichloromethane (100 mL) was cooled to 0° C. and treated dropwise with trichloroacetylchloride (12 mmol) in dichloromethane (20 mL). The solution was maintained at 0° C. for two hours and then allowed to warm to room temperature overnight. The solution was then treated with methanol (25 mL) and stirring was continued for 2 hours. The solution was washed with 0.1N hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated to yield the title compound as a white solid, m.p. 153–154° C. (dec.). Anal. Calcd. for C 15 H 14 N 2 O 4 +0.06C 4 H 8 O 2 +0.07C 3 H 6 O: C, 62.77; H, 5.08; N, 9.48. Found: C, 62.26; H, 5.22; N, 9.37. 
     Step B. 10-(Methoxycarbonyl)-[N-methyl-N-(1-methyl-piperidin-4-yl)]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     The title compound was prepared by coupling the 10-(methoxycarbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of step A with 1-methyl-4-(methylamino)piperidine (1.2 equiv.), in the manner of Example 38. 
     Step C. N-Methyl-N-(1-methyl-piperidin-4-yl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     A solution of 10-(methoxycarbonyl)-[N-methyl-N-(1-methyl-piperidin-4-yl)]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide (5 mmol) of Step B in methanol (50 mL) was treated with potassium carbonate and stirred at room temperature overnight. Water was then added to the solution and the pH adjusted to 6 with 6N hydrochloric acid. The solution was extracted with ethyl acetate, and the combined organic layers were dried over anhydrous magnesium sulfate, and evaporated to dryness The residual oil was triturated with ethyl acetate and hexane to yield the title compound as a powder. 
     Step D. 10-[(6-Phenyl-pyridin-3-yl)carbonyl]-N-methyl-N-(1-methyl-piperidin-4-yl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     A solution of 6-phenyl-nicotinyl chloride (6 mmol) (prepared by the method of Ogawa et al., WO 9534540) in dichloromethane (2OmL) was added dropwise to a cold (0° C.) solution of N-Methyl-N-(1-methyl-piperidin-4-yl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide of Step C (5 mmol) and N,N-diisopropylethyl amine (6 mmol) in dichloromethane (100 mL). The solution was stirred at 0° C. for 2 hours and then allowed to warm to room temperature overnight. The solution was washed with pH, 6 buffer, and brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was chromatographed on silica gel using 5% methanol in chloroform containing 0.5% ammonium hydroxide, to provide the title compound. 
     EXAMPLE 41 
     [4-(3-Dimethylaminopropyl)-piperazin-1-yl]-[10-[(2′-methoxy-2-methyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]-benzodiazepin-3-yl]-methanone 
     Prepared by treatment of 10-[(2′-methoxy-2-methyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 9, with 1-[(3-dimethylamino)propyl]-piperazine (1.2 equiv.) in the manner of Example 4. 
     EXAMPLE 42 
     N-[2-(Dimethylamino)ethyl]-10-{[6-chloro-3-methoxy-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3 carboxamide 
     Prepared by treatment of 10-{[6-chloro-3-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 15 with 3-(dimethylamino)ethy-1-methylamine (1.2 equiv.), in the manner of Example 22. 
     EXAMPLE 43 
     10-[(2′-Chloro-6-chloro-3-methoxy-[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methylpiperidin-4-yl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     To a stirred solution of 10-{[2′-chloro-6-chloro-3-methoxy-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 16, Step C (0.250 g, 0.49 mmol) was added 1-methyl-4-(methylamino)piperidine (0.076 g, 0.59 mmol) followed by 1-hydroxybenzotriazole (0.073 g, 0.54 mmol), 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.093 g, 0.54 mmol), and N,N-diisopropylethyl amine (0.096 g, 0.74 mmol). After stirring overnight, the reaction mixture was diluted with chloroform, washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was flash chromatographed over silica gel eluting with 5% methanol in chloroform containing 0.5% ammonium hydroxide, to provide the title compound as white powder (0.100 g), 92.95% pure by analytical HPLC [Primesphere C-18 column (2.0×150 mm); mobile phase:gradient from 10 to 90% acetonitrile/water containing 0.1% phosphoric acid, 2 to 20 minute gradient]. 
       1 H NMR (DMSO-d 6 , 400 MHz) δ 1.22 (s, 1H), 1.77 (br, 2H), 1.97 (br, 2H ), 2.89 (s, 3H), 3.44 (br, 3H), 5.29 (s, 2H), 6.08 (d, 1H), 6.26 (d, 1H), 6.68 (s, 1H), 6.97–7.61 (m, 10H). MS [(+)ESI, m/z]: 617[M+H] + . Anal. Calcd. for C 34 H 34 Cl 2 N 4 O 3 +0.25C 4 H 8 O 2 : C, 65.73; H, 5.67; N, 8.76. Found: C, 65.95; H, 5.82; N, 8.49. 
     EXAMPLE 44 
     {3-[4-(3-Dimethylamino-propyl)-piperazin-1-yl]carbonyl}-[4-(4-methyl-naphthalen-1-yl)phenyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl-methanone 
     Step A. 10-{[4-(4-Methyl-naphthalen-1-yl)phenyl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 
     Prepared from [4-(4-methyl-naphthalen-1-yl)-phenyl]-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-yl]methanone of Example 25 by treatment with trichloroacetyl chloride, followed by basic hydrolysis of the intermediate trichloroacetate ester in the manner of Example 1, Steps E and F. 
     Step B. {3-[4-(3-Dimethylamino-propyl)-piperazin-1-yl]carbonyl}-[4-(4-methyl-naphthalen-1-yl)phenyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl-methanone 
     Prepared by the coupling of 10-{[4-(4-methyl-naphthalen-1-yl)phenyl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Step A, with 1-[3-(dimethylamino)propyl]-piperazine (1.2 equiv.) in the manner of Example 4. 
     EXAMPLE 45 
     10-{[6-(Naphthalen-1-yl)-pyridin-3-yl]carbonyl}-N-methyl-N-(1-methyl-piperidin-4-yl)-10,11-dihydro-5H-pyrrolo[1,2-c][1,4]benzodiazepine-3-carboxamide 
     Step A. 10-{[6-(Naphthalen-1-yl)-pyridin-3-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[1,2-c][1.4]benzodiazepine-3-carboxylic acid 
     Prepared from [6-(naphthalen-1-yl)-pyridin-3-yl][10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone of Example 28 by treatment with trichloroacetyl chloride, followed by basic hydrolysis of the intermediate trichloroacetate ester in the manner of Example 40, Step A. 
     Step B. 10-{[6-(Naphthalen-1-yl)-pyridin-3-yl]carbonyl}-N-methyl-N-(1-methyl-piperidin-4-yl)-10,11-dihydro-5H-pyrrolo[1,2-c][1,4]benzodiazepine-3-carboxamide 
     Prepared by the coupling of 10-{[6-(naphthalen-1-yl)-pyridin-3-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[1,2-c][1.4]benzodiazepine-3-carboxylic acid of Step A, and 1-methyl-4-(methylamino)-piperidine (1.25 equiv) in the manner of Example 40, Step B. 
     EXAMPLE 46 
     {[10-(3,6-Dimethoxy)-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-[(2S)-[(2-pyrrolidin-1-yl)methyl]-pyrrolidin-1-yl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-yl-methanone 
     Step A. 10-{[3,6-Dimethoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]-carbonyl}-10,11-dihydro-5H-pyrrolo[1,2-c][1,4]benzodiazepine-3-carboxylic acid 
     Prepared from 10-{[3,6-dimethoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]-carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Example 32 and trichloroacetyl chloride, followed by basic hydrolysis of the intermediate trichloroacetate ester, in the manner of Example 1, Steps E and F. 
     Step B. {[10-(3,6-Dimethoxy)-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-[(2S)-[(2-pyrrolidin-1-yl)methyl]-pyrrolidin-1-yl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-yl-methanone 
     Prepared from 10-{[(3,6-dimethoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]-carbonyl}-10,11-dihydro-5H-pyrrolo[1,2-c][1,4]benzodiazepine-3-carboxylic acid of Step A and (S)-(+)-1-[(2-pyrrolidin-1-yl)methyl]-pyrrolidine (1 equiv.) in the manner of Example 33. 
     The following examples were prepared according to the General Procedures A–K described below. 
     General Procedure A 
     Step A. An appropriately substituted haloaryl carboxylic acid (1.1 mol) was converted to the acid chloride by using oxalyl chloride (1.5 mmol) and a catalytic amount of N,N-dimethylformamide in dichloromethane. Upon consumption of the acid as determined by HPLC analysis, all volatiles were removed in vacuo. The resulting residue was dissolved in dichloromethane and added dropwise to a stirred and cooled (0° C.) solution of an appropriately substituted 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1 mmol) and N,N-diisopropylethyl amine (1.2 mmol) in dichloromethane. After 1–16 hours, the mixture was diluted with dichloromethane and washed with 10% aqueous sodium bicarbonate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated. 
     Step B. To the residue was added an appropriately substituted boronic acid (1.2 mmol), potassium carbonate (2.5 mmol), tetrabutylammonium bromide (1 mmol), palladium(II) acetate (3% mole) and water/acetonitrile (1:1.2 mL). The mixture was heated to 70° C. for 1.5 hours, then ethyl acetate was added and the organic phase washed with water. The solution was filtered through a small plug of Celite and concentrated to dryness. 
     Step C. The residue was dissolved in dichloromethane and N,N-diisopropylethyl amine (2 mmol) was added. The flask was purged with nitrogen and trichloroacetyl chloride was added dropwise to the stirred reaction mixture. After 16 hours, the reaction was quenched by adding aqueous potassium carbonate (100g/300 mL) and the organic phase removed. The aqueous layer was extracted with additional dichloromethane and the combined extracts dried over anhydrous sodium sulfate, filtered and concentrated . 
     Step D. The crude product from Step C was dissolved in tetrahydrofuran (1 mL) and 2N sodium hydroxide (1.5 mL) was added. The mixture was heated (70° C.) for 1.5 hours, 2N hydrochloric acid was added and the product extracted with ethyl acetate. The organic phase was dried, filtered and concentrated. The residue was purified by column chromatography using a gradient of ethyl acetate in hexane containing 1% glacial acetic acid as the eluant. 
     Step E. To a stirred solution of a carboxylic acid of Step D above (1.85 mmol) in anhydrous tetrahydrofuran (14 mL) was added 1,1′-carbonyl diimidazole in one portion. The mixture was stirred at room temperature (6–8 hours). The progress of the reaction was monitored by HPLC and when the starting carboxylic acid was consumed, the mixture was worked up to provide the intermediate imidazolide. 
     Step F. An aliquot of a tetrahydrofuran solution (400 μL, 0.05 mmole) containing the imidazolide of Step E (0.05 mmol) was treated with a 0.25 M solution of an appropriate amine (0.1 mmol). The mixture was heated at 60° C. and the progress of the reaction followed by HPLC. The solvent was removed and the residue dissolved in dichloromethane (1 mL). The organic phase was washed with brine-water (1:1, v/v, 1 mL) and the aqueous layer extracted with additional dichloromethane. The combined extracts were dried and evaporated to dryness and the residue purified by flash chromatography on silica gel. The column (prepacked in 2.5% methanol in dichloromethane containing 1% triethylamine) was eluted with a solvent gradient from 2.5 to 5% methanol in dichloromethane, to provide desired title compound. The desired title compounds were either obtained as crystalline solids by exposure to diethyl ether or were further converted into their salts by any of the following procedures. 
     Step G. Compounds prepared according to Step E that dissolved in diethyl ether were treated with a stoichiometric amount of 1N hydrochloric acid in diethyl ether whereby the hydrochloride salts precipitated out as white solids. Compounds that did not conform to the above category, were dissolved in the minimal amount of tetrahydrofuran, then diluted with diethyl ether. The hydrochloride salts were formed upon addition of 1 N hydrochloric acid in diethyl ether with stirring. Compounds that did not immediately precipitate out of solution were stirred for 12–16 hours whereupon a white solid precipitated out. 
     General Procedure B 
     To a stirred solution of an appropriately substituted carboxylic acid of General Procedure A, Step D (2 mmol), 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide (0.229 g, 2.2 mmol) and a catalytic amount of 4-(dimethylamino)pyridine in dichloromethane (6 mL) was added the appropriately substituted amine (2.2 mmol) in dichloromethane (2 mL). The reaction was allowed to stir at room temperature for 16 hours, then diluted with dichloromethane. The organic layer was washed with water, saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and evaporated to dryness. The residue was purified by flash chromatography on silica gel (prepacked in dichloromethane containing 2.5% methanol and 1% triethylamine and eluted with a solvent gradient of 2.5 to 5% methanol in dichloromethane) to provide the desired title compound. 
     General Procedure C 
     Triphosgene (742 mg, 2.5 mmol) was added to a stirred solution of a carboxylic acid of General Procedure A, Step D (5.0 mmol) in dichloromethane (10 mL). The clear solution was allowed to stir at room temperature (14 hours) after which time the solution turned red. To the reaction mixture was added a solution of the required amine (10.0 mmol) and N,N-diisopropylethyl amine (10.0 mmol) in dichloromethane (5 mL). The mixture was diluted with dichloromethane and washed with water and brine. The organic phase was dried, filtered and concentrated to afford a residue which was purified by flash chromatography on silica gel. The column (prepacked in 2.5% methanol in dichloromethane containing 1% triethylamine) was eluted with a solvent gradient from 2.5 to 5% methanol in dichloromethane, to provide the title compound. 
     General Procedure D 
     A stirred solution of a carboxylic acid of General Procedure A, Step D (3.54 mmol) and the appropriately substituted amine (3.72 mmol) in N,N-dimethylformamide (10 mL) was cooled to 0° C. N,N-diisopropylethyl amine (3.89 mmol) was added and the mixture stirred for five minutes. O-(1-Benzotriazolyl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (1.42 g, 3.72 mmol) was added to the mixture in one portion. HPLC analysis revealed that the reaction was complete within five minutes. The solvent was removed at reduced pressure. The residue was diluted with water and extracted with ethyl acetate. The combined extracts were dried and concentrated to dryness. The residue was purified by flash chromatography on silica gel (prepacked in ethyl acetate containing 2% triethylamine and eluted with 100% ethyl acetate) to provide the title compound. 
     General Procedure E 
     To a 0.25 M solution of a carboxylic acid of General Procedure A, Step D (200 μL) in N,N-dimethylformamide was added sequentially a 0.5 M solution of N,N-diisopropylethyl amine (200 μL) in N,N-dimethylformamide, and a 0.25 M solution of O-(7-aza-1-benzotriazolyl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (210 μL) in N,N-dimethylformamide. The mixture was stirred vigorously at room temperature and then a 0.25 M solution of the appropriately substituted amine (200 μL) in N,N-dimethylformamide was added. Stirring was continued for 24 hours at room temperature, then the mixture was diluted with ethyl acetate, and washed with 1:1 water/brine. The organic layer was dried and concentrated to dryness. The residue was purified by flash chromatography on silica gel (prepacked in ethyl acetate containing 2% triethylamine and eluted with 100% ethyl acetate) to provide the title compound. 
     General Procedure F 
     Step A. To a solution of an appropriately substituted anilino carboxylic acid in methanol was added thionyl chloride. The mixture was heated for 16 hours. The volatiles were removed under reduced pressure and the hydrochloride salt of the carboxylic acid methyl ester was recovered after trituration with methanol/diethyl ether. The solid was dissolved in concentrated hydrochloric acid and cooled. An aqueous solution of sodium nitrite was added and the mixture was stirred at 0° C. for one hour. An aqueous solution of KI/I 2  was prepared and added to the cooled mixture so that the reaction temperature did not exceed 0° C. After 1–2 hours the reaction was complete as evidenced by TLC/HPLC analysis. The product was recovered by extraction with ethyl acetate. The combined extracts were dried, filtered and concentrated to afford the desired substituted aryl iodide which could be further purified by recrystallization. 
     Step B. To a solution of an appropriately substituted aryl halide methyl ester of Step A (2 mmol) and an appropriately substituted boronic acid (2 mmol) in 20% aqueous acetone was added cesium carbonate (3 mmol) followed by palladium(II) acetate (60 μmol). The mixture was heated (70° C.) with stirring for 8–16 hours. The reaction was concentrated to remove the acetone after TLCIHPLC analysis indicated the reaction was complete. The aqueous phase was extracted with ethyl acetate and the combined extracts were filtered through a pad of Celite. The filtrate was washed with 5% aqueous sodium bicarbonate and brine, dried over anhydrous sodium sulfate, filtered and evaporated to dryness. The residue was purified by flash chromatography on silica gel . 
     Step C. The product from Step B was dissolved in tetrahydrofuran (1 mL) and 2N sodium hydroxide (1.5 mL) was added. The mixture was heated (70° C.) for 1.5 hours, 2N hydrochloric acid was added and the product extracted with ethyl acetate. The organic phase was dried, filtered and concentrated. The residue was purified by column chromatography using ethyl acetate in hexane contaning 1% glacial acetic acid as the eluant. 
     Step D. To a suspension of the carboxylic acid of Step C (60 μmol) in dichloromethane (100 μL) was added a 0.45 M solution of oxalyl chloride (200 μL) in dichloromethane followed by dichloromethane (100 μL) containing a catalytic amount of N,N-dimethylformamide. The mixture was allowed to sit at room temperature for 16 hours, then the volatiles were removed in vacuo to afford the crude acid chloride. A solution of the acid chloride in tetrahydrofuran (0.3 M, 200 μL), was utilized to acylate a solution (0.3 M, 200 μL) of an appropriately substituted 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine in tetrahydrofuran according to the General Procedure A, Step A. 
     General Procedure G 
     A mixture of an appropriately substituted aryl bromide methyl ester (or an aryl iodide methyl ester of General Procedure F, Step A) (8.3 mmol), an appropriately substituted boronic acid (9.1 mmol), potassium carbonate (20.8 mmol), tetrabutylammonium bromide (or iodide) (8.3 mmol), palladium(II) acetate and water (8–9 mL) was stirred with heating (70° C.) for 1.5 hours, whereupon the reaction was deemed complete by HPLC analysis. The oily upper layer was extracted with ethyl acetate, the extracts washed with brine , dried and concentrated to dryness. The residue was filtered through a column of silica gel to provide the desired coupled product of General Procedure F, Step B. 
     General Procedure H 
     The coupling of an appropriately substituted aryl bromide methyl ester (or an aryl iodide methyl ester of General Procedure F, Step A) (8.3 mmol) to an appropriately substituted pyridyl borane was carried out using potassium hydroxide as the base, in the presence of tetrabutylammonium bromide (or iodide) and a tetrakis(triphenylphoshine) palladium (0) catalyst essentially according to the published procedure of M. Ishikura,  Synthesis,  936–938 (1994), to provide the desired coupled product of General Procedure F, Step B. 
     General Procedure I 
     The coupling of an appropriately substituted aryl bromide methyl ester (or an iodide methyl ester of General Procedure F, Step A) (8.3 mmol) to an appropriately substituted boronic acid was carried out essentially according to General Procedure F, Step B except that the solvent was acetonitrile. 
     General Procedure J 
     The desired substituted aryl iodide of General Procedure F, Step A was prepared by reaction of an appropriately substituted amino carboxylic acid in concentrated hydrochloric acid at 0° C. with an aqueous solution of sodium nitrite followed by the addition of an aqueous solution of KI/I 2  at 0° C., followed by esterification of the resulting iodo aryl carboxylic acid with methanolic hydrochloric acid. 
     General Procedure K 
     The acylation of an activated appropriately substituted arylpyridine carboxylic acid of Procedure H was carried out by dissolving the acid (0.06 mmol) in a solution of oxalyl chloride in dichloromethane (12 mg/200 μL) followed by a catalytic amount of N,N-dimethylformamide in dichloromethane (100 μL). After stirring at room temperature for 16 hours, the volatiles were removed and tetrahydrofuran added, followed by the addition of a solution of the appropriately substituted 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine and N,N-diisopropylphenyl amine (1:2 molar ratio) in tetrahydrofuran. After stirring for 20 hours, the reaction was worked up essentially as described in General Procedure A, Step A. 
     EXAMPLE 47 
     {10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 569.23190 [M+H] + . Calcd. for C 33 H 34 ClN 4 O 3 : 569.23140 
     EXAMPLE 48 
     {10-[(2′-Methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 521.25443 [M+H] + . Calcd. for C 32 H 33 N 4 O 3 : 521.25472. 
     EXAMPLE 49 
     {10-[(2′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 535.26907 [M+H] + . Calcd. for C 33 H 35 N 4 O 3 : 535.27037 
     EXAMPLE 50 
     {10-[(2,2′-Dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 519.27490 [M+H] + . Calcd. for C 33 H 35 N 4 O 2 : 519.27546. 
     EXAMPLE 51 
     {10-[(3′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 535.26968 [M+H] + . Calcd. for C 33 H 35 N 4 O 3 : 535.27037 
     EXAMPLE 52 
     {10-[(2′-Methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 505.25870 [M+H] + . Calcd. for C 32 H 33 N 4 O 2 : 505.25981 
     EXAMPLE 53 
     {10-[(2-Methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 535.26942 [M+H] + . Calcd for C 33 H 35 N 4 O 3 : 535.27037 
     EXAMPLE 54 
     {10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 585.22598 [M+H] + . Calcd. for C 33 H 34 ClN 4 O 4 : 585.22631. 
     EXAMPLE 55 
     {10-[3-Methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 571.26974 [M+H] + . Calcd. for C 36 H 35 N 4 O 3 : 571.27037. 
     EXAMPLE 56 
     {10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 551.26482 [M+H] + . Calcd. for C 33 H 35 N 4 O 4 : 551.26529 
     EXAMPLE 57 
     {10-[(2,3′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 551.26514 [M+H] + . Calcd. for C 33 H 35 N 4 O 4 : 551.26529 
     EXAMPLE 58 
     {10-[2-Chloro-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 575.22071 [M+H] + . Calcd. for C 35 H 32 ClN 4 O 2 : 575.22083 
     EXAMPLE 59 
     (4-Methyl-1,4-diazepan-1-yl)(10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)methanone 
     HRMS [(+)ESI, m/z]: 587.26266 [M+H] + . Calcd. for C 34 H 34 F 3 N 4 O 2 : 587.26284 
     EXAMPLE 60 
     {10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 583.24744 [M+H] + . Calcd. for C 34 H 36 ClN 4 O 3 : 583.24705 
     EXAMPLE 61 
     {10-[(2′-Methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 535.26998 [M+H] + . Calcd. for C 33 H 35 N 4 O 3 : 535.27037 
     EXAMPLE 62 
     {10-[(2′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 549.28533 [M+H] + . Calcd. for C 34 H 37 N 4 O 3 : 549.28602 
     EXAMPLE 63 
     {10-[(2,2′-Dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 533.29054 [M+H] + . Calcd. for C 34 H 37 N 4 O 2 : 533.29111 
     EXAMPLE 64 
     {10-[(3′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 549.28413 [M+H] + . Calcd. for C 34 H 37 N 4 O 3 : 549.28602 
     EXAMPLE 65 
     {10-[(2′-Methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 519.27474 [M+H] + . Calcd. for C 33 H 35 N 4 O 2 02: 519.27546 
     EXAMPLE 66 
     {10-[(2-Methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 549.28529 [M+H] + . Calcd. for C 34 H 37 N 4 O 3 : 549.28602 
     EXAMPLE 67 
     {10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 599.24153 [M+H] + . Calcd. for C 34 H 36 ClN 4 O 4 : 599.24196 
     EXAMPLE 68 
     {10-[3-Methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [ESI(+), m/z]: 585.28342 [M+H] + . Calcd. for C 37 H 37 N 4 O 3 : 585.28602 
     EXAMPLE 69 
     {10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 565.28058 [M+H] + . Calcd. for C 37 H 37 N 4 O 3 : 565.28094 
     EXAMPLE 70 
     {10-[(2,3′-Dimethoxy[ 1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 565.28111 [M+H] + . Calcd. for C 34 H 37 N 4 O 4 : 565.28094 
     EXAMPLE 71 
     {10-[2-Chloro-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 589.23633 [M+H] + . Calcd. for C 36 H 34 ClN 4 O 2 : 589.23648 
     EXAMPLE 72 
     N-[3-(Dimethylamino)propyl]-10-[(2′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 537.28687 [M+H] + . Calcd. for C 33 H 37 N 4 O 3 : 537.28602 
     EXAMPLE 73 
     N-[3-(Dimethylamino)propyl]-10-[(2,2′-dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 521.29049 [M+H] + . Calcd. for C 33 H 37 N 4 O 2 : 521.29111 
     EXAMPLE 74 
     N-[3-(Dimethylamino)propyl]-10-[(3′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [ESI(+), m/z]: 537.28588 [M+H] + . Calcd. for C 33 H 37 N 4 O 3 : 537.28602 
     EXAMPLE 75 
     N-[3-(Dimethylamino)propyl]-10-[(2′-methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 523.26977 [M+H] + . Calcd. for C 32 H 35 N 4 O 3 : 523.27037 
     EXAMPLE 76 
     N-[3-(Dimethylamino)propyl]-10-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 507.27437 [M+H] + . Calcd. for C 32 H 35 N 4 O 2 : 507.27546 
     EXAMPLE 77 
     N-[3-(Dimethylamino)propyl]-10-[(2-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 537.28577 [M+H] + . Calcd. for C 33 H 7 N 4 O 3 : 537.28602 
     EXAMPLE 78 
     10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[3-(dimethylamino)propyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 571.24731 [M+H] + . Calcd. for C 33 H 36 ClN 4 O 3 : 571.24705 
     EXAMPLE 79 
     10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[3-(dimethylamino)propyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 587.24161 [M+H] + . Calcd. for C 33 H 36 ClN 4 O 4 : 587.24196 
     EXAMPLE 80 
     N-[3-(Dimethylamino)propyl]-10-[3-methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 573.28422 [M+H] + . Calcd. for C 36 H 37 N 4 O 3 : 573.28602 
     EXAMPLE 81 
     10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[3-(dimethylamino)propyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 553.27855 [M+H] + . Calcd. for C 33 H 37 N 4 O 4 : 553.28094 
     EXAMPLE 82 
     10-[(2,3′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[3-(dimethylamino)propyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 553.28083 [M+H] + . Calcd. for C 33 H 37 N 4 O 4 : 553.28094 
     EXAMPLE 83 
     10-[2-Chloro-4-(1-naphthyl)benzoyl]-N-[3-(dimethylamino)propyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 577.23637 [M+H] + . Calcd. for C 35 H 34 ClN 4 O 2 : 577.23648 
     EXAMPLE 84 
     N-[3-(Dimethylamino)propyl]-10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1 .4]benzodiazepine-3-carboxamide 
     HRMS [(+),ESI m/z]: 575.26427 [M+H] + . Calcd. for C 33 H 33 F 3 N 4 O 2 : 575.26284 
     EXAMPLE 85 
     N-[2-(Dimethylamino)ethyl]-N-methyl-10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 575.26180 [M+H] + . Calcd. for C 33 H 34 F 3 N 4 O 2 : 575.26284 
     EXAMPLE 86 
     10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(dimethylamino)ethyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESi, m/z]: 571.24735 [M+H] + . Calcd. for C 33 H 36 ClN 4 O 3 : 571.24705 
     EXAMPLE 87 
     10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(dimethylamino)ethyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 587.24165 [M+H] + . Calcd. for C 35 H 36 ClN 4 O 4 : 587.24196 
     EXAMPLE 88 
     N-[2-(Dimethylamino)ethyl]-10-[(2′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 537.28481 [M+H] + . Calcd. for C 33 H 37 N 4 O 3 : 537.28602 
     EXAMPLE 89 
     N-[2-(Dimethylamino)ethyl]-10-[(3′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 537.28523 [M+H] + . Calcd. for C 33 H 37 N 4 O 3 : 537.28602 
     EXAMPLE 90 
     N-[2-(Dimethylamino)ethyl]-10-[(2′-methoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 523.26992 [M+H] + . Calcd. for C 32 H 35 N 4 O 3 : 523.27037 
     EXAMPLE 91 
     N-[2-(Dimethylamino)ethyl]-N-methyl-10-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 507.27458 [M+H] + . Calcd. for C 32 H 35 N 4 O 2 : 507.27546 
     EXAMPLE 92 
     N-[2-(Dimethylamino)ethyl]-10-[(2-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 537.28550 [M+H] + . Calcd. for C 33 H 37 N 4 O 3 : 537.28602 
     EXAMPLE 93 
     N-[2-(Dimethylamino)ethyl]-10-[3-methoxy-4-(1-naphthyl)benzoyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 573.28467 [M+H] + . Calcd. for C 36 H 37 N 4 O 3 : 573.28602 
     EXAMPLE 94 
     10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(dimethylamino)ethyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 553.28019 [M+H] + . Calcd. for C 33 H 37 N 4 O 4 : 553.28094 
     EXAMPLE 95 
     10-[(2,3′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(dimethylamino)ethyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 553.28093 [M+H] + . Calcd. for C 33 H 37 N 4 O 4 : 553.28094 
     EXAMPLE 96 
     10-[2-Chloro-4-(1-naphthyl)benzoyl]-N-[2-(dimethylamino)ethyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 577.23624 [M+H] + . Calcd. for C 35 H 34 ClN 4 O 2 : 577.23648 
     EXAMPLE 97 
     N-[3-(Dimethylamino)propyl]-N-methyl-10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 589.27641 [M+H] + . Calcd. for C 34 H 36 F 3 N 4 O 2 : 589.27849 
     EXAMPLE 98 
     10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[3-(dimethylamino)propyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 585.26286 [M+H] + . Calcd. for C 34 H 38 ClN 4 O 3 : 585.26270 
     EXAMPLE 99 
     10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[3-(dimethylamino)propyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [ESI(+), m/z]: 601.25755 [M+H] + . Calcd. for C 34 H 38 ClN 4 O 4 : 601.25761 
     EXAMPLE 100 
     N-[3-(Dimethylamino)propyl]-10-[(2′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 551.30068 [M+H] + . Calcd. for C 34 H 39 N 4 O 3 : 551.30167 
     EXAMPLE 101 
     N-[3-(Dimethylamino)propyl]-10-[(2,2′-dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 535.30614 [M+H] + . Calcd. for C 34 H 39 N 4 O 2 : 535.30676 
     EXAMPLE 102 
     N-[3-(Dimethylamino)propyl]-10-[(3′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 551.30006 [M+H] + . Calcd. for C 34 H 39 N 4 O 3 : 551.30167 
     EXAMPLE 103 
     N-[3-(Dimethylamino)propyl]-10-[(2′-methoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 537.28544 [M+H] + . Calcd. for C 33 H 37 N 4 O 3 : 537.28602 
     EXAMPLE 104 
     N-[3-(Dimethylamino)propyl]-N-methyl-10-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI m/z]: 521.28955 [M+H] + . Calcd. for C 33 H 37 N 4 O 2 : 521.29111 
     EXAMPLE 105 
     N-[3-(Dimethylamino)propyl]-10-[(2-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 551.30117 [M+H] + . Calcd. for C 34 H 39 N 4 O 3 : 551.30167 
     EXAMPLE 106 
     N-[3-(Dimethylamino)propyl]-10-[3-methoxy-4-(1-naphthyl)benzoyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 587.30108 [M+H] + . Calcd. for C 37 H 39 N 4 O 3 : 587.30167 
     EXAMPLE 107 
     10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[3-(dimethylamino)propyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 567.29434 [M+H] + . Calcd. for C 34 H 3 9N 4 O 4 : 567.29659 
     EXAMPLE 108 
     10-[(2,3′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[3-(dimethylamino)propyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 567.29641 [M+H] + . Calcd. for C 34 H 39 N 4 O 4 : 567.29659 
     EXAMPLE 109 
     10-[2-Chloro-4-(1-naphthyl)benzoyl]-N-[3-(dimethylamino)propyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 591.25210 [M+H] + . Calcd. for C 36 H 36 ClN 4 O 2 : 591.25213 
     EXAMPLE 110 
     {10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 637.29447 [M+H] + . Calcd. for C 38 H 42 ClN 4 O 3 : 637.29400 
     EXAMPLE 111 
     {10-[(2′-Methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 589.31729 [M+H] + . Calcd. for C 37 H 41 N 4 O 3 : 589.31732 
     EXAMPLE 112 
     {10-[(2-Methyl-2′-methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 603.33228 [M+H] + . Calcd. for C 38 H 43 N 4 O 3 : 603.33297 
     EXAMPLE 113 
     {10-[(2-Methyl-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 587.33759 [M+H] + . Calcd. for C 38 H 43 N 4 O 2 : 587.33806 
     EXAMPLE 114 
     {10-[(2-Methyl-3′-methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 603.33180 [M+H] + . Calcd. for C 38 H 43 N 4 O 3 : 603.33297 
     EXAMPLE 115 
     {10-[(2′-Methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 573.32176 [M+H] + . Calcd. for C 37 H 41 N 4 O 2 : 573.32241 
     EXAMPLE 116 
     {10-[(2-Methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 603.33259 [M+H] + . Calcd. for C 38 H 43 N 4 O 3 : 603.33297 
     EXAMPLE 117 
     {10-[(6-Chloro-3-methoxy-3′-methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 653.28981 [M+H] + . Calcd. for C 38 H 42 ClN 4 O 4 : 653.28891 
     EXAMPLE 118 
     {10-[3-Methoxy-4-(1-naphthyl)-benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 639.33115 [M+H] + . Calcd. for C 41 H 43 N 4 O 3 : 639.33297 
     EXAMPLE 119 
     {10-[(2,2′-Dimethoxy-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 619.32688 [M+H] + . Calcd. for C 38 H 43 N 4 O 4 : 619.32789 
     EXAMPLE 120 
     {10-[(2,3′-Dimethoxy-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 619.32835 [M+H] + . Calcd. for C 38 H 43 N 4 O 4 : 619.32789 
     EXAMPLE 121 
     {10-[(2-Chloro-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 643.28413 [M+H] + . Calcd. for C 40 H 40 ClN 4 O 2 : 643.28343 
     EXAMPLE 122 
     {10-[(2-Methyl-2′-(trifluoromethyl) -[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 641.30863 [M+H] + . Calcd. for C 38 H 40 F 3 N 4 O 2 : 641.30979 
     EXAMPLE 123 
     N-[3-(1H-Imidazol-1-yl)propyl]-10-[(2′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 560.26553 [M+H] + . Calcd. for C 34 H 34 N 5 O 3 : 560.26562 
     EXAMPLE 124 
     10-[(2,2′-Dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[3-(1H-imidazol-1-yl)propyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 544.26958[M+H] + . Calcd. for C 34 H 34 N 5 O 2 : 544.27071 
     EXAMPLE 125 
     N-[3-(1H-Imidazol-1-yl)propyl]-10-[(3′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 560.26510 [M+H] + . Calcd. for C 34 H 34 N 5 O 3 : 560.26562 
     EXAMPLE 126 
     N-[3-(1H-Imidazol-1-yl)propyl]-10-[(2′-methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 546.24888 [M+H] + . Calcd. for C 33 H 32 N 5 O 3 : 546.24997 
     EXAMPLE 127 
     N-[3-(1H-Imidazol-1-yl)propyl]-10-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/]: 530.25497 [M+H] + . Calcd. for C 33 H 32 N 5 O 2 : 530.25506 
     EXAMPLE 128 
     N-[3-(1H-Imidazol-1-yl)propyl]-10-[(2-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 560.26575 [M+H] + . Calcd. for C 34 H 34 N 5 O 3 : 560.26562 
     EXAMPLE 129 
     10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[3-(1H-imidazol-1-yl)propyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 594.22579 [M+H] + . Calcd. for C 34 H 33 ClN 5 O 3 : 594.22665 
     EXAMPLE 130 
     10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[3-(1H-imidazol-1-yl)propyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 610.22084 [M+H] + . Calcd. for C 34 H 32 ClN 5 O 4 : 610.22156 
     EXAMPLE 131 
     N-[3-(1H-Imidazol-1-yl)propyl]-10-[3-methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 596.26527 [M+H] + . Calcd. for C 37 H 34 N 5 O 3 : 596.26562 
     EXAMPLE 132 
     10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[3-(1H-imidazol-1-yl)propyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 576.26044 [M+H] + . Calcd. for C 34 H 34 N 5 O 4 : 576.26054 
     EXAMPLE 133 
     10-[(2,3′-Dimethoxy[1,1′-biphenyl]4-yl)carbonyl]-N-[3-(1H-imidazol-1-yl)propyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 576.26011 [M+H] + . Calcd. for C 34 H 34 N 5 O 4 : 576.26054 
     EXAMPLE 134 
     10-[2-Chloro-4-(1-naphthyl)benzoyl]-N-[3-(1H-imidazol-1-yl)propyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 600.21491 [M+H] + . Calcd. for C 36 H 31 ClN 5 O 2 : 600.21608 
     EXAMPLE 135 
     N-[3-(1H-Imidazol-1-yl)propyl]-10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 598.24213 [M+H] + . Calcd. for C 34 H 31 F 3 N 5 O 2 : 598.24244 
     EXAMPLE 136 
     {10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 623.27800 [M+H] + . Calcd. for C 37 H 40 ClN 4 O 3 : 623.27835 
     EXAMPLE 137 
     {10-[(2′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 589.31713 [M+H] + . Calcd. for C 37 H 41 N 4 O 3 : 589.31732 
     EXAMPLE 138 
     {10-[(2,2′-Dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 573.32179 [M+H] + . Calcd. for C 37 H 41 N 4 O 2 : 573.32241 
     EXAMPLE 139 
     {10-[(3′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 589.31726 [M+H] + . Calcd. for C 37 H 41 N 4 O 3 : 589.31732 
     EXAMPLE 140 
     {10-[(2′-Methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 575.30111 [M+H] + . Calcd. for C 36 H 39 N 4 O 3 : 575.30167 
     EXAMPLE 141 
     {10-[(2′-Methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 559.30724 [M+H] + . Calcd. for C 36 H 39 N 4 O 2 : 559.30676 
     EXAMPLE 142 
     {10-[(2-Methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 589.31781 [M+H] + . Calcd. for C 37 H 41 N 4 O 3 : 589.31732 
     EXAMPLE 143 
     {10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 639.27294 [M+H] + . Calcd. for C 37 H 40 ClN 4 O 4 : 639.27326 
     EXAMPLE 144 
     {10-[3-Methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 625.31794 [M+H] + . Calcd. for C 40 H 41 N 4 O 3 : 625.31732 
     EXAMPLE 145 
     {10-[(2,2′-Dimethoxy[1,1′-biphenyl]4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-l -piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 605.31251 [M+H] + . Calcd. for C 37 H 41 N 4 O 4 : 605.31224 
     EXAMPLE 146 
     {10-[(2,3′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 605.31137 [M+H] + . Calcd. for C 37 H 41 N 4 O 4 : 605.31224 
     EXAMPLE 147 
     {10-[2-Chloro-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 629.26756 [M+H] + . Calcd. for C 39 H 38 ClN 4 O 2 : 629.26778 
     EXAMPLE 148 
     (10-{[2-Methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z]: 627.29365 [M+H] + . Calcd. for C 37 H 38 F 3 N 4 O 2 : 627.29414 
     EXAMPLE 149 
     10-[(2′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 563.30179 [M+H] + . Calcd. for C 35 H 39 N 4 O 3 : 563.30167 
     EXAMPLE 150 
     10-[(2,2′-Dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+) ESI, m/z]: 547.30585 [M+H] + . Calcd. for C 35 H 39 N 4 O 2 : 547.30676 
     EXAMPLE 151 
     10-[(3′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 563.30189 [M+H] + . Calcd. for C 35 H 39 N 4 O 3 : 563.30167 
     EXAMPLE 152 
     10-[(2′-Methoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 549.28510 [M+H] + . Calcd. for C 34 H 37 N 4 O 3 : 549.28602 
     EXAMPLE 153 
     10-[(2′-Methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 533.29111 [M+H] + . Calcd. for C 34 H 37 N 4 O 2 : 533.29111 
     EXAMPLE 154 
     10-[(2-Methoxy-2′-methyl[1,1′-biphenyl]4-yl)carbonyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 563.30195 [M+H] + . Calcd. for C 35 H 39 N 4 O 3 : 563.30167 
     EXAMPLE 155 
     10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 597.26203 [M+H] + . Calccd. for C 35 H 38 ClN 4 O 3 : 597.26270 
     EXAMPLE 156 
     10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 613.25706 [M+H] + . Calcd. for C 35 H 38 ClN 4 O 4 : 613.25761 
     EXAMPLE 157 
     10-[3-Methoxy-4-(1-naphthyl)benzoyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 599.30190 [M+H] + . Calcd. for C 38 H 39 N 4 O 3 : 599.30167 
     EXAMPLE 158 
     10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 579.29668 [M+H] + . Calcd. for C 35 H 39 N 4 O 4 : 579.29659 
     EXAMPLE 159 
     10-[(2,3′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 579.29558 [M+H] + . Calcd. for C 35 H 39 N 4 O 4 : 579.29659 
     EXAMPLE 160 
     10-[2-Chloro-4-(1-naphthyl)benzoyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 603.25172 [M+H] + . Calcd. for C 37 H 36 ClN 4 O 2 : 603.25213 
     EXAMPLE 161 
     10-{[2-Methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 601.27838 [M+H] + . Calcd. for C 35 H 36 F 3 N 4 O 2 : 601.27849 
     EXAMPLE 162 
     10-[(2′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 563.30191 [M+H] + . Calcd. for C 35 H 39 N 4 O 3 : 563.30167 
     EXAMPLE 163 
     10-[(2,2′-Dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 547.30573 [M+H] + . Calcd. for C 35 H 39 N 4 O 2 : 547.30676 
     EXAMPLE 164 
     10-[(3′-Methoxy-2-methyl[1′1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 563.30176 [M+H] + . Calcd. for C 35 H 39 N 4 O 3 : 563.30167 
     EXAMPLE 165 
     10-[(2′-Methoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 549.28483 [M+H] + . Calcd. for C 34 H 37 N 4 O 3 : 549.28602 
     EXAMPLE 166 
     10-[(2′-Methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 533.29125 [M+H] + . Calcd. for C 34 H 37 N 4 O 2 : 533.29111 
     EXAMPLE 167 
     10-[(2-Methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 563.30226 [M+H] + . Calcd. for C 35 H 39 N 4 O 3 : 563.30167 
     EXAMPLE 168 
     10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 597.26179 [M+H] + . Calcd. for C 35 H 38 ClN 4 O 3 : 597.26270 
     EXAMPLE 169 
     10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 613.25723 [M+H] + . Calcd. for C 35 H 38 ClN 4 O 4 : 613.25761 
     EXAMPLE 170 
     10-[3-Methoxy-4-(1-naphthyl)benzoyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 599.30196 [M+H] + . Calcd. for C 38 H 39 N 4 O 3 : 599.30167 
     EXAMPLE 171 
     10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 579.29682 [M+H] + . Calcd. for C 35 H 39 N 4 O 4 : 579.29659 
     EXAMPLE 172 
     10-[(2,3′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 579.29546 [M+H] + . Calcd. for C 35 H 39 N 4 O 4 : 579.29659 
     EXAMPLE 173 
     10-[2-Chloro-4-(1-naphthyl)benzoyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 603.25172 [M+H] + . Calcd. for C 37 H 36 ClN 4 O 2 : 603.25213 
     EXAMPLE 174 
     N-[2-(1-Methyl-2-pyrrolidinyl)ethyl]-10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 601.27811 [M+H] + . Calcd. for C 35 H 36 F 3 N 4 O 2 : 601.27849 
     EXAMPLE 175 
     10-[(2′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-4-piperidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 563.30205 [M+H] + . Calcd. for C 35 H 39 N 4 O 3 : 563.30167 
     EXAMPLE 176 
     10-[(3′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-4-piperidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 563.30249 [M+H] + . Calcd. for C 35 H 39 N 4 O 3 : 563.30167 
     EXAMPLE 177 
     10-[(2′-Methoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-4-piperidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 549.28510 [M+H] + . Calcd. for C 34 H 37 N 4 O 3 : 549.28602 
     EXAMPLE 178 
     N-Methyl-10-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-(1-methyl-4-piperidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 533.29178 [M+H] + . Calcd. for C 34 H 37 N 4 O 2 : 533.29111 
     EXAMPLE 179 
     10-[(2-Methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-4-piperidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 563.30250 [M+H] + . Calcd. for C 35 H 39 N 4 O 3 : 563.30167 
     EXAMPLE 180 
     10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-4-piperidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 597.26325 [M+H] + . Calcd. for C 35 H 38 ClN 4 O 3 : 597.26270 
     EXAMPLE 181 
     10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl4-piperidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 613.25636 [M+H] + . Calcd. for C 35 H 38 ClN 4 O 4 : 613.25761 
     EXAMPLE 182 
     10-[3-Methoxy-4-(1-naphthyl)benzoyl]-N-methyl-N-(1-methyl-4-piperidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 599.30260 [M+H] + . Calcd. for C 38 H 39 N 4 O 3 : 599.30167 
     EXAMPLE 183 
     10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-4-piperidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 579.29711 [M+H] + . Calcd. for C 35 H 39 N 4 O 4 : 579.29659 
     EXAMPLE 184 
     N-Methyl-N-(1-methyl-4-piperidinyl)-10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 601.27917 [M+H] + . Calcd. for C 35 H 36 F 3 N 4 O 2 : 601.27849 
     EXAMPLE 185 
     10-[(2′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-3-pyrrolidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 549.28649 [M+H] + . Calcd. for C 34 H 37 N 4 O 3 : 549.28602 
     EXAMPLE 186 
     10-[(3′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-3-pyrrolidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 549.28621 [M+H] + . Calcd. for C 34 H 37 N 4 O 3 : 549.28602 
     EXAMPLE 187 
     10-[(2′-Methoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-3-pyrrolidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 535.26930 [M+H] + . Calcd. for C 33 H 35 N 4 O 3 : 535.27037 
     EXAMPLE 188 
     N-Methyl-10-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-(1-methyl-3-pyrrolidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 519.27588 [M+H] + . Calcd. for C 33 H 35 N 4 O 2 : 519.27546 
     EXAMPLE 189 
     10-[(2-Methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-3-pyrrolidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 549.28615[M+H] + . Calcd. for C 34 H 7 N 4 O 3 : 549.28602 
     EXAMPLE 190 
     10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-3-pyrrolidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 583.24598 [M+H] + . Calcd. for C 34 H 36 ClN 4 O 3 : 583.24705 
     EXAMPLE 191 
     10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-3-pyrrolidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 599.24156 [M+H] + . Calcd. for C 34 H 36 ClN 4 O 4 : 599.24196 
     EXAMPLE 192 
     10-[3-Methoxy-4-(1-naphthyl)benzoyl]-N-methyl-N-(1-methyl-3-pyrrolidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 585.28612 [M+H] + . Calcd. for C 37 H 37 N 4 O 3 : 585.28602 
     EXAMPLE 193 
     10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-N-methyl-N-(1-methyl-3-pyrrolidinyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 565.28108 [M+H] + . Calcd. for C 34 H 37 N 4 O 4 : 565.28094 
     EXAMPLE 194 
     N-Methyl-N-(1-methyl-3-pyrrolidinyl)-10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [ESI(+), m/z]: 587.26289 [M+H] + . Calcd. for C 34 H 34 F 3 N 4 O 2 : 587.26284 
     EXAMPLE 195 
     {4-[2-(Dimethylamino)ethyl]-1-piperazinyl}{10-[(2′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 592.32843 [M+H] + . Calcd. for C 36 H 42 N 5 O 3 : 592.32822 
     EXAMPLE 196 
     {4-[2-(Dimethylamino)ethyl]-1-piperazinyl}(10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)methanone 
     HRMS [(+)ESI, m/z]: 630.30472 [M+H] + . Calcd. for C 36 H 39 F 3 N 5 O 2 : 630.30504 
     EXAMPLE 197 
     {10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(dimethylamino)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 626.28869 [M+H] + . Calcd. for C 36 H 41 ClN 5 O 3 : 626.28925 
     EXAMPLE 198 
     {4-[2-(Dimethylamino)ethyl]-1-piperazinyl}{10-[(2,2′-dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 576.33266 [M+H] + . Calcd. for C 36 H 42 N 5 O 2 : 576.33331 
     EXAMPLE 199 
     {4-[2-(Dimethylamino)ethyl]-1-piperazinyl{}10-[(3′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 592.32832 [M+H] + . Calcd. for C 36 H 42 N 5 O 3 : 592.32822 
     EXAMPLE 200 
     {4-[2-(Dimethylamino)ethyl]-1-piperazinyl}{10-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 562.31789 [M+H] + . Calcd. for C 35 H 40 N 5 O 2 : 562.31766 
     EXAMPLE 201 
     {4-[2-(Dimethylamino)ethyl]-1-piperazinyl}{10-[(2-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 592.32869 [M+H] + . Calcd. for C 36 H 42 N 5 O 3 : 592.32822 
     EXAMPLE 202 
     {10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(dimethylamino)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 642.28388 [M+H] + . Calcd. for C 36 H 41 ClN 5 O 4 : 642.28416 
     EXAMPLE 203 
     {4-[2-(Dimethylamino)ethyl]-1-piperazinyl}{10-[3-methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 628.32892 [M+H] + . Calcd. for C 39 H 42 N 5 O 3 : 628.32822 
     EXAMPLE 204 
     {10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(dimethylamino)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 608.32361 [M+H] + . Calcd. for C 36 H 42 N 5 O 4 : 608.32314 
     EXAMPLE 205 
     {10-[2-Chloro-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(dimethylamino)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 632.27795 [M+H] + . Calcd. for C 38 H 39 ClN 5 O 2 : 632.27868 
     EXAMPLE 206 
     {10-[(2′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 634.33902 [M+H] + . Calcd. for C 38 H 44 N50 4 : 634.33879 
     EXAMPLE 207 
     {10-[(2′-Methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 620.32261 [M+H] + . Calcd. for C 37 H 42 N 5 O 4 : 620.32314 
     EXAMPLE 208 
     {10-[(3′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 634.33860 [M+H] + . Calcd. for C 38 H 44 N 5 O 4 : 634.33879 
     EXAMPLE 209 
     {10-[(2′-Methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 604.32832 [M+H] + . Calcd. for C 37 H 42 N 5 O 3 : 604.32822 
     EXAMPLE 210 
     {10-[(2-Methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 634.33915 [M+H] + . Calcd. for C 38 H 44 N 5 O 4 : 634.33879 
     EXAMPLE 211 
     {10-[(2,3′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 650.33299 [M+H] + . Calcd. for C 38 H 44 N 5 O 5 : 650.33370 
     EXAMPLE 212 
     {10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyi}methanone 
     HRMS [(+)ESI, m/z]: 684.29459 [M+H] + . Calcd. for C 38 H 43 ClN 5 O 5 : 684.29473 
     EXAMPLE 213 
     {10-[3-Methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 670.33934 [M+H] + . Calcd. for C 41 H 44 N 5 O 4 : 670.33879 
     EXAMPLE 214 
     {10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 650.33399 [M+H] + . Calcd. for C 38 H 44 N 5 O 5 : 650.33370 
     EXAMPLE 215 
     {10-[2-Chloro-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin -3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 674.28820 [M+H] + . Calcd. for C 40 H 41 ClN 5 O 3 : 674.28925 
     EXAMPLE 216 
     (10-{[2-Methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepin-3-yl){4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 672.31528 [M+H] + . Calcd. for C 38 H 41 F 3 N 5 O 3 : 672.31560 
     EXAMPLE 217 
     {10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 668.29857 [M+H] + . Calcd. for C 38 H 43 ClN 5 O 4 : 668.29981 
     EXAMPLE 218 
     {10-[(2,2′-Dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 618.34297 [M+H] + . Calcd. for C 38 H 44 N 5 O 3 : 618.34387 
     EXAMPLE 219 
     (4-Allyl-1-piperazinyl){10-[(6-chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 595.24716 [M+H] + . Calcd. for C 35 H 36 ClN 4 O 3 : 595.24705 
     EXAMPLE 220 
     (4-Allyl-1-piperazinyl){10-[(2,2′-dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 545.29099 [M+H] + . Calcd. for C 35 H 37 N 4 O 2 : 545.29111 
     EXAMPLE 221 
     (4-Allyl-1-piperazinyl){10-[(2′-methoxy[1,1′-biphenyl]4-yl)carbonyl]-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 547.27057 [M+H] + . Calcd. for C 34 H 35 N 4 O 3 : 547.27037 
     EXAMPLE 222 
     (4-Allyl-1-piperazinyl){10-[(2′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 561.28578 [M+H] + . Calcd. for C 35 H 37 N 4 O 3 : 561.28602 
     EXAMPLE 223 
     (4-Allyl-1-piperazinyl){10-[(3′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 561.28603 [M+H] + . Calcd. for C 35 H 37 N 4 O 3 : 561.28602 
     EXAMPLE 224 
     (4-Allyl-1-piperazinyl){10-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 531.27586 [M+H] + . Calcd. for C 34 H 35 N 4 O 2 : 531.27546 
     EXAMPLE 225 
     (4-Allyl-1-piperazinyl){10-[(2-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 561.28574 [M+H] + . Calcd. for C 35 H 37 N 4 O 3 : 561.28602 
     EXAMPLE 226 
     (4-Allyl-1-piperazinyl){10-[(6-chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 611.24297 [M+H] + . Calcd. for C 35 H 36 ClN 4 O 4 : 611.24196 
     EXAMPLE 227 
     (4-Allyl-1-piperazinyl){10-[(2,2′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 577.28073 [M+H] + . Calcd. for C 35 H 37 N 4 O 4 : 577.28094 
     EXAMPLE 228 
     (4-Allyl-1-piperazinyl){10-[(2,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 577.28057 [M+H] + . Calcd. for C 35 H 37 N 4 O 4 : 577.28094 
     EXAMPLE 229 
     (4-Allyl-1-piperazinyl){10-[2-chloro-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 601.23590 [M+H] + . Calcd. for C 37 H 34 ClN 4 O 2 : 601.23648 
     EXAMPLE 230 
     (4-Allyl-1-piperazinyl)(10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)methanone 
     HRMS [(+)ESI, m/z]: 599.26246 [M+H] + . Calcd. for C 35 H 34 F 3 N 4 O 2 : 599.26284 
     EXAMPLE 231 
     (4-Allyl-1-piperazinyl){10-[3-methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 597.28585 [M+H] + . Calcd. for C 38 H 37 N 4 O 3 : 597.28602 
     EXAMPLE 232 
     (4-Isopropyl-1-piperazinyl){10-[(2′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 563.30161 [M+H] + . Calcd. for C 35 H 39 N 4 O 3 : 563.30167 
     EXAMPLE 233 
     {10-[(2,2′-Dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-isopropyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 547.30657 [M+H] + . Calcd. for C 35 H 39 N 4 O 2 : 547.30676 
     EXAMPLE 234 
     (4-Isopropyl-1-piperazinyl){10-[(2′-methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 549.28582 [M+H] + . Calcd. for C 34 H 37 N 4 O 3 : 549.28602 
     EXAMPLE 235 
     (4-Isopropyl-1-piperazinyl){10-[(3′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 563.30191 [M+H] + . Calcd. for C 35 H 39 N 4 O 3 : 563.30167 
     EXAMPLE 236 
     (4-Isopropyl-1-piperazinyl){10-[3-methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 599.30222 [M+H] + . Calcd. for C 38 H 39 N 4 O 3 : 599.30167 
     EXAMPLE 237 
     (4-isopropyl-1-piperazinyl){10-[(2-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 563.30167 [M+H] + . Calcd. for C 35 H 39 N 4 O 3 : 563.30167 
     EXAMPLE 238 
     {10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H -pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-isopropyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 597.26324 [M+H] + . Calcd. for C 35 H 38 ClN 4 O 3 : 597.26270 
     EXAMPLE 239 
     {10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-isopropyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 613.25831 [M+H] + . Calcd. for C 35 H 38 ClN 4 O 4 : 613.25761 
     EXAMPLE 240 
     (4-Isopropyl-1-piperazinyl)(10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)methanone 
     HRMS [(+)ESI, m/z]: 601.27873 [M+H] + . Calcd. for C 35 H 36 F 3 N 4 O 2 : 601.27849 
     EXAMPLE 241 
     {10-[(2,2′-Dimethoxy[1,1-biphenyl]4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-isopropyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 579.29699 [M+H] + . Calcd. for C 35 H 39 N 4 O 4 : 579.29659 
     EXAMPLE 242 
     {10-[(2,3′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-isopropyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 579.29628 [M+H] + . Calcd. for C 35 H 39 N 4 O 4 : 579.29659 
     EXAMPLE 243 
     {10-[2-Chloro-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-isopropyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 603.25170 [M+H] + . Calcd. for C 37 H 36 ClN 4 O 2 : 603.25213 
     EXAMPLE 244 
     {10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-isopropyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 533.29134 [M+H] + . Calcd. for C 34 H 37 N 4 O 2 : 533.29111 
     EXAMPLE 245 
     {4-[3-(Dimethylamino)propyl]-1-piperazinyl}{10-[(2′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 606.34402 [M+H] + . Calcd. for C 37 H 44 N 5 O 3 : 606.34387 
     EXAMPLE 246 
     {4-[3-(Dimethylamino)propyl]-1-piperazinyl}{10-[(2′-methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 592.32795 [M+H] + . Calcd. for C 36 H 42 N 5 O 3 : 592.32822 
     EXAMPLE 247 
     {4-[3-(Dimethylamino)propyl]-1-piperazinyl}{10-[(2,2′-dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 590.34875 [M+H] + . Calcd. for C 37 H 44 N 5 O 2 : 590.34896 
     EXAMPLE 248 
     {4-[3-(Dimethylamino)propyl]-1-piperazinyl}{10-[(3′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 606.34364 [M+H] + . Calcd. for C 37 H 44 N 5 O 3 : 606.34387 
     EXAMPLE 249 
     {4-[3-(Dimethylamino)propyl]-1-piperazinyl}{10-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 576.33344 [M+H] + . Calcd. for C 36 H 42 N 5 O 2 : 576.33331 
     EXAMPLE 250 
     {4-[3-(Dimethylamino)propyl]-1-piperazinyl}{10-[(2-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 606.34409 [M+H] + . Calcd. for C 37 H 44 N 5 O 3 : 606.34387 
     EXAMPLE 251 
     {10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[3-(dimethylamino)propyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 640.30437 [M+H] + . Calcd. for C 37 H 43 ClN 5 O 3 : 640.30490 
     EXAMPLE 252 
     {10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[3-(dimethylamino)propyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 656.29921 [M+H] + . Calcd. for C 37 H 43 ClN 5 O 4 : 656.29981 
     EXAMPLE 253 
     {4-[3-(Dimethylamino)propyl]-1-piperazinyl}{10-[3-methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 642.34363 [M+H] + . Calcd. for C 40 H 44 N 5 O 3 : 642.34387 
     EXAMPLE 254 
     {10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[3-(dimethylamino)propyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 622.33914 [M+H] + . Calcd. for C 37 H 44 N 5 O 4 : 622.33879 
     EXAMPLE 255 
     {10-[(2,3′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[3-(dimethylamino)propyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 622.33845 [M+H] + . Calcd. for C 37 H 44 N 5 O 4 : 622.33879 
     EXAMPLE 256 
     {10-[2-Chloro-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[3-(dimethylamino)propyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 646.29385 [M+H] + . Calcd. for C 39 H 41 ClN 5 O 2 : 646.29433 
     EXAMPLE 257 
     {10-[(2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[3-(dimethylamino)propyl]-1-piperazinyl}-methanone 
     HRMS [ESI(+), m/z: 644.32017 [M+H] + . Calcd. for C 37 H 41 F 3 N 5 O 2 : 644.32069 
     EXAMPLE 258 
     (10-{[2-Methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 627.29381 [M+H] + . Calcd. for C 37 H 38 F 3 N 4 O 2 : 627.29414 
     EXAMPLE 259 
     {10-[(2′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 589.31760 [M+H] + . Calcd. for C 37 H 41 N 4 O 3 : 589.31732 
     EXAMPLE 260 
     {10-[(2,2′-Dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 573.32214 [M+H] + . Calcd. for C 37 H 41 N 4 O 2 : 573.32241 
     EXAMPLE 261 
     {10-[2-Chloro-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 629.26794 [M+H] + . Calcd. for C 39 H 38 ClN 4 O 2 : 629.26778 
     EXAMPLE 262 
     {10-[3-Methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 625.31761 [M+H] + . Calcd. for C 40 H 41 N 4 O 3 : 625.31732 
     EXAMPLE 263 
     {10-[(3′-Methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 589.31770 [M+H] + . Calcd. for C 37 H 41 N 4 O 3 : 589.31732 
     EXAMPLE 264 
     {10-[(2′-Methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 559.30704 [M+H] + . Calcd. for C 36 H 39 N 4 O 2 : 559.30676 
     EXAMPLE 265 
     {10-[(2′-Methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 575.30152 [M+H] + . Calcd. for C 36 H 39 N 4 O 3 : 575.30167 
     EXAMPLE 266 
     {10-[(2-Methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 589.31773 [M+H] + . Calcd. for C 37 H 41 N 4 O 3 : 589.31732 
     EXAMPLE 267 
     {10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 623.27896 [M+H] + . Calcd. for C 37 H 40 ClN 4 O 3 : 623.27835 
     EXAMPLE 268 
     {10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 639.27238 [M+H] + . Calcd. for C 37 H 40 ClN 4 O 4 : 639.27326 
     EXAMPLE 269 
     {10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 605.31257 [M+H] + . Calcd. for C 37 H 41 N 4 O 4 : 605.31224 
     EXAMPLE 270 
     {10-[(2,3′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 605.31209 [M+H] + . Calcd. for C 37 H 41 N 4 O 4 : 605.31224 
     EXAMPLE 271 
     [(3R)-3-(Dimethylamino)pyrrolidinyl](10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)methanone 
     HRMS [(+)ESI, m/z]: 587.26200 [M+H] + . Calcd. for C 34 H 34 F 3 N 4 O 2 : 587.26284 
     EXAMPLE 272 
     [(3R)-3-(Dimethylamino)pyrrolidinyl]{10-[(2′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 549.28581 [M+H] + . Calcd. for C 34 H 37 N 4 O 3 : 549.28602 
     EXAMPLE 273 
     {10-[(6-Chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(3R)-3-(dimethylamino)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 583.24837 [M+H] + . Calcd. for C 34 H 36 ClN 4 O 3 : 583.24705 
     EXAMPLE 274 
     [(3R)-3-(Dimethylamino)pyrrolidinyl]{10-[(2,2′-dimethyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 533.29105 [M+H] + . Calcd. for C 34 H 37 N 4 O 2 : 533.29111 
     EXAMPLE 275 
     {10-[(6-Chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(3R)-3-(dimethylamino)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 599.24184 [M+H] + . Calcd. for C 34 H 36 ClN 4 O 4 : 599.24196 
     EXAMPLE 276 
     [(3R)-3-(Dimethylamino)pyrrolidinyl]{10-[3-methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 585.28535 [M+H] + . Calcd. for C 37 H 37 N 4 O 3 : 585.28602 
     EXAMPLE 277 
     {10-[2-Chloro-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(3R)-3-(dimethylamino)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 589.23703 [M+H] + . Calcd. for C 36 H 34 ClN 4 O 2 : 589.23648 
     EXAMPLE 278 
     [(3R)-3-(Dimethylamino)pyrrolidinyl]{10-[(3′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 549.28594 [M+H] + . Calcd. for C 34 H 37 N 4 O 3 : 549.28602 
     EXAMPLE 279 
     [(3R)-3-(Dimethylamino)pyrrolidinyl]{10-[(2′-methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 535.27042 [M+H] + . Calcd. for C 33 H 35 N 4 O 3 : 535.27037 
     EXAMPLE 280 
     [(3R)-3-(Dimethylamino)pyrrolidinyl]{10-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 519.27502 [M+H] + . Calcd. for C 33 H 35 N 4 O 2 : 519.27546 
     EXAMPLE 281 
     [(3R)-3-(Dimethylamino)pyrrolidinyl]{10-[(2-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 549.28607 [M+H] + . Calcd. for C 34 H 37 N 4 O 3 : 549.28602 
     EXAMPLE 282 
     {10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl][(3R)-3-(dimethylamino)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 565.28071 [M+H] + . Calcd. for C 34 H 37 N 4 O 4 : 565.28094 
     EXAMPLE 283 
     {10-[(2,3′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(3R)-3-(dimethylamino)pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 565.28058 [M+H] + . Calcd. for C 34 H 37 N 4 O 4 : 565.28094 
     EXAMPLE 284 
     N-[(1S)-2-Amino-1-(1H-imidazol-4-ylmethyl)-2-oxoethyl]-10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 627.23303 [M+H] + . Calcd. for C 34 H 30 F 3 N 6 O 3 : 627.23260 
     EXAMPLE 285 
     N-[(1S)-2-Amino-1-(1H-imidazol-4-ylmethyl)-2-oxoethyl]-10-[(2′-methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 575.23897 [M+H] + . Calcd. for C 33 H 31 N 6 O 4 : 575.24013 
     EXAMPLE 286 
     N-[(1S)-2-Amino-1-(1H-imidazol-4-ylmethyl)-2-oxoethyl]-10-[(2,2′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 605.24974 [M+H] + . Calcd. for C 34 H 33 N 6 O 5 : 605.25070 
     EXAMPLE 287 
     N-[(1S)-2-Amino-1-(1H-imidazol-4-ylmethyl)-2-oxoethyl]-10-[(6-chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 639.21102 [M+H] + . Calcd. for C 34 H 32 ClN 6 O 5 : 639.21173 
     EXAMPLE 288 
     N-[(1S)-2-Amino-1-(1H-imidazol-4-ylmethyl)-2-oxoethyl]-10-[(2′-methoxy-2-methyl[1,1′-biphenyl]4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 589.25637 [M+H] + . Calcd. for C 34 H 33 N6O 4 : 589.25578 
     EXAMPLE 289 
     1H-Imidazol-1-yl-{10-[(3′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 503.20731 [M+H] + . Calcd. for C 31 H 27 N 4 O 3 : 503.20777 
     EXAMPLE 290 
     1H-Imidazol-1-yl-{10-[(2-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 503.20834 [M+H] + . Calcd. for C 31 H 27 N 4 O 3 : 503.20777 
     EXAMPLE 291 
     1H-Imidazol-1-yl-{10-[3-methoxy-4-(1-naphthyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 539.20754 [M+H] + . Calcd. for C 34 H 27 N 4 O 3 : 539.20777 
     EXAMPLE 292 
     1H-Imidazol-1-yl-{10-[(2′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 503.20760 [M+H] + . Calcd. for C 31 H 27 N 4 O 3 : 503.20777 
     EXAMPLE 293 
     {10-[(2,2′-Dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(1H-imidazol-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 519.20285 [M+H] + . Calcd. for C 31 H 27 N 4 O 4 : 519.20269 
     EXAMPLE 294 
       1 H-Imidazol-1-yl(10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)methanone 
     HRMS [(+)ESI, m/z]: 541.18438 [M+H] + . Calcd. for C 31 H 24 F 3 N 4 O 2 : 541.18459 
     EXAMPLE 295 
     N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-10-[(2′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 561.28517 [M+H] + . Calcd. for C 35 H 37 N 4 O 3 : 561.28602 
     EXAMPLE 296 
     N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-10-[(2′-methoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 547.26933 [M+H] + . Calcd. for C 34 H 35 N 4 O 3 : 547.27037 
     EXAMPLE 297 
     N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-10-[(6-chloro-3-methoxy-2′-methyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 595.24661 [M+H] + . Calcd. for C 35 H 36 ClN 4 O 3 : 595.24705 
     EXAMPLE 298 
     N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-10-[(2′-methoxy-2-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 561.28489 [M+H] + . Calcd. for C 35 H 37 N 4 O 3 : 561.28602 
     EXAMPLE 299 
     N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-10-[(2,2′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 577.28113 [M+H] + . Calcd. for C 35 H 37 N 4 O 4 : 577.28094 
     EXAMPLE 300 
     N-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-10-[(2,2′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 577.28101 [M+H] + . Calcd. for C 35 H 37 N 4 O 4 : 577.28094 
     EXAMPLE 301 
     N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-10-{[2-methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 599.26211 [M+H] + . Calcd. for C 35 H 34 F 3 N 4 O 2 : 599.26284 
     EXAMPLE 302 
     tert-Butyl (5S)-6-amino-5-[({10-[(6-chloro-3,3′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}carbonyl)amino]-6-oxohexylcarbamate 
     HRMS [(+)ESI, m/z]: 730.29945 [M+H] + . Calcd. for C 39 H 45 ClN 5 O 7 : 730.30021 
     EXAMPLE 303 
     tert-Butyl (5S)-6-amino-5-[({10-[(2,2′-dimethoxy[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}carbonyl)amino]-6-oxohexylcarbamate 
     HRMS [(+)ESI, m/z]: 696.33935 [M+H] + . Calcd. for C 39 H 46 N 5 O 7 : 696.33918 
     EXAMPLE 304 
     tert-Butyl (5S)-6-amino-5-[({10-[(6-chloro-3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}carbonyl)amino]-6-oxohexylcarbamate 
     HRMS [(+)ESI, m/z]: 714.30505 [M+H] + . Calcd. for C 39 H 45 ClN 5 O 6 : 714.30529 
     EXAMPLE 305 
     {10-(3-Methoxy-4-pyridin-3-y1-benzoyl)-10,11-dihydro-5H-pyrrolo[1,2-c][1,4]benzodiazepin-3-yl}-[4-(1-piperidinyl)-1-piperidinyl]-methanone 
     MS [(+)ESI, m/z]: 590 [M+H] + . Calcd. for C 36 H 40 N 5 O 3 : 590.313 
     The following examples were prepared according to the General Procedure L described below. 
     General Procedure L 
     Step A. To a stirred cooled (0° C.) solution of an appropriately substituted 10-(4-amino)benzoyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (10 mmol) in dichloromethane (20 mL) was added N,N-diisopropylethyl amine (2.09 mL, 12 mmol) followed by the addition of 9-fluorenylmethyl chloroformate (2.85 g, 11 mmol) in one portion. The reaction was allowed to warm to room temperature. TLC analysis was used to monitor the progress of the reaction and after 8 hours, indicated that a single product was formed. The reaction mixture was diluted with dichloromethane and washed with water and brine. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by flash column chromatography (Biotage Flash 40S, gradient elution from 10 to 20% ethyl acetate in hexanes) to provide the desired appropriately substituted 4-(fluorenylmethoxycarbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine. 
     Step B. Trichloroacetyl chloride (3.35 mL, 30 mmol) was added to a solution of an appropriately substituted 4-(fluorenylmethoxycarbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step A (10 mmol) and N,N-diisopropylethyl amine (3.48 mL, 20 mmol) in dichloromethane, and the solution was stirred at ambient temperature for 2 hours. An aqueous solution of sodium bicarbonate (0.5 M) was added to the mixture and the organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was dissolved in a solution of piperidine in N,N-dimethylformamide (20%, v/v) and stirred until the starting material was no longer observed by HPLC/TLC analysis. The mixture was diluted with ethyl acetate and washed with water. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. The desired appropriately substituted 2,2,2-trichloro-1-[10-(4-aminobenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}-ethanone was isolated by flash chromatography (Biotage, Flash 40M, gradient elution from 20 to 30% ethyl acetate in hexanes). 
     Step C. An appropriately substituted 1,4-diketone (25 mmol) was added to a vial containing an appropriately substituted aniline of Step B (4.4 mmol) followed by the addition of acetic acid (1 mL). The contents of the vial were stirred and heated (80° C.) without the vial capped (to allow for the removal of water). After 1 hour the solution was diluted with ethyl acetate (20 mL). The organic phase was washed with water, aqueous sodium bicarbonate and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by flash column chromatography to afford the desired appropriately substituted 2,2,2-trichloro-1-{10-{4-(1H-pyrrol-1-yl)-benzoyl]-10,11-dihydro[2,1-c][1,4]benzodiazepin-3-yl}-ethanone. 
     Step D. The material from Step C (3.85 mmol) was dissolved in tetrahydrofuran (10 mL) and treated with aqueous sodium hydroxide (2 N, 3 mL). The mixture was allowed to stir with heating (80° C.) overnight. After cooling to room temperature, aqueous hydrochloric acid (2 N, 3.2 mL) was added and product was recovered by extraction with ethyl acetate. The combined extracts were evaporated and the residue purified by flash column chromatography, eluting with a gradient of 20 to 50% ethyl acetate in hexanes to provide the desired appropriately substituted title compound. 
     EXAMPLE 306 
     {10-[4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1-piperazinyl)methanone 
     HRMS [(+)ESI, m/z]: 538.28136 [M+H] + . Calcd. for C 32 H 36 N 5 O 3 : 538.28127 
     EXAMPLE 307 
     {10-[4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-methyl-1,4-diazepan-1-yl)methanone 
     HRMS [(+)ESI, m/z]: 552.29613 [M+H] + . Calcd. for C 33 H 38 N 5 O 3 : 552.29692 
     EXAMPLE 308 
     N-[3-(Dimethylamino)propyl]-10-[4-(2,5-dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 540.29503 [M+H] + . Calcd. for C 32 H 38 N 5 O 3 : 540.29692 
     EXAMPLE 309 
     N-[2-(Dimethylamino)ethyl]-10-[4-(2,5-dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 540.29642 [M+H] + . Calcd. for C 32 H 38 N 5 O 3 : 540.29692 
     EXAMPLE 310 
     N-[3-(Dimethylamino)propyl]-10-[4-(2,5-dimethyl-i H-pyrrol-1-yl)-3-methoxybenzoyl]-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 554.31172 [M+H] + . Calcd. for C 33 H 40 N 5 O 3 : 554.31257 
     EXAMPLE 311 
     {10-[4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3-methoxy-benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-piperidinyl)-1-piperidinyl]-methanone 
     HRMS [(+)ESI, m/z]: 606.34354 [M+H] + . Calcd. for C 37 H 44 N 5 O 3 : 606.34387 
     EXAMPLE 312 
     10-[4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-N-[3-(1H-imidazol-1-yl)propyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 563.27492 [M+H] + . Calcd. for C 33 H 35 N 6 O 3 : 563.27652 
     EXAMPLE 313 
     {10-[4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[4-(1-pyrrolidinyl)-1-piperidinyl]methanone 
     HRMS [(+)ESI, m/z: 592.32816 [M+H] + . Calcd. for C 36 H 42 N 5 O 3 : 592.32822 
     EXAMPLE 314 
     10-[4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-N-[2-(1-piperidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z]: 566.31192 [M+H] + . Calcd. for C 34 H 40 N 5 O 3 : 566.31257 
     EXAMPLE 315 
     10-[4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide 
     HRMS [(+)ESI, m/z: 566.31226 [M+H] + . Calcd. for C 34 H 40 N 5 O 3 : 566.31257 
     EXAMPLE 316 
     {4-[2-(Dimethylamino)ethyl]-1-piperazinyl}{10-[4-(2,5-dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 595.33898 [M+H] + . Calcd. for C 35 H 43 N 6 O 3 : 595.33912 
     EXAMPLE 317 
     {10-[4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}{4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methanone 
     HRMS [(+)ESI, m/z]: 637.34914 [M+H] + . Calcd. for C 37 H 45 N 6 O 4 : 637.34968 
     EXAMPLE 318 
     (4-Allyl-1-piperazinyl){10-[4-(2,5-dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 564.29788 [M+H] + . Calcd. for C 34 H 38 N 5 O 3 : 564.29692 
     EXAMPLE 319 
     {10-[4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}(4-isopropyl-1-piperazinyl)methanone 
     WAC-510342 
     HRMS [(+)ESI, m/z]: 566.31184 [M+H] + . Calcd. for C 34 H 40 N 4 O 3 : 566.31257 
     EXAMPLE 320 
     {4-[3-(Dimethylamino)propyl]-1-piperazinyl}{10-[4-(2,5-dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 609.35380 [M+H] + . Calcd. for C 36 H 45 N 6 O 3 : 609.35477 
     EXAMPLE 321 
     {10-[4-(2,5-Dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}[(2S)-2-(1-pyrrolidinylmethyl) pyrrolidinyl]methanone 
     HRMS [(+)ESI, m/z]: 592.32768 [M+H] + . Calcd. for C 36 H 42 N 5 O 3 : 592.32822 
     EXAMPLE 322 
     [(3R)-3-(Dimethylamino)pyrrolidinyl]{10-[4-(2,5-dimethyl-1H-pyrrol-1-yl)-3-methoxybenzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}methanone 
     HRMS [(+)ESI, m/z]: 552.29598 [M+H] + . Calcd. for C 33 H 38 N 5 O 3 : 552.29692 
     EXAMPLE 323 
     [3-(4-Methyl-piperazine-1-carbonyl)-4H-10H-3a,5,9-triaza-benzo[f]azulen-9-yl]-(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)-methanone 
     Step A. 2-Chloromethyl-pyridine-3-carboxylic acid methyl ester 
     A solution of methyi 2-methyinicotinate (20.0 g, 0.132 mol) and trichloroisocyanuric acid (46.0 g, 0.198 mol) in dichloromethane (100 mL) was stirred at room temperature overnight. The reaction mixture was then washed with saturated aqueous sodium carbonate and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and the solvent evaporated in vacuo to provide the title compound as a yellow liquid (11. 2 g), which is used as such in the next step. 
     Step B. 2-(2-Formyl-pyrrol-1-ylmethyl)-pyridine-3-carboxylic acid methyl ester 
     To a suspension of sodium hydride (5.8 g, 0.12 mol) in dry N,N-dimethylformamide (25 mL) was added slowly under nitrogen a solution of pyrrole 2-carboxaldehyde (10.5 g, 0.11 mol) in N,N-dimethylformamide (10 mL), and the reaction mixture was stirred at room temperature for 30 minutes. The reaction was then cooled to 5° C. and 2-chloromethyl-pyridine-3-carboxylic acid methyl ester of Step A was added slowly, the temperature being maintained at or below 20° C. After the addition was complete, the reaction was stirred at room temperature for 30 minutes. The mixture was evaporated to dryness, and the residue was dissolved in ethyl acetate (250 mL). This solution was washed with water and dried over anhydrous magnesium sulfate. The solvent was then removed in vacuo leaving a dark crystalline solid (23.4 g), which was purified by chromatography on silica gel eluting with a gradient of ethyl acetate/petroleum ether to provide the title compound as a tan crystalline solid (13.75 g), m.p. 91–93° C. 
     Step C. 1-(3-Phenacetyl-pyridin-2-yl methyl)carbamic acid benzyl ester 
     To a stirred solution of 2-(2-formyl-pyrrol-1-ylmethyl)-pyridine-3-carboxylic acid methyl ester of Step B (13.65 g, 55.9 mmol) in methanol (50 mL) was added sodium hydroxide (2.2 g, 55.9 mmol.). The reaction mixture was refluxed under nitrogen for 2 hours, and then the solvent was removed in vacuo. A portion of the residual yellow solid (5 g) was suspended in a mixture of benzyl alcohol (20 mL) and benzene (30 mL). Diphenylphosphoryl azide (6.54 g, 1.2 equiv.) was added, and the reaction was slowly heated to reflux. After refluxing for 1 hour, the mixture was cooled and washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness to provide the title compound as a tan crystalline solid (4.4 g), m.p. 109–111° C. 
     Step D. 9,10-Dihydro-4H-3a,5,9-triaza-benzo[f]azulene 
     A stirred mixture of 1-(3-phenacetyl-pyridin-2-yl methyl)-carbamic acid benzyl ester of Step C (1.0 g), in ethyl acetate (10 mL) containing 10% palladium on charcoal (10 mg.), magnesium sulfate (0.010 g) and 5 drops of acetic acid was hydrogenated at atmospheric pressure until hydrogen uptake ceased. The reaction mixture was then filtered through Celite and the solvent removed in vacuo. The crude product (yellow crystalline solid, 0.530 g) was purified by chromatography on silica gel eluting with a gradient of ethyl acetate in petroleum ether to provide the title product as a yellow crystalline solid, m.p. 171–172° C. 
     Step E. (4-Bromo-3-methyl-phenyl)-(4H,10H-3a,5,9-triaza-benzo[f]azulen-9-yl)-methanone 
     To a stirred solution of the 9,10-dihydro-4H-3a,5,9-triaza-benzo[f]azulene of Step D (1.0 g) in dichloromethane (10 mL) was added 3-methyl-4-bromobenzoyl chloride (1.39 g) and triethylamine (1.1 mL). After stirring for 2.5 hours, the reaction mixture was washed with water, dried over anhydrous magnesium sulfate, filtered and the solvent removed in vacuo to provide the title product as a tan crystalline solid (2.3 g), which was used without further purification. 
     Step F. (2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)-(4H,10H-3a,5,9-triaza-benzo[f]azulen-9-yl)-methanone 
     A stirred mixture of (4-bromo-3-methyl-phenyl)-(4H,10H-3a,5,9-triaza-benzo[f]azulen-9-yl)-methanone of Step E (1.0 g), 2-trifluoromethyl-boronic acid (1.49 g, 3.0 equiv.), potassium phosphate (2.2 g) and a catalytic amount (0.050 g) of tetrakis(triphenylphosphine) palladium (0) in dioxane (10 mL) was refluxed for 2 hours. The solvent was then removed in vacuo and the residue dissolved in dichloromethane. The solution was then washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was then chromatographed on silica gel eluting with 5% ethyl acetate in dichloromethane to yield a colorless gum which crystallized upon addition of a little diethyl ether to provide the title compound as a cream-colored crystalline solid (0.500 g), m.p. 153–155° C. 
       1 H NMR (DMSO-d 6 , 400 MHz): δ 1.85 (s, 3H), 5.10 (s, 2H), 5.40 (s, 2H), 5.90 (t, 1H), 6.00 (s, 1H), 6.90 (t, 1H), 6.94 (d, 1H), 7.03 (d, 1H), 7.12 (dd, 1H), 7.23 (d, 1H), 7.28 (s, 1H), 7.37 (d, 1H), 7.58 (t, 1H), 7.68 (t, 1H), 7.80 (d, 1H), 8.27 (d, 1H) MS [(+)ESI, m/z]: 448 [M+H] + . Anal. Calcd. for C 26 H 20 F 3 N 3 O: C, 69.79; H, 4.51; N, 9.39. Found: C, 69.91; H, 4.30; N, 9.26. 
     Step G. 2,2,2-Trichloro-1-{[9-(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carbonyl]-9,10-dihydro-4H-3a,5,9-triaza-benzo[f]azulen-3-yl}-ethanone 
     To a solution of (2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)-(4H, 10H-3a,5,9-triaza-benzo[f]azulen-9-yl)-methanone in methylene chloride was added trichloroacetyl chloride (1.1 equiv.) and triethylamine (1.5 equiv,) After stirring overnight at room temperature, the reaction was washed with water, dried over anhydrous magnesium sulfate, and evaporated to dryness to provide the crude title compound which was used as such in the next step. 
     Step H. 9-[(2-Methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4yl)carbonyl]-9,10-dihydro-3a,5,9-triaza-benzo[f]azulen-3-carboxylic acid 
     To a solution of 2,2,2-trichloro-1-{[9-(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carbonyl]-9,10-dihydro-4H-3a,5,9-triaza-benzo[f]azulen-3-yl}-ethanone of Step G in acetone was added 2.5 N sodium hydroxide (1.0 equiv.). After stirring overnight, the solvent was removed in vacuo leaving the crude sodium salt of the carboxylic acid. This was dissolved in anhydrous ethanol and treated with 2 N hydrochloric acid (1.0 equiv.). The solvent was removed in vacuo, the residue redissolved in anhydrous ethanol and the solvent again removed in vacuo. The crude title compound was then dried in vacuo over phosphorus pentoxide. 
     Step I. [3-(4-Methyl-piperazine-1-carbonyl)-4H-10H-3a,5,9-triaza-benzo[f]azulen-9-yl]-(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)-methanone 
     To a solution of the 9-[(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4yl)carbonyl]-9,10-dihydro-3a,5,9-triaza-benzo[f]azulen-3-carboxylic acid (3.38 mmol) of Step H in N,N-dimethylformamide (20 mL) was added 1-hydroxybenzotriazole (1.1 equiv.) and [3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1.2 equiv. ), followed by 4-methyl-piperazine (1.2 equiv.) and N,N-diisopropylethyl amine (1.5 equiv.). The reaction mixture was stirred overnight, then diluted with ethyl acetate and washed with water and saturated aqueous sodium bicarbonate. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification of the residue was effected by chromatography on silica gel eluting with a gradient of methanol in ethyl acetate to provide the title compound as a white foam.